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1.  High Dose Intraveneous Vitamin C and Chikungunya Fever: A Case Report 
The Chikungunya (CHIKV) fever is a viral disease produced by a single-stranded RNA Alphavirus from the Togaviridae genus. Its transmission occurs only through mosquito vectors, principally Aedes aegypti. It requires a human-mosquito-human transmission cycle. It is associated with severe arthritis/arthralgias, myalgias, high fever, headache, and maculopapular rash. Joint ache appears to be symmetrical. The virus has an incubation period of 2 to 7 days, where the high fever is typically presented. It is followed by arthralgias and myalgias, and rashes, which last for 3 to 5 days. However, the arthralgias can persist for months after the infection, which can contribute to severe arthritis. As of now, no vaccine exists for the virus and no official treatment has been developed aside from standard procedures of the use of acetaminophen (paracetamol), and non-steroidal anti-inflammatory drugs. This is a case report of a 54-year old Hispanic individual that reported left shoulder pain, left knee pain and fever. The symptoms started on a Saturday in September 2014 in middle of the night. The patient was treated with high doses of intravenous vitamin C over two days. The symptoms resolved after the infusions without any side effects. Based on the positive outcome in this case, we propose that intravenous vitamin C should be studied further as a potential treatment for acute viral infections.
PMCID: PMC4335641
2.  Evidence of Tree Species’ Range Shifts in a Complex Landscape 
PLoS ONE  2015;10(1):e0118069.
Climate change is expected to change the distribution of species. For long-lived, sessile species such as trees, tracking the warming climate depends on seedling colonization of newly favorable areas. We compare the distribution of seedlings and mature trees for all but the rarest tree species in California, Oregon and Washington, United States of America, a large, environmentally diverse region. Across 46 species, the mean annual temperature of the range of seedlings was 0.120°C colder than that of the range of trees (95% confidence interval from 0.096 to 0.144°C). The extremes of the seedling distributions also shifted towards colder temperature than those of mature trees, but the change was less pronounced. Although the mean elevation and mean latitude of the range of seedlings was higher than and north of those of the range of mature trees, elevational and latitudinal shifts run in opposite directions for the majority of the species, reflecting the lack of a direct biological relationship between species’ distributions and those variables. The broad scale, environmental diversity and variety of disturbance regimes and land uses of the study area, the large number and exhaustive sampling of tree species, and the direct causal relationship between the temperature response and a warming climate, provide strong evidence to attribute the observed shifts to climate change.
PMCID: PMC4310600  PMID: 25634090
3.  Alterations in functional connectivity between hippocampus and prefrontal cortex as a correlate of depressive symptoms in temporal lobe epilepsy 
Epilepsy & behavior : E&B  2013;29(3):10.1016/j.yebeh.2013.09.039.
Depression is a common comorbidity in temporal lobe epilepsy (TLE) that is thought to have a neurobiological basis. This study investigated the functional connectivity (FC) of medial temporal networks in depression symptomatology of TLE and the relative contribution of structural versus FC measures. Volumetric and functional connectivity MRI (fcMRI) were performed on nineteen patients with TLE and 20 controls. The hippocampi and amygdalae were selected as seeds, and five prefrontal and five cingulate regions of interest (ROIs) were selected as targets. Low-frequency blood-oxygen-level-dependent signals were isolated from fcMRI data, and ROIs with synchronous signal fluctuations with the seeds were identified. Depressive symptoms were measured by the Beck Depression Inventory-II. Patients with TLE showed greater ipsilateral hippocampal atrophy (HA) and reduced FC between the ipsilateral hippocampus and ventral posterior cingulate cortex (vPCC). Neither HA nor hippocampal-vPCC FC asymmetry was a robust contributor to depressive symptoms. Rather, hippocampal-anterior prefrontal FC was a stronger contributor to depressive symptoms in left TLE (LTLE). Conversely, right amygdala FC was correlated with depressive symptoms in both patient groups, with a positive and negative correlation in LTLE and right TLE (RTLE), respectively. Frontolimbic network dysfunction is a strong contributor to levels of depressive symptoms in TLE and a better contributor than HA in LTLE. In addition, the right amygdala may play a role in depression symptomatology regardless of side of the epileptogenic focus. These findings may inform the treatment of depressive symptoms in TLE and inspire future research to help guide surgical planning.
PMCID: PMC3876964  PMID: 24176688
Temporal Lobe Epilepsy; Functional Connectivity; Hippocampus; Amygdala; Asymmetry
4.  Abnormal P600 word repetition effect in elderly persons with Preclinical Alzheimer’s disease 
Cognitive neuroscience  2013;4(0):10.1080/17588928.2013.838945.
We sought cognitive event-related potential (ERP) biomarkers of “Preclinical Alzheimer’s disease” (Pre-AD) using an incidental verbal learning paradigm with high sensitivity to prodromal AD. Seven elderly persons, with normal cognition at the time of ERP recordings, but who showed subsequent cognitive decline or AD pathology at autopsy (n=5, mean Braak stage=2.8), were compared to 12 “robust” normal elderly (RNE) who remained cognitively normal (Mfollow-up=9.0 years). EEG was recorded during a word repetition paradigm (semantically congruous (50%) and incongruous target words repeat ~10–140 seconds later). The RNE P600 congruous word repetition ERP effects (New minus Old congruous words) were significantly larger than in Pre-AD (mean amplitudes = 3.28 vs. 0.10 µV, p= 0.04). High group discrimination (84%) was achieved (by a P600 amplitude cutoff of ~1.5 µV). Abnormal P600 word repetition effects in cognitively normal elderly persons may be an important sign of synaptic dysfunction and Preclinical AD.
PMCID: PMC3841188  PMID: 24090465
Mild Cognitive Impairment; EEG; memory; Alzheimer’s disease; Event-related potentials
5.  Functional Connectivity of the Hippocampus in Temporal Lobe Epilepsy: Feasibility of a Task-Regressed Seed-Based Approach 
Brain Connectivity  2013;3(5):464-474.
Objective: Resting-state functional connectivity (FC) has revealed marked network dysfunction in patients with temporal lobe epilepsy (TLE) compared to healthy controls. However, the nature and the location of these changes have not been fully elucidated nor confirmed by other methodologies. We assessed the presence of hippocampal FC changes in TLE based on the low frequency residuals of task-related functional magnetic resonance imaging data after the removal of task-related activation [i.e., task-regressed functional connectivity MRI (fcMRI)]. Method: We employed a novel, task-regressed approach to quantify hippocampal FC, and compare hippocampal FC in 17 patients with unilateral TLE (9 left) with 17 healthy controls. Results: Our results suggest widespread FC reductions in the mesial cortex associated with the default mode network (DMN), and some local FC increases in the lateral portions of the right hemisphere. We found more pronounced FC decreases in the left hemisphere than in the right, and these FC decreases were greatest in patients with left TLE. Moreover, the FC reductions observed between the hippocampus and posterior cingulate, inferior parietal, paracentral regions are in agreement with previous resting state studies. Conclusions: Consistent with the existing literature, FC reductions in TLE appear widespread with prominent reductions in the medial portion of the DMN. Our data expand the literature by demonstrating that reductions in FC may be greatest in the left hemisphere and in patients with left TLE. Overall, our findings suggest that task-regressed FC is a viable alternative to resting state and that future studies may extract similar information on network connectivity from already existing datasets.
PMCID: PMC3796326  PMID: 23869604
default mode network; DMN; fMRI; fMRI methods; resting-state; seed-based; task-regressed
6.  Treatment of multiple traumatized anterior teeth associated with an alveolar bone fracture in a 20-year-old patient: A 3-year follow up 
Intrusive luxation is a type of recognizable luxation injury represented by a deeper axial displacement of the tooth toward the alveolar bone. Treatment strategies include waiting for the tooth to return to its position, immediate surgical repositioning, and repositioning through dental traction by orthodontic devices. The aim of this case report was to present the management of severe dental trauma and later restoration following IADT. A 20-year-old patient was presented after fainting at home four hours before, resulting in a dento-alveolar trauma. Clinical examinations revealed a traumatic intrusion, in 1.2, 1.1 and 2.1, uncomplicated crown fractures in 1.1 and 2.1 and a complicated crown-root fracture in 2.2. The diagnosis was confirmed with CBCT. Following IADT protocol, the emergency treatment consisted of the surgical repositioning and semi-rigid splinting using orthodontic wire-composite, replacing the buccal bone plate, and postoperative instructions to the patient regarding oral hygiene. After 2 weeks the root canal treated and filled with fiberglass posts in 1.2, 1.1, 2.1 and 2.2. Splint was removed after 4 weeks and the IADT reassessment protocol followed, with revisions at 6-8 weeks, 6 months, a year and annual reviews for 5 years. A year after the treatment, the traumatized teeth were restored with minimally invasive preparations of feldspathic ceramic. Esthetics and function were recorded with a 3-year follow-up period.
Key words:Intrusive luxation, dental trauma, crown-root fracture, dento-alveolar trauma, permanent tooth, CBCT.
PMCID: PMC4282913  PMID: 25593668
7.  Isokinetic Leg Strength and Power in Elite Handball Players 
Journal of Human Kinetics  2014;41:227-233.
Isokinetic strength evaluation of the knee flexion and extension in concentric mode of contraction is an important part of the comprehensive evaluation of athletes. The aims of this study were to evaluate the isokinetic knee peak torque in both the extension and flexion movement in the dominant and non-dominant leg, and the relationship with jumping performance. Twelve elite male handball players from the top Spanish handball division voluntary participated in the study (age 27.68 ± 4.12 years; body mass 92.89 ± 12.34 kg; body height 1.90 ± 0.05 m). The knee extensor and flexor muscle peak torque of each leg were concentrically measured at 60º/s and 180º/s with an isokinetic dynamometer. The Squat Jump and Countermovement Jump were performed on a force platform to determine power and vertical jump height. Non-significant differences were observed between legs in the isokinetic knee extension (dominant= 2.91 ± 0.53 Nm/kg vs non-dominant = 2.70 ± 0.47 Nm/kg at 60º/s; dominant = 1.90 ± 0.31 Nm/kg vs non-dominant = 1.83 ± 0.29 Nm/kg at 180º/s) and flexion peak torques (dominant = 1.76 ± 0.29 Nm/kg vs non-dominant = 1.72 ± 0.39 Nm/kg at 60º/s; dominant = 1.30 ± 0.23 Nm/kg vs non-dominant = 1.27 ± 0.35 Nm/kg at 180º/s). Low and non-significant correlation coefficients were found between the isokinetic peak torques and vertical jumping performance (SJ = 31.21 ± 4.32 cm; CMJ = 35.89 ± 4.20 cm). Similar isokinetic strength was observed between the legs; therefore, no relationship was found between the isokinetic knee flexion and extension peak torques as well as vertical jumping performance in elite handball players.
PMCID: PMC4120456  PMID: 25114749
isokinetic; handball; peak torque; power; jumping
9.  Tacalcitol in the Treatment of Acquired Perforating Collagenosis 
Case Reports in Dermatology  2014;6(1):69-73.
Acquired perforating collagenosis (APC) is a rare perforating dermatosis characterized by transepidermal collagen elimination. We describe a 65-year-old patient, with long-standing type 2 diabetes mellitus and a 2-year history of itchy hyperkeratotic nodules situated on the back, who was subsequently diagnosed with APC. Treatment included topical corticosteroids and antihistamines, without improvement of the lesions. However, therapy with topical tacalcitol administered for 2 months produced a significant response leading to complete remission of APC.
PMCID: PMC3975195  PMID: 24707254
Acquired perforating collagenosis; Perforating collagenosis; Elastosis perforans serpiginosa; Vitamin D3 analogues; Tacalcitol
10.  Radiographic technical quality of root canal treatment performed ex vivo by dental students at Valencia University Medical and Dental School, Spain 
Objectives: To evaluate radiographically the quality of root canal fillings and compare manual and rotary preparation performed on extracted teeth by undergraduate dental students. Study Design: A total of 561 premolars and molars extracted teeth were prepared using nickel-titanium rotary files or manual instrumentation and filled with gutta-percha using a cold lateral condensation technique, by 4th grade undergraduate students. Periapical radiographs were used to assess the technical quality of the root canal filling, evaluating three variables: length, density and taper. These data were recorded, scored and used to study the “technical success rate” and the “overall score”. The length of each root canal filling was classified as acceptable, short and overfilled, based on their relationship with the radiographic apex. Density and taper of filling were evaluated based on the presence of voids and the uniform tapering of the filling, respectively. Statistical analysis was used to evaluate the quality of root canal treatment, considering p < 0.05 as a statistical significant level. Results: The percentage of technical success was 44% and the overall score was 7.8 out of 10. Technical success and overall score were greater with rotary instruments (52% against 28% with a manual one, p < 0.001; 8.3 against 6.7 respectively, p < 0.001). Conclusions: It appears that inexperienced operators perform better root canal treatment (RCT) with the use of rotary instrumentation.
Key words:Dental education, endodontics, rotary instrumentation, radiographs, root canal treatment, undergraduate students.
PMCID: PMC3909440  PMID: 24121911
11.  Lipid raft-mediated Akt signaling as a therapeutic target in mantle cell lymphoma 
Blood Cancer Journal  2013;3(5):e118-.
Recent evidence shows that lipid raft membrane domains modulate both cell survival and death. Here, we have found that the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway is present in the lipid rafts of mantle cell lymphoma (MCL) cells, and this location seems to be critical for full activation and MCL cell survival. The antitumor lipids (ATLs) edelfosine and perifosine target rafts, and we found that ATLs exerted in vitro and in vivo antitumor activity against MCL cells by displacing Akt as well as key regulatory kinases p-PDK1 (phosphatidylinositol-dependent protein kinase 1), PI3K and mTOR (mammalian TOR) from lipid rafts. This raft reorganization led to Akt dephosphorylation, while proapoptotic Fas/CD95 death receptor was recruited into rafts. Raft integrity was critical for Ser473 Akt phosphorylation. ATL-induced apoptosis appeared to correlate with the basal Akt phosphorylation status in MCL cell lines and primary cultures, and could be potentiated by the PI3K inhibitor wortmannin, or inhibited by the Akt activator pervanadate. Classical Akt inhibitors induced apoptosis in MCL cells. Microenvironmental stimuli, such as CD40 ligation or stromal cell contact, did not prevent ATL-induced apoptosis in MCL cell lines and patient-derived cells. These results highlight the role of raft-mediated PI3K/Akt signaling in MCL cell survival and chemotherapy, thus becoming a new target for MCL treatment.
PMCID: PMC3674457  PMID: 23727661
mantle cell lymphoma; lipid rafts; PI3K/Akt signaling; Akt phosphorylation; apoptosis; synthetic antitumor lipids
12.  MRI Analysis in Temporal Lobe Epilepsy: Cortical Thinning and White Matter Disruptions Are Related to Side of Seizure Onset 
Epilepsia  2011;52(12):2257-2266.
Past studies reported more widespread structural brain abnormalities in patients with left compared to right temporal lobe epilepsy (TLE), but the profile of these differences remain unknown. This study investigated the relationship between cortical thinning, white matter compromise, epilepsy variables, and the side of seizure onset, in patients with TLE.
We performed diffusion tensor imaging tractography and cortical thickness analyses of 18 patients with left TLE (LTLE), 18 patients with right TLE (RTLE), and 36 controls. We investigated the relationship between brain structural abnormalities, side of seizure onset, age of seizure onset, and disease duration.
Key findings
TLE groups displayed cortical thinning and white matter compromise, predominately on the side ipsilateral to the seizure onset. Relative to RTLE, patients with LTLE showed more widespread abnormalities, particularly in white matter fiber tracts. Greater compromise in white matter integrity was associated with earlier age of seizure onset, while cortical thinning was marginally associated with disease duration.
These data support previous findings of LTLE showing greater structural compromise than RTLE, and suggest that mechanisms may not be uniform for gray and white matter compromise in patients with LTLE and RTLE. These results may indicate that LTLE is different than RTLE, possibly due to greater vulnerability of the left hemisphere to early injury and the progressive effects of seizures.
PMCID: PMC3230670  PMID: 21972957
epilepsy; MRI; diffusion tensor imaging; cortical thickness
13.  Multilocus Family-Based Association Analysis of Seven Candidate Polymorphisms with Essential Hypertension in an African-Derived Semi-Isolated Brazilian Population 
Background. It has been widely suggested that analyses considering multilocus effects would be crucial to characterize the relationship between gene variability and essential hypertension (EH). Objective. To test for the presence of multilocus effects between/among seven polymorphisms (six genes) on blood pressure-related traits in African-derived semi-isolated Brazilian populations (quilombos). Methods. Analyses were carried out using a family-based design in a sample of 652 participants (97 families). Seven variants were investigated: ACE (rs1799752), AGT (rs669), ADD2 (rs3755351), NOS3 (rs1799983), GNB3 (rs5441 and rs5443), and GRK4 (rs1801058). Sensitivity analyses were further performed under a case-control design with unrelated participants only. Results. None of the investigated variants were associated individually with both systolic and diastolic BP levels (SBP and DBP, respectively) or EH (as a binary outcome). Multifactor dimensionality reduction-based techniques revealed a marginal association of the combined effect of both GNB3 variants on DBP levels in a family-based design (P = 0.040), whereas a putative NOS3-GRK4 interaction also in relation to DBP levels was observed in the case-control design only (P = 0.004). Conclusion. Our results provide limited support for the hypothesis of multilocus effects between/among the studied variants on blood pressure in quilombos. Further larger studies are needed to validate our findings.
PMCID: PMC3463917  PMID: 23056922
14.  fMRI congruous word repetition effects reflect memory variability in normal elderly 
Neurobiology of aging  2008;31(11):1975-1990.
Neural circuits mediating repetition effect for semantically congruous words on functional MRI were investigated in seventeen normal elderly (mean age = 70). Participants determined if written words were semantically congruent (50% probability) with spoken statements. Subsequent cued-recall revealed robust explicit memory only for congruous items (83% versus 8% for incongruous). Event-related BOLD responses to New > Old congruous words were found in the left > right cingulate and fusiform gyri, left parahippocampal cortex, middle and inferior frontal gyri (IFG). A group with above-median subsequent recall had markedly more widespread BOLD responses than a Low-Recall subgroup, with larger responses in the left medial temporal lobe (LMTL), IFG, and bilateral cingulate gyri. The magnitude of LMTL activation (New–Old) correlated with subsequent cued-recall, while the spatial extent of LMTL activation (New > Old) correlated with recall and recognition. Both magnitude and spatial extent of left fusiform activation correlated with subsequent recall/recognition. A neural circuit of left-hemisphere brain regions, many identified as P600 generators by invasive electrophysiological studies, was activated by New > Old congruous words, likely mediating successful verbal encoding.
PMCID: PMC2946424  PMID: 19062135
Aging; Memory; Neuroimaging; Learning; Semantic; Language; Medial temporal lobe; Fusiform gyrus
15.  Perioperative and short-term advantages of mini-open approach for lumbar spinal fusion 
European Spine Journal  2009;18(8):1194-1201.
It has been widely reported a vascular and neurologic damage of the lumbar muscles produced in the classic posterior approach for lumbar spinal fusions. The purpose of this study is to demonstrate a better clinical and functional outcome in the postoperative and short term in patients undergoing minimal invasive surgery (“mini-open”) for this lumbar spinal arthrodesis. We designed a prospective study with a 30 individuals cohort randomized in two groups, depending on the approach performed to get a instrumented lumbar circumferential arthrodesis: “classic posterior” (CL group) or “mini-open” approach (MO group). Several clinical and functional parameters were assessed, including blood loss, postoperative pain, analgesic requirements and daily life activities during hospital stay and at the 3-month follow-up. Patients of the “mini-open approach” group had a significant lower blood loss and hospital stay during admission. They also had significant lower analgesic requirements and faster recovery of daily life activities (specially moderate efforts) when compared to the patients of the “classic posterior approach” group. No significant differences were found between two groups in surgery timing, X-rays exposure or sciatic postoperative pain. This study, inline with previous investigations, reinforces the concept of minimizing the muscular lumbar damage with a mini-open approach for a faster and better recovery of patients’ disability in the short term. Further investigations are necessary to confirm these findings in the long term, and to verify the achievement of a stable lumbar spinal fusion.
PMCID: PMC2899516  PMID: 19399538
Mini-invasive; Surgery; Lumbar fusion; Discopathy; Arthrodesis
16.  What does testosterone do for red deer males? 
Testosterone has been proposed to have a dual effect, enhancing sexual traits while depressing parasite resistance in males. Here, we test this hypothesis in red deer, examining males from captive populations during the whole annual cycle and males from natural populations during the breeding season. We first explored the effects of body size, age and sampling date on testosterone to avoid confounding effects. Our results show that in captive populations seasonal changes in testosterone levels were mirrored by changes in testes size, and that during the rut there was a strong correlation between both. In natural populations, males with higher testosterone levels had larger testes, improved sperm quality, smaller burr diameter, stronger antlers, higher haematocrit levels, and increased nematode parasite load. By contrast, no significant relationship was found between testosterone and spleen size or tick parasite load. We conclude that testosterone (i) improves males' reproductive investment and physical stamina, (ii) improves antler strength but reduces burr diameter, and (iii) imposes a cost in terms of depressed parasite resistance.
PMCID: PMC2664362  PMID: 19129132
immunocompetence handicap hypothesis; testosterone; antler; haematocrit; testes; sperm quality
17.  Angiosarcoma of the nasal cavity: a case report 
Cases Journal  2009;2:104.
Angiosarcomas are malignant neoplasias of rapid growth that develop from endothelial cells. They represent 2% of all sarcomas and only 1–4% are located in the aerodigestive tract. Since 1977, only 16 cases have been reported.
We present a 33-year-old male with spontaneous epistaxis that was refractory to cauterization. During physical examination, a smooth purplish tumor of 1.5 cm × 1.5 cm was identified. A CT scan showed a nonenhanced tumor in the left nostril on the uncinate process. A biopsy revealed an intermediate-grade angiosarcoma. Surgical removal followed by radiation therapy was performed with good result. Aerodigestive angiosarcomas have a better prognosis than angiosarcomas of other locations due to better cell differentiation and the presence of early symptoms. Recurrence can occur because of tumor tissue left during resection. Our patient continues tumor free after three years.
PMCID: PMC2640346  PMID: 19178724
18.  Absent event-related potential (ERP) word repetition effects in mild Alzheimer’s disease 
We hypothesized that an ERP word repetition paradigm, which reliably elicits and modulates the P600 and N400 components, would be particularly sensitive to the memory deficits and altered synaptic plasticity in mild Alzheimer’s disease (AD). The P600 (a late positive component, or ‘LPC’), and the N400, are sensitive indices of memory encoding and semantic processing, respectively.
We studied 11 patients with mild AD (mean MMSE = 22.9) and 11 elderly (mean age = 77.1) normal controls (NC) on a paradigm in which semantically ‘congruous’ category statement/exemplar pairs (50%) and ‘incongruous’ category statement/non-exemplar pairs (50%) repeat at 10–140 s intervals. A minimum of 19 channels ERP data were recorded and submitted to split-plot ANOVAs.
Normal ERP data showed: (1) a significant word repetition effect for congruous words, with a wide-spread late positivity between ~300 and 800 ms post-stimulus (P600) that is larger for New than Old words; (2) a significant N400 repetition effect for incongruous words, with a right posterior negativity that is reduced for Old relative to New words. By contrast, neither of these word repetition effects was reliably present in the mild AD group. Good group discrimination was achieved by requiring that both these repetition effects were ≥ the 10th percentile, with 100% sensitivity and 82% specificity.
We found significant abnormalities of the N400 and P600 in mild AD, with both potentials showing markedly reduced sensitivity to word repetition.
The absence of normal N400 and LPC/P600 word repetition effects suggests impaired functioning of their neural generators, several of which are located in medial temporal lobe predilection sites (e.g. anterior fusiform, parahippocampal gyrus, hippocampus) for AD/tau pathology.
PMCID: PMC1544116  PMID: 16644278
N400; LPC; P600; Memory; N100
19.  Virulence Characteristics of Klebsiella and Clinical Manifestations of K. pneumoniae Bloodstream Infections 
Emerging Infectious Diseases  2007;13(7):986-993.
Differences in clinical manifestations are due to virulence factors expressed by the organism.
We studied 455 consecutive episodes of Klebsiella pneumoniae bacteremia occurring in 7 countries. Community-acquired pneumonia and an invasive syndrome of liver abscess, meningitis, or endophthalmitis occurred only in Taiwan and South Africa. Infections by K1 and K2 capsular serotype, the mucoid phenotype, and aerobactin production were important determinants of virulence. The mucoid phenotype was seen in 94% of isolates in patients with community-acquired pneumonia and in 100% of isolates that caused the invasive syndrome in Taiwan and South Africa, compared with only 2% of isolates elsewhere. Mortality of mice injected with mucoid strains (69%) was strikingly higher than that occurring in mice injected with nonmucoid strains (3%, p<0.001). Differences in clinical features of bacteremic infection with K. pneumoniae are due to the virulence factors expressed by the organism.
PMCID: PMC2878244  PMID: 18214169
Klebsiella pneumoniae; gram-negative bacteremia; virulence; epidemiology; research
20.  Expression of SHV-2 β-Lactamase and of Reduced Amounts of OmpK36 Porin in Klebsiella pneumoniae Results in Increased Resistance to Cephalosporins and Carbapenems 
Antimicrobial Agents and Chemotherapy  2002;46(11):3679-3682.
A Klebsiella pneumoniae clinical isolate was resistant to cefoxitin, cefotaxime, ceftazidime, ceftazidime-clavulanate, piperacillin-tazobactam (MICs, >256 μg/ml in all cases), and meropenem (MIC, 16 μg/ml) and was intermediate to imipenem (MIC, 8 μg/ml). Decreased expression of the OmpK36 porin and expression of an SHV-2 β-lactamase contributed to the observed resistance to these β-lactam-containing agents.
PMCID: PMC128712  PMID: 12384391
21.  Role of the htrA Gene in Klebsiella pneumoniae Virulence  
Infection and Immunity  2002;70(9):4772-4776.
We recently described the use of mini-Tn5 to generate complement-sensitive mutants derived from a complement-resistant Klebsiella pneumoniae clinical isolate deficient in the lipopolysaccharide O side chain. One mutant with a reduced capacity to survive in nonimmune human sera carried the transposon inserted in the htrA gene. We cloned and sequenced the gene and predicted from the deduced amino acid sequence that the putative HtrA homolog contains structural features similar to those of previously described HtrA proteins. To investigate the biological functions and the role of the htrA gene in the virulence of K. pneumoniae, we constructed an isogenic mutant by insertion-duplication mutagenesis. Characterization of the mutant showed that it had greater sensitivity to temperature (50°C) and oxidative stress (H2O2) than the parent strain. Furthermore, the htrA mutant produced less capsule, bound more molecules of complement component C3, and was more sensitive to complement and whole-blood killing than was the parent strain. Finally, disruption of the htrA gene in a virulent K. pneumoniae strain caused a reduction of its virulence in a mice model. Our results indicate that the htrA gene plays an important role in the virulence of K. pneumoniae.
PMCID: PMC128236  PMID: 12183518
22.  Restriction fragment length polymorphism of the L-myc gene is not a prognostic factor in bladder cancer patients 
British Journal of Cancer  1999;79(11-12):1855-1858.
The L-myc restriction fragment length polymorphism has been suggested to be of prognostic significance in some types of primary tumours. We examined the prognostic and susceptibility significance of the L-myc genotype in a group of 98 bladder cancer patients. The L-myc genotype did not correlate with any pathologic parameter and does not offer any clinical utility in patients with bladder cancer. © 1999 Cancer Research Campaign
PMCID: PMC2362815  PMID: 10206304
proto-oncogenes; restriction fragment length polymorphism; bladder cancer; prognostic factors
23.  Capsular Polysaccharide Is a Major Complement Resistance Factor in Lipopolysaccharide O Side Chain-Deficient Klebsiella pneumoniae Clinical Isolates 
Infection and Immunity  2000;68(2):953-955.
We have previously demonstrated the existence of Klebsiella pneumoniae clinical isolates deficient in the lipopolysaccharide O side chain, the major factor for resistance to complement-mediated killing in this bacterial species. These isolates are complement resistant, and their mechanisms to resist complement were investigated by selecting transposon-generated complement-sensitive mutants. One mutant with a drastically reduced capacity to grow in nonimmune human serum carried the transposon inserted in an open reading frame of a gene cluster involved in capsule synthesis. This mutant produced less capsule, bound more molecules of the complement component C3, and was more sensitive to complement-mediated and opsonophagocytic killings than was the parent strain. Four additional clinical isolates representing four different K serotypes were studied, and results showed that capsular polysaccharide is a major complement resistance factor in these O side chain-deficient isolates.
PMCID: PMC97229  PMID: 10639470
24.  Identification and Characterization of a New Porin Gene of Klebsiella pneumoniae: Its Role in β-Lactam Antibiotic Resistance 
Journal of Bacteriology  1999;181(9):2726-2732.
Klebsiella pneumoniae porin genes were analyzed to detect mutations accounting for the porin deficiency observed in many β-lactam-resistant strains. PCR and Southern blot analysis revealed the existence of a third porin gene in addition to the OmpK36 and OmpK35 porin genes previously described. This new porin gene was designated ompK37 and is present in all of the clinical isolates tested. The OmpK37 porin gene was cloned, sequenced, and overexpressed in Escherichia coli. In contrast to that of the major porins, OmpK37 porin expression was only detectable by Western blot analysis in porin-deficient β-lactam-resistant strains, suggesting strong down regulation under standard laboratory conditions. Functional characterization suggested a narrower pore for the OmpK37 porin than for K. pneumoniae porins OmpK36 and OmpK35. This correlated with the susceptibility to certain β-lactam antibiotics, since a K. pneumoniae strain expressing porin OmpK37, but not porin OmpK36 or OmpK35, was less susceptible to β-lactam antibiotics than the same strain expressing either porin OmpK36 or OmpK35.
PMCID: PMC93711  PMID: 10217760
25.  Development of Resistance during Antimicrobial Therapy Caused by Insertion Sequence Interruption of Porin Genes 
We have demonstrated by using an in vitro approach that interruption of the OmpK36 porin gene by insertion sequences (ISs) is a common type of mutation that causes loss of porin expression and increased resistance to cefoxitin in Klebsiella pneumoniae. This mechanism also operates in vivo: of 13 porin-deficient cefoxitin-resistant clinical isolates of K. pneumoniae, 4 presented ISs in their ompK36 gene.
PMCID: PMC89229  PMID: 10103203

Results 1-25 (28)