CD4+CD25high+regulatory T cells (Tregs) are considered to be of vital importance for maintaining immunologic self-tolerance and preventing autoimmune diseases. These cells have been found to be deficient in skin lesions and in the peripheral blood of patients with psoriasis.
To investigate the role of Tregs in the pathogenesis of psoriasis and to evaluate the changes in Tregs in relation to the severity and the clinical course of psoriasis.
Immunohistochemistry (CD3, 4, 8, 79 and FOXP3) was performed in 22 psoriatic patients compared to 5 normal controls. Flow cytometry (CD3, 4, 8, 25 and FOXP3) was performed in 18 psoriatic patients and 8 normal volunteers and reverse transcriptase polymerase chain reaction (foxp3 mRNA) was performed in 8 psoriasis patients.
An increase in the FOXP3+ cell fraction was detected in the lesional psoriatic skin irrespective of the severity of psoriasis as compared with the normal skin. However, a decrease in FOXP3+ cells was observed in the samples obtained from psoriasis of 'acute course'. FOXP3+ Treg populations in the blood of the 'acute course' psoriasis was not different compared to that of 'chronic course' psoriasis and normal controls.
The deficiency of FOXP3+ Tregs in the lesional psoriatic skin might be responsible for the exacerbation of psoriasis.
CD4+CD25high+regulatory T cells; FOXP3; Psoriasis
AIM: To investigate the relationship between the function of vagus nerve and peptide YY3-36 and ghrelin levels after subtotal gastrectomy.
METHODS: We enrolled a total of 16 patients who underwent subtotal gastrectomy due to gastric cancer. All surgeries were performed by a single skilled surgeon. We measured peptide YY3-36, ghrelin, leptin, insulin, growth hormone levels, and body weight immediately before and one month after surgery.
RESULTS: Vagus nerve preservation group showed less body weight loss and less increase of peptide YY3-36 compared with vagotomy group (-5.56 ± 2.24 kg vs -7.85 ± 1.57 kg, P = 0.037 and 0.06 ± 0.08 ng/mL vs 0.19 ± 0.12 ng/mL, P = 0.021, respectively). Moreover, patients with body weight loss of less than 10% exhibited reduced elevation of peptide YY3-36 level, typically less than 20% [6 (66.7%) vs 0 (0.0%), P = 0.011, odd ratio = 3.333, 95% confidence interval (1.293, 8.591)].
CONCLUSION: Vagus nerve preservation contributes to the maintenance of body weight after gastrectomy, and this phenomenon may be related to the suppressed activity of peptide YY3-36.
Anal cushion; Anal incontinence; Liquids continence test; Wexner score; Hemorrhoidectomy
AIM: To investigate the efficacy of cap-fitted colonoscopy (CFC) with regard to cecal intubation time.
METHODS: Two hundred and ninety-five patients undergoing screening colonoscopy at Gospel Hospital, Kosin University College of Medicine were enrolled in this randomized controlled trial between January and December 2010. Colonoscopies were conducted by a single endoscopist. Patient characteristics including age, sex, body mass index, history of abdominal surgery, quality of preparation, and the presence of diverticulosis were recorded.
RESULTS: One hundred and fifty patients were allocated into a CFC group and 145 into a non-CFC (NCF) group. Cecal intubations were achieved in all patients. Cecal intubation time in the CFC group was significantly shorter than in the NCF group for specific conditions: age ≥ 60 years, prior abdominal surgery, and poor bowel preparation. The number of detected adenomas was higher in the CFC group than in the NCF group (P = 0.040).
CONCLUSION: CFC facilitated shortening of the cecal intubation time in difficult cases, and was more sensitive for detecting adenomas than was NCF.
Colonoscopy; Cap-fitted colonoscopy; Cecal intubation
A 32‐year‐old woman without a remarkable history presented at the emergency department with strangulation of the neck. CT scans of the neck revealed a displaced cricoid fracture. Six days after admission to hospital, hoarseness and dyspnoea disappeared. On the 10th day, the patient was discharged without complications. The traditional treatment guidelines for laryngeal trauma have recommended an early surgical intervention after immediate tracheotomy in cases of displaced fractures of the cricoid cartilage. The patient could be treated successfully through continuous monitoring of airway obstruction without surgical management.
Microneedles provide a minimally invasive means to transport molecules into the skin. A number of specific strategies have been employed to use microneedles for transdermal delivery.
The purpose of this study was to investigate the safety of two new digital microneedle devices (Digital Hand® and Digital Pro®; Bomtech Electronics Co., Ltd., Seoul, Korea) for the perforation of skin in skin-hairless-1 mice. This device replaces conventional needles and is designed specifically for intradermal delivery.
We used two newly developed digital microneedle devices to perforate the skin of skin-hairless-1 mice. We conducted a comparative study of the two digital microneedle devices and DTS® (Disk type-microneedle Therapy System; DTS lab., Seoul, Korea). To evaluate skin stability, we performed visual and dermatoscopic inspections, measurements of transepidermal water loss, and biopsies.
The two novel digital microneedle devices did not induce significant abnormalities of the skin on visual or dermatoscopic inspection, regardless of needle size (0.25~2.0 mm). No significant histopathological changes, such as inflammatory cell infiltration, desquamation of the stratum corneum, or disruption of the basal layer, were observed. The digital microneedle devices and microneedle therapy system produced similar results on measures of skin stability.
These two novel digital microneedle devices are safe transdermal drug delivery systems.
Digital; Mesotherapy; Safety; Water loss
Spontaneous reporting systems have several weak points, such as low reporting rates and insufficient clinical information. Active surveillance programs, such as ward rounds and a clinical data repository (CDR), may supplement the weak points of such systems. We developed active surveillance programs and compared them with existing spontaneous reporting.
We collected adverse drug event (ADE) cases, which comprised 1,055 cases of spontaneous reporting, 309 reported by ward rounds, and 229 found using a CDR. The clinical features and causative drugs were evaluated.
Active surveillance programs detected additional serious ADEs compared to those of spontaneous reporting programs. The ADEs identified by CDR (22.9%) were more likely to be classified as "serious" than those reported spontaneously (5.2%) or identified during ward rounds (10.3%). Causative drugs also differed. Opioids, antibiotics, and contrast media were the most common drugs causing ADEs in the spontaneous reporting system, whereas the active surveillance programs identified antibiotics as the most common causative drug. Clinical features also differed. ADEs with gastrointestinal manifestations were reported most frequently by spontaneous reporting programs. ADEs reported from active surveillance more reliably identified events associated with changes in laboratory values, such as hepatobiliary toxicity, hematologic manifestations, and nephrologic manifestations, compared with spontaneous reporting programs.
Our findings suggest that active surveillance programs can supplement spontaneous reporting systems in hospitals. ADEs related to laboratory abnormalities were monitored more closely by active surveillance programs and may be useful for identification of serious ADEs.
Drug toxicity; Spontaneous reporting; Active surveillance
Mucinous cystadenocarcinoma (MCA) in the breast is a rare neoplasm. There have been 13 cases of primary breast MCA reported. The MCA presents as a large, partially cystic mass in postmenopausal woman with a good prognosis. The microscopic findings resemble those of ovarian, pancreatic, or appendiceal MCA. The aspiration findings showed mucin-containing cell clusters in the background of mucin and necrotic material. The cell clusters had intracytoplasmic mucin displacing atypical nuclei to the periphery. Histologically, the tumor revealed an abundant mucin pool with small floating clusters of mucin-containing tumor cells. There were also small cysts lined by a single layer of tall columnar mucinous cells, resembling those of the uterine endocervix. The cancer cells were positive for mucin (MUC) 5 and negative for MUC2 and MUC6. This mucin profile is different from ordinary mucinous carcinoma and may be a unique characteristic of breast MCA.
Mucinous cystadenocarcinoma; Breast; MUC5; MUC2
The classic Dieulafoy lesion is a minute gastric mucosal defect which bleeds massively from an exposed artery. The typical endoscopic appearance of this lesion is a single, round mucosal defect with an artery protruding from its base in the absence of surrounding ulceration. We encountered an 89-year-old man who developed sudden massive fresh rectal bleeding. The source of hemorrhage was found at colonoscopy after careful irrigation and inspection to be a Dieulafoy lesion situated in rectum. Hemostasis was achieved successfully with epinephrine injection and endoscopic hemostatic clipping.
Hematochezia; Hemostasis; Colonoscopy; Clip
Glycogen rich clear cell carcinoma (GRCC) of the breast is a rare subtype of invasive ductal carcinoma and involves a poor prognosis. In the literature, less than 150 cases have been reported. Many researchers have attempted to characterize GRCC according to electron microscope, flow cytometry, or clinical data. However, an organized study of the immunophenotype of GRCC has yet to be reported.
Materials and Methods
Here, we present three cases of GRCC and their immunohistochemical profiles.
Histologically, all three cases contained periodic acid stain (PAS) positive and d-PAS labile granules in their clear cytoplasm. Case I showed positivity for only estrogen receptor (ER) and c-erbB2. Case II exhibited positivity for progesterone receptor and negativity for ER and c-erbB2. Case III presented with triple negative invasive carcinoma. The expression pattern of E-cadherin was concordant with epidermal growth factor receptor and c-kit, but discordant with ki-67. Among these three cases, p53-positive cases exhibited a low proliferative index (ki-67: 15%), while p53-negative cases showed a high proliferative index (ki-67: 50-60%).
In conclusion, the immunophenotype of GRCC is not uniform, but is similar to that of conventional ductal carcinoma.
Breast; carcinoma; clear cell; glycogen; immunohistochemistry
Bleeding from ectopic varices is rare and accounts for only 1% and 5% of all variceal bleeding. However, once the bleeding starts, it becomes difficult to control and is sometimes fatal. We faced a 65-year-old man with ruptured duodenal varices and injected N-butyl-2-cyanoacrylate into the spurting duodenal varices. As a result, oozing was successfully controlled. Subsequently, the patient remained hemodynamically stable, and no repeat -butyl-2-cyanoacrylate injection was needed. He was finally discharged one week later and has been followed-up for the last one year with no signs and symptoms to suggest any recurrence of bleeding.
Duodenum; Varice; Rupture
Transduction of mechanical stimuli by receptor neurons is essential for senses such as hearing, touch, and pain1–4. Ion channels play a role in neuronal mechanotransduction in invertebrates1; however, functional conservation of these ion channels in mammalian mechanotransduction is not observed. For example, NOMPC, a TRP ion channel, acts as a mechanotransducer in Drosophila melanogaster5 and Caenorhabditis elegans6,7; however, it has no orthologues in mammals. DEG/ENaC family members are mechanotransducers in C. elegans8 and potentially in D. melanogaster9; however, a direct role of its mammalian homologues in sensing mechanical force is not shown. Recently, Piezo1 and Piezo2 were identified as components of mechanically activated (MA) channels in mammals10. Piezos represent an evolutionary conserved family of transmembrane proteins. It is unknown whether Piezos function in mechanical sensing in vivo, and if they do, which mechanosensory modalities they mediate. Here, we study the physiological role of the single Piezo member in D. melanogaster (dpiezo). dpiezo expression in human cells induces mechanically activated currents, similar to its mammalian counterparts [Coste et al., accompanying paper11]. Behavioral responses to noxious mechanical stimuli were severely reduced in dpiezo knockout larvae, while responses to another noxious stimulus or touch were not affected. Knocking down dpiezo in sensory neurons that mediate nociception and express the DEG/ENaC ion channel pickpocket (ppk) was sufficient to impair responses to noxious mechanical stimuli. Furthermore, expression of dpiezo in these same neurons rescued the phenotype of the constitutive dpiezo knockout larvae. Accordingly, electrophysiological recordings from ppk-positive neurons revealed a dpiezo dependent, mechanically-activated current. Finally, we found that dpiezo and ppk function in parallel pathways in ppk-positive cells, and that mechanical nociception is abolished in the absence of both channels. These data demonstrate physiological relevance of Piezo family in mechanotransduction in vivo, supporting a role of Piezo proteins in mechanosensory nociception.
Mechanotransduction plays a crucial role in physiology. Biological processes including sensing touch and sound waves require yet unidentified cation channels that detect pressure. Mouse piezo1 (mpiezo1) and mpiezo2 induce mechanically activated cationic currents in cells; however, it is unknown if piezos are pore-forming ion channels or modulate ion channels. We show that Drosophila piezo (dpiezo) also induces mechanically activated currents in cells, but through channels with remarkably distinct pore properties including sensitivity to the pore blocker ruthenium red and single channel conductances. mpiezo1 assembles as a ~1.2 million-Dalton tetramer, with no evidence of other proteins in this complex. Finally, purified mpiezo1 reconstituted into asymmetric lipid bilayers and liposomes forms ruthenium red-sensitive ion channels. These data demonstrate that piezos are an evolutionarily conserved ion channel family involved in mechanotransduction.
The first X-ray crystal structure of the Y. pestis protein tyrosine phosphatase YopH in complex with an isothiazolidinone-based lead-fragment compound is reported.
Isothiazolidinone (IZD) heterocycles can act as effective components of protein tyrosine phosphatase (PTP) inhibitors by simultaneously replicating the binding interactions of both a phosphoryl group and a highly conserved water molecule, as exemplified by the structures of several PTP1B–inhibitor complexes. In the first unambiguous demonstration of IZD interactions with a PTP other than PTP1B, it is shown by X-ray crystallography that the IZD motif binds within the catalytic site of the Yersinia pestis PTP YopH by similarly displacing a highly conserved water molecule. It is also shown that IZD-based bidentate ligands can inhibit YopH in a nonpromiscuous fashion at low micromolar concentrations. Hence, the IZD moiety may represent a useful starting point for the development of YopH inhibitors.
YopH; isothiazolidinone; Yersinia pestis; protein tyrosine phosphatases
Targeting protein-protein interactions is gaining greater recognition as an attractive approach to therapeutic development. An example of this may be found with the human cellular protein encoded by the tumor susceptibility gene 101 (Tsg101), where interaction with the p6 C-terminal domain of the nascent viral Gag protein is required for HIV-1 particle budding and release. This association of Gag with Tsg101 is highly dependent on a “Pro-Thr-Ala-Pro” (“PTAP”) peptide sequence within the p6 protein. Although p6-derived peptides offer potential starting points for developing Tsg101-binding inhibitors, the affinities of canonical peptides are outside the useful range (Kd values greater than 50 μM). Reported herein are crystal structures of Tsg101 in complex with two structurally-modified PTAP-derived peptides. This data define new regions of ligand interaction not previously identified with canonical peptide sequences. This information could be highly useful in the design of Tsg101-binding antagonists.
protein-protein interactions; Tsg101; X-ray crystal structure; peptide analogues
Autophagy proteins are normally involved in the formation of double-membrane autophagosomes that mediate bulk cytoplasmic and organelle degradation. Here we report the modification of single-membrane vacuoles in cells by autophagy proteins. Light Chain 3 (LC3), a component of autophagosomes, is recruited to single-membrane entotic vacuoles, macropinosomes, and phagosomes harboring apoptotic cells, in a manner dependent on lipidation machinery including Atg5 and Atg7, and the class III PI-3-kinase Vps34. These downstream components of autophagy machinery, but not the upstream mTor-regulated Ulk- Atg13-Fip200 complex, facilitate lysosome fusion to single membranes and the degradation of internalized cargo. For entosis, a live cell engulfment program, the autophagy protein-dependent fusion of lysosomes to vacuolar membranes leads to the death of internalized cells, which are killed by their hosts. As pathogen-containing phagosomes can be targeted in a similar manner, the death of epithelial cells by this mechanism mimics pathogen destruction. These data define the targeting of single-membrane vacuoles as a property of autophagy pathway proteins in cells in the absence of pathogenic organisms.
Our current study reports the first KM optimization of a library of nitrophenylphosphate-containing substrates for generating an inhibitor lead against the Yersinia pestis outer protein phosphatase (YopH). A high activity substrate identified by this method (KM = 80 μM was converted from a substrate into an inhibitor by replacement of its phosphate group with difluoromethylphosphonic acid and by attachment of an aminooxy handle for further structural optimization by oxime-ligation. A co-crystal structure of this aminooxy-containing platform in complex with YopH allowed the identification of a conserved water molecule proximal to the aminooxy group that was subsequently employed for the design of furanyl-based oxime derivatives. By this process, a potent (IC50 = 190 nM) and non-promiscuous inhibitor was developed with good YopH selectivity relative to a panel of phosphatases. The inhibitor showed significant inhibition of intracellular Y. pestis replication at a non-cytotoxic concentration. The current work presents general approaches to PTP inhibitor development that may be useful beyond YopH.
Epidemiological studies suggest an inverse relationship between helminth infections and allergic disease, and several helminth-derived products have been shown to suppress allergic responses in animals. This study was undertaken to evaluate the effect of a crude extract of Caenorhabditis elegans on allergic airway inflammation in a murine model of asthma. Allergic airway inflammation was induced in BALB/c mice by sensitization with ovalbumin. The effect of the C. elegans crude extract on the development of asthma and on established asthma was evaluated by analyzing airway hyperresponsiveness, serum antibody titers, lung histology and cell counts and cytokine levels in the bronchoalveolar lavage fluid. The role of IFN-γ in the suppression of asthma by the C. elegans crude extract was investigated in IFN-γ knockout and wild-type mice. When mice were sensitized with ovalbumin together with the crude extract of C. elegans, cellular infiltration into the lung was dramatically reduced in comparison with the ovalbumin-treated group. Treatment of mice with the C. elegans crude extract significantly decreased methacholine-induced airway hyperresponsiveness and the total cell counts and levels of IL-4, IL-5 and IL-13 in the bronchoalveolar lavage fluid but increased the levels of IFN-γ and IL-12. Sensitization with the C. elegans crude extract significantly diminished the IgE and IgG1 responses but provoked elevated IgG2a levels. However, the suppressive effect of the C. elegans crude extract was abolished in IFN-γ knockout mice, and the Th2 responses in these mice were as strong as those in wild-type mice sensitized with ovalbumin. The crude extract of C. elegans also suppressed the airway inflammation associated with established asthma. This study provides new insights into immune modulation by the C. elegans crude extract, which suppressed airway inflammation in mice not only during the development of asthma but also after its establishment by skewing allergen-induced Th2 responses to Th1 responses.
The overactive bladder (OAB) syndrome is characterized by urgency usually with frequency and nocturia. Tamsulosin, α1-adrenergic receptor antagonist, is widely used to reduce symptoms of urinary obstruction and prostatic hyperplasia. Tamsulosin can across the blood-brain barrier. We investigated the effects of tamsulosin on the symptoms of OAB in relation to neuronal activity using rats.
Adult female Sprague-Dawley rats, weighing 250±10 g (9 weeks old), were used in this study. The animals were divided into five groups (n=8 in each group): control group, OAB-induced group, OAB-induced and 0.01 mg/kg tamsulosin-treated group, OAB-induced and 0.1 mg/kg tamsulosin-treated group, and OAB-induced and 1 mg/kg tamsulosin-treated group. OAB was induced by intraperitoneal injection of cyclophosphamide (75 mg/kg) every third day for 10 days. The rats in the tamsulosin-treated groups orally received tamsulosin once a day for 14 consecutive days at the respective dose of the groups, starting 1 day after the induction of OAB. Cystometry for bladder pressure determination, immunohistochemistry for c-Fos, nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry for nitric oxide synthase (NOS) in the neuronal voiding centers and western blot for inducible NOS in the bladder were conducted.
Cyclophosphamide injection enhanced contraction pressure and time, representing the induction of OAB. Contraction pressure and time were significantly suppressed by tamsulosin treatment. c-Fos and NOS expressions in the neuronal voiding centers were enhanced by induction of OAB. OAB-induced c-Fos and NOS expressions were suppressed by tamsulosin treatment.
Tamsulosin exerts inhibitory effect on neuronal activation in the neuronal voiding centers of OAB. The present results suggest the possibility that tamsulosin is effective therapeutic modality for ameliorating the symptoms of OAB.
Overactive bladder; Cyclophosphamide; Tamsulosin; Rats
Calcinosis cutis involves the inappropriate deposition of calcium within the dermis layer of the skin, and is often associated with rheumatoid disease. A 42-year-old woman presented for evaluation of a hard palpable mass on the left upper eyelid. After everting the eyelid, a large papillomatous mass with a broad base was identified on the superior area of the tarsus. The lesion was partially excised posteriorly under local anesthesia, and pathologists identified the mass as calcinosis cutis. The patient had no systemic or trauma history, and the serum levels of calcium and phosphorous were normal. Idiopathic calcinosis cutis should be included in the differential diagnosis for a protruding papillomatous mass of the tarsal plate, and surgical debulking could be a viable option for large protruding lesions, although more follow-up is necessary to monitor regrowth.
Calcinosis cutis; Idiopathic; Papillomatous mass; Tarsus
Osteoclasts, together with osteoblasts, control the amount of bone tissue and regulate bone remodeling. Osteoclast differentiation is an important factor related to the pathogenesis of bone-loss related diseases. Reactive oxygen species (ROS) acts as a signal mediator in osteoclast differentiation. Simvastatin, which inhibits 3-hydroxy-3-methylglutaryl coenzyme A, is a hypolipidemic drug which is known to affect bone metabolism and suppresses osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL). In this study, we analyzed whether simvastatin can inhibit RANKL-induced osteoclastogenesis through suppression of the subsequently formed ROS and investigated whether simvastatin can inhibit H2O2-induced signaling pathways in osteoclast differentiation. We found that simvastatin decreased expression of tartrate-resistant acid phosphatase (TRAP), a genetic marker of osteoclast differentiation, and inhibited intracellular ROS generation in RAW 264.7 cell lines. ROS generation activated NF-κB, protein kinases B (AKT), mitogen-activated protein kinases signaling pathways such as c-JUN N-terminal kinases, p38 MAP kinases as well as extracellular signal-regulated kinase. Simvastatin was found to suppress these H2O2-induced signaling pathways in osteoclastogenesis. Together, these results indicate that simvastatin acts as an osteoclastogenesis inhibitor through suppression of ROS-mediated signaling pathways. This indicates that simvastatin has potential usefulness for osteoporosis and pathological bone resorption.
bone resorption; mitogen-activated protein kinases; osteoclast; RANK ligand; reactive oxygen species; simvastatin
This study was performed to investigate the ability of recombinant human-bone morphogenic protein-2 immobilized on a heparin-grafted bone substrate to enhance the osteoblastic functions.
MATERIALS AND METHODS
The Bio-Oss®, not coated with any material, was used as a control group. In rhBMP-2-Bio-Oss® group, rhBMP-2 was coated with Bio-Oss® using only deep and dry methods (50 ng/mL, 24 h). In heparinized rhBMP-2-Bio-Oss® group, dopamine was anchored to the surface of Bio-Oss®, and coated with heparin. rhBMP-2 was immobilized onto the heparinized- Bio-Oss® surface. The release kinetics of the rhBMP-2-Bio-Oss® and heparinized rhBMP-2-Bio-Oss® were analyzed using an enzyme-linked immunosorbent assay. The biological activities of the MG63 cells on the three groups were investigated via cytotoxicity assay, cell proliferation assay, alkaline phosphatase (ALP) measurement, and calcium deposition determination. Statistical comparisons were carried out by one-way ANOVA test. Differences were considered statistically significant at *P<.05 and **P<.001.
The heparinized rhBMP-2-Bio-Oss® showed more sustained release compared to the rhBMP-2-Bio-Oss® over an extended time. In the measurement of the ALP activity, the heparinized group showed a significantly higher ALP activity when compared with the non-heparinized groups (P<.05). The MG63 cells cultivated in the group with rhBMP-2 showed increased calcium deposition, and the MG63 cells from the heparinized group increased more than those that were cultivated in the non-heparinized groups.
Heparin increased the rhBMP-2 release amount and made sustained release possible, and heparinized Bio-Oss® with rhBMP-2 successfully improved the osteoblastic functions.
Heparin; rhBMP-2; Osteoblast-like cell; Bovine bone
This study was to investigate the effects of recombinant human platelet-derived growth factor (rhPDGF-BB) and heparin to titanium surfaces for enhancement of osteoblastic functions and inhibition of inflammation activity.
MATERIALS AND METHODS
The anodized titanium discs, not coated with any material, were used as a control group. In heparinized- Ti group, dopamine was anchored to the surface of Ti substrates, and coated with heparin. In PDGF-Ti group, rhPDGF-BB was immobilized onto heparinized Ti surface. The surface morphologies were investigated by the scanning electron microscope in each group. The release kinetics of rhPDGF-BB were analyzed, and cytotoxicity tests for each group were conducted. The biocompatibilities were characterized by measuring cell proliferation, alkaline phosphatase activity, and calcium deposition using MG-63 cells. Statistical comparisons were carried out by one-way ANOVA tests. Differences were considered statistically significant at *P<.05 and **P<.001.
The combination of rhPDGF-BB and heparin stimulated alkaline phosphatase activity and OCN mRNA expression in osteoblastic cells (*P<.05 and **P<.001). MG-63 cells grown on PDGF-Ti had significantly higher amounts of calcium deposition than those grown on anodized Ti (**P<.001). Heparinized Ti was more anti-inflammatory compared to anodized Ti, when exposed to lipopolysaccharide using the transcript levels of TNF-α and IL-6 of proinflammatory cytokine (*P<.05 and **P<.001).
The result of this study demonstrated that the incorporation of rhPDGF-BB and heparin onto Ti surface enhanced osteoblastic functions and inhibited inflammation.
Titanium; Heparin; rhPDGF-BB; Anti-inflammation; Osteoblastic function
Fabry's disease is an X-linked lysosomal storage disorder caused by abnormalities in the α-galactosidase A (GLA) gene, which leads to a GLA deficiency and to the intracellular deposition of globotriaosylceramide (Gb3) within vascular endothelium and other tissues. It manifests as progressive multiple organ dysfunctions caused by the deposition of Gb3. On the other hand, congenital agammaglobulinemia is usually caused by mutations in Bruton's tyrosine kinase (Btk) gene with X-linked dominence, suppresses B cell maturation, and causes recurrent pyogenic infections. In former reports, the distance between the loci in the Xq22 region of the human X chromosome was found to be about 69 kilobases. A 23-yr-old man diagnosed with congenital agammaglobulinemia at age 5, showed typical clinical and laboratory and histopathological findings of Fabry's disease. The genetic basis of this combination of the two syndromes was studied in this patient. Here, we report a case of Fabry's disease with congenital agammaglobulinemia.
Fabry Disease; Agammaglobulinemia; α-galactosidase A Gene; Btk Gene
microRNAs (miRs) modulate the expression levels of mRNAs and proteins and can thus contribute to cancer initiation and progression. In addition to their intracelluar function, miRs are released from cells and shed into the circulation. We postulated that circulating miRs could provide insight into pathways altered during cancer progression and may indicate responses to treatment. Here we focus on pancreatic cancer malignant progression. We report that changes in miR expression patterns during progression of normal tissues to invasive pancreatic adenocarcinoma in the p48-Cre/LSL-KrasG12D mouse model mirrors the miR changes observed in human pancreatic cancer tissues. miR-148a/b and miR-375 expression were found decreased whereas miR-10, miR-21, miR-100 and miR-155 were increased when comparing normal tissues, premalignant lesions and invasive carcinoma in the mouse model. Predicted target mRNAs FGFR1 (miR-10) and MLH1 (miR-155) were found downregulated. Quantitation of nine microRNAs in plasma samples from patients distinguished pancreatic cancers from other cancers as well as non-cancerous pancreatic disease. Finally, gemcitabine treatment of control animals and p48-Cre/LSL-KrasG12D animals with pancreatic cancer caused distinct and up to 60-fold changes in circulating miRs that indicate differential drug effects on normal and cancer tissues. These findings support the significance of detecting miRs in the circulation and suggests that circulating miRs could serve as indicators of drug response.