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1.  Combined pituitary hormone deficiency with unique pituitary dysplasia and morning glory syndrome related to a heterozygous PROKR2 mutation 
Abstract
Recent reports have indicated the role of the prokineticin receptor 2 gene (PROKR2) in the etiology of congenital hypopituitarism, including septo-optic dysplasia and Kallmann syndrome. In the present study, using next-generation targeted sequencing, we identified a novel heterozygous PROKR2 variant (c.742C>T; p.R248W) in a female patient who had combined pituitary hormone deficiency (CPHD), morning glory syndrome and a severely malformed pituitary gland. No other mutation was present in 27 genes related to hypogonadotropic hypogonadism, pituitary hormone deficiency and optic nerve malformation. The substituted amino acid was located on the third intracellular loop of the PROKR2 protein, which is a G protein-coupled receptor. Computational analyses with two programs (SIFT and PolyPhen-2) showed that the substitution was deleterious to PROKR2 function. The p.R248W mutation was transmitted from the patient’s mother, who had a slightly delayed menarche. Collectively, we provide further genetic evidence linking heterozygous PROKR2 mutations and the development of CPHD.
doi:10.1297/cpe.24.27
PMCID: PMC4322290
combined pituitary hormone deficiency (CPHD); morning glory syndrome; pituitary dysplasia; PROK2; PROKR2
2.  Simplification and Transformation of ASTM F1292 Measurement Procedure for Fall Accident Injury Criteria 
Industrial Health  2014;52(5):407-413.
Abstract: Protecting children from injuries caused by fall accidents from playground equipment is important. Therefore, measures toward minimizing the risk of fall accident injuries are required. The risk of injury can be evaluated using ASTM F1292. In this test, G-max and the HIC are used to estimate the risk of injury. However, the measurement procedure is too complicated for application to a large number of installed equipment. F1292 requires simplified by reducing the number of phases, even with a small risk of loss in accuracy. With this in mind, this study proposes a shortened measurement procedure and a transformation equation to estimate the risk as same as F1292. As the result of experiments, it was revealed that G-max and the HIC values for both procedures linearly increase with drop height. The differences in outcomes between the regression equations of the standardized procedure and those of the shortened procedure can be used as a correction value. They can be added to the value measured by the shortened procedure. This suggests that the combination of the shortened procedure and transformation equation would be equivalent to F1292, with the advantage of being more easily and efficiently applied to the evaluation of installed playground equipment.
doi:10.2486/indhealth.2014-0096
PMCID: PMC4246529  PMID: 25088989
Fall accident; Playground equipment; ASTM F1292; HIC; G-max; Regression analysis
3.  Expression and characterization of the first snail-derived UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 
Glycoconjugate Journal  2013;30(9):825-833.
UDP-GalNAc:polypeptide GalNAc transferase (ppGalNAcT; EC 2.4.1.41) catalyzes the first step in mucin-type O-glycosylation. To date, several members of this large enzyme family have been analyzed in detail. In this study we present cloning, expression and characterization of the first representative of this type of glycosyltransferase from mollusk origin, namely from Biomphalaria glabrata. The full length sequence of the respective gene was obtained by screening of a cDNA library using homology-based PCR. The entire gene codes for a protein consisting of 600 amino acids comprising the features of a typical type II membrane protein containing a cytoplasmic tail at the N-terminus, a transmembrane and a catalytic domain as well as a ricin-like motif at the C-terminus. Sequence comparison with ppGalNAcTs from various species revealed high similarities in terms of structural architecture. The enzyme is O-glycosylated but does not have any putative N-glycosylation sites. All four tested acceptor peptides were functional substrates, with Muc2 being the best one. Further biochemical parameters tested, confirmed a close relationship to the family of yet known ppGalNAcTs.
doi:10.1007/s10719-013-9486-6
PMCID: PMC3825155  PMID: 23877648
ppGalNAcT; GalNAc-transferase; O-glycosylation; Snail; O-glycoprotein; Biomphalaria glabrata
4.  Association Between Graves’ Disease and Renal Coloboma Syndrome: A Case Report 
Renal coloboma syndrome is an autosomal dominant condition characterized by renal lesions and optic nerve abnormalities. We report an 11-yr-old Japanese girl with familial renal coloboma syndrome, who also had Graves’ disease. Four affected family members had a previously reported heterozygous mutation (c.76dupG, p.Val26Glyfs*28) in the PAX2 gene. We hypothesized that PAX2 mutations may increase the risk of autoimmune diseases through alterations of human β-defensin 1 expression.
doi:10.1297/cpe.22.45
PMCID: PMC3748283  PMID: 23966757
renal coloboma syndrome; PAX2; mutation; Graves’ disease
5.  Involvement of murine β-1,4-galactosyltransferase V in lactosylceramide biosynthesis 
Glycoconjugate journal  2010;27(7-9):685-695.
Human β-1,4-galactosyltransferase (β-1,4-GalT) V was shown to be involved in the biosynthesis of N-glycans, O-glycans and lactosylceramide (Lac-Cer) by in vitro studies. To determine its substrate specificity, enzymatic activity and its products were analyzed using mouse embryonic fibroblast (MEF) cells from β-1,4-GalT V (B4galt5)-mutant mice. Analysis of expression levels of the β-1,4-GalT I-VI genes revealed that the expression of the β-1,4-GalT V gene in B4galt5+/−- and B4galt5−/−-derived MEF cells are a half and null when compared to that of B4galt5+/+-derived MEF cells without altering the expression levels of other β-1,4-GalT genes. These MEF cells showed no apparent difference in their growth. When β-1,4-GalT activities were determined towards GlcNAcβ-S-pNP, no significant difference in its specific activity was obtained among B4galt5+/+-, B4galt5+/−- and B4galt5−/−-derived MEF cells. No significant differences were obtained in structures and amounts of N-glycans and lectin bindings to membrane glycoproteins among B4galt5+/+-, B4galt5+/−- and B4galt5−/−-derived MEF cells. However, when cell homogenates were incubated with glucosylcer-amide in the presence of UDP-[3H]Gal, Lac-Cer synthase activity in B4galt5+/−- and B4galt5−/−-derived MEF cells decreased to 41% and 11% of that of B4galt5+/+-derived MEF cells. Consistent with this, amounts of Lac-Cer and its derivative GM3 in B4galt5−/−-derived MEF cells decreased remarkably when compared with those of B4galt5+/+ derived MEF cells. These results indicate that murine β-1,4-GalT V is involved in Lac-Cer biosynthesis.
doi:10.1007/s10719-010-9313-2
PMCID: PMC3568439  PMID: 21057870
B4galt5−/− mice; MEF cells; β-1; 4-GalT V; Lactosylceramide
6.  HIV prevention through extended education encompassing students, parents, and teachers in Japan 
Objectives
We developed an extended HIV prevention program for students, parents, and school teachers, and then evaluated its effectiveness.
Methods
The participants were 490 students, aged 13–14 years, attending four public junior high schools in Saga Prefecture, Japan. They were divided into two groups: control and intervention. All the students received group education by health professionals. In the control group, students received only two group education sessions given by health professionals. In the intervention group, there were three intervention components: parent education, teacher education, and student individual counseling by health professionals. Before and 3 months after the intervention, participants underwent evaluation of their frequency of communication about AIDS with parents or teachers, their knowledge of HIV/AIDS, and attitudes to sexual intercourse, self-esteem, and high-risk behavior.
Results
A total of 135 students (80 boys and 55 girls) from the intervention group and 236 students (115 boys and 121 girls) from the control group participated in the evaluation 3 months after intervention. Adolescents in the intervention group showed more positive changes than those in the control group from baseline to follow-up. Intervention had a significant impact on the frequency of communication about AIDS with teachers (p = 0.027) and HIV/AIDS knowledge among females (p = 0.023), and intervention also had a significant impact on refusal of sexual activity by males (p = 0.045).
Conclusions
These findings suggest that effective prevention of HIV might be achieved by an expanded education program for students and teachers such as that described, and individual counseling that takes into consideration the sexual differences of Japanese adolescents.
doi:10.1007/s12199-010-0205-7
PMCID: PMC3206978  PMID: 21431811
HIV prevention; Parent; Teacher; Adolescent; Japan
7.  Iatrogenic Creutzfeldt-Jakob Disease, Final Assessment 
Emerging Infectious Diseases  2012;18(6):901-907.
The book on iatrogenic Creutzfeldt-Jakob disease (CJD) in humans is almost closed. This form of CJD transmission via medical misadventures was first detected in 1974. Today, only occasional CJD cases with exceptionally long incubation periods still appear. The main sources of the largest outbreaks were tissues from human cadavers with unsuspected CJD that were used for dura mater grafts and growth hormone extracts. A few additional cases resulted from neurosurgical instrument contamination, corneal grafts, gonadotrophic hormone, and secondary infections from blood transfusions. Although the final solution to the problem of iatrogenic CJD is still not available (a laboratory test to identify potential donors who harbor the infectious agent), certain other measures have worked well: applying special sterilization of penetrating surgical instruments, reducing the infectious potential of donor blood and tissue, and excluding donors known to have higher than normal risk for CJD.
doi:10.3201/eid1806.120116
PMCID: PMC3358170  PMID: 22607808
Creutzfeldt-Jakob disease; dura mater; human growth hormone; iatrogenic disease; PRNP codon 129; variant Creutzfeldt-Jakob disease; prions and related diseases
8.  Cyclical and Patch-Like GDNF Distribution along the Basal Surface of Sertoli Cells in Mouse and Hamster Testes 
PLoS ONE  2011;6(12):e28367.
Background and Aims
In mammalian spermatogenesis, glial cell line-derived neurotrophic factor (GDNF) is one of the major Sertoli cell-derived factors which regulates the maintenance of undifferentiated spermatogonia including spermatogonial stem cells (SSCs) through GDNF family receptor α1 (GFRα1). It remains unclear as to when, where and how GDNF molecules are produced and exposed to the GFRα1-positive spermatogonia in vivo.
Methodology and Principal Findings
Here we show the cyclical and patch-like distribution of immunoreactive GDNF-positive signals and their close co-localization with a subpopulation of GFRα1-positive spermatogonia along the basal surface of Sertoli cells in mice and hamsters. Anti-GDNF section immunostaining revealed that GDNF-positive signals are mainly cytoplasmic and observed specifically in the Sertoli cells in a species-specific as well as a seminiferous cycle- and spermatogenic activity-dependent manner. In contrast to the ubiquitous GDNF signals in mouse testes, high levels of its signals were cyclically observed in hamster testes prior to spermiation. Whole-mount anti-GDNF staining of the seminiferous tubules successfully visualized the cyclical and patch-like extracellular distribution of GDNF-positive granular deposits along the basal surface of Sertoli cells in both species. Double-staining of GDNF and GFRα1 demonstrated the close co-localization of GDNF deposits and a subpopulation of GFRα1-positive spermatogonia. In both species, GFRα1-positive cells showed a slender bipolar shape as well as a tendency for increased cell numbers in the GDNF-enriched area, as compared with those in the GDNF-low/negative area of the seminiferous tubules.
Conclusion/Significance
Our data provide direct evidence of regionally defined patch-like GDNF-positive signal site in which GFRα1-positive spermatogonia possibly interact with GDNF in the basal compartment of the seminiferous tubules.
doi:10.1371/journal.pone.0028367
PMCID: PMC3235125  PMID: 22174794
9.  Structural conversion of neurotoxic amyloid-β(1–42) oligomers to fibrils 
The Aβ42 peptide rapidly aggregates to form oligomers, protofibils and fibrils en route to the deposition of amyloid plaques associated with Alzheimer's disease. We show that low temperature and low salt can stabilize disc-shaped oligomers (pentamers) that are significantly more toxic to murine cortical neurons than protofibrils and fibrils. We find that these neurotoxic oligomers do not have the β-sheet structure characteristic of fibrils. Rather, the oligomers are composed of loosely aggregated strands whose C-terminus is protected from solvent exchange and which have a turn conformation placing Phe19 in contact with Leu34. On the basis of NMR spectroscopy, we show that the structural conversion of Aβ42 oligomers to fibrils involves the association of these loosely aggregated strands into β-sheets whose individual β-strands polymerize in a parallel, in-register orientation and are staggered at an inter-monomer contact between Gln15 and Gly37.
doi:10.1038/nsmb.1799
PMCID: PMC2922021  PMID: 20383142
10.  Increased Plasma Levels of 8-Hydroxydeoxyguanosine Are Associated with Development of Colorectal Tumors 
Increased oxidative stress is generally thought to be associated with tumorigenesis. In this cross-sectional study, we evaluated plasma 8-hydroxydeoxyguanosine (8-OHdG) levels in patients with colorectal adenoma and cancer, as a surrogate marker of oxidative damage to deoxyribonucleic acid (DNA). We collected blood samples from 58 patients with adenoma, 32 with early cancer, 25 with advanced cancer, and 36 without polyps or cancer (as controls), and measured plasma levels of 8-OHdG by enzyme-linked immunosorbent assay. Univariate analysis by logistic regression showed that an increased level of 8-OHdG was a significant risk for adenoma [odds ratio (OR) 1.393, 95% confidence interval (CI) 1.008–1.926, p = 0.045]. In patients with early cancer, univariate analysis revealed significant differences for age, body mass index (BMI), systolic blood pressure, and 8-OHdG level. Subsequent multivariate analysis revealed that 8-OHdG [OR 1.627, 95% CI 1.079–2.453, p = 0.020] and BMI [OR 1.283, 95% CI 1.038–1.585, p = 0.021] were significant risk factors for early cancer. However, 8-OHdG was not a significant risk factor for advanced cancer. Our results suggest that an increased plasma level of 8-OHdG is associated with development of colorectal adenoma and cancer.
doi:10.3164/jcbn.10-12
PMCID: PMC2901765  PMID: 20664732
oxidative stress; tumorigenesis; reactive oxygen species; colonoscopy; early cancer
11.  Decreased levels of plasma adiponectin associated with increased risk of colorectal cancer 
AIM: To investigate the association between adiponectin levels and risk of colorectal adenoma and cancer (early and advanced).
METHODS: A cross-sectional study in a cohort of hospital-based patients was conducted between January 2004 and March 2006 at Yamagata University Hospital. Male subjects, who had colorectal tumors detected by endoscopic examination, were enrolled according to inclusion and exclusion criteria. Based on the T factor of the TNM system, intraepithelial carcinoma and submucosally invasive carcinoma were defined as early cancer, and invasion into the muscularis propria or deeper was defined as advanced cancer. The plasma levels of glucose, insulin, total cholesterol, triglyceride, high sensitivity C-reactive protein, insulin like growth factor (IGF)-1, IGF binding protein-3, adiponectin, leptin, and resistin were measured. Each factor level was designated low or high, and the risk of adenoma or cancer was estimated by univariate and multivariate logistic regression analysis.
RESULTS: We enrolled 124 male subjects (47 with adenoma, 34 with early cancer, 17 with advanced cancer, and 26 without tumors as controls). In patients with adenoma, high triglyceride and low adiponectin were associated with a significant increase in the odds ratio (OR) by univariate analysis. Only a low adiponectin level was related to increased adenoma risk, with an adjusted OR for low level (< 11 μg/mL) to high (≥11 μg/mL) of 5.762 (95% confidence interval (CI): 1.683-19.739, P = 0.005). In the patients with early cancer, high body mass index, high triglyceride, and low adiponectin were associated with a significant increase in OR in univariate analysis. In multivariate analysis, only low adiponectin was significantly associated with early cancer, with an adjusted OR of 4.495 (95% CI: 1.090-18.528, P = 0.038). However, in patients with advanced cancer, low adiponectin was not recognized as a significant risk factor for advanced cancer.
CONCLUSION: A decreased level of adiponectin is strongly associated with an increased risk of colorectal adenoma and early cancer. These data call for further investigation, including a controlled prospective study.
doi:10.3748/wjg.v16.i10.1252
PMCID: PMC2839179  PMID: 20222170
Adenoma; Early colorectal cancer; Metabolic syndrome; Adipokines; Colonoscopy; Resistin; Leptin; Body mass index
12.  High resolution 1H MAS RFDR NMR of biological membranes 
The combination of magic angle spinning (MAS) with the high-resolution 1H NOESY NMR experiment is an established method for measuring through-space 1H…1H dipolar couplings in biological membranes. The segmental motion of the lipid acyl chains along with the overall rotational diffusion of the lipids provides sufficient motion to average the 1H dipolar interaction to within the range where MAS can be effective. One drawback of the approach is the relatively long NOESY mixing times needed for relaxation processes to generate significant crosspeak intensity. In order to drive magnetization transfer more rapidly, we use solid-state radiofrequency driven dipolar recoupling (RFDR) pulses during the mixing time. We compare the 1H MAS NOESY experiment with a 1H MAS RFDR experiment on dimyristoylphosphocholine, a bilayer forming lipid, and show that the 1H MAS RFDR experiment provides considerably faster magnetization exchange than the standard 1H MAS NOESY experiment. We apply the method to model compounds containing basic and aromatic amino acids bound to membrane bilayers to illustrate the ability to locate the position of aromatic groups that have penetrated to below the level of the lipid headgroups.
doi:10.1016/j.jmr.2008.12.009
PMCID: PMC2802820  PMID: 19121592
13.  Amyloidogenic Processing but not AICD Production Requires a Precisely Oriented APP Dimer Assembled by Transmembrane GXXXG Motifs 
The Journal of biological chemistry  2008;283(12):7733-7744.
The β-amyloid peptide (Aβ) is the major constituent of the amyloid core of senile plaques found in the brain of patients with Alzheimer's disease (AD). Aβ is produced by the sequential cleavage of the Amyloid Precursor Protein (APP) by β- and γ-secretases. Cleavage of APP by γ-secretase also generates the APP Intracellular C-terminal Domain (AICD) peptide, which might be involved in regulation of gene transcription. APP contains three glycine-xxx-glycine (GxxxG) motifs in its juxtamembrane and transmembrane (TM) regions. Such motifs are known to promote dimerization via close apposition of TM sequences. We demonstrate that pairwise replacement of glycines by leucines or isoleucines, but not alanines, in a GxxxG motif led to a drastic reduction of Aβ40 and Aβ42 secretion. β-Cleavage of mutant APP was not inhibited, and reduction of Aβ secretion resulted from inhibition of γ-cleavage. It was anticipated that decreased γ-cleavage of mutant APP would result from inhibition of its dimerization. Surprisingly, mutations of the GxxxG motif actually enhanced dimerization of the APP C-terminal fragments, possibly via a different TM α-helical interface. Increased dimerization of the TM APP C-terminal domain did not affect AICD production. These results clearly demonstrate that both orientation and dimerization of the APP TM domain differently affect Aβ and AICD production.
doi:10.1074/jbc.M707142200
PMCID: PMC2702479  PMID: 18201969
14.  Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan, 1999–2008 
Emerging Infectious Diseases  2009;15(2):265-271.
Surgery or blood transfusion had little effect on the incidence of sCJD.
To elucidate the association between medical procedures and sporadic Creutzfeldt-Jakob disease (sCJD), we analyzed medical procedures (any surgical procedure, neurosurgery, ophthalmic surgery, and blood transfusion) for patients registered by the CJD Surveillance Committee in Japan during 1999–2008. We conducted an age-stratified case–control study with 753 sCJD patients and 210 controls and a study of patients who underwent neurosurgical or ophthalmic surgical procedures at the same hospital. Although the control group was relatively small, no evidence was found that prion disease was transmitted through the investigated medical procedures before onset of sCJD. After onset of sCJD, 4.5% of the sCJD patients underwent operations, including neurosurgical for 0.8% and ophthalmic for 1.9%; no special precautions against transmission of prion diseases were taken. Fortunately, we have not identified patients with prion disease attributed to these operations. Our findings indicate that surgical procedures or blood transfusion had little effect on the incidence of sCJD.
doi:10.3201/eid1502.080749
PMCID: PMC2657619  PMID: 19193271
Prion; Creutzfeldt-Jakob disease; medical procedure; surgery; neurosurgery; ophthalmic surgery; blood transfusion; Japan; research
15.  Inhibitors of amyloid toxicity based on β-sheet packing of Aβ40 and Aβ42 
Biochemistry  2006;45(17):5503-5516.
Amyloid fibrils associated with Alzheimer’s disease and a wide range of other neurodegenerative diseases have a cross β-sheet structure where main chain hydrogen bonding occurs between β-strands in the direction of the fibril axis. The surface of the β-sheet has pronounced ridges and grooves when the individual β-strands have a parallel orientation and the amino acids are in-register with one another. Here we show that in Aβ amyloid fibrils, Met35 packs against Gly33 in the C-terminus of Aβ40 and against Gly37 in the C-terminus of Aβ42. These packing interactions suggest that the protofilament subunits are displaced relative to one another in the Aβ40 and Aβ42 fibril structures. We take advantage of this corrugated structure to design a new class of inhibitors that prevent fibril formation by placing alternating glycine and aromatic residues on one face of a β-strand. We show that peptide inhibitors based on a GxFxGxF framework disrupt sheet-to-sheet packing and inhibit the formation of mature Aβ fibrils as assayed by thioflavin T fluorescence, electron microscopy and solid-state NMR spectroscopy. The alternating large and small amino acids in the GxFxGxF sequence are complementary to the corresponding amino acids in the IxGxMxG motif found in the C-terminal sequence of Aβ40 and Aβ42. Importantly, the designed peptide inhibitors significantly reduce the toxicity induced by Aβ42 on cultured rat cortical neurons.
doi:10.1021/bi052485f
PMCID: PMC2593882  PMID: 16634632
amyloid fibrils; Alzheimer’s disease; solid-state NMR; GxxxG motif
16.  Under-diagnosis of alcohol-related problems and depression in a family practice in Japan 
Aim
The aim of this survey was to assess the accuracy of a family physician's diagnosis of depression and alcoholism.
Methods
Consecutive new adult patients attending a family practice in Japan between April 2004 and August 2006 were enrolled. Excluded were those with dementia or visual disturbance, and emergency cases. Participants completed a questionnaire regarding their complaints and socio-demographics. A research nurse conducted the Japanese version of the Mini-International Neuropsychiatric Interview (J-MINI) in the interview room. The doctor independently performed usual practice and recorded his own clinical diagnoses. A researcher listed the clinical diagnoses and complaints, including J-MINI or clinically-diagnosed alcoholism and depression, using the International Classifications for Primary Care, Second Edition (ICPC-2) and calculated kappa statistics between the J-MINI and clinical diagnoses.
Results
Of the 120 adult first-visit patients attending the clinics, 112 patients consented to participate in the survey and were enrolled. Fifty-one subjects were male and 61 female, and the average age was 40.7 ± 13.2 years. Eight alcohol-related disorders and five major depressions were diagnosed using the J-MINI, whereas no cases of alcoholism and eight depressions were diagnosed by the physician. Clinically overlooked patients tended to have acute illnesses like a common cold. Concordance between the clinical and research diagnosis was achieved only for three episodes of Major depression, resulting in a kappa statistic of 0.43.
Conclusion
Although almost half of the major depressions were identified, all alcoholism was missed. A mental health screening instrument might be beneficial in family practice, especially to detect alcoholism.
doi:10.1186/1447-056X-7-3
PMCID: PMC2572132  PMID: 18973707
17.  A Human Lung Carcinoma Cell Line Supports Efficient Measles Virus Growth and Syncytium Formation via a SLAM- and CD46-Independent Mechanism▿  
Journal of Virology  2007;81(21):12091-12096.
Measles virus (MV) propagates mainly in lymphoid organs throughout the body and produces syncytia by using signaling lymphocyte activation molecule (SLAM) as a receptor. MV also spreads in SLAM-negative epithelial tissues by unknown mechanisms. Ubiquitously expressed CD46 functions as another receptor for vaccine strains of MV but not for wild-type strains. We here show that MV grows and produces syncytia efficiently in a human lung adenocarcinoma cell line via a SLAM- and CD46-independent mechanism using a novel receptor-binding site on the hemagglutinin protein. This infection model could advance our understanding of MV infection of SLAM-negative epithelial cells and tissues.
doi:10.1128/JVI.01264-07
PMCID: PMC2168767  PMID: 17715217
18.  Ophthalmic Surgery in Prion Diseases 
Emerging Infectious Diseases  2007;13(1):162-164.
Eleven (1.8%) of 597 patients underwent ophthalmic surgery within 1 month before the onset of prion disease or after the onset. All ophthalmologists reused surgical instruments that had been incompletely sterilized to eliminate infectious prion protein. Ophthalmologists should be aware of prion diseases as a possible cause of visual symptoms and use disposable instruments whenever possible.
doi:10.3201/eid1301.061004
PMCID: PMC2725820  PMID: 17370537
Prion diseases; prion; Creutzfeldt-Jakob disease; ophthalmic surgery; cataract; dispatch
19.  Erythroid progenitors differentiate and mature in response to endogenous erythropoietin 
Journal of Clinical Investigation  2000;106(2):263-270.
We reported previously that stimulation of glycoprotein 130 (gp130) by a combination of human IL-6 and soluble IL-6 receptor (sIL-6R) could support proliferation, differentiation, and terminal maturation of erythroid cells in the absence of erythropoietin (EPO) from human CD34+ cells in culture with stem cell factor (SCF). This observation suggested that differentiation of hematopoietic stem/progenitor cells to erythroid cells progressed according to an intrinsic program and that EPO receptor (EPOR) could be replaced by other cytokine receptors. In other words, EPOR appeared to be dispensable for erythropoiesis. Here we examined the role of EPOR in erythropoiesis stimulated by SCF, sIL-6R, and IL-6. Surprisingly, reduction of EPOR expression using antisense oligodeoxynucleotides suppressed erythropoiesis stimulated not only by SCF and EPO, but also by SCF, sIL-6R, and IL-6. EPO mRNA was detected in erythroid cells but not myeloid cells cultured in the presence of SCF, sIL-6R, and IL-6. Furthermore, high concentrations of anti–EPO-neutralizing antibody abrogated erythropoiesis in cultures without exogenous EPO. Based on these results, we suggest that erythroid progenitors themselves secrete EPO and that they have the potential to differentiate and mature in response to this endogenous EPO.
PMCID: PMC314307  PMID: 10903342
20.  SUICIDE ATTEMPTS BY AGRICULTURAL CHEMICALS 
Indian Journal of Psychiatry  1993;35(4):209-210.
SUMMARY
Forty three patients (42%) used agricultural chemicals as a method of suicide over nine and a half years (from Oct. 1981 to March 1991), and most cases were reported in June (agricultural activity) and December (year′s end). The highest prevalence was inpatients in their fifties (34.9%). 58.1% of these patients who committed suicide were farmers or had no fixed occupation. Main precipitating factor was difficulties in interpersonal relationships (30.9%), and the largest number of patients (25.6%) were diagnosed as having manic-depressive psychosis, depressed type.
PMCID: PMC2980642  PMID: 21743647

Results 1-20 (20)