Biomedical subjects
Publications and source records attributed to Y Dong.
C-8-methoxy fluoroquinolones were more lethal than C-8-bromine, C-8-ethoxy, and C-8-H derivatives for Staphylococcus aureus, especially when topoisomerase IV was resistant. The methoxy group also increased lethality against wild-type cells when protein synthesis was inhibited. These properties encourage refinement of C-8-methoxy fluoroquinolones to kill staphylococci.
Rotaviruses are major pathogens causing life-threatening dehydrating gastroenteritis in children and animals. One of the nonstructural proteins, NSP4 (encoded by gene 10), is a transmembrane, endoplasmic reticulum-specific glycoprotein. Recently, our laboratory has shown that NSP4 causes diarrhea in 6- to 10-day-old mice by functioning as an enterotoxin. To confirm the role of NSP4 in rotavirus pathogenesis, we sequenced gene 10 from two pairs of virulent and attenuated porcine rotaviruses, the OSU and Gottfried strains. Comparisons of the NSP4 sequences from these two pairs of rotaviruses suggested that structural changes between amino acids (aa) 131 and 140 are important in pathogenesis. We next expressed the cloned gene 10 from the OSU virulent (OSU-v) and OSU attenuated (OSU-a) viruses by using the baculovirus expression system and compared the biological activities of the purified proteins. NSP4 from OSU-v virus increased intracellular calcium levels over 10-fold in intestinal cells when added exogenously and 6-fold in insect cells when expressed endogenously, whereas NSP4 from OSU-a virus had little effect. NSP4 from OSU-v caused diarrhea in 13 of 23 neonatal mice, while NSP4 from OSU-a caused disease in only 4 of 25 mice (P < 0.01). These results suggest that avirulence is associated with mutations in NSP4. Results from site-directed mutational analyses showed that mutated OSU-v NSP4 with deletion or substitutions in the region of aa 131 to 140 lost its ability to increase intracellular calcium levels and to induce diarrhea in neonatal mice, confirming the importance of amino acid changes from OSU-v NSP4 to OSU-a NSP4 in the alteration of virus virulence.
Inhibins are glycoprotein members of the transforming growth factor-beta family that have been implicated in the control of spermatogenesis by exerting a negative feedback on FSH secretion. In addition, locally produced inhibins may play a role in paracrine regulation of testicular function. Immunoassays were used to measure the two biologically active dimeric forms of inhibin (inhibin A and B) in serum, seminal plasma, and urine. To better define their actions, inhibins were measured in the male during infancy, sexual maturation, and senescence. Inhibin B but not A was measurable in the serum of male newborns, infants, children, and adults. In adult males, measurable levels of inhibin B were detected in the seminal plasma but not the urine. The circulating levels of inhibin B increased shortly after birth and peaked at 4-12 months of age (210 +/- 31 pg/mL). The concentration measured in the serum then decreased to a low of 81 +/- 12 pg/mL of inhibin B from 3-9 yr of age followed by a gradual increase beginning with the onset of puberty and reaching another peak of 167 +/- 20 pg/mL in males who were 20-30 yr of age. Inhibin B levels then gradually declined with increasing age up through 90 yr of age. Serum levels of gonadotropins and total testosterone production were also measured in these same males. There was a brief increase in the gonadotropins (FSH and LH) during the few months of postnatal development, followed by a decrease to basal levels until the onset of puberty at 10-14 yr of age. Testosterone was also increased in the serum of infants from day 1 through 12 months of age, which decreased in young children but increased again following the elevation of gonadotropins during puberty. In adults aged 20-90 yr, serum levels of inhibin B were inversely proportional to levels of FSH but not LH or testosterone. In males in which a semen analysis was performed, those males with normal semen analysis had a significantly higher inhibin B levels, sperm production, and lower FSH levels than males with either oligospermia or nonobstructive azoospermia. The levels of Inhibin B found in circulation were a good marker for testicular function and could be useful in the diagnosis of patients with semen abnormalities or a complete absence of spermatogenesis. Because this glycoprotein is secreted in high amounts in the prepubertal testis up to 3 yr of age, inhibin B could potentially be used as a marker in the diagnosis of cryptorchidism and precocious puberty.
Interconversion of estrogens by osteoblasts may play a role in regulating bone mass. As a first step toward exploring this possibility, we investigated the expression and activity of 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) in cultured human osteoblasts (HOB) and osteoblast-like osteosarcoma cells (MG63, TE85, and SaOS-2). Significant 17beta-HSD activity was detected in cell-free extracts of all bone cells with oxidation of estradiol to estrone predominating over reduction. Reverse transcription-polymerase chain reaction (RT-PCR) experiments showed that the mRNA for 17beta-HSD I was detectable only in MG63 cells, albeit at low levels, while 17beta-HSD II was present in MG63, TE85, and HOB, but not SaOS-2, and 17beta-HSD III was absent from each bone cell type. 17Beta-HSD IV was the only isoform present in all bone cells analyzed. Further analysis of the expression of 17beta-HSD IV in these bone cells by immunoblotting revealed both the full-length 83 kDa protein and the proteolytic 38 kDa form. The kinetic parameters for estradiol oxidation by purified recombinant 17beta-HSD IV (Km = 49.7 microM, Vmax = 79.4 nmol/minute/mg of protein) and its HSD-domain (Km = 79.4 microM, Vmax = 476 nmol/minute/mg of protein) were significantly higher than previously reported, but consistent with the values obtained with crude cell-free extracts of SaOS-2 cells (Km = 98.8 microM, Vmax = 0.07 nmol/minute/mg of protein) which contain only 17beta-HSD IV based on RT-PCR. These studies show that bone cells have the capacity to interconvert circulating estrogens and suggest that bone cell 17beta-HSDs serve primarily to attenuate the continuing actions of estradiol through conversion to its less potent form, estrone, under certain conditions.
3,902 serum samples in different populations were tested for anti-HCV by ELISA. Among 100 samples of them, genotypes of HCV were detected by PCR with type-specific primers. The results showed: a) anti-HCV positive rates in general populations were 0.42%-1.66%; b) anti-HCV positive rates in the group of post-transfusion hepatitis and sporadic hepatitis (excluding HAV, HBV, EBV, CMV infection), hepatitis B post hepatitis cirrhosis (excluding HBV infection) and primary hepatocarcinoma were significantly higher than the group of patients without liver diseases or the group of patients without transfusion (P < 0.01); c) in HCV genotyping, HCV-II, HCV-III, II/III mixed type were 58%, 27%, 14% respectively. The rate of infection with HCV-III, was 80% in normal population but 91.7% with type II HCV in the group of patients with cirrhosis. These results suggested: (1) patients with different liver diseases were under high risk of HCV infection; (2) type HCV-II was predominant followed by HCV-III as well as II/III mixed in HCV genotype distribution of Shenyang area. Different genotypes of HCV might be related to the severity of hepatitis C.
OBJECTIVE: To test anti-Sa antibody in different autoimmune connective tissue diseases and analyze the relationship between Sa antibody and clinical manifestations and laboratory tests in rheumatoid arthritis. METHOD: Sa antigen was extracted from human placenta. Anti-Sa antibody was tested in 40 normal people and 478 connective tissue disease (CTD) patients using Western Blotting (WB). RESULTS: Sa antigen was a protein with molecular weights of 50 kD and 55 kD. Anti-Sa antibody was positive in 31.9% (61/191) rheumatoid arthritis (RA), 3.0% (2/67) Sjögren's syndrome (SS), 4.3% (2/46) systemic lupus erythmatosus (SLE) and 0% (0/66) Behcet's disease, 0% (0/60) polymyositis/dermatomyositis (PM/DM), 0% (0/66) other CTD and 0% (0/40) normal controls. Anti-Sa antibody was different from other auto-antibodies in RA. In rheumatoid arthritis its sensitivity, specificity, positive prediction rate, negative prediction rate were 31.9%, 98.6%, 93.8% and 68.5% respectively. Anti-Sa antibody positive patients were significantly different from anti-Sa antibody negative patients in moming stiffness, ESR, ANA and X-ray grade. CONCLUSION: Anti-Sa antibody was a new auto-antibody for the diagnosis of RA. Anti-Sa antibody positive patients seem to have more serious inflammation and more advanced disease process.
OBJECTIVE: To evaluate the incidence and spectrum of malignancy of primary Sjögren's syndrome (pSS). METHODS: 250 pSS who were followed-up in Peking Union Medical College (PUMC) Hospital were analyzed. RESULTS: Four of them were diagnosed with histopathological findings of 2 non-Hodgkin Lymphoma, 1 AILD, 1 multiple myeloma. Two died of secondary infection while receiving chemotherapy for lymphoma, 2 remained remitted. CONCLUSIONS: The risk factors were persistent enlargement of major salivary glands, appearance of monoclonal serum lg, and disappearance of auto antibodies.
OBJECTIVE: To evaluate the incidence, severity, clinical manifestations and immunological features relevant to liver involvement in 135 cases of primary Sjögren's syndrome. METHODS: One hundred and thirty-five patients with definite primary Sjögren's syndrome were analyzed retrospectively for liver involvement by the abnormalities of the liver enzymes, bilirubin level and liver biopsied section. RESULTS: The liver involvement in 30 patients (22.2%) could be etiologically ascribed to Sjögren's syndrome itself. The clinical spectrum and severity of this entity differed widely, 36.6% showed no relevant clinical symptoms, however jaundice was found in 46.7% of patients. Six patients showed pathological changes of chronic active hepatitis. 73.3% of all patients with liver involvement responded to steroid and immunosuppressive drugs, yet with a tendency to relapse (two cases). Liver cirrhosis was developed in five cases. The spectrum of serum autoantibodies in the patients with liver involvement showed no difference from those without liver involvement. Most of them were compatible with the serum profile of autoimmune hepatitis type-1. CONCLUSIONS: Liver involvement was complicated in 22.2% patients of primary Sjögren's syndrome. Clinical manifestations were non-specific and the main pathological change was chronic active hepatitis. The differential diagnosis between Sjögren's syndrome with liver involvement and type-1 autoimmune hepatitis could be only ascribed to other systemic clinical manifestations of Sjögren's syndrome.
OBJECTIVE: To assess the incidence of renal involvement in patients with systemic sclerosis (SSc) as well as its clinical and pathological changes. METHODS: The renal involvement was studied clinicopathologically in 93 patients who were compatible with the diagnosis of SSc retrospectively. RESULTS: Eighteen patients (19.4%) were diagnosed as renal involvement by one or more of the following: proteinuria, renal hypertension, elevated levels of blood urea nitrogen (BUN) and/or serum creatinine (sCr). Renal impairment was observed in 5 patients (5.4%). The mortality rate was 12.9%, and 5 patients died of renal failure. Histological study was performed in 5 patients. The thickening of interlobular arterioles with intimal proliferation was found in 4 of the patients who also showed mild nonspecific glomerular changes. Two had no clinical features of renal involvement, 1 had renal hypertension and 1 died of renal failure. Another patient with a 22-year disease duration showed chronic glomerulonephritis with nephrosclerosis. CONCLUSIONS: SSc patients should be followed-up clinically and renal biopsy performed if necessary in order to discover early renal involvement and to insert rational therapy to improve its prognosis.
Studies involving infectious, wild type HIV-1 must be performed under strict BSL-3 practice. We have employed a defective (deltaTat/Rev)MC99 and cloned 1A2 line, ie, mutated HIV-1 and Tat/Rev transfected cells to verify anti-HIV-1 activity in a BSL-2 laboratory. A number of extracts from various parts of 11 species of plants were studied. Results were correlated with those of an anti-HIV-1 reverse transcriptase (RT) assay.
OBJECTIVE: To clinically evaluate the protective effect of procaine blocking on nerves. METHODS: Electrophysiological examination before and after procaine blocking was conducted on 32 nerves during operation, 18 of which were donor nerves and 14 were injured ones. RESULTS: The latency of somatosensory evoked potentials (SEPs) was lengthened (15.30%) and the amplitude was lowered (18.47) after procaine blocking. Compared with the values before procaine blocking, the differences were significant (P < 0.01 and P < 0.05, respectively). SEP waves disappeared after procaine blocking in some cases (28.13%). CONCLUSION: Latency of SEP is lengthened and amplitude is lowered after procaine blocking. In some cases, SEPs even disappear.
OBJECTIVE: To evaluate the significance of measuring serum antilipoarabinomannan IgG (LAM-IgG), an anti-Mycobacterium tuberculosis antibody, in diagnosis of tuberculosis. METHOD: Sensitivity and specificity of the antibody in diagnosis of tuberculosis were detected. Results of the antibody detection, sputum smear and PPD examination were compared, and the relationship between the level of the antibody and the situation of the disease was also observed. RESULT: The sensitivity of the antibody in diagnosis of tuberculosis was found to be 71.9%, while the specificity 91.9%. The consistent rates of the antibody with sputum smear and PPD test were 80.2% and 61.6% respectively. The level of the antibody was related with the situation of the disease. CONCLUSION: Detection of the antibody is helpful for diagnosing tuberculosis and can be used to evaluate the prognosis of the disease.
OBJECTIVE: To evaluate whether tea drinking in a Chinese way in the Chinese population would affect fluoride in plaque and saliva. METHODS: Two groups of students were involved. Group 1, 41 subjects, did not drink tea regularly. Group 2, 34 subjects, drank tea every day in a very regular way. During a study period of three weeks, Group 2 was requested to drink selected (known fluoride concentration) types of tea, and subdivided by the type of tea they drank into two subgroups, Groups 2a and 2b. Group 2a drank lower fluoride tea, while Group 2b drank higher fluoride tea. Plaque and saliva samples were collected at the 2nd and the 3rd end of week, respectively. Fluoride levels were determined with fluoride selective electrode. RESULTS: Both plaque and saliva fluoride were higher in the tea drinking group compared with non-tea drinking group. Plaque fluoride in tea drinking group at the end of three week was significantly higher than the value of non-tea drinking group (t test, P = 0.02). In tea drinking group, three week plaque fluoride was higher than two week plaque. Plaque fluoride level was also significantly corresponded to fluoride in tea. Drinking higher fluoride tea resulted in higher fluoride in plaque. But saliva fluoride was not shown the correlation with tea. CONCLUSION: Tea is an important fluoride source. Plaque is a main resorvior of fluoride. Saliva has not the ability to store fluoride up. When considering tea as a fluoride source, the type of tea which may contain different concentration of fluoride should be borne in mind.
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This paper reports the development of the determination of trace metal Fe in doxycycline hydrochloric acid by flame atomic absorption spectrophotometry. The method is convenient to determine elements in doxycycline hydrochloric acid. The results show that the method offers good precision and accuracy. The relative standard deviation for Fe was 0.54% and the rate of recovery was 99.2%.
BACKGROUND: T-lymphocyte depletion 7 days before transplantation with immunotoxin FN 18-CRM9 has resulted in tolerance to subsequent renal allografts. We tested the effect of giving immunotoxin on the day of the transplantation and evaluated its effect on rhesus monkey and allograft survival, on antibody production, and on T-cell recovery. METHODS: Major histocompatibility complex mismatched renal allografts were performed in rhesus monkeys. Immunotoxin was given starting on the day of transplantation, with and without prednisone and mycophenolate mofetil for 3 days. T-cell subsets and alloantibody levels were measured by flow cytometry. The ability of treated monkeys to develop antibody to tetanus, diphtheria, and xenoantibody was measured. Histology of renal transplants was read in a blinded manner. RESULTS: Immunotoxin started on the day of transplantation resulted in prolonged allograft survival in all treatment groups. Graft loss between days 50 and 135 was most often due to interstitial nephritis. Later graft loss was due to chronic rejection. Monkeys had intact antibody responses to alloantigen, tetanus, diphtheria, and xenoantibody. Their CD4 cells recovered gradually over 6 months. CONCLUSIONS: Immunotoxin reliably prolongs renal allograft survival when started on the day of transplantation, but interstitial nephritis and chronic rejection limit the development of long-term tolerance. T-cell-dependent B-cell responses remain intact after treatment.
Paraffin sections (n = 168, 27 benign, 16 low malignant potential [LMP] and 125 malignant tumours) from epithelial ovarian tumours were evaluated immunohistochemically for expression of retinoblastoma gene product (pRB) and p53 protein, and the relationship among pRB, p53 and cyclin-dependent kinase inhibitor 2 (CDKN2) gene product p16INK4A (p16) was analysed, following our previous study of p16. Forty-one percent of the benign, 50% of the LMP and most (71%) of the malignant tumours showed high pRB expression. High expression of pRB (>50% pRB-positive cells) significantly correlated with non-mucinous histological subtypes. Reduced pRB expression, substage and residual disease were significant predictors for poor prognosis in stage I patients. All the benign and most of the LMP (81%) tumours were in either the p53-negative or low p53-positive category, but nearly half of the malignant tumours had high p53 expression. High p53 accumulation was found in non-mucinous, high grade and late stage tumours. For well-differentiated carcinomas, high p53 expression was a predictor of poor prognosis. However, even though high p53 expression was not associated with histological subtype, stage or the presence of residual disease, high p53 expression was not an independent predictor when all clinical parameters were combined. For all ovarian cancers, a close correlation was found between high p53 and high p16 expression. The relationship between the expression of pRB and p16 depended on tumour stage. In stage I tumours, high pRB was associated with low p16 reactivity. On the other hand, most advanced tumours showed both high pRB and high p16 reactivity.
Selective inhibition of T cell costimulation using the B7-specific fusion protein CTLA4-Ig has been shown to induce long-term allograft survival in rodents. Antibodies preventing the interaction between CD40 and its T cell-based ligand CD154 (CD40L) have been shown in rodents to act synergistically with CTLA4-Ig. It has thus been hypothesized that these agents might be capable of inducing long-term acceptance of allografted tissues in primates. To test this hypothesis in a relevant preclinical model, CTLA4-Ig and the CD40L-specific monoclonal antibody 5C8 were tested in rhesus monkeys. Both agents effectively inhibited rhesus mixed lymphocyte reactions, but the combination was 100 times more effective than either drug alone. Renal allografts were transplanted into nephectomized rhesus monkeys shown to be disparate at major histocompatibility complex class I and class II loci. Control animals rejected in 5-8 days. Brief induction doses of CTLA4-Ig or 5C8 alone significantly prolonged rejection-free survival (20-98 days). Two of four animals treated with both agents experienced extended (>150 days) rejection-free allograft survival. Two animals treated with 5C8 alone and one animal treated with both 5C8 and CTLA4-Ig experienced late, biopsy-proven rejection, but a repeat course of their induction regimen successfully restored normal graft function. Neither drug affected peripheral T cell or B cell counts. There were no clinically evident side effects or rejections during treatment. We conclude that CTLA4-Ig and 5C8 can both prevent and reverse acute allograft rejection, significantly prolonging the survival of major histocompatibility complex-mismatched renal allografts in primates without the need for chronic immunosuppression.