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Biomedical subjects

R Cheung

Publications and source records attributed to R Cheung.

At least 37 records · Page 2Linked to original sources
PubMed1997

Molecular cloning of murine ICA69: diabetes-prone mice recognize the human autoimmune-epitope, Tep69, conserved in splice variants from both species.

The islet cell antigen ICA69 is an autoimmune target in most patients with insulin-dependent diabetes. Understanding its role in diabetic autoimmunity would be facilitated by an animal model. We therefore cloned mouse ICA69. The different splice variants now identified conserve Tep69, the single T cell epitope recognized by patient T cells. We show that diabetes-prone NOD mice had Tep69-specific, autoreactive T cell repertoires and thus provide a relevant model for the study of ICA69's role in diabetic autoimmunity.

Alternative Splicing↗
PubMed1997

Loss of self-tolerance to ICA69 in nonobese diabetic mice.

Islet cell antigen p69 (ICA69) is a target autoantigen in IDDM. Studies of T-cells from newly diabetic children suggested possible antigenic mimicry between human ICA69 (in particular the Tep69 T-cell epitope, aa 36-47) and the ABBOS region in bovine serum albumin (BSA; aa 152-169), one of several cow's milk proteins that evoke abnormal immunity in diabetes-prone hosts. We recently found the sequence of Tep69 regions to be identical in the four alternatively spliced human and rodent ICA69 isoforms. Immunization of nonobese diabetic (NOD) mice with BSA or ICA69 generates fully cross-reactive T-cell responses to both Tep69 and ABBOS as the immunodominant, naturally generated, and presented T-cell mimicry epitopes. Such responses are absent or weak in healthy strains of mice. NOD mouse recipients of adoptive spleen cell grafts from diabetic donors spontaneously generate easily detectable pools of T-cells specific for ICA69/BSA, as well as the unrelated GAD65. NOD mice injected neonatally with ABBOS or Tep69 show cross-tolerance, but ABBOS-induced tolerance is transient. Neonatal injection of Tep69 reduces disease incidence (23 vs. 68% IDDM, P < 0.02), while neonatal injection of ABBOS has little effect. In contrast, systemic immunization of young NOD females with ABBOS (but not Tep69) reduces the diabetes incidence and delays disease expression, with protected mice generating ABBOS-specific T-cell repertoires unable to recognize the Tep69 mimicry antigen. Our observations demonstrate a loss of self-tolerance to ICA69 in NOD mice, and they establish antigenic mimicry between the two T-cell epitopes in ICA69 and BSA. Further studies are necessary to understand the molecular basis of this mimicry and how either T-cell peptide can modify the disease course.

Adoptive Transfer↗
PubMed1996

Crystal structure of a mammalian phosphoinositide-specific phospholipase C delta.

Mammalian phosphoinositide-specific phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The 2.4-A structure of phospholipase C delta 1 reveals a multidomain protein incorporating modules shared by many signalling proteins. The structure suggests a mechanism for membrane attachment and Ca2+-dependent hydrolysis of second-messenger precursors. The regulation and reversible membrane association of PI-PLC may serve as a model for understanding other multidomain enzymes involved in phospholipid signalling.

Amino Acid Sequence↗
PubMed1996

Strontium increases vertebral bone volume in rats at a low dose that does not induce detectable mineralization defect.

Low doses of strontium and fluoride were shown to increase bone formation and trabecular bone density in rodents. To assess whether strontium or fluoride affect the quality of the mineral at doses known to increase bone density, we have determined the effects of low doses of strontium and fluoride on bone formation and bone mineral characteristics in rats. Adult rats were given strontium alone (0.20%), fluoride alone (1 mg/kg per day), or the combined treatment for 8 weeks. Strontium levels in serum and femur were similar in groups treated with strontium alone or in combination, being about 5% of calcium levels. Biochemical and neutron activation analyses in femur showed that calcium and magnesium contents did not differ in the four group of rats, suggesting that strontium was incorporated in the apatite lattice of the bone minerals in the strontium-treated rats. The mineralized bone volume was significantly increased by 17% in the strontium-treated group, by 20% in the fluoride-treated group, and by 19% in rats given with the combined treatment. This was associated with increased osteoid surface, osteoblast surface, and double tetracycline labeled surfaces in the strontium-treated and fluoride-treated groups, showing that the number of bone forming sites was increased. However, the mineral apposition rate, the osteoid thickness, and the mineralization lag time were similar in controls and treated groups, reflecting the lack of deleterious effects of low doses of strontium and fluoride on bone mineralization. The density fractionation analysis measured in the femur also showed that neither strontium, nor fluoride at the low doses used, significantly altered the mineralization profile. The results indicate that treatment with low doses of strontium or fluoride increase the number of bone forming sites and vertebral bone volume in rats, but does not have detectable adverse effects on the mineral profile, bone mineral chemistry or bone matrix mineralization.

Analysis of Variance↗
PubMed1995

Phospholipase C delta 1 requires a pleckstrin homology domain for interaction with the plasma membrane.

The structural requirements of phospholipase C delta 1 for interaction with the plasma membrane were analysed by immunofluorescence after microinjection into living cells. Microinjection of deletion mutants revealed that the region required for membrane attachment and binding of inositol 1,4,5-trisphosphate in vitro corresponded to the pleckstrin homology domain, a structural module described in more than 90 proteins.

3T3 Cells↗
PubMed1995

Biliary sludging in critically ill trauma patients.

We used serial weekly ultrasonography to prospectively screen 19 critically ill trauma victims for the development of biliary sludge. Fourteen patients had sludge formation during their hospitalization. Sludge development was positively associated with increased transfusion requirements, but not with any other laboratory or clinical findings, including injury severity scores. The enteral feedings administered to most patients did not prevent sludge formation in the majority of cases; all five patients receiving total parenteral nutrition had sludge. Three patients had complications that could possibly be attributed to the sludge (one case of acalculous cholecystitis and two cases of mild pancreatitis). No such problems occurred in the five patients who did not have sludge. No long-term clinical problems related to sludge have occurred. We conclude that gallbladder sludge frequently develops in critically ill trauma patients and that sludge may be associated with pancreatobiliary complications.

Adolescent↗
PubMed1994

T cells from children with IDDM are sensitized to bovine serum albumin.

Epidemiological and experimental evidence suggested that denial of dietary cow milk protein early in life protects genetically susceptible children and animals from insulin-dependent diabetes (IDDM). Bovine serum albumin (BSA) was proposed as a candidate milk-borne mimicry antigen responsible for the diabetogenic cow milk effect. Elevated anti-BSA antibodies have been observed in patients and diabetic rodents, and these antibodies precipitate p69 from islet cell lysates. IDDM is a T cell mediated disorder but efforts to detect BSA-specific T cells in diabetic children have so far failed. We describe here a culture system which allowed the detection of BSA-specific T cells and we mapped this response to the ABBOS peptide (pre-BSA position 152-169) previously identified as a possible mimicry epitope. ABBOS-sensitized T cells were found in 28/31 children with recent onset IDDM but not in non-diabetic controls nor in children with SLE or JRA. T cell proliferative responses declined within the first few years of diabetes diagnosis. Although no effector cell role for BSA/ABBOS specific T lymphocytes has been demonstrated, the presence of BSA peptide-specific T cells strengthens the postulated link between a cow milk protein and IDDM.

Adolescent↗
PubMed1994

A cell surface protein that binds avian hepatitis B virus particles.

We have identified a 180-kDa cellular glycoprotein (gp180) that binds with high affinity to duck hepatitis B virus (DHBV) particles. The protein was detected by coprecipitating labeled duck hepatocyte proteins with virions or recombinant DHBV envelope proteins, using nonneutralizing monoclonal antibodies to the virion envelope. Binding of gp180 requires only the pre-S region of the viral large envelope protein, since recombinant fusion proteins bearing only this region efficiently coprecipitate gp180. The DHBV-gp180 interaction is blocked by two independent neutralizing monoclonal antibodies. The protein is found on both internal and surface membranes of the cell, and the species distribution of gp180 binding activity mirrors the known host range of DHBV infection. Functional gp180 is expressed in a wide variety of tissues in susceptible ducks.

Animals↗
PubMed1993

Diethylstilbestrol liver carcinogenicity and modification of DNA in rats.

Administration of diethylstilbestrol to female Sprague-Dawley rats at 10 mg/kg body weight daily by gavage for 1 year induced liver adenomas and carcinomas and pituitary adenomas. Using the 32P-postlabeling assay for DNA alterations, at 24 h after administration of a single dose of 100 mg/kg, modified bases were found.

Adenoma↗
PubMed1992

Diagnosis of nasopharyngeal carcinoma by DNA amplification of tissue obtained by fine-needle aspiration.

BACKGROUND: In nasopharyngeal carcinoma the primary lesion is often difficult to find. Metastatic lesions occur frequently but are difficult to distinguish from other head and neck tumors. The viral genome of the Epstein-Barr virus (EBV) can be identified in the cells of this carcinoma. METHODS: We used the polymerase chain reaction (PCR) to test for the presence of EBV genomes in 15 samples of metastatic squamous-cell carcinoma of the neck obtained by fine-needle aspiration and in 26 samples obtained by biopsy of lymph nodes. For controls we used disease-free lymph nodes from 10 patients with various head and neck tumors, tonsillar tissue from 46 subjects, blood from 59 EBV-seropositive blood donors, and mononuclear cells from 8 patients with fatal lymphoproliferative lesions. RESULTS: Of the 41 malignant lesions examined, only the nine nasopharyngeal carcinomas (one primary lesion and eight metastases) contained EBV genomes. None of the 20 nodes with other types of cancer, the 10 disease-free nodes, or any of the 105 normal control samples contained detectable EBV. In two patients with suspected metastases from occult primary tumors, the presence of EBV was predictive of nasopharyngeal carcinoma; in both cases overt nasopharyngeal carcinoma developed within one year. CONCLUSIONS: In patients with suspected nasopharyngeal carcinoma, fine-needle aspiration can provide tissue for diagnosis by DNA amplification of EBV genomes. The presence of EBV in metastases from an occult primary tumor is predictive of the development of overt nasopharyngeal carcinoma.

Base Sequence↗
PubMed1992

Hepatitis C viremia in patients with hepatitis C virus infection.

Sera from 103 patients were tested for hepatitis C virus RNA by nested polymerase chain reaction assay. Using primers from the highly conserved 5'-untranslated region, we detected hepatitis C virus RNA in 67 (88.2%) of 76 patients positive for antibody to hepatitis C virus by both second-generation and neutralization enzyme immunoassays. Hepatitis C virus RNA was detected in 93% of patients who had been infected for 10 yr or less and in 89% of those who had been infected for longer than 10 yr. Hepatitis C virus RNA was detected in all patients with chronic hepatitis, active cirrhosis or hepatocellular carcinoma and in 50% of those with nonspecific reactive hepatitis or inactive cirrhosis. Hepatitis C virus RNA was not detected in sera from 22 patients negative for antibody to hepatitis C virus or in 5 patients positive for antibody to hepatitis C virus by second-generation but not by neutralization enzyme immunoassay. Using primers from the less conserved nonstructural region 4, we detected hepatitis C virus RNA at a lower frequency, in 66% of patients who were positive for antibody to hepatitis C virus by both second-generation and neutralization enzyme immunoassays. The detection rate was higher in patients with frequent parenteral exposure. Our study showed that hepatitis C viremia can be detected in most patients with hepatitis C virus infection, including those with long-standing infection or advanced liver disease.

Base Sequence↗
PubMed1992

Microalbuminuria and other cardiovascular risk factors in nondiabetic subjects.

The association between urinary albumin:creatinine ratio and other cardiovascular risk factors such as age, blood pressure, obesity, glycemic indices, insulin and lipid profile was examined in a population in a Chinese community consisting of 795 men (mean age 35.8 +/- 8.8 yr) and 538 women (mean age 37.9 +/- 8.9 yr) with a normal glucose tolerance defined by WHO criteria. Men with a urinary albumin:creatinine ratio above the 90th percentile had higher systolic and diastolic blood pressures, fasting plasma glucose, 2-h glucose after a 75 g oral glucose load, and fasting serum insulin. Women with high urinary albumin:creatinine values had higher systolic and diastolic blood pressures, body mass index, waist-hip ratio, fasting insulin and triglycerides. Multivariate analysis showed that only systolic blood pressure and fasting glucose in men, and diastolic blood pressure and fasting insulin in women, independently contributed to urinary albumin:creatinine. When the effect of blood pressure was eliminated by excluding subjects with systolic blood pressure > 140 and diastolic > 90 mm Hg, only fasting insulin was associated with urinary albumin:creatinine in women. No associations were found for men. We conclude that microalbuminuria may be a marker for cardiovascular disease only because of its association with blood pressure in men, while in women, there is an additional independent association with fasting serum insulin.

Adult↗
PubMed1992

Aerobic fitness and opioidergic inhibition of cardiovascular stress reactivity.

The role of endogenous opioids in aerobic fitness-induced decrements in cardiovascular stress reactivity was examined by comparing the effects of opioid antagonism with naltrexone on responses to stress in young adults with high versus low levels of aerobic fitness. Two hundred forty subjects were given an activity questionnaire and males with the highest (Fit) and lowest (Nonfit) aerobic activity profiles were recruited for maximal oxygen consumption (VO2max) treadmill testing and psychological stress testing (final sample N = 28). Heart rate and blood pressures were measured during performance on a computer-controlled arithmetic task after pretreatment with either naltrexone (Trexan, DuPont) or a placebo. During placebo challenges, Fit subjects, compared with Nonfit, showed lower heart rate reactivity during stress and lower mean arterial blood pressures immediately before and during recovery from stress. Naltrexone eliminated these reactivity differences by increasing heart rate reactivity and raising mean arterial blood pressure in Fit subjects. These data suggest that aerobic fitness is associated with enhanced opioidergic inhibition of circulatory stress reactivity. Opioidergic modulatory effects on stress reactivity may comprise an important mechanism in fitness-associated risk reduction for cardiovascular disease.

Adult↗
PubMed1992

Differential bacteriology in adenoid disease.

In order to define the differential bacteriology in adenoid disease, adenoids were obtained from 10 children with adenoid hypertrophy and 29 children with chronic adenoiditis. The patients' ages ranged from 18 months to 13 years. After removal of the adenoids, the surface organisms were destroyed by alcohol and flame disinfection. One gram of tissue was sampled for aerobic and anaerobic culture. There was an average of 4.8 isolates per specimen, with 4.2 aerobes and 0.6 anaerobes. The most common isolates were: Haemophilus influenzae (84%), diphtheroids (66%), non-pathogenic Neisseria species (66%), alpha-hemolytic streptococci (64%) and non-hemolytic streptococci (59%). Anaerobes were present in 56% of all cases. The distribution of organisms was similar, regardless of clinical diagnosis. Only eight (21%) of the 39 cases had 'significant' (> or = 10(5) organisms/gm) colony counts. Our study detected no difference in either organism distribution or in total colony counts in chronic adenoiditis vs. adenoid hypertrophy.

Adenoids↗
PubMed1991

Immunoreactivity to peptides belonging to the pancreatic polypeptide family (NPY, aPY, PP, PYY) and to glucagon-like peptide in the endocrine pancreas and anterior intestine of adult lampreys, Petromyzon marinus: an immunohistochemical study.

Immunoreactivity of antisera directed against human neuropeptide Y (NPY), anglerfish polypeptide YG (aPY), bovine pancreatic polypeptide (bPP), salmon pancreatic polypeptide (sPP), porcine peptide tyrosine tyrosine (PYY), and salmon glucagon-like peptide (GLP) was investigated in the endocrine pancreas and anterior intestine of adult lampreys, Petromyzon marinus, by immunohistochemical analysis. There was no immunoreactivity to anti-sPP and anti-bPP in any tissue and anti-GLP immunostaining was only present in the anterior intestine. The immunoreactivity to antisera raised against NPY, aPY, and PYY was colocalized within the same small number of cells in the caudal and cranial pancreas of juveniles and the caudal pancreas of upstream migrant adults. These antibodies did not immunostain B- or D-cells and thus, NPY, aPY, and PYY were likely localized in a third cell type (3a) in the lamprey pancreas. Immunostaining of a few cells with only anti-aPY suggested the possibility of a fourth cell type (3b). Immunoreactivity was similar in the cranial and caudal pancreas of male upstream migrants; however, in the female cranial pancreas, a few cells demonstrated intense immunoreaction to anti-aPY, while weaker immunostaining with this antiserum was observed in B-cells. In the intestine of juvenile and upstream migrant lampreys, positive immunostaining to GLP, NPY, aPY, and PYY antibodies was colocalized within the same cell. We believe that this cell may contain PYY/glucagon family peptides. Other intestinal cells immunostained with either GLP or somatostatin-34 antiserum.

Amino Acid Sequence↗
PubMed1991

Distribution of two forms of somatostatin and peptides belonging to the pancreatic polypeptide family in tissues of larval lampreys, Petromyzon marinus L.: an immunohistochemical study.

Immunohistochemistry on tissues of larval lampreys, Petromyzon marinus L., was used to determine the distribution of invariant somatostatin-14 (SST-14) and lamprey somatostatin-34 (SST-34) in the brain while antisera against porcine peptide tyrosine tyrosine (PYY), human neuropeptide Y (NPY), anglerfish peptide YG (aPY), salmon glucagon-like peptide (GLP), SST-14, and SST-34 were used in studies of the pancreas and anterior intestine. In the brain, SST-14 is the major form of somatostatin. SST-14- and SST-34-immunoreactive nerve fibers are distributed throughout the telencephalon, diencephalon, and mesencephalon. In the latter region SST-14 immunoreactivity is concentrated in nerve tracts in the nucleus interpeduncularis. Nerve cells within the olfactory bulbs are immunoreactive only to anti-SST-34. Cells immunostained with anti-SST-14 were localized within the ependymal and subependymal layers of the pars ventralis hypothalami and the subependymal layers of the pars dorsalis thalami. SST-14-immunoreactive perikarya are also distributed within the tegmentum mesencephali. Nerve fibers and cells immunoreactive to anti-SST-34 are detected in the pars ventralis hypothalami but these cells do not colocalize SST-14. Pancreatic islets, distributed within the epithelium and in the submucosal connective tissue at the esophageal-intestinal junction, are only immunoreactive to anti-insulin. The antisera revealed three distinct cell types in the intestinal epithelium: type 1 colocalizes aPY, NPY, and PYY; type 2 colocalizes SST-14 and SST-34; and type 3 demonstrates immunoreactivity only to anti-SST-34. Immunoreactivity to anti-GLP is absent.

Animals↗
PubMed1990

Distribution of two forms of somatostatin in the brain, anterior intestine, and pancreas of adult lampreys (Petromyzon marinus).

The distribution of two major immunoreactive forms of somatostatin, somatostatin-14 and somatostatin-34, within the brain, pancreas and intestine of adult lampreys, Petromyzon marinus, was identified using antisera raised against these peptides. Immunostaining of the brain is similar in juveniles and upstream migrants, and somatostatin-14 is the major somatostatin form demonstrated. A few somatostatin-34-containing cells are localized within the olfactory bulbs, thalamus and hypothalamus, but cells immunoreactive to anti-somatostatin-34 in the hypothalamus and thalamus do not co-localize somatostatin-14. Immunostaining of pinealocytes within the pineal pellucida with anti-somatostatin-14 may infer a novel function for this structure. Somatostatin-14 and somatostatin-34 are co-localized within D-cells of the cranial pancreas and caudal pancreas of juveniles and upstream migrants. Numerous somatostatin-34-immunoreactive cells are distributed within the epithelial mucosa of the anterior intestine but not all of these cells cross-react with anti-somatostatin-14. It appears that somatostatin-34 is the major somatostatin in the pancreo-gastrointestinal system of adult lampreys.

Animals↗