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Biomedical subjects

R Chen

Publications and source records attributed to R Chen.

At least 451 records · Page 25Linked to original sources
PubMed1995

Reversible renin mediated massive proteinuria successfully treated by nephrectomy.

We report on a patient with severe hypertension and nephrotic range proteinuria, which were renin mediated in origin. Aortography demonstrated occlusion of the right renal artery and renal vein renin measurements lateralized strongly to the right kidney. Removal of the right kidney led to amelioration of hypertension and proteinuria. Massive proteinuria in this setting is due to high levels of intrarenal angiotensin II and is reversible with deactivation of the renin-angiotensin system.

Aged↗
PubMed1995

Host cell proteins binding to domain IV of the 5' noncoding region of poliovirus RNA.

Translation of poliovirus RNA occurs by the binding of ribosomes to an internal segment of RNA sequence within the 5' untranslated region of the viral RNA. This region is predicted to consist of six domains (I to VI) that possess complex secondary and tertiary structures. Domain IV is a large region in which alterations in the sequence or structure markedly reduce translational efficiency. In this study, we employed RNA mobility shift assays to demonstrate that a protein(s) from uninfected HeLa cell extracts, as well as from neuroblastoma extracts, interacts with the domain IV structure. A mutation in domain IV caused reduced binding of HeLa cell proteins and reduced translation both in vitro and in vivo, suggesting that the binding of at least one of these proteins plays a role in the mechanism of viral translation. UV cross-linking indicated that a protein(s) with a size of approximately 40 kDa interacted directly with the RNA. Using streptavidin beads to capture biotinylated RNA bound to proteins, we were able to visualize a number of HeLa and neuroblastoma cell proteins that interact with domain IV. These proteins have molecular masses of approximately 39, approximately 40, and approximately 42 kDa.

Animals↗
PubMed1995

Familial pancreatic adenocarcinoma: association with diabetes and early molecular diagnosis.

We report a large pedigree in which pancreatic cancer is inherited in an autosomal dominant fashion. Diabetes and exocrine insufficiency was observed in all family members who eventually developed pancreatic cancer. The presence of diabetes, often years before the diagnosis of cancer, allowed identification of those people who had inherited the predisposing allele and who were thus at high risk for the development of malignancy. This family shows that genetic factors can have a striking effect on the development of pancreatic malignancy and diabetes mellitus. Moreover, preclinical diagnosis of pancreatic cancer in family members provided a unique opportunity to study early molecular changes that accompany the development of human pancreatic cancer. Finally, the molecular approach applied here to the early diagnosis of pancreatic cancer may prove valuable in this family for identification of subjects at risk.

Adenocarcinoma↗
PubMed1995

Electrophysiological study of diaphragmatic myoclonus.

This is the first reported detailed electrophysiological study of diaphragmatic myoclonus. An 86 year old woman had rapid, intermittent epigastric pulsations. Neurological examination and imaging studies of the brain and spinal cord were normal. Needle EMG showed rhythmic contractions of the diaphragm and external intercostal muscles at 4 to 5 Hz. These contractions were often associated with suppression of normal breathing and were capable of maintaining adequate ventilation. Both diaphragms were involved but showed considerable variability in their relative latencies. Automated interference pattern analysis suggested a change in recruitment order, with selective activation of large phrenic motoneurons. The supraspinal mechanisms mediating diaphragmatic myoclonus are different from that of voluntary and involuntary rhythmic breathing, and seem to be unrelated to palatal myoclonus. The generator source is likely related to respiratory centres in the rostral medulla.

Aged↗
PubMed1995

Renal denervation attenuates the sodium retention and hypertension associated with obesity.

Recent studies have indicated that obesity is associated with hypertension, sodium retention, and increased sympathetic nervous system activity. The purpose of this study was to determine the role of renal nerves in mediating the sodium retention and hypertension associated with obesity. We determined the hemodynamic and renal excretory responses to a high-fat diet in control (n = 6) and bilaterally renal-denervated (n = 7) chronically instrumented dogs. After a control period of 8 days, dogs were placed on a high-fat diet for 5 weeks. In response to a high-fat diet, body weight increased from 19.9 +/- 2.2 to 29.9 +/- 2.4 kg in the control group and from 21.1 +/- 2.0 to 32.4 +/- 1.9 kg in the bilaterally renal-denervated group. Heart rate increased from 81 +/- 8 to 113 +/- 7 beats per minute in the control group and from 79 +/- 7 to 103 +/- 8 beats per minute in the bilaterally renal-denervated group. Arterial pressure increased significantly from 95 +/- 2 to 109 +/- 4 mm Hg in the control group. In contrast, 5 weeks of a high-fat diet in the bilaterally renal-denervated group did not significantly increase arterial pressure (which went from 87 +/- 3 to 90 +/- 4 mm Hg). Furthermore, the decrease in sodium excretion in response to the high-fat diet was significantly greater in the control group than in the bilaterally renal-denervated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The reporting sensitivities of two passive surveillance systems for vaccine adverse events.

To evaluate reporting sensitivities for vaccine adverse events, reporting rates were estimated by dividing the number of events reported to the Monitoring System for Adverse Events Following Immunization and the Vaccine Adverse Event Reporting System in a given period by the number of doses administered or distributed during the same period. Reporting sensitivity was calculated as the ratio of the rates at which events were reported to each passive surveillance system (numerator) and occurred in controlled studies (denominator). Reporting sensitivities were generally better in the public sector than in the private sector. The significant underreporting of known outcomes, together with the nonspecific nature of most adverse event reports, highlights the limitations of passive surveillance systems in assessing the incidence of vaccine adverse events.

Adverse Drug Reaction Reporting Systems↗
PubMed1995

Primary diffuse leptomeningeal oligodendroglioma. Case report.

The authors describe a case of a diffuse primary leptomeningeal oligodendroglioma in a 17-year-old girl who presented with raised intracranial pressure and hydrocephalus. She underwent imaging studies and a left frontotemporal craniotomy that revealed a cystic oligodendroglioma in the suprasellar cistern and spread of neoplastic cells to the spinal leptomeninges. The tumor showed little response to maximum radiotherapy and chemotherapy, and the patient died from complications of high-dose chemotherapy 2 years after diagnosis. Postmortem examination of the brain and spinal cord revealed diffuse meningeal infiltration by neoplastic cells and no evidence of an intraparenchymal origin. Glial heterotopias were noted at several sites along the brain base, adding circumstantial support to the theory that leptomeningeal gliomas are derived from ectopic glial tissue in the subarachnoid space.

Adolescent↗
PubMed1995

Lung cancer mortality update and prevalence of smoking among copper miners and smelters.

OBJECTIVES: The aim of this investigation was to study the cancer mortality of Chinese copper miners and smelters further, with particular reference to that from lung cancer, and smoking prevalence. METHODS: From an earlier follow-up (1970-1985) of the mortality of the two cohorts, all new death cases registered since 1985 were recorded, and the mortality analysis was extended through 1992. A questionnaire survey of smoking habits was carried out in three samples, randomly chosen from the copper miners (N = 1125), smelters (N = 603), and local residents (N = 1517) of Tongling city. RESULTS: Lung cancer was significantly increased among the copper miners [standardized mortality ratio (SMR) 152, 95% confidence interval (95% CI) 123-187], but not among the copper smelters (SMR 102, 95% CI 53-178). Smoking was more prevalent among copper miners than among local male residents (71.7 versus 64.3%, P < 0.001), whereas among the smelters it was significantly less prevalent (57.4 versus 64.3%, P < 0.005). Similar patterns were found for the average number of cigarettes smoked daily among the miners (21.6 +/- 7.2), smelters (15 +/- 7.1), and local male residents (19.2 +/- 7.3). CONCLUSIONS: In addition to occupational exposures, cigarette smoking may partly play a role in influencing mortality from lung cancer among Chinese copper miners and smelters.

Adult↗
PubMed1995

Direct preparation and meiotic analysis of human semen.

A meiotic study of human semen specimens was carried out in 60 cases. Among them, 20 were normal controls, 20 suffered from infertility, and 20 had a history of recurrent spontaneous abortions. Of the cases of infertility and abortion, 50% were found to have numerical and/or structural chromosomal aberrations in spite of the normal blood karyotype. It is suggested that chromosomal aberrations may be the cause of sterility and abortion. The success rate of semen chromosome G-banding in the infertility, abortion and control groups was 70%, 55% and 25% respectively. The semen samples of three cases of heterozygous carriers with reciprocal chromosomal translocation were also studied. The ring quadrivalents were identified in all cases. The results may explain the recurrent abortions in these patients.

Abortion, Habitual↗
PubMed1995

Selective modulation of elements of the immune system by low molecular weight nucleosides.

To optimally modulate a system as complex as the immune system, one must ultimately control its elements individually. Up to this time, use of polyclonal immune stimulants has necessarily involved modulation of a block of immune functions, frequently including undesired activities as well as the activity of interest. We now report selective modulation of individual elements of the immune system by low molecular weight nucleosides, within the context of a fully functional immune system. Loxoribine (7-allyl-8-oxoguanosine) is a well characterized pleiotropic agonist of the immune system in a variety of species, including mouse and humans. In B-cells it binds to soluble cytoplasmic binding proteins, which upregulate transcription upon translocation to the nucleus. By altering specific portions of the loxoribine molecule, multiple distinct, bioactivity profiles have now been obtained. These include: 1) selective augmentation of antibody responses without effects on B-cell proliferation or NK-cell activity; 2) selective enhancement of NK-cell activity and B-cell proliferation in the absence of antibody responses; and 3) selective enhancement of NK-cell activity and antibody responses without B-cell proliferation. Predominant NK-cell responses with minimal B-cell activity of either type also can be generated. The pattern of cytokine mRNA transcription induced is consistent with the spectrum of cellular activities observed. Thus, it is possible to modulate selective activities of the immune system by relatively minor structural modifications of a broad-spectrum immunomodulator in an unseparated cell system.

Adjuvants, Immunologic↗
PubMed1995

Expression of immune regulatory molecules in Epstein-Barr virus-associated nasopharyngeal carcinomas with prominent lymphoid stroma. Evidence for a functional interaction between epithelial tumor cells and infiltrating lymphoid cells.

Undifferentiated nasopharyngeal carcinomas (UNPC) are characterized by an association with Epstein-Barr virus and an abundant lymphoid stroma. The role of this lymphoid stroma is uncertain but is mostly thought to represent an immune response against viral or tumor antigens. We have analyzed the expression of immune regulatory receptor/ligand pairs in snap-frozen biopsies of 20 UNPCs. All cases were Epstein-Barr virus positive and the virus-encoded latent membrane protein, LMP1, was expressed in 6 cases. By immunohistochemistry, we have demonstrated the expression of CD70 and CD40 in the tumor cells of 16 and 18 cases, respectively. Infiltrating lymphoid cells expressing CD27, the CD70 receptor, and the CD40 ligand were present in all cases. The Bcl-2 protein was detected in 17 cases. Unexpectedly, tumor cells of 5 cases expressed at least one member of the B7 family (CD80, CD86, and B7-3) and many lymphoid cells expressing the corresponding counter-receptor, CD28, were detected in all cases. Interestingly, 5 of 6 LMP1-positive cases also expressed B7, whereas all 14 LMP1-negative cases were also B7 negative. Our results indicate that T cells and carcinoma cells communicate in the microenvironment of UNPCs and suggest that the presence of a lymphoid stroma may be a requirement for UNPC growth at least in certain stages of tumor development.

Carcinoma↗
PubMed1995

[The diagnosis and treatment of focalized pancreatitis: report of 16 cases].

We report 16 patients of focalized pancreatitis. All patients presented mass in the head of pancreas and obstructive jaundice (13 patients), characterized by spontaneous mass shrinkage and jaundice subsidence within two weeks after admission without any surgical intervention. Sonography, ERCP, exploration and intraoperative biopsy are of value in differentiating FP from carcinoma. Six patients received conservative therapy. Operations aimed to drain the commonbile duct and pancreatic duct (T tube drainage of commonbile duct, choledochojejunostomy, pancretojejunostomy) were performed in 7 patients. Pancretoduodenectomy were performed in 3 patients on tentative diagnosis of carcinoma in the head of the pancreas. Follow-up in 12 patients showed satisfactory results.

Choledochostomy↗
PubMed1995

Biotransformation of losartan to its active carboxylic acid metabolite in human liver microsomes. Role of cytochrome P4502C and 3A subfamily members.

Losartan is a 4-chloro-5-hydroxymethylimidazole derivative that is a potent and highly selective angiotensin II receptor antagonist. Losartan is metabolized in vivo in rats, monkeys, and humans to a carboxylic acid derivative E3174 that is pharmacologically more active than the parent compound. We have investigated the mechanism of this biotransformation in human liver preparations. The oxidation of both losartan and the putative aldehyde intermediate E3179 was catalyzed by the microsomal fraction, required both NADPH and molecular oxygen, and was inhibited by SKF 525-A, implicating cytochrome P450 (CYP). When incubations with each substrate were performed under an atmosphere of 18O2, the extent of 18O incorporation into the carboxylic acid product was consistent with a mechanism for losartan oxidation involving an aldehyde intermediate. To substantiate the involvement of CYP in these reactions, incubations with losartan and the aldehyde E3179 were performed in the presence of isoform-selective inhibitors. Inhibitors of CYP3A4/5 (gestodene and ketoconazole) and CYP2C9/10 (sulfaphenazole) attenuated the oxidation of both substrates. It was then demonstrated that microsomes containing either recombinant human liver CYP2C9 or CYP3A4 were capable of oxidizing both losartan and the aldehyde E3179 to the carboxylic acid E3174. Subsequently, it was shown that rabbit anti-CYP2C9 and anti-CYP3A3/4 inhibited the oxidation of losartan to E3174 in incubations with human liver microsomes. These studies support the hypothesis that the aldehyde E3179 is an intermediate in the oxidation of losartan and that this two-step reaction is catalyzed in human liver microsomes by members of the CYP3A and CYP2C subfamilies.

Adult↗
PubMed1995

[An observation on pathological changes in retinal ultrastructure of rat with hypertension and after its life-long treatment with captopril].

The fundus and retinal ultrastructural changes of rats with hypertension and such rats having taken life-long captopril treatment were examined by funduscope, light and transmission electron microscopes. The normal rats were the controls. The results showed that in the hypertension group, the ratio of the diameter of the retinal artery to that of the vein was 1:2, the arteries were spastic and narrowed, their light reflexes were widened and their calibers of the lumens were uneven, the fundus appearances being consistent with grade I and II retinal changes of systemic hypertension. Under the light microscope, it was discovered that the basement membranes of the retinal capillaries were thickened and their lumens narrowed, resulting in retinal ischemia and anoxia. Under the transmission electron microscope, the main pathological changes involved the external segments of photoreceptors and ganglionic cells. The pathological changes were hazy renewed membranous discs at the basal portions of the external segments of photoreceptors, edematous ganglionic cells being the majority, their cytoplasm stained pale, mitochondrial vacuolization, enlargement of smooth endoplasmic reticula and degranulation of rough endoplasmic reticula. In the group of rats with hypertension having taken life-long captopril treatment, the fundi and blood pressure remained normal and no significant ultrastructural changes had taken place in their retinae.

Animals↗
PubMed1995

[A hot-spot mutation of p53 gene in nasopharyngeal carcinoma].

Using DNA sequencing and immunohistochemical staining, p53 gene mutation and overexpression were investigated in 23 formalin-fixed and paraffin-embedded specimens of nasopharyngeal carcinoma (NPC). All patients were from regions of low NPC incidence in China. Sequencing of exon 7 and exon 8, revealed p53 gene mutation in 15 of the 23 specimens (65.2%). All the mutations were at codon 273(CGT-->CAT), so that arginine encoded by this codon was replaced by histidine. In addition, p53 overexpression was found in another NPC specimen without mutation in exon 7 or 8 of p53 gene. The results suggest that p53 gene mutation is of common occurrence in NPC. The hot-spot mutation at codon 273 might be related to some special carcinogen in the environment, or this change be essential in the multi-step process of carcinogenesis of the nasopharynx.

Base Sequence↗