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Biomedical subjects

J W Yoon

Publications and source records attributed to J W Yoon.

At least 145 records · Page 8Linked to original sources
PubMed1983

Virus-induced diabetes in autoimmune New Zealand mice.

Infection of autoimmune New Zealand mice with the D variant of encephalomyocarditis (EMC) virus results in beta-cell damage and clinical diabetes. The induction of diabetes in parental NZB and NZW strains was independent of sex. However, the susceptibility to virus-induced diabetes in their F1 offspring was sex dependent. This susceptibility was significantly higher in male (NZB X NZW) F1 mice as compared with female F1 mice. Castration of male F1 mice significantly reduced the susceptibility to diabetes. These results suggest that parental NZB and NZW strains have recessive genes at different loci which do not allow sex hormones to influence the susceptibility to diabetes. It is concluded that both the genetic background of the host and sex hormones influence the development of virus-induced diabetes in autoimmune New Zealand mice.

Animals↗
PubMed1982

Cell culture and in vitro studies of fresh and cryopreserved human insulinoma.

Dispersed cells from both fresh and cryopreserved human insulinoma have been maintained in cell culture. Initial yield of viable cells was 50% for fresh and 25% for cryopreserved tissue. Viability of cells in culture was documented by increasing numbers of cells (doubling time approximately 5 d initially and 2 d at the sixth subculture for both fresh and cryopreserved tissue) and continued release of insulin over time (approximately 100 ng/ml per 10(5) cells at 10 d and 175 ng/ml per 10(5) cells at 30 d of culture for both fresh and cryopreserved tissue). Evidence that cells growing in culture were beta cells was provided by: (a) recovery of intracellular and extracellular immunoreactive insulin (IRI), (b) electron microscopic morphology, and (c) immunohistochemical staining. Cells from fresh insulinoma incubated with increasing concentrations of extracellular glucose released increasing amounts of IRI up to approximately 15 mM glucose, which paralleled changes in plasma insulin obtained during a preoperative glucose tolerance test.

Adenoma, Islet Cell↗
PubMed1982

Virus-induced diabetes mellitus. Glucose abnormalities produced in mice by the six members of the Coxsackie B virus group.

The capacity of Coxsackie B viruses (CBVs) to produce diabetes in mice was studied before and after passage in various cell types. CBVs that had been passaged in monkey kidney cells or in mouse embryo fibroblasts failed to produce abnormal glucose tolerance tests, whereas virus passaged five or more times in the pancreata of mice or in beta-cell cultures produced transient abnormal glucose tolerance tests. Immunofluorescence and histologic studies revealed that passage of CBVs in cultured beta-cells changed the tropism of these viruses from the acinar pancreas to the islets of Langerhans. Although all six CBV serotypes that had been passaged in beta-cell cultures behaved very similarly, substantial variation was observed with the different virus passages and in some experiments, beta-cell damage and the glucose abnormalities were minimal. From these and other experiments, we conclude that the six members of the CBV group have the potential for infecting and damaging pancreatic beta-cells in mice.

Animals↗
PubMed1981

Rhabdomyolysis in diabetic ketoacidosis.

A 2-year-old boy became ill with diabetic ketoacidosis complicated by severe rhabdomyolysis. He completely recovered from the rhabdomyolysis, but has persistent insulin-dependent diabetes mellitus (IDDM). Serological studies showed that the patient's serum contained high titers of coxsackievirus B4 antibody, suggesting that the development of rhabdomyolysis and IDDM may have been related to this infection. A review of the records of 133 patients admitted with onset of IDDM disclosed one additional patient with marked myoglobinuria, and 11 patients with orthotolidine-positive urine in the absence of hematuria. These findings suggest that myoglobinuria may not be uncommon at the onset of IDDM.

Child, Preschool↗
PubMed1981

Human leukocyte interferon treatment of two children with insulin dependent diabetes.

Two patients with newly diagnosed insulin dependent diabetes mellitus were treated with human leukocyte interferon based on the hypothesis that the diabetes was induced by an active viral infection in the pancreatic islets and could be arrested. High peak levels of serum interferon were achieved (100-200 U/ml) with minimal systemic side effects. There was no sustained therapeutic benefit as measured by increased production of endogenous insulin, or of C-peptide, or by a lower requirement for exogenous insulin. Further trials with interferon treatment should be undertaken only if evidence of active viral infection (culture, antigen detection) can be associated with insulin dependent diabetes onset and these markers followed during treatment.

Blood Glucose↗
PubMed1981

Infection of cultured human pancreatic B cells with reovirus type 3.

The capacity of reovirus type 3 to infect insulin-producing B cells was studied in human pancreatic cell cultures. Antibody to reovirus was labelled with fluorescein isothiocyanate and antibody to insulin was labelled with tetramethyl rhodamine isothiocyanate. By using a double-labelled immunofluorescent antibody technique, it was shown that only about 6% of the insulin-containing human B cells in culture became infected when inoculated with unpassaged reovirus type 3. However, by repeated passage of the virus in human pancreatic B cell cultures, the percentage of infected B cells increased to 27%, and the virus titre in cultures rose from 8.0 X 19(4) pfu/ml in the first passage, to 4.9 X 10(6) pfu/ml in the 5th passage. As measured by radioimmunoassay, the intracellular immunoreactive insulin began to decrease at 24 h after infection. This decrease roughly paralleled the increase in virus titre. In contrast, there was relatively little change in immunoreactive insulin in cultures inoculated with unpassaged reovirus type 3. These studies show that the ability of reovirus type 3 to infect human B cells is enhanced by serial passage in human pancreatic cell cultures and that the infection resulted in the destruction of B cells and release of insulin.

Cells, Cultured↗
PubMed1980

Induction of diabetes by cumulative environmental insults from viruses and chemicals.

Encephalomyocarditis virus (EMC) induces diabetes in certain inbred strains of mice by infecting and destroying pancreatic beta cells, the severity of the diabetes depending on the number of beta cells destroyed. In strains of mice resistant to EMC-induced diabetes, insufficient beta cells are damaged to alter glucose homeostasis. However, diabetes can be produced in many species by streptozotocin, a highly specific beta-cell toxin. Here, we used concentrations of streptozotocin that did not produce diabetes, but reduced the beta-cell reserve. When strains of mice normally resistant to EMC-induced diabetes were first treated with sub-diabetogenic doses of streptozotocin, then infected with EMC virus, diabetes developed. Furthermore, when mice were infected with viruses such as Coxsackie B3 and B5, which ordinarily produce little if any beta-cell damage, diabetes developed if the mice were first treated with sub-diabetogenic doses of streptozotocin. These findings suggest that diabetes may result from cumulative beta-cell damage induced by sequential environmental insults.

Animals↗
PubMed1980

Virus-induced diabetes mellitus. XVIII. Inhibition by a nondiabetogenic variant of encephalomyocarditis virus.

Plaque purification of the M variant of encephalomyocarditis (EMC) virus resulted in the isolation of two stable variants: one diabetogenic and designated D and the other nondiabetogenic and designated B. When the D variant was inoculated into SJL/J male mice, hypoinsulinemia and hyperglycemia developed in > 90% of the animals. In contrast, none of the mice inoculated with the B variant developed diabetes. Histologic examination of pancreata from mice infected with the D variant revealed insulitis and necrosis of beta cells, whereas islets from mice infected with the B variant showed little, if any, change. When islets were assayed for infectious virus, approximately 10 times more virus was recovered from animals inoculated with the D as compared with the B variant. Moreover, approximately 60% of islet cells from mice infected with the D variant contained viral antigens when stained with fluorescein-labeled anti-EMC virus antibody, whereas < 5% of islet cells from animals infected with the B variant contained viral antigens. Co-infection experiments showed that the induction of diabetes by the D variant was inhibited by the B variant. When the B and D variants were mixed together at B:D ratios of 1, 9, and 99, diabetes developed in 60, 11, and 0% of the mice, respectively. Tissue-culture experiments revealed that the B variant induced considerably more interferon than the D variant, and studies in animals showed that interferon appeared earlier and in greater amounts in the circulation of mice infected with the B as compared with the D variant. These studies suggest that the induction of interferon by the B variant is, at least in part, responsible for the inhibition of diabetes by the D variant.

Animals↗
PubMed1979

Isolation of a virus from the pancreas of a child with diabetic ketoacidosis.

A healthy 10-year-old boy was admitted to the hospital in diabetic ketoacidosis within three days of onset of symptoms of a flu-like illness. He died seven days later and post-mortem examination showed lymphocytic infiltration of the islets of Langerhans and necrosis of beta cells. Inoculation of mouse, monkey and human cell cultures with homogenates from the patient's pancreas led to isolation of a virus. Serologic studies revealed a rise in the titer of neutralizing antibody to this virus from less than 4 on the second hospital day to 32 on the day of death. Neutralization data showed that the virus was related to a diabetogenic variant derived from Coxsackievirus B4. Inoculation of mice with the human isolate produced hyperglycemia, inflammatory cells in the islets of Langerhans and beta-cell necrosis. Staining of mouse pancreatic sections with fluorescein-labeled antiviral antibody revealed viral antigens in beta cells. Both the clinical picture and animal studies suggested that the patient's diabetes was virus induced.

Animals↗
PubMed1978

Virus-induced diabetes mellitus. XV. Beta cell damage and insulin-dependent hyperglycemia in mice infected with coxsackie virus B4.

Coxsackie virus B4 that had been passaged in cultures enriched for pancreatic beta cells produced a diabetes-like syndrome when inoculated into SJL/J mice. The infection resulted in insulitis and destruction of beta cells. Viral antigens were found in beta cells by staining with fluorescein-labeled antibody to Coxsackie virus B4. The destruction of beta cells led to a decrease in the immunoreactive insulin content of the pancreas and hypoinsulinemia. The reduction in immunoreactive insulin correlated inversely with the elevation of glucose in the blood and over 80% of the animals were found to be hyperglycemic within 14 days after infection. The percentage of animals with hyperglycemia decreased with time and at the end of 60 days, less than 5% of the animals were still hyperglycemic. However, many of the normoglycemic mice were found to be metabolically abnormal when evaluated by glucose tolerance tests. Studies on the susceptibility of the host showed that only certain inbred strains of mice became diabetic when infected with Coxsackie virus B4. It is concluded that both the passage history of the virus and the strain of the host influence the development of diabetes.

Animals↗
PubMed1978

Virus-induced diabetes mellitus: reovirus infection of pancreatic beta cells in mice.

Reovirus type 3, passaged in pancreatic beta-cell cultures, produced an insulitis when inoculated into 1- to 2-week-old mice. By means of a double-label antibody technique, in which we used fluorescein-labeled antibody to reovirus and rhodamine-labeled antibody to insulin, reovirus antigens were found in beta cells. By electron microscopy, viral particles in different stages of morphogenesis were observed in insulin-containing beta cells but not glucagon-containing alpha cells. The infection resulted in destruction of beta cells, reduction in the insulin content of the pancreas, and alteration in the host's capacity to respond normally to a glucose tolerance test.

Animals↗
PubMed1978

Virus-induced diabetes in mice: a quantitative evaluation of islet cell population by immunofluorescence technique.

The endocrine cell populations of pancreatic islets in encephalomyocarditis (EMC)-virus infected mice were assessed quanititatively by immunofluorescence using specific antisera against 4 islet hormones. A marked reduction of the volume of insulin-containing (B-) cells (up to one tenth of control values) was observed at all stages studied in the hyperglycaemic mice. This was accompanied by the inversion of the normal ratio between B- and non B-cells. The volume of the latter cell types was also modified at different time points after infection: glucagon-cells were augmented 14 days after infection; PP-cells were decreased 2--3 days and 21 days after infection; somatostatin-cells decreased to one-fourth of control values in hyperglycaemic animals 21 days after infection. The latter results suggest that non B-cells are also involved in islet reaction to virus infection.

Animals↗