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Biomedical subjects

J Fung

Publications and source records attributed to J Fung.

At least 181 records · Page 10Linked to original sources

Prophylactic use of OKT3 in liver transplantation. A review.

Liver rejection in the era of cyclosporine-based immunosuppression is approximately 60-70%. Approximately 15-25% of liver transplant patients will require hemodialysis following transplantation. These facts argue for a potent, less nephrotoxic immunosuppressive regimen, especially during the period of vulnerability to these events. Prophylactic use of OKT3 has been suggested as a means to decrease the need for hemodialysis while maintaining potent immunosuppression. The goal of this review is to examine potential benefits and pitfalls of this regimen. A lack of documentation of long-term patient and graft survival, the potential susceptibility to infectious complications, development of sensitization, and the cost must be weighed against the decreased need for hemodialysis and the control of early rejection episodes.

Graft Rejection↗

PCR primers for human chromosomes: reagents for the rapid analysis of somatic cell hybrids.

Rapid analysis of somatic cell hybrids can be facilitated by using the polymerase chain reaction (PCR) to assay for genes assigned to specific human chromosomes. We describe PCR primer pairs for genes on the short and long arms of the 22 autosomes and the X chromosome. Some of the primers were designed from the 3' untranslated region of cDNA sequences, whereas others were derived from genomic sequence. Each primer set was tested for its specificity and mapped to a chromosome by screening a somatic cell hybrid panel. Two of the primer pairs (APOC2 and G6PD) detect CA dinucleotide repeat polymorphisms.

Base Sequence↗

H-reflex modulation during walking in spastic paretic subjects.

Hoffman (H) reflexes were elicited from the soleus muscle during treadmill walking in 21 spastic paretic patients. The soleus and tibialis anterior muscles were reciprocally activated during walking in most patients, much like that observed in healthy individuals. The pattern of H-reflex modulation varied considerably between patients, from being relatively normal in some patients to a complete absence of modulation in others. The most common pattern observed was a lack of H-reflex modulation through the stance phase and slight depression of the reflex in the swing phase, considerably less modulation than that of normal subjects under comparable walking conditions. The high reflex amplitudes during periods of the step cycle such as early stance seems to be related to the stretch-induced large electromyogram bursts in the soleus in some subjects. The abnormally active reflexes appear to contribute to the clonus encountered during walking in these patients. In three patients who were able to walk for extended periods, the effect of stimulus intensity was examined. Two of these patients showed a greater degree of reflex modulation at lower stimulus intensities, suggesting that the lack of modulation observed at higher stimulus intensities is a result of saturation of the reflex loop. In six other patients, however, no reflex modulation could be demonstrated even at very low stimulus intensities.

Adult↗

Hepatotrophic effects of FK506 in dogs.

Portacaval shunt (Eck fistula) in dogs causes hepatocyte atrophy and organelle disruption, as well as tripling of hepatocyte mitoses. After submitting dogs to this procedure, FK506 was infused into the tied-off left portal vein. The size, anatomic quality, and replication of hepatocytes were enhanced in the portion of liver infused with FK506, with a significant spillover effect in the noninfused portion. These hepatotrophic qualities of FK506 may explain part of FK506's efficacy for the treatment of chronic liver rejection. Also, the observations support a trial with this drug for the treatment of autoimmune liver diseases because, in addition to turning off the immunologic genesis of such disorders, repair and regeneration of the damaged liver may be augmented. Finally, these hepatrophic qualities are part of an emerging spectrum of biologic effects caused by drugs that may modulate the enzyme cis-trans peptidyl-prolyl isomerase (PPIase), the principal constituent of the cytosolic binding sites of FK506, repatomycin, cyclosporine, and presumably other immunosuppressive drugs as yet undiscovered.

Amino Acid Isomerases↗

In vivo effect of FK506 on human pancreatic islets.

The purpose of this study was to evaluate the in vivo effect of FK506 on human pancreatic islets. Twenty-five nude mice were made diabetic by one intravenous injection of streptozotocin. Approximately 600 islets were administered in the renal subcapsular space 3-5 days following streptozotocin administration. One week after transplantation, the mice were divided in four groups. In group 1, the animals received 1 injection of 0.5 ml of diluent i.p. daily for one week. In groups 2, 3, and 4 the treatments were daily i.p. injection of 0.3, 1, and 3 mg/kg FK506, respectively. After treatment, the functional integrity of the transplanted human islets was tested by measuring the plasma glucose and human C-peptide response to intraperitoneal glucose injection in groups 1 and 4. IPGTT alone was assessed in groups 2 and 3. The results indicate that i.p. administration of FK506 for one week at a dose 0.3 mg/kg/day did not result in any significant alteration of glucose disappearance and C-peptide response to IPGTT. Higher doses of FK506 produced a significant delay in glucose disappearance in groups 3 and 4, and a significant inhibition of glucose-mediated C-peptide response in group 4.

Anti-Bacterial Agents↗

The question of FK 506 nephrotoxicity after liver transplantation.

Formal studies have not been published on the nephrotoxicity of FK 506 when the drug was used from the outset. This kind of information was sought in 101 recipients of primary livers, 24 hearts, and 3 double lungs or heart-lung. Perioperative renal dysfunction was commonly seen, which appeared to be related to FK 506 doses and plasma levels, particularly when the drug was given IV. This was reversible. Late renal function has been generally satisfactory in all three cohorts of patients, and the incidence of hypertension has been low. The therapeutic index of FK 506 is a good one, as revealed by these observations in patients whose most notable achievement was a low mortality.

Anti-Bacterial Agents↗

Long survival in rats after multivisceral versus isolated small-bowel allotransplantation under FK 506.

Abdominal multivisceral allotransplantation (MVTX) from Brown Norway donor rats to Lewis recipient rats was performed under a 14-day course of low (0.32 mg/kg) or high-dose (0.64 mg/kg) intramuscular FK 506 to which weekly further injections were added in some of the high-dose animals. With all three regimens, long survival was frequently achieved with good intestinal adsorption and weight gain, but histopathologic evidence of intestinal rejection existed in the most lightly treated animals. The liver, stomach, and pancreas had only minor abnormalities. Rejection of isolated intestinal grafts was more difficult to control based on histopathologic criteria, and satisfactory results were obtained only with the most aggressive treatment protocol, suggesting that the liver in the MVTX had provided an advantage to the companion organs of the graft, of which the intestine was most vulnerable. Histopathologically, the lymphoid elements of the intestine, including the Peyer's patches, appeared to be the most immunogenic component of the intestine. Epithelium near lymphoid areas was secondarily involved with villous atrophy, cryptitis, and abscess formation. Beginning within 12 days in successful MVTX experiments, the lymphoreticular components of the graft intestine, including the Peyer's patches, lamina propria, and mesenteric nodes, were shown with anti-Ia monoclonal antibodies to be repopulated with recipient cells. This finding in grafts that appeared to be permanently accepted was surprising and contrary to expectations from the literature on intestinal allotransplantation.

Animals↗

Notes on FK 506.

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Anti-Bacterial Agents↗