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Biomedical subjects

S Ryu

Publications and source records attributed to S Ryu.

At least 91 records · Page 5Linked to original sources

Reinnervation of allografted pancreatic islets in the rat liver.

Rat pancreatic islets were allografted in the liver and were studied morphologically in order to evaluate possible reinnervation. Islets isolated from rat pancreas were allotransplanted in the liver of streptozocin-induced diabetic rats via the portal vein. Electron microscopy revealed nerve endings with synaptic vesicles in the transplanted islets 100 days after transplantation, whereas axons in the islets appeared to degenerate several hours after isolation and prior to transplantation. These findings suggest that the nerve endings observed in the transplanted islets regenerate from nerves that innervate the recipient's liver. The tissue specimens were also investigated immunohistochemically using antityrosine hydroxylase antibody, and histochemically by the modified Karnovsky and Roots' method for visualizing acetylcholinesterase. Some nerve endings in the transplanted islets reacted positively to antityrosine hydroxylase antibody. Acetylcholinesterase was visualized in other nerves. These results indicate that norepinephrine- and acetylcholinesterase-containing nerves may reinnervate the transplanted islets.

Acetylcholinesterase↗

In vitro release of vasoactive intestinal polypeptide and pancreatic polypeptide from human VIPoma cells and its inhibition by somatostatin analogue (SMS 201-995).

BACKGROUND: The purpose of the present study was to determine whether vasoactive intestinal polypeptide (VIP) is released from the tumor cells of VIPoma and if so then to attempt to show how its release is regulated by cultured human VIPoma cells. METHODS: A resected specimen of a pancreatic tumor from a patient with watery diarrhea, hypokalemia, and achrohydria syndrome was examined. The dissociated cells were obtained by collagenase digestion of the tumor tissue and were cultured in vitro. RESULTS: The extraction of tumor cells disclosed that the cells contained VIP and pancreatic polypeptide (PP). Neither insulin, glucagon, somatostatin nor pancreastatin was detected. Immunohistochemically, 40% to 60% of the cells in the tumor stained positively for VIP and 1% to 5% stained positively for PP. The dissociated cells became reaggregated in the culture (50 to 300 microns) and could be maintained in vitro. Incubation experiments revealed a simultaneous in vitro release of VIP and PP with a significant increase by either carbachol or phorbol myristate acetate but not by theophylline or caerulein. Atropine completely abolished the stimulatory effects of carbachol on VIP and PP release. Octreotide (somatostatin analogue [SMS 201-995]) significantly inhibited the carbachol and phorbol myristate acetate-stimulated VIP and PP release. CONCLUSIONS: These findings show the in vitro release of VIP and PP from the VIPoma cells and also provide evidence for the direct inhibitory effect of somatostatin analogue on both the VIP and PP release from the tumor cells.

Adult↗

Pivotal role of amino acid at position 138 in the allosteric hinge reorientation of cAMP receptor protein.

The cAMP receptor protein (CRP) of Escherichia coli needs cAMP for an allosteric change to regulate gene expression by binding to specific DNA sites. The hinge region connecting the DNA-binding domain to the cAMP-binding domain has been proposed to participate in the cAMP-induced allosteric change necessary to adjust C and D alpha-helices for movement of the DNA-binding F alpha-helix away from the protein surface. The role of the hinge region for a conformation change in CRP was tested by studying the effects of single amino acid substitutions at residue 138 located within the hinge. Physiological studies of wild-type and mutant cells and biochemical analysis of purified wild-type and mutant CRP revealed at least three groups of altered CRPs: (i) CRP that behaves like wild type (CRP+); (ii) CRP that binds cAMP but does not complete the structural changes required for specific DNA binding, proteolytic cleavage, and transcription activation (CRPallo); and (iii) CRP that shows some or all of these conformational changes without cAMP (CRP*). These results show a pivotal role of position 138 from which change emanates and provide further evidence that a hinge reorientation involving residue 138 is involved in the interhelical adjustments.

Allosteric Site↗

A 48 kilodalton enterotoxin-related protein from Clostridium perfringens vegetative and sporulating cells.

Sporulating and vegetative cell extracts of enterotoxin-positive and enterotoxin-negative strains of Clostridium perfringens were examined by Western blotting using enterotoxin antiserum. A 48-kDa enterotoxin-related protein was found in vegetative and sporulating cell extracts of both toxin types. The results question previous reports about the ability of vegetative cells and presumptive enterotoxin-negative strains of this organism to produce enterotoxin, a protein with a molecular weight of 34 kDa.

Blotting, Western↗

Diabetogenic effects of FK506 on renal subcapsular islet isografts in rat.

Previously we demonstrated prevention of immune rejection in rat islet allografts by continuous subcutaneous (s.c.) administration of FK506 and also showed that FK506 might have diabetogenic effects (Ryu and Yasunami (1991) Transplantation, 52, 599-605). The purpose of the present study was to characterize further diabetogenic effects of FK506 on renal subcapsular islet isografts in rat. Continuous s.c. administration of FK506 (3 mg/kg/day) for 35 days produced glucose intolerance in the recipients as demonstrated by intravenous (i.v.) glucose tolerance test at the end (35 days) and after discontinuation (90 days) of FK506 administration. Morphologically, beta cells in the grafts of FK506-treated group were degranulated at 35 and 120 days after transplantation. Electron microscopically, degranulation, marked swelling of rough endoplasmic reticulum, Golgi apparatus and mitochondria were detected in beta cells of the grafts treated with FK506 at 35 days, and at 120 days there was moderate structural recovery in the organella. These findings clearly demonstrate that FK506 has diabetogenic effects on renal subcapsular islet isografts in rat and also suggests potential reversibility of damages by FK506 in beta cells of the grafts.

Animals↗

Enhancement of radiation response on human carcinoma cells in culture by pentoxifylline.

PURPOSE: Pentoxifylline, a methylxanthine, has been shown to improve tumor tissue oxygenation in hypoxic murine tumors and prevent the late radiation injury of normal tissues in mice. The present cell culture studies were carried out to determine whether pentoxifylline would enhance the cellular radiation response of several human carcinoma cells in culture under various culture conditions. METHODS AND MATERIALS: Experiments were carried out with three human carcinoma cells grown in Eagle's MEM supplemented with 10% FCS. Cell survival was assayed by the colony forming ability of single plated cells to obtain dose-survival curves. RESULTS: Cells irradiated and exposed to pentoxifylline for 24 hr showed a significant enhancement of radiation-induced cytotoxicity. Pre-irradiation treatment with the drug did not change cellular response to radiation. The magnitude of radiation enhancement was dependent on the concentration of drug and exposure time up to the time corresponding to one cell cycle time. Among the three human carcinoma cells used (HeLa S-3 cervix carcinoma, MCF-7 breast carcinoma, and HT-29 colon carcinoma), HeLa S-3 cells were most susceptible to the combined treatment with the enhancement ratio of 1.4 at 1 mM. Among the derivatives of methylxanthines, caffeine and pentoxifylline were equally effective on a molar basis. The combined effect of pentoxifylline and purine nucleosides, including guanosine and deoxyguanosine, further enhanced the sensitizing effect of pentoxifylline. CONCLUSION: The present data along with other radiobiological effects of the drug suggest that pentoxifylline should be considered as a radiation enhancer for clinical radiotherapy.

Cell Hypoxia↗

Stimulation of the onset of sporulation of Clostridium perfringens type A by netropsin and distamycin.

The basic peptide antibiotics, netropsin and distamycin, previously shown to inhibit sporulation of Bacillus subtilis, stimulated low levels of sporulation of Clostridium perfringens strain NCTC 8798 at concentrations of 1.0 and 0.1 microgram/ml respectively. Most sporulating cells produced in the presence of the antibiotics were defective. These were blocked at Stage III of sporulation, and many possessed forespores exterior to the sporangium. The same antibiotics could also inhibit the caffeine-induced stimulation of sporulation of this strain.

Clostridium perfringens↗

Mitomycin C, vindesine, and cisplatin in advanced non-small-cell lung cancer. A phase II study.

Between August 1985 and June 1986, 49 previously untreated patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) were treated with the combination of cisplatin 80 mg/m2 i.v. on day 1, vindesine 3 mg/m2 i.v. on days 1 and 8, and mitomycin-C 8 mg/m2 i.v. on day 1 (MVP), repeating after an interval of 4 weeks, and thereafter every 6 weeks. The median age for all patients was 62 years, with a range of 21 to 77 years. All patients had a performance status of 0, 1, or 2 (ECOG scale) and measurable disease. Histologic types included squamous cell carcinoma (22 patients), adenocarcinoma (22 patients), and large-cell carcinoma (6 patients). Forty-eight patients were evaluable for response. Out of 48 patients, one (2%) achieved a complete response and 24 patients (50%) achieved a partial response, resulting in an overall response rate of 52% (95% confidence interval, 38-68%). The response rates were 52% for squamous cell carcinoma, 45% for adenocarcinoma, and 80% for large-cell carcinoma, respectively. The median duration of response was 4.2 months and the median duration of survival for all patients was 10.6 months. The major toxicity was myelosuppression. Leukopenia and thrombocytopenia of grade 3 or 4 occurred in 85% and 33%, respectively. One patient died of sepsis associated with leukopenia. Other toxicities were manageable and reversible. In conclusion, the MVP regimen was active and tolerable in patients with advanced NSCLC. Prospective randomized study comparing the MVP regimen with the two-drug combination of vindesine and cisplatin is warranted.

Adult↗

The necessity of differential immunosuppression for prevention of immune rejection by FK506 in rat islet allografts transplanted into the liver or beneath the kidney capsule.

The purpose of the present study was to achieve prevention of immune rejection in rat islet allografts by FK506. WKA/Qdj (RT1u) islets were transplanted either into the liver via the portal vein (p.v.) or beneath the kidney capsule (k.c.) of streptozotocin (60 mg/kg) induced diabetic Lewis (RT1(1)) rats. Fresh or cultured (24 degrees C, 1 week) islets were used as donors. A miniosmotic pump (0.2 ml, Alzet 2001) containing 5 mg FK was implanted s.c. at the time of transplantation for continuous delivery of FK506 for 7 days after transplantation. The mean survival time (MST) of the fresh p.v. grafts with a pump was offater than 61.4 +/- 37.2 days (mean +/- SD, n = 17) (control 5.5 +/- 0.6, n = 4). Ten out of 17 were normoglycemic for more than 90 days after transplantation. When low-temperature cultured islets were used and FK506 was delivered for 7 days, all the rats were normoglycemic for more than 90 days after transplantation. The MST of the fresh or cultured k.c. grafts with a pump was 22.0 +/- 14.2 or 24.7 +/- 5.0 days, respectively. Long-term administration of FK506 by repeated implantations (5 times; days 0, 7, 14, 21, and 28) of pumps containing 5 mg FK506 produced marked prolongation of the fresh or cultured k.c. graft survival with an MST of greater than 58.7 +/- 22.1 or greater than 56.9 +/- 18.0 days, respectively. These findings clearly demonstrate that the prevention of immune rejection in the islet allografts transplanted into the liver was achieved by short-term post-transplant administration of FK506 and low-temperature culture of donor islets, and also show that long-term continuous administration of FK506 was needed for the prolongation of the graft survival when the renal subcapsular space was the site for implantation of islets. Thus, the present study indicates that in different transplant sites different immunosuppressive regimes are needed for the control of rejection by FK506 in rat islet allografts.

Animals↗

Sensitivity and specificity of lung cancer screening in Osaka, Japan.

Sensitivity and specificity were evaluated for lung cancer screening conducted at 8 municipalities in Osaka Prefecture during 1981-1985. As a screening policy, all attendants were examined by miniature chest X-ray, and the high-risk group, defined as those who smoked cigarettes or had bloody sputum, were also examined by 3-day pooled sputum cytology. A total of 33,599 screening tests for 19,028 people who were 40 years old or more at the time of screening were conducted, resulting in 33,490 miniature chest X-ray examinations for 18,992 people and 11,420 sputum cytologies for 7,070 people. As a result, 43 lung cancer cases were detected. All test-negatives were followed by means of record linkage with the files of the Osaka Cancer Registry up to the end of 1986. There were 24 cases who were diagnosed as having lung cancer without having given a positive screening result in 1981-1986. Assuming the preclinical detectable phase of lung cancer to be one year uniformly, the sensitivity and specificity for the lung cancer screening were estimated to be 71.6% and 95.3%, respectively. The feasibility of increasing the sensitivity is discussed.

Adult↗