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Biomedical subjects

T Kanai

Publications and source records attributed to T Kanai.

At least 253 records · Page 14Linked to original sources
PubMed1989

Successful treatment of experimental diabetes by sequential transplantations of multiple-donor pancreatic islet allografts.

Fifty hand-picked islets were freshly prepared from DBA/2 mice and transplanted four times into a streptozotocin-induced diabetic B6AF1 mouse without immunosuppression. Blood sugar levels decreased progressively and all recipients became normoglycemic after the 4th grafting. Four repeated transplantations at 2-4-day or 14-day intervals restored normoglycemia for more than 200 days in virtually all recipients. However, a majority of recipients given four transplantations of 50 DBA/2 islets at 7-day intervals or four transplantations of 100 DBA/2 islets at 4-day or 14-day intervals acutely rejected their grafts. When handpicked islets were freshly prepared from each of four histoincompatible donors (DBA/2, DBA/1, A.SW, and C3H) and sequentially transplanted four times (islets from one donor for each transplantation) into diabetic B6AF1 recipients, virtually all recipients maintained normoglycemia for more than 200 days regardless of the number of islets per grafting or intervals between transplantations. Since the purity of human islet preparations to date has been at the level of crude-digested islets, crude islets were used in sequential transplantation. Four transplantations of approximately 50 crude islets prepared from each of four donors achieved marked prolongation of graft survival. In sharp contrast, transplantation of 250-500 single-donor crude islets or four sequential transplantations of DBA/2 50 crude islets resulted in acute graft rejection.

Animals↗
PubMed1989

[Cardiovascular effects of beraprost sodium (TRK-100), a prostacyclin analogue in the dog].

Effect of prostacyclin analogue, beraprost sodium (Sodium (+/-)-(1R*, 2R*, 3aS*, 8bS*)-2, 3,3a,8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen+ ++-6- ynyl]-1H-cyclopenta-[b]benzofuran-5-butyrate, TRK-100), on the cardiovascular system of the anesthetized dog was investigated. TRK-100 was injected intra-arterially and intravenously to study the vasodilating effect of the drug by a magnetic flow meter. Intra-arterial injection of TRK-100 augmented blood flow of vertebral, coronary, renal, supramesenteric, hepatic and femoral artery at a dose range of 0.0003 to 3,000 micrograms/bed. The threshold doses of TRK-100 and PGI2 in the mesenteric artery were 0.003 micrograms and 0.0003 micrograms, respectively, and the same values were obtained in the splenic artery. Those were slightly lower than those of other arteries. Intravenous injection of TRK-100 augmented mesenteric and renal arterial flow to 193 +/- 30% and 118 +/- 4%, respectively. In this system augmentation of mesenteric and renal arterial flow was 179 +/- 19% and 135 +/- 1%, respectively, while vertebral, carotid, and femoral arterial flow decreased, respectively, to 71.4 +/- 2.1%, 80.0 +/- 9.4% and 61.4 +/- 5.6% by TRK-100 and 70.6 +/- 5.6%, 79.5 +/- 6.9% and 67.1 +/- 4.7% by PGI2. Inhibitory effects on heart functions such as cardiac output, left ventricular pressure, LV dP/dt, oxygen consumption, and cardiac work were seen. The effect was similar to PGI2. Coronary vascular resistance, total peripheral resistance and systemic blood pressure were also decreased by TRK-100 and PGI2.

Anesthesia↗
PubMed1989

Effect of gamma-irradiation on mouse pancreatic islet-allograft survival.

Elimination or inactivation of lymphoid tissue in the pancreatic islet preparation achieves prolongation of islet-allograft survival. In this study we examined the effect of gamma-irradiation on mouse islet-allograft survival. In a B6AF1 isograft model, irradiation up to 2400 rad did not induce deterioration of islet function over 200 days, but greater doses caused cessation of graft function between 83 and 186 days. When DBA/2 crude islets were transplanted into B6AF1 recipients, all nonirradiated allografts were acutely rejected. Marked prolongation of allograft survival was achieved by islet irradiation with doses between 800 and 12,000 rad. With higher doses, significant numbers of allografts survived beyond the controls, but many lost function between 78 and 180 days, with none surviving greater than 200 days. Irradiation with 16,000 rad caused acute radiation damage. Because most secondary islet allografts in recipient mice that lost primary islet-graft function between 84 and 195 days survived greater than 100 days, late functional loss was probably due to the radiation injury. Combined use of recipient treatment with cyclosporin A and graft irradiation (2400 rad) achieved prolongation of DBA/2 islets in B6AF1 mice.

Animals↗
PubMed1989

General pharmacology of beraprost sodium. 2nd communication: effect on the autonomic, cardiovascular and gastrointestinal systems, and other effects.

Beraprost sodium (sodium (+/-)-(1R*,2R*,3as*,8bS*)-2,3,3a,8b-tetrahydro-2- hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H- cyclopenta[b]benzofuran-5-butyrate, TRK-100) is an orally active epoprostenol (prostaglandin I2, PGI2) analogue. Its general pharmacological effects on peripheral organs were studied. 1. In isolated organs, beraprost sodium relaxed the trachea and increased atrial beating rate (2.4 x 10(-5) mol/l). It also dose-dependently contracted the stomach, aorta, ileum and uterus (2.4 x 10(-7)-2.4 x 10(-4) mol/l). These effects of beraprost sodium were similar, but inferior to those of PGI2 and PGE1. 2. Intravenous administration of beraprost sodium produced a dose-related decrease in blood pressure (BP), its potency being about 1/3 times that of PGI2 in anesthetized rats and dogs. Beraprost sodium and PGI2 had no effects on heart rate (HR), and enhanced respiration in conjugation with a decrease in BP. Oral administration of beraprost sodium in high doses (1-3 mg/kg in rats and 0.3 mg/kg in dogs) caused a decrease in BP. A compensatory tachycardia and an elevated plasma renin activity (PRA) occurred after low doses (0.1-0.3 mg/kg) in rats. In contrast, a change of HR and PRA in rabbits and dogs was mild. 3. Beraprost sodium produced suppression of digestive organs: markedly, gastric motility and secretion and intestinal transport; slightly, but significantly, biliary secretion. On the other hand, it enhanced ileal motility at a high dose (300 micrograms/kg i.v.). 4. Oral administration of beraprost sodium caused a decrease in urinary volume and electrolyte excretion in rats. 5. Oral administration of beraprost sodium prolonged bleeding time in mice, while it had no effect on the blood coagulation system in vitro. In addition, beraprost sodium had no hemolytic action. 6. The other effects of beraprost sodium were weak. Beraprost sodium had no local anesthetic activity and no effect on salivation, pupil size and neuromuscular transmission in the skeletal muscle. Beraprost sodium slightly contracted the uterus of non-pregnant rats in situ and dose-independently inhibited carrageenin-induced paw edema. In conclusion, beraprost sodium produced various effects on the autonomic, cardiovascular, and gastrointestinal systems. Probably, these effects may be based on its own action like PGI2.

Anesthetics, Local↗
PubMed1989

Release of the serum immunosuppressive factor by monocytes in patients with Crohn's disease.

We investigated the in vitro immunosuppressive effect of the sera and the culture supernatants of the peripheral blood mononuclear cells obtained from patients with Crohn's disease. Sera from Crohn's disease markedly suppressed the proliferative response of mouse spleen cells, compared with sera from ulcerative colitis, intestinal tuberculosis and normal controls. The culture supernatants of the adherent mononuclear cells from Crohn's disease showed a remarkable suppressive effect (96 +/- 1%), while the culture supernatants of the non-adherent mononuclear cells had no suppressive activity (-10 +/- 16%). The culture supernatants of the adherent and non-adherent mononuclear cells from normal controls had no suppressive activity. The fractionization of the culture supernatants of the adherent cells from the Crohn's disease patients demonstrated that the fractions with high suppressive activity had similar or identical biochemical properties to the serum immunosuppressive fractions which has been reported previously. These results indicate that monocytes may release the serum immunosuppressive factor in Crohn's disease. This factor may contribute to the depression of the immune reactivity in the mucosal lesion and to the persistence of the stimulation of abnormal immune response in the intestinal wall.

Adolescent↗
PubMed1989

[Two cases of Hermansky-Pudlak syndrome with interstitial pneumonia].

Two cases of Hermansky-Pudlak syndrome with interstitial pneumonia were reported. Both patients had evidence of pulmonary involvement characterized by diffuse bilateral infiltrates. They had oculocutaneous albinism. Case 1 was a 55 year-old female who had a history of easy bruising. Her two sisters were albino and had died of pulmonary fibrosis. One of them was diagnosed as Hermansky-Pudlak syndrome on autopsy. Bone marrow aspirate disclosed typical macrophages with ceroid-like pigment. Transbronchial lung biopsy showed alveolar wall thickening. Lumi-aggregometer showed a decrease of platelet aggregation and an absence of ATP release. Case 2 was a 43 year-old female and had a bleeding tendency during a surgical procedure. Lumi-aggregometer showed normal platelet aggregation but an absence of ATP release. BALF analysis did not disclose macrophages with ceroid-like pigment.

Adult↗
PubMed1988

Interaction function gamma(x) for Chinese hamster cells treated with hypertonic phosphate-buffered saline after irradiation.

The repair of potentially lethal damage (PLD) in stationary-phase V79 Chinese hamster cells, which was expressible by a postirradiation treatment with hypertonic (0.5 M NaCl) phosphate-buffered saline (PBS), was analyzed within the framework of the theory of dual radiation action. The interaction function gamma(x) was estimated for cells permitted to repair PLD for various intervals of time. The experimental data indicated that 50-60% of the lethal lesions produced at the time of irradiation were repaired in 120 min. The repair of PLD was implicitly involved in the probability of the interaction of sublesions. That is, g(x,trep) was defined as the probability that two sublesions separated by distance x interact to produce a lethal lesion which will not be repaired until the fixation by treatment with hypertonic PBS at time trep after irradiation. It is concluded that the time dependence of the repair of PLD is not independent of the interaction distance x. Three conclusions are drawn: (1) The repair of a lesion produced by a long distance interaction is not detectable by postirradiation treatment with hypertonic PBS. (2) A lesion produced by a short distance interaction is rapidly repaired in about 20 min. (3) A lesion produced by the interaction of sublesions separated by a distance of about 100 nm is repaired slowly.

Animals↗
PubMed1988

Multiple donor allotransplantation. A new approach to pancreatic islet transplantation.

Currently it is not feasible to isolate sufficient numbers of islets from a single pancreas for clinical transplantation. We examined whether small numbers of islets obtained from multiple donors could be used for transplantation. Islets were isolated from four inbred strains of mice (DBA/2, DBA/1, C3H, and A.SW) by a stationary collagenase digestion and Ficoll separation and transplanted into the renal subcapsular space of streptozotocin-induced diabetic B6AF1 mice. At least 200 handpicked islets were required to produce normoglycemia in syngeneic and allogeneic diabetic recipient mice. None of the mice given 50 islets became normoglycemic within 2 weeks postgrafting. When various numbers of purified islets from a single donor were transplanted, the survival was significantly better for 200-islet allografts than for 800-islet and 400-islet allografts. When a 200-islet composite graft was prepared from four donors (50 fresh handpicked islets from each donor), the survival of the composite graft as measured by sustained normoglycemia in nonimmunosuppressed recipients was dramatic, with 17 of 18 recipients maintaining normoglycemia indefinitely (greater than 200 days). Similarly, when islets isolated from four donors and cultured for various periods were mixed and transplanted (200 islets/recipient) all recipient mice (n = 8) enjoyed indefinite graft survival. Use of higher numbers of purified islets or crude islets in a composite multiple-donor islet allograft was less effective in achieving indefinite graft survival. Thus, transplantation of a composite graft made up with subtherapeutic numbers of islets from multiple histoincompatible donors to provide adequate therapeutic numbers is a practical solution to the lack of islet availability. In addition, composite islet grafts appear to possess immunological advantages, with significantly prolonged survival over that produced by single-donor islet grafts.

Animals↗
PubMed1988

Pharmacological effects of urapidil on bronchospasm, myocardial hypoxia and postural hypotension in experimental animals.

We studied the effects of urapidil on bronchospasm, myocardial hypoxia and postural hypotension in experimental animals. Urapidil dose-dependently inhibited bronchospasm induced by histamine in anaesthetized guinea pigs and the contraction of isolated trachea induced by noradrenaline or phenylephrine. Urapidil markedly delayed the appearance of severe dyspnoea induced by histamine aerosol in guinea pigs. Further, urapidil inhibited isoproterenol-induced ST depression in rats and inhibited histamine-induced ST depression in rabbits. The postural hypotension induced by prazosin was greater than that induced by urapidil in equihypotensive doses in conscious rabbits. Urapidil induced a lesser alpha-blockade in the vein than in the artery compared with prazosin. These combined properties of urapidil suggest that the drug is worth investigation in hypertensive patients with bronchial asthma or ischaemic heart disease.

Animals↗
PubMed1987

Pathology of small hepatocellular carcinoma. A proposal for a new gross classification.

Review of 61 surgically resected small hepatocellular carcinomas (HCC) less than or equal to 3 cm in diameter yielded a simple gross classification system of five types based on tumor shape, which is highly correlated with microscopic and clinical features, including prognosis. Type 1 (single nodular type) tumors (n = 13) are expansile, roughly spheric, and often encapsulated. In Type 2 tumors (single nodular type with extranodular growth) (n = 21), replacing growth is often seen in the area of extranodular growth. Type 3 tumors (contiguous multinodular type) (n = 19) consist of small nodules growing in contiguity, often with replacing growth at the periphery. Type 4 (poorly demarcated nodular type) is a rare tumor showing infiltrating growth at its border. The authors define early HCC (n = 5) as the presence of tumor without destruction of the underlying liver structure. The lesions experienced are tiny (less than or equal to 1.2 cm) and well differentiated. Poorly differentiated histologic characteristics and elevated alpha fetoprotein are more common in Types 2 and 3 than in Type 1. Type 1 has the highest rates of positive serum hepatitis B surface antigen and liver cirrhosis; portal vein tumor thrombus (PT) and/or intrahepatic metastasis (IM) is rare (7.7%), and the effect of transcatheter arterial embolization (TAE) is remarkable. This contrasts with Type 2, which has a high rate of PT and/or IM (71.4%) and multiple local recurrences (40%), and with Type 3, which shows a poor response to TAE.

Adult↗
PubMed1987

Expression of Lewis blood group antigens in cancerous and non-cancerous liver.

The expression of Lewis blood group antigens, Lewisa, Lewisb, Lewisx and Lewisy, in 40 non-cancerous livers and in 20 hepatocellular carcinomas (HCC), 5 cholangiocarcinomas (CC), and 6 combined hepatocellular and cholangiocarcinomas (Comb) was studied by immunohistochemistry using monoclonal antibodies. Although normal hepatocytes did not express any of the four Lewis antigens, Lewisy expression was detected in some hepatocytes at the periphery of pseudolobules in cirrhotic liver. While Lewisx in bile duct epithelial cells was undetectable in normal livers, it was detected in some cases with non-cancerous liver diseases. Lewisx and Lewisy were detected in 30% of HCC and 100% of CC and Comb. Non-cancerous bile duct epithelial cells in almost all instances were stained strongly by anti-Lewisa and/or anti-Lewisb antibody. Proliferating bile ductules within Glisson's sheath and pseudolobules could be clearly detected by Lewisa and Lewisb staining. Lewisa and Lewisb were never detected in non-cancerous hepatocytes, and were only rarely detected in HCC, but were expressed in most cases of CC and Comb. These results suggested that Lewisa and Lewisb are useful markers for differentiation towards biliary epithelial cells in the liver, and that Lewisx and Lewisy expression might be associated with states of increased or altered cell proliferation.

Adenoma, Bile Duct↗
PubMed1987

Monoclonal antibody highly sensitive for the detection of ras p21 in immunoblotting analysis.

Four murine monoclonal antibodies (NCC-RAS-001, -004, -005, -017) reactive with ras p21 were produced by using recombinant c-Ha-ras p21 as an immunogen. Among these antibodies, NCC-RAS-004 was extremely sensitive when used in immunoblotting analysis, facilitating semiquantitative detection of c-Ha-, c-Ki- and N-ras p21 in cell and tissue lysates. In cells carrying a point-mutationally activated ras, p21 with abnormal mobility upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis was clearly detected.

Antibodies, Monoclonal↗