Biomedical subjects

T Toyota

Publications and source records attributed to T Toyota.

At least 217 records · Page 12Linked to original sources

PubMed1994

Role of nitric oxide in the pancreatic blood flow response to caerulein.

To clarify the role of nitric oxide (NO) in the pancreas, blood flow in the rat pancreas (pancreatic blood flow: PBF) was investigated by the hydrogen clearance technique using a specific NO synthase inhibitor, N omega-nitro-L-arginine (L-NNA). Continuous infusion of caerulein at doses of 5 and 20 micrograms/kg/h caused a significant increase in PBF in the early phase of caerulein infusion. The caerulein-induced increase in PBF was not affected significantly by atropine sulfate (100 micrograms/kg), nor by phenoxybenzamine (5 mg/kg) plus propranolol (50 micrograms/kg). Administration of L-NNA (0.5, 5, or 30 mg/kg) did not affect the basal PBF, but at 5 mg/kg it inhibited completely the caerulein-induced increase in PBF. The inhibitory action of L-NNA was reversed by a large dose of L-arginine (100 mg/kg bolus, i.v., followed by a continuous infusion at 400 mg/kg/h), but not by its enantiomer D-arginine. These results strongly suggest that NO has a mediator role in the early phase vascular response of the pancreas to superphysiologic doses of caerulein.

Amino Acid Oxidoreductases↗

PubMed1994

Changes in neuropeptide-containing nerves in human colonic mucosa with inflammatory bowel disease.

The distribution abnormality of vasoactive intestinal polypeptide-containing nerves (VIP-nerves) and substance P-containing nerves (SP-nerves) was immunohistochemically investigated in the colonic mucosa with inflammatory bowel disease (IBD) in relation to colonic glands and blood vessels in the lamina propria. In active ulcerative colitis (UC), VIP- and SP-nerves decreased in severe inflammatory lesions. VIP-nerves were almost absent particularly around crypt abscesses. Even in resolving and quiescent UC, VIP-nerves still decreased, depending on the decrease of glands and blood vessels. On the other hand, both nerves increased in some hypervascular lesions. In the uninvolved mucosa of UC, they did not change their distribution. In Crohn's disease, the distribution abnormality of both nerves resembled that of UC. These results suggest that the changes in VIP- and SP-nerve distributions in the mucosa with IBD are subsequent to mucosal inflammation and damage. However, these peptides are known to be immunoregulators, and their distribution abnormalities may induce the disorder of immunoregulation in the IBD mucosa and cause the mucosal damage and/or chronicity.

Adolescent↗

PubMed1994

NADPH-diaphorase activity as a marker for nitric oxide synthase in neurons of the guinea pig respiratory tract.

Recent studies in physiology have suggested that part of the inhibitory nonadrenergic noncholinergic (iN-ANC) response of airway smooth muscle is mediated by nitric oxide (NO). To examine this point morphologically, the guinea pig respiratory tract was investigated histochemically for nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (NADPH-d), a marker for NO synthase (NOS). In addition, coexpression of NOS and vasoactive intestinal peptide (VIP) or calcitonin gene-related peptide (CGRP) was studied using a combination of histochemistry for NADPH-d and immunohistochemistry for VIP or CGRP. Nerve fibers showing NADPH-d activity were abundantly observed in the respiratory tract. They were distributed throughout smooth-muscle bundles, lamina propria, submucosal glands, and around bronchial and pulmonary arteries. NADPH-d-containing nerve-cell bodies were occasionally found within airway ganglia. The colocalization study demonstrated that NADPH-d-containing nerve fibers frequently coincided with VIP-like immunoreactive nerve fibers but not with CGRP-like immunoreactive nerve fibers. Among nonneural tissues, NADPH-d activity was noticed in the endothelium of both bronchial and pulmonary vessels, and in the pleura. These observations indicated that NO may be produced by neurons and vascular endothelium of the guinea pig respiratory tract, and may function as a neuronal mediator as well as endothelium-derived relaxing factor (EDRF). Colocalization of NADPH-d and VIP-like immunoreactivity in nerve fibers suggested that NO and VIP may function as cotransmitters.

Amino Acid Oxidoreductases↗

PubMed1994

Therapeutic effect of reticuloendothelial system (RES)-avoiding liposomes containing a phospholipid analogue of 5-fluorouracil, dipalmitoylphosphatidylfluorouridine, in Meth A sarcoma-bearing mice.

Reticuloendothelial system (RES)-avoiding liposomes are known to accumulate in tumor tissues due to passive targeting. Dipalmitoylphosphatidylfluorouridine (DPPF), a potent antitumor agent readily incorporated into the lipid bilayer, was embedded in RES-avoiding liposomes modified with a uronic acid derivative, palmityl-D-glucuronide (PGlcUA). The therapeutic effect of DPPF in PGlcUA-liposomes was examined in tumor-bearing mice. Free or liposomal DPPF was injected intravenously into BALB/c mice bearing subcutaneously implanted Meth A sarcomas. The RES-avoiding liposomal formulation using PGlcUA was effective in reducing tumors, and prolonging survival time compared with free DPPF and also DPPF in conventional liposomes. Therefore, PGlcUA-liposomes might be of practical use as drug carriers for anticancer agents, especially their derivatives for embedding in liposomal membranes.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1994

Changes of serum hepatitis C virus levels in patients with chronic hepatitis C treated with two courses of interferon administration.

To assess the efficacy of repeated interferon (IFN) administration in patients with chronic hepatitis C unresponsive to initial therapy, serum hepatitis C virus (HCV)-RNA levels were measured in 12 patients who had failed prior IFN therapy. Serum HCV-RNA was assayed by measuring DNA complementary to HCV-RNA using a quantitative reverse transcription-polymerase chain reaction assay. The mean total dose of IFN was 227.8 mega-units for first treatment and 270.7 mega-units for second treatment. Five responders with a normal alanine aminotransferase (ALT) concentration (less than 40 IU/liter) at the end of the first treatment also had a normal ALT concentration at the end of the second treatment. By contrast, all nonresponders with an elevated ALT concentration during the first treatment likewise had an elevated ALT concentration at the end of the second treatment. HCV-RNA levels before the first treatment varied from 10(6) to 10(8) copies/microliters. The serum HCV-RNA levels fell in 9 out of 10 patients after the first treatment and in 11 out of 12 patients after the second treatment. One patient had unchanged normal serum ALT levels after two courses of IFN treatment. These results suggested that the outcome of a second course of IFN treatment was similar biochemically and virologically to a first course, and that patients who did not respond initially seldom respond to additional IFN therapy. Therefore, readministration of IFN should be restricted to patients who respond biochemically and virologically to initial treatment. The optimal second dose shall be determined with further studies.

Adult↗

PubMed1994

[An autopsy case of AIDS with hemophilia A who died of DIC and gastrointestinal bleeding associated with gastric carcinoma (signet ring cell carcinoma)].

We describe a 39 years-old male hemophilia A patient with acquired immunodeficiency syndrome (AIDS) developing to disseminated intravascular coagulation (DIC) due to gastric carcinoma. He had been diagnosed as human immunodeficiency virus (HIV) sero-positive in 1990. Since then, he has been treated by the oral administration of zidovudine (AZT), dideoxyinosine (ddI) and intravenous administration of glycyrrhizin. In September 1990, he suddenly complained abdominal pain with bloody stool. His condition deteriorated in spite of our intensive treatment for DIC. He died of multiple organ failure (MOF) due to DIC. The autopsy findings showed gastric carcinoma, defined of signet ring cell carcinoma histopathologically. But neither opportunistic infection nor other cause of DIC were observed.

Acquired Immunodeficiency Syndrome↗

PubMed1994

[A study on the dosage of carboplatin for bronchial arterial infusion in combination with radiation therapy].

Radiation therapy holds an important position as one of the multidisciplinary methods of treating lung cancer (non-small cell carcinoma). As a result of the development of platinum preparations such as cisplatin (CDDP) and wide use of digital subtraction angiography (DSA), selective bronchial arterial infusion (BAI) therapy made possible more effective use of anti-lung cancer drugs. The use of radiation therapy in combination with BAI is now recommended as a more effective method. Meanwhile carboplatin (CBDCA) has recently been developed as a second generation platinum preparation with less side effects, and is being used for BAI, too. However, the maximum tolerated dose (MTD) of CB DCA for BAI to be used in combination with radiation therapy is not known yet. We, therefore, carried out a phase-study to determine MTD of CBD CA for combination with radiation therapy. The results show that the MTD of CBDCA is 400 mg/m2, and that clinically recommendable infusion limit is 350 mg/m2. In an angiographic study performed at the same time, a plural number of tumor affected blood vessels were found in 81.3% of the patients with lung cancer. Therefore, infusion of a drug for such patients should be carefully applied.

Aged↗

PubMed1994

Gallbladder emptying to endogenous and exogenous stimulation in chronic pancreatitis patients.

OBJECTIVES: The present study was designed to analyze the underlying mechanism of gallbladder motor disturbance in chronic pancreatitis patients. METHODS: Gallbladder emptying to endogenous (oral test meal, Daiyan 13 g) and exogenous stimulation (iv cerulein, 30 ng/kg for 5 min) was examined by real-time ultrasonography in 12 patients with chronic pancreatitis and 10 normal subjects (controls). Plasma cholecystokinin levels during the endogenous stimulation were measured by bioassay. RESULTS: In chronic pancreatitis patients compared with controls, the fasting gallbladder volume was significantly increased (29.5 +/- 2.2 vs. 21.5 +/- 2.8 ml), whereas the gallbladder emptying (percent change of the basal volume) to oral test meal was significantly decreased. Neither cholecystokinin secretion induced by the test meal, nor the gallbladder emptying response to intravenous cerulein, differed significantly between the two groups. However, when chronic pancreatitis patients were divided according to pathogenesis, it became clear that gallbladder emptying to intravenous cerulein was significantly greater in patients with alcoholic chronic pancreatitis than in patients with idiopathic pancreatitis. CONCLUSIONS: Gallbladder emptying during the intestinal phase is generally reduced in patients with chronic pancreatitis, but gallbladder responsiveness to exogenous stimulation might be heterogeneous according to the pathogenesis.

Adult↗

PubMed1993

An immunohistochemical study of the c-erbB-2 oncogene product in intraductal mucin-hypersecreting neoplasms and in ductal cell carcinomas of the pancreas.

BACKGROUND: Intraductal mucin-hypersecreting neoplasm of the pancreas (IMHN) is a unique tumor that has a tendency to spread intraductally. The clinical outcome of IMHN generally is far better than that of pancreatic ductal cell carcinoma. Because of the presence of various cell atypia within the same tumor, it sometimes is difficult to make an accurate histopathologic diagnosis and, therefore, predict its biologic behavior. It has been shown that overexpression of c-erbB-2 protein in breast cancer with lymph node metastases is related to a poor prognosis. Overexpression of c-erbB-2 protein has been reported as an infrequent event in pancreatic ductal cell carcinoma, but little is known in the case of IMHN. METHODS: The expression of c-erbB-2 protein was immunohistochemically investigated in the formaldehyde-fixed, paraffin-embedded tissues of 17 cases of IMHN, and 14 cases of pancreatic ductal cell carcinoma (8 cases with lymph node metastasis), using polyclonal and monoclonal c-erbB-2(p185) antibodies by the avidin-biotin method. RESULTS: Both the polyclonal and monoclonal antibodies showed similar immunostaining for the c-erbB-2 product. Overexpression of the c-erbB-2 product was observed frequently in IMHN (13/17), especially in that with moderate- to high-grade cell atypia (12/12), whereas it was detected in only 1 of 14 cases of pancreatic ductal cell carcinoma (1/14). Among eight cases of pancreatic ductal cell carcinoma with lymph node metastases, overexpression of the c-erbB-2 product in metastatic lesions was detected in two, one of whose primary lesions also overexpressed the oncogene product. CONCLUSIONS: These observations suggest the genetic expression of c-erbB-2 is related to the pathogenesis of IMHN.

Adenocarcinoma, Mucinous↗

PubMed1993

Prevention of type I diabetes with lymphotoxin in BB rats.

We previously reported that nonspecific immunomodulations with a streptococcal preparation (OK-432), an inducer of tumor necrosis factor (TNF), or with recombinant TNF prevented development of insulin-dependent diabetes mellitus (IDDM) in animal models (NOD mice and BB rats). Recently we have further reported that lymphotoxin (LT), a cytokine with functional and structural characteristics similar to those of TNF, also protected NOD mice from diabetes. In this study, we have extended our observation on the LT to BB rats. Male and female BB/Wor rats were treated intraperitoneally with recombinant human LT three times a week from 4 to 11 weeks of age. The cumulative incidence of diabetes by 14 weeks of age was 24/30 (80.0%) in nontreated control rats, whereas it was 10/26 (38.5% vs control, P < 0.01) and 4/29 (13.8% vs control, P < 0.0001) in the rats treated with 1 x 10(3) and 1 x 10(4) of LT, respectively. There was no significant difference in nonfasting blood glucose levels and body weights between nontreated control and LT-treated rats, which were nondiabetic. In the LT-treated rats, intensity of insulitis was significantly reduced in comparison with the nontreated rats. Concanavalin A-stimulated TNF/LT productivity of spleen cells was significantly lower in BB/Wor and BB/Sendai rats than in Wistar rats or other normal rat strains. On the other hand, there was no difference between BB/Sendai and Wistar rats in the in vivo TNF/LT productivity induced with LPS or with IFN-gamma plus LPS, and the TNF/LT productivity of these rats was lower on stimulation with LPS alone, but higher with IFN-gamma plus LPS than the other normal rats. These results indicate that treatment with LT, as well as TNF, modulated autoimmunity and prevented development of IDDM in BB/Wor rats which may be low producers of TNF/LT.

Animals↗

PubMed1993

The point mutation of c-Ki-ras at codon 12 in carcinoma of the pancreatic head region and in intraductal mucin-hypersecreting neoplasm of the pancreas.

In order to clarify whether the detection of a point mutation in the c-Ki-ras gene at codon 12 in tumor tissues can assist in predicting the tumor's biological grade of malignancy, two types of tumors were investigated; one was called "carcinoma in the pancreatic head region," and the other was intraductal mucin-hypersecreting neoplasm of the pancreas (IMHN). Dot hybridization and a modified PCR technique developed by Haliassos et al. were employed. Among 16 cases of tumors in the pancreatic head region, the point mutation was detected with a high frequency only in pancreatic ductal cell carcinomas (five out of six cases, 83.3%), but was not detected in extrahepatic bile duct carcinomas (0/5) or in ampullary carcinomas (0/5). In pancreatic ductal cell carcinomas, no relation was found between the occurrence of the point mutation and the histological type of the tumor. Among 20 cases of IMHNs, the point mutation was found in 11 cases (55%). No relation was found between the occurrence of the mutation and the size of IMHNs. However, as the grade of cell atypia increased, the frequency of the mutation tended to become higher. These results suggest that detection of this point mutation might be useful for distinguishing pancreatic ductal cell carcinoma from those of other origins in the pancreatic head region, and for the determination of the histopathological grade of malignancy in IMHNs.

Aged↗

PubMed1993

NADPH-diaphorase activity in neurons of the mammalian pancreas: coexpression with vasoactive intestinal polypeptide.

BACKGROUND: To provide a morphological basis for understanding the role of nitric oxide in the pancreas, the present study was designed to clarify the localization and distribution of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity, a marker of NO synthase, in the pancreas of several mammalian species, including humans. METHODS: NADPH-d activity was examined in the rat, guinea pig, dog, and human pancreas by histochemistry. In addition, the possibility of coproduction of NO and vasoactive intestinal polypeptide (VIP) was investigated by a combined use of histochemistry and immunohistochemistry. RESULTS: In the pancreas, NADPH-d activity was localized in nerve fibers, nerve cell bodies, and the vascular endothelium. Nerve fibers with the enzyme activity were chiefly distributed in the exocrine pancreas and showed species differences in the distribution. Nerve fibers stained for NADPH-d were also observed in the endocrine pancreas, but the enzyme activity was not detected in the islet cells. Part of the nerve fibers and nerve cell bodies coexpressed NADPH-d activity and VIP-immunoreactivity. CONCLUSIONS: These results suggest that NO may act as a neuronal mediator and an endothelium-derived relaxing factor and may physiologically interact with VIP in the mammalian pancreas.

Amino Acid Oxidoreductases↗

PubMed1993

Lipo-PGE1, a new lipid-encapsulated preparation of prostaglandin E1: placebo-and prostaglandin E1-controlled multicenter trials in patients with diabetic neuropathy and leg ulcers.

Several clinical trials have shown that prostaglandin E1 (PGE1) is effective in treating peripheral occlusive vascular disease, but not definitely for diabetic neuropathy. We developed a new preparation of PGE1 incorporated in lipid microspheres (lipo-PGE1) that was designed to accumulate at vascular lesions. The effect of lipo-PGE1 (10 micrograms/day) was compared with placebo and the normal dose of a free PGE1 preparation (PGE1-CD, 40 micrograms/day) in two studies (double-blind and well-controlled) which enrolled 364 diabetic patients with neuropathy and/or leg ulcers. The drugs were given intravenously (bolus or drip infusion) for 4 weeks. Clinical improvement was noted in 61.6% of the lipo-PGE1 group and 30.0% of the placebo group in Trial 1 (p < 0.01), while the figures were 58.3% in the lipo-PGE1 group and 37.1% in the PGE1-CD group in Trial 2 (p < 0.01). Leg ulcers became smaller in the lipo-PGE1 groups in both trials (p < 0.01). In Trial 2, motor conduction velocity improved in the lipo-PGE1 group (p = 0.016). Side effects occurred in few patients receiving lipo-PGE1 or placebo, but more patients developed local side effects in the PGE1-CD group (p < 0.01). Thus, bolus intravenous injection of lipo-PGE1 improved diabetic neuropathy and leg ulcers with minimal side effects.

Adult↗

PubMed1993

Leukotriene B4 omega-hydroxylase activity in polymorphonuclear leukocytes from patients with inflammatory bowel disease.

omega-oxidation is regarded as the major pathway for the catabolism of leukotriene B4 (LTB4). To determine how LTB4 omega-hydroxylase is modulated in inflammatory bowel disease, we investigated the kinetic characteristics of this enzyme in 10 patients with Crohn's disease (CD), nine with ulcerative colitis (UC) and eight healthy control subjects. After incubating polymorphonuclear leukocytes with various concentrations of 3H-labeled LTB4, omega-oxidation products were separated by high performance liquid chromatography (HPLC) and the radioactivity was measured by a liquid scintillation counter. The apparent Vmax values were significantly higher in both disease than in healthy control subjects, although the difference between CD and UC was insignificant. There was no difference in the apparent Km values. And the Vmax/Km ratios of patients with CD were significantly higher than that of healthy control subjects. It is suggested that LTB4 metabolism is activated in inflammatory bowel disease (IBD) and that the modulation of this enzyme activity has an important role in the pathogenesis of inflammatory bowel disease.

Adolescent↗

PubMed1993

Physiological characteristics of spontaneously developed diabetes in male WBN/Kob rat and prevention of development of diabetes by chronic oral administration of synthetic trypsin inhibitor (FOY-305).

The male WBN/Kob rats spontaneously develop diabetes mellitus with age. In this study, we examined how glucose tolerance, potency of insulin release, and histology of the pancreas were changed with age in this model. Furthermore, we examined the effect of FOY-305, a synthetic trypsin inhibitor, on this model. Male WBN/Kob rats were divided into two groups: one group fed on standard pellet diet (STD group) and the other on pellet containing 0.1% FOY-305 (FOY group) for 56 weeks after age 4 weeks. Oral glucose (2 g/kg) tolerance test, histology of the pancreas, and glucose (8.3 mM)- and arginine (10 mM)-stimulated insulin release from the isolated perfused pancreas were examined at 8, 20, 40, and 60 weeks of age in both groups. Pancreatic insulin content was examined at 60 weeks. In the STD group, impairment of glucose tolerance and destruction and fibrosis of pancreatic tissues progressed with age. Glucose-stimulated insulin release was remarkably reduced with age, while arginine-stimulated insulin release was preserved. By contrast, in the FOY group, development of glucose intolerance was delayed and the pancreas showed fewer pathologic changes compared with the STD group. Insulin releases in response to both glucose and arginine were preserved at all ages examined. Total pancreatic insulin content at 60 weeks of age was significantly greater than that of the STD group. The male WBN/Kob rat is a new type of diabetic model that shows a similar pattern of insulin release to that in rat with non-insulin-dependent diabetes mellitus and also shows unique histopathological changes in exocrine pancreas. FOY-305 was effective in preventing the development of diabetes in this model, although its mechanism is still unknown.

Administration, Oral↗

PubMed1993

Neurons containing gastrin releasing peptide-like immunoreactivity in the human pancreas.

Gastrin releasing peptide (GRP) is known to stimulate pancreatic enzyme and islet hormone secretion. In the present immunohistochemical study, the localization and distribution of GRP-like immunoreactivity were investigated in the human pancreas using two antisera with different specificities. GRP-like immunoreactivity (GRP-LI) was observed in numerous nerve fibers diffusely distributed to the exocrine pancreas, but was not seen in intrapancreatic nerve cells of normal pancreatic specimens examined. Nerve fibers and terminals with GRP-LI were found in abundance around pancreatic acini and capillaries, with moderate density around ductules and in the walls of arterioles, and a few were seen in islets. This distribution pattern was quite similar to that of vasoactive intestinal polypeptide (VIP)-LI nerve fibers. The study, using the antibody elution method, strongly suggests the co-localization of GRP- and VIP-LIs within a part of VIP-containing nerve fibers. In the chronic pancreatitis specimens, neurons with GRP-LI were frequently found, and > 90% of intrapancreatic nerve cells were VIP-immunoreactive. Immunostainings for GRP and for VIP on serial adjacent sections of intrapancreatic ganglia from chronic pancreatitis specimens suggested the co-localization of the two immunoreactivities in > 70% of intrapancreatic neurons. The present findings may provide a morphological basis for neurotransmitter and/or neuromodulator roles of GRP in the human pancreas.

Antibody Specificity↗

PubMed1993

An evaluation of mass screening using fecal occult blood test for colorectal cancer in Japan: a case-control study.

There is as yet no firm evidence showing that mass screening for colorectal cancer using fecal occult blood tests (FOBTs) reduces the mortality from this cancer. Therefore we evaluated the effectiveness of the screening by a case-control study in Miyagi Prefecture, Japan. The study included as case subjects 28 individuals who had died from colorectal cancer and had had an opportunity to participate in the mass screening before the date of diagnosis as colorectal cancer, and 3 controls for each case subject randomly selected from residents who were alive on the date of death of case subjects and matched by sex, age (within 3 years) and living area using residential files. For each set, i.e., a case subject and 3 controls, screening histories before the date of the diagnosis of the case as colorectal cancer were examined. Both the case subjects and the controls who had participated in the screening at least once within 3 years before the date of diagnosis of the case were classified as "screened." The 28 case subjects consisted of 12 males and 16 females (average age: 60.8 years). The odds ratio of death from colorectal cancer for the screened versus the non-screened persons was 0.24 (95% confidence interval = 0.08-0.76) by the Mantel-Haenszel method. The present study suggests that mass screening using FOBTs for colorectal cancer significantly reduces the mortality from this cancer epidemiologically.

Aged↗

PubMed1993

A case of drug-induced ductopenia resulting in fatal biliary cirrhosis.

A 50-year-old woman suffered from a diffuse skin rash, high fever and jaundice immediately after a second injection of glutathion and Stronger Neo-minophagen C which contains glycyrrhizin. Liver biopsy performed 11 months after the onset showed mild spotty hepatocyte necrosis, marked cholestasis in parenchyma, and some lymphocyte infiltration in the portal area. Interlobular bile ducts had undergone vacuolar degeneration or were absent in some portal tracts. In her hospital course, unremitting jaundice persisted and biliary cirrhosis developed with signs of portal hypertension; she died from liver failure 26 months after the onset. A liver specimen at her death revealed that most of the interlobular bile ducts had vanished. Based on the clinical course and pathology, drug-induced ductopenia, possibly due to an adverse reaction to glycyrrhizin, is the most likely diagnosis. While drug-related biliary cirrhosis is rarely fatal, this case presented an unusually rapid course of fatal biliary cirrhosis.

Bile Duct Diseases↗