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Biomedical subjects

T Kanda

Publications and source records attributed to T Kanda.

At least 343 records · Page 19Linked to original sources

Immunohistochemical localization of two types of fatty acid-binding proteins in rat ovaries during postnatal development and in immature rat ovaries treated with gonadotropins.

BACKGROUND: The ovary of adult rats expresses two types of cytoplasmic fatty acid binding proteins (FABP), i.e., heart FABP (H-FABP) and intestinal 15 kDa protein (I-15P). We studied immunohistochemically the cellular localizations of these FABPs in the ovaries of rats at various postnatal ages and in the ovaries of immature (3-week-old) rats treated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (HCG). METHODS: The cryosections of ovaries were incubated with polyclonal antibodies against H-FABP and I-15P, and the immunoreactions were visualized at both light and electron microscopic levels. RESULTS: The immunoreactivity for H-FABP occurred temporarily in the follicular epithelial (granulosa) cells from 3 days to 2 weeks post partum, and then was localized exclusively to the theca/interstitial gland cells from 2 weeks to adulthood. In contrast, the immunoreactivity for I-15P appeared temporarily in a small subset of theca/interstitial gland cells from 2 to 3 weeks, disappeared at 4 weeks, and was localized exclusively to the corpus luteum cells after the onset of ovulation in the animal around 5 weeks. In the immature rat ovaries induced to ovulate by treatment with gonadotropins, I-15P-immunoreactive cells were first recognized in the luteinized granulosa layer of large preovulatory follicles, and increased in number progressively in the developing corpora lutea after the ovulation. CONCLUSIONS: Two types of FABPs are expressed in distinct steroid-producing cell types of rat ovary, and their expressions seem to be regulated in coincidence with the expressions of respective steroid hormones. These results suggest that FABPs play specific roles in the ovarian hormone synthesis.

Aging↗

Semotiadil inhibits the development of right ventricular hypertrophy and medial thickening of pulmonary arteries in a rat model of pulmonary hypertension.

This study was designed to compare the effects of semotiadil, a novel calcium antagonist, with those of diltiazem on the development of right ventricular hypertrophy and medial thickening of pulmonary arteries in a rat model of pulmonary hypertension. Pulmonary hypertension was induced by a single injection of monocrotaline (80 mg/kg). Twenty-four hours later (day 1), oral administration of semotiadil (10, 30, or 100 mg/kg per day) or diltiazem (100 or 300 mg/kg per day) was initiated. The wall thickness of the right ventricle (RV), the RV myocardial fiber diameter, the percent medial pulmonary artery thickness, and the percent area of smooth muscle in pulmonary arteries were determined on day 28. The magnitude of all parameters was significantly less in the group of seven rats that received semotiadil at 100 mg/kg per day than in the group of seven rats treated with diltiazem at 300 mg/kg per day. Semotiadil at 100 mg/kg per day inhibits the development of RV hypertrophy and medial thickening of pulmonary arteries significantly more effectively than diltiazem at 300 mg/kg per day.

Administration, Oral↗

Sandostatin inhibits development of medial proliferation of pulmonary arteries in a rat model of pulmonary hypertension.

We investigated the effects of subcutaneous administration of 50 and 100 micrograms/kg/day of sandostatin on monocrotaline-induced medial proliferation of pulmonary arteries and right ventricular overload in rats. In a dosage of 100 micrograms/kg/day, sandostatin significantly reduced right ventricular systolic pressure, the mass ratio of the right ventricular free wall to the left ventricle, the right ventricular wall thickness, the right ventricular myofiber diameter, the percent medial pulmonary artery thickness, the percent area of smooth muscle cell, and proliferating cell nuclear antigen activity. Our results suggest that sandostatin inhibits development of medial proliferation of pulmonary arteries and right ventricular overload in a dosage of 100 micrograms/kg/day.

Animals↗

Effect of nerve growth factor and forskolin on glycosyltransferase activities and expression of a globo-series glycosphingolipid in PC12D pheochromocytoma cells.

The glycosphingolipid (GSL) composition of cells changes dramatically during cellular differentiation. Nerve growth factor (NGF) or forskolin (FRK) are known to induce cellular differentiation including process formation in PC12 pheochromocytoma cells. In this respect, we present the NGF/FRK-dependent regulation of glycosyltransferase activities and the corresponding GSL expression in PC12D cells. After treatment of PC12D cells with NGF or FRK, the cell processes, including varicoses and growth cones, became strongly immunoreactive with an antibody against a unique globo-series neutral GSL, Gal alpha 1-3Gal alpha 1-4Gal beta 1-4Glc beta 1-1'Cer (GalGb3), and the activity of GalGb3-synthase increased significantly. Other glycosyltransferase activities, including GM1 containing blood group B determinant (BGM1)-, GM3-, GD1a-, and GM2-synthases, also increased significantly upon NGF treatment, but the immunoreactivity against BGM1 did not show any appreciable change. For the parent PC12 cells, NGF/FRK treatment significantly increased the percentage of anti-GalGb3 positive cells and induced some immunoreactive cell processes. Because the parent PC12 cells do not express appreciable amounts of GalGb3, and because PC12D cells are considered to be more differentiated than the parent PC12 cells, the expression of GalGb3 and the increase of GalGb3-synthase activity may be closely related to the cellular differentiation process in this cell line.

Animals↗

Importance of 6-O-sulfate groups of glucosamine residues in heparin for activation of FGF-1 and FGF-2.

Treatment of the pyridinium salts of heparin with N-methyltrimethylsilyl-trifluoroacetamide (MTSTFA) in pyridine for 2 h at various temperatures caused specific 6-O-desulfations from trisulfated disaccharide units to various degrees without detectable depolymerization or other chemical changes. In order to assess the importance of 6-O-sulfate groups in N-sulfated glucosamine (GlcNS) residues to promote FGF-1 and FGF-2 activities, various 6-O-desulfated (6-O-DS-) heparins were quantitatively examined for activity as enhancers or inhibitors of specific FGF-1- and FGF-2-induced proliferation of BALB/c3T3 clone A31 (A31) cells and the chlorate-treated cells. The present results suggested that a high content of 6-O-sulfate groups in GlcNS residues was required for activation of FGF-1, but not FGF-2. However, complete 6-O-desulfation of trisulfated disaccharide units in heparin resulted in loss of the ability to activate FGF-2, although the desulfated product bound strongly to FGF-2.

Animals↗

Comparative effects of losartan, captopril, and enalapril on murine acute myocarditis due to encephalomyocarditis virus.

Losartan, a recently developed nonpeptide angiotensin II (AII) receptor antagonist, was orally administered for 14 days to mice with viral myocarditis, beginning 7 days after encephalomyocarditis virus inoculation. The angiotensin-converting enzyme inhibitors (ACEI) captopril and enalapril were also administered in the same manner to compare the therapeutic effects of these three drugs on the degree of myocarditis, acute heart failure, and left ventricular (LV) hypertrophy. Heart weight and the heart weight/body weight ratio were reduced by losartan (60 mg/kg/day) and captopril (7.5 mg/kg/day), but not by enalapril (1 mg/kg/day). LV wall thickness and cavity dimension were decreased in the losartan and captopril groups. Captopril reduced both myocardial necrosis and inflammation, whereas enalapril reduced myocardial necrosis but not inflammation. However, none of the studied losartan doses (1.2, 12, 60 mg/kg/day) influenced myocardial necrosis and inflammation resulting from viral infection. Thus, specific blockade of AII is beneficial in congestive heart failure (CHF) and LV hypertrophy but is not effective in viral-evoked inflammation and injury.

Acute Disease↗

Prolongation of the QT interval observed in a Japanese patient with vivax malaria following treatment with halofantrine.

In 1992, some 90 countries or territories where 42% of the world's population resided were considered malarious and estimation of deaths from malaria worldwide per year were in the order of 1.4 of 2.8 million. The higher the number of Japanese who go abroad becomes (the total number in 1994 was 13,578,934: Records of Statistical Division of the Ministry of Justice), the greater is the risk of their contracting malaria. Indeed, the reported annual number of imported malaria cases increased to not less than 100. Now, malaria should first be presumed if a patient complains of a higher fever after a visit to a tropical country. And the importance of instituting prompt diagnosis and proper treatment should also be stressed. One of the antimalarials which has been highlighted for its effectiveness is halofantrine. This drug has been used for treatment of human malaria since 1984, and to date clinical trials have involved about 3.4 million patients in more than 30 countries (personal communication). Several patients successfully treated with halofantrine without any treatment failure have also been documented in Japan. However, in 1993, a clinical study involving 400 patients on the Thai-Burmese border revealed cardiac effects of antimalarial treatment with halofantrine, including one sudden death after the treatment. There have also been some spontaneous reports of serious ventricular dysrythmiasis with prolongation of the QT intervals, rarely associated with death. The pharmaceutical company producing Halfan has reported 8 cardiac arrests, leading to 6 deaths, when a higher dose than recommended was used, there was recent or concomitant treatment with mefloquine, there was pre-existing prolongation of the QT interval or the patient had a thiamine deficiency. Finally, the World Health Organization (WHO) announced a "drug alert" on halofantrine advising a change in recommendations for its use. In the present paper, we discuss the first Japanese vivax malaria patient whose QT interval was prolonged after treatment with halofantrine.

Adult↗

Intestinal fatty acid binding protein is available for diagnosis of intestinal ischaemia: immunochemical analysis of two patients with ischaemic intestinal diseases.

Mesenteric infarction and other acute ischaemic intestinal diseases are still a challenging diagnostic problem. Based on animal experiments, intestinal fatty acid binding protein (I-FABP), which is uniquely localised to the bowel, has recently been proposed as a new serum marker for intestinal ischaemia. This paper reports on two cases with acute intestinal ischaemic diseases, and the measurement of serum I-FABP by western blot analysis. The concentrations of ordinary serum markers were normal and the bowel necrosis was not diagnosed until surgical exploration. Immunochemical analysis showed that the I-FABP concentrations in the patients' serum samples were high at the time of admission, and that I-FABP was undetectable in the samples obtained after bowel resection and in healthy control subjects. This paper suggests that I-FABP is released into the circulation in the acute phase of intestinal ischaemia and that I-FABP can be used in establishing the diagnosis of ischaemic intestinal diseases.

Acute Disease↗

Occurrence of the antibody against human papillomavirus type 16 virion protein L2 in patients with cervical cancer and dysplasia.

Infection with HPV 16 is believed to be a major risk factor for cervical cancer. To correlate HPV 16 infection and carcinogenesis in the cervix, we examined by ELISA 326 sera from healthy females and patients with cervical cancer, cervical intraepithelial neoplasia, or dysplasia, for the presence of IgG antibodies against HPV 16 virion protein L2 expressed in Escherichia coli. Whereas 2 of 208 were positive in the healthy females, 4 of 23 and 6 of 90 were positive in the patients with cervical cancer and dysplasia, respectively. The findings indicate that infection with HPV 16 is related to cancer and dysplasia of the cervix. The anti-L2 antibody did not occur coincidentally with the antibodies against the HPV 16 early proteins E4 and E7, which are specifically but independently associated with patients with cervical cancer.

Adolescent↗

Myocardial uptake of an iodinated branched fatty acid analog, assessed by SPECT, may detect metabolic derangement of the myocardium in diabetic patients with coronary heart disease.

The clinical implications of single-photon emission computed tomography using both a beta-methyl-branched fatty acid analog, 123I-15-(p-iodophenyl)-3-methyl-pentadecanoic acid (BMIPP), and thallium-201 (201Tl) were assessed in 30 patients with myocardial infarction (MI), 8 diabetics, 4 patients with impaired glucose tolerance, and 18 nondiabetic patients. Discordant decreases in BMIPP uptake, as compared with 201Tl uptake, in diabetic patients were significantly (p < 0.01) more frequent than in nondiabetic patients. The left ventricular (LV) ejection fraction in diabetics was significantly (p < 0.05) reduced and the LV diastolic dimension was significantly increased (p < 0.01), as compared with those in nondiabetic subjects. Analysis of peripheral blood showed no significant differences among the three test groups in metabolic abnormality. A discordant decrease in BMIPP uptake, as compared with Tl uptake, in cardiac tomography may indicate a metabolic derangement of the myocardium in diabetic patients with MI.

Adenosine Triphosphate↗

Myocardial infarction secondary to coronary aneurysm in systemic lupus erythematosus. An autopsy case.

The authors report a thirty-seven-year-old woman with systemic lupus erythematosus (SLE), a coronary aneurysm, and myocardial infarction. SLE was diagnosed at twenty-three years of age and treated with prednisolone. Seven years later, she developed inferior myocardial infarction, and coronary angiography showed an aneurysm in the proximal right coronary artery without associated stenosis. At the age of thirty-seven years, she died from cerebral infarction and sepsis. Autopsy revealed an aneurysm (6 mm in diameter) in the proximal right coronary artery and an old inferior myocardial infarction. Histologic examination showed recanalization and fibrosis in the media of the aneurysm wall. This case suggests that coronary aneurysm may cause myocardial infarction in SLE and that aneurysm formation may be a sequela of arteritis.

Adult↗

Immunohistochemical distribution of intestinal 15 kDa protein in human tissues.

The distribution of human intestinal 15 kDa protein (I-15P), a new fatty acid-binding protein (FABP), was observed in normal tissues using immunohistochemical techniques. The antiserum against human I-15P intensely reacted with the villous epithelium of the terminal ileum but not with the enterocytes of the crypts. Although the surface epithelium of the stomach and villous epithelium of the duodenum showed weak reactivities, the epithelial cells of the jejunum, proximal ileum, colon and rectum, and also glandular epithelia with intestinal metaplasia of the stomach were not immunostained. The other human tissues examined were negative for anti-human I-15P antibody. Human I-15P thus represents a distinctive, confined tissue distribution different from the other FABPs and is expected to serve as a useful cellular marker of terminal ileal enterocytes.

Carrier Proteins↗

Observation of apical part and nerve terminals of human vestibular hair cells.

The human vestibular sensory epithelia of macula utriculi in 3 cases of acoustic neurinoma were examined by conventional and intermediate voltage electron microscopes. The apical part and the nerve terminals of hair cells were studied by means of a computer-aided three-dimensional (3-D) reconstruction technique. The sensory epithelia were fairly well preserved. Most type I and all type II hair cells appeared as those described in the other reports. However, some type I hair cells were incompletely surrounded by nerve calyces and received direct contacts from the efferent nerve endings. These type I hair cells were also innervated by a few neighbouring afferent nerve calyces. The stereocilia and the cuticular plate of type I hair cells differed from those of type II hair cells. The mean diameter of type I hair cell stereocilia was 488 +/- 59 nm and that of type II hair cells was 373 +/- 21 nm. The cuticular plate of type I hair cells resembled a cone and was about several times as thick as that of type II hair cells which was similar to a flat disc.

Cell Membrane↗

Atypical innervation pattern of human vestibular hair cells.

Human vestibular sensory epithelia of macula utriculi were examined in 3 cases with acoustic neurinoma by intermediate voltage electron microscope. The innervation pattern of vestibular hair cells was studied by means of computer aided three-dimensional reconstruction technique. The sensory epithelia were fairly well preserved. Most of type I and all of type II hair cells appeared normal. However, some type I hair cells were incompletely surrounded by nerve calyces and received direct contact from the efferent nerve endings. These type I hair cells were also innervated by a few neighboring afferent nerve calyces. These atypical type I hair cells constituted 5-8% of the total number of hair cells.

Culture Techniques↗

[A study of osteopenia in elderly diabetic patients].

It is well known that IDDM cases can be complicated with osteopenia, but most of these results were reported using single photon absorptiometry. There have been few reports of diabetic osteopenia using dual energy X-ray absorptiometry (DXA), a method that is excellent for precise bone mineral measurement. Osteoarthritis and osteophytes of unknown origin in the lumbar vertebrae are often observed in elderly NIDDM patients. In this study, we examined the clinical characteristics of decreased bone mineral density (BMD) and whether anteroposterior (AP) scanning of the lumbar vertebrae (L2-L4) provides sufficient informations concerning osteopenia in elderly diabetic patients. The study was performed using DXA, which can quantify regional BMD throughout the body. The BMD in the total body and that in the lumbar vertebrae were measured by DXA (Lunar Co.) in 68 diabetics over age 60, 33 males and 35 females, mean age 68 +/- 8 yr, (mean +/- SD) and in 94 middle-aged diabetics (40 to 59), 56 males and 38 females, mean age 51 +/- 4 yr. The percentage of decrease in regional BMD in diabetic patients differed significantly by age and gender. The BMD in the head and spine especially decreased after menopause in women. However, the BMD of the leg and spine did not decrease with age in men. When the BMD of the lumbar vertebrae was plotted against the Y axis and the BMD in the total body against the X axis, the slope of the curve showed a greater increase in elderly diabetics than that in middle aged diabetics (1.8 vs 1.5) suggesting the BMD in the lumbar vertebrae has been overestimated.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Synergistic effects of tacrolimus and human interferon-alpha A/D in murine viral myocarditis.

The effects of interferon-alpha A/D (IFN) therapy in combination with various immunosuppressants were investigated in a murine model of viral myocarditis. Viral infection is an important cause of morbidity in immunocompromised hosts and transplant recipients. Human IFN therapy reduces viral replication, reducing the virus-induced myocardial destruction. Groups consisting of 25 C3H/He mice received i.p. injections of prednisolone, azathioprine, 15-deoxyspergualin, cyclosporine or tacrolimus (FK506), for 16 days beginning 2 days before inoculation with 500 plaque-forming units of encephalomyocarditis virus (EMCV). IFN, 10(4) U/g daily, was administered i.p. alone or in combination with immunosuppressants to separate groups of mice beginning on the day of viral inoculation. Animals were sacrificed at random at 4 or 10 days after inoculation with EMCV. The survival rate was significantly higher in mice treated with azathioprine, 15-deoxyspergualin, cyclosporine or FK506 in combination with IFN than in infected controls (P < .01) and was similar to the rate in the IFN monotherapy group. Survival in mice treated with prednisolone resembled that in infected controls and was significantly lower than in mice treated with IFN (P < .01). Heart weight was lower and cellular infiltration in the myocardium was reduced in mice treated with both FK506 and IFN compared with mice given IFN monotherapy. The results suggest that the effect of IFN therapy in viral myocarditis differs depending on which immunosuppressants is used. The findings suggest that the combination of FK506 and IFN may have beneficial effects in hosts with viral myocarditis by reducing cellular infiltration of heart.

Animals↗

Cardiac accumulation of 125I-labeled monoclonal antibody to atrial natriuretic peptide in a rat model of myocardial infarction.

Atrial natriuretic peptide (ANP) may be an important factor in myocardial infarction and subsequent congestive heart failure. In the failing heart, ANP is expressed in both the atrium and the ventricle. ANP has now been localized with 125I-labeled monoclonal antibodies (MAbs) in vivo in a rat model of myocardial infarction. Myocardial infarction was produced in 3-month-old Wistar rats by ligating the left anterior coronary artery. Two MAbs to rat alpha-ANP accumulated in the infarcted left ventricles of treated rats to a significantly greater extent (p < 0.01) than in the noninfarcted left ventricles of control rats. However, an irrelevant MAb also accumulated to a significantly greater extent in infarcted myocardium than in control myocardium. Thus, the accumulation of the two MAbs to ANP in infarcted tissue seems to be nonspecific and may be due to increased permeability of the injured myocardium.

Animals↗