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Biomedical subjects

K Uchida

Publications and source records attributed to K Uchida.

At least 973 records · Page 54Linked to original sources
PubMed1992

A novel class of platelet activating factor (PAF) antagonists. II. Modification of the 2-position of the glycerol backbone of PAF-sulfonamide isosteres.

In a continuing effort to obtain more potent platelet activating factor (PAF) antagonists, we tried to synthesize a series of PAF-sulfonamide isosteres in which the substituent at the 2-position was modified to an acetoxy equivalent other than the methoxy group. These modifications produced highly active PAF antagonists. Compound 3-[2-(5-methyl-2H-tetrazol-2-yl)-3-(octadecylcarbamoyloxy) propylaminosulfonyl]propylquinolinium iodide (52) showed the most potent activity in the in vitro inhibitory effect on PAF-induced platelet aggregation in rabbit platelet-rich plasma (IC50 = 125 nM) and also in the in vivo protective effect on PAF-induced lethality in mice, with prolonged duration of action. Optically active enantiomers of this compound were synthesized and the (S)-(-)-isomer (IC50 = 87 nM) was found to be three times more potent that the (R)-(+)-isomer (IC50 = 289 nM), clearly exemplifying the enantioselectivity in the PAF-antagonist action of this novel compound.

Animals↗
PubMed1992

Immunohistochemical analysis of constituents of senile plaques and cerebro-vascular amyloid in aged dogs.

Immunohistochemical analysis of constituents of senile plaques and cerebro-vascular amyloid in the brain of aged dogs was performed using antisera against beta protein, cystatin C, ubiquitin, tau, and neurofilament (NF). All types of senile plaques and cerebro-vascular amyloid in aged dogs were labeled by anti-beta protein serum. Cystatin C immunoreactivity was detected in neuronal cell bodies, primitive or classical plaques, and amyloid deposited around cerebral capillaries, but not in diffuse plaques and amyloid deposited in the media tunica of cerebro-meningeal arterioles. Ubiquitin-positive granules distributed widely in both gray and white matter of aged dogs, while they were very small in number in young dogs. Swollen neurites-like materials in primitive plaques or classical plaques were immunoreactive for anti-ubiquitin serum. Tau immunostaining labeled commonly axons and several neuronal or glial cells after hydrate autoclave pretreatment. Tau-positive components were observed very rarely in the corona of classical plaques. Most of swollen neurites-like structures of primitive or classical plaques were not reactive for anti-NF serum, and only a few plaques contained small numbers of NF-positive elements.

Aging↗
PubMed1992

Immunohistochemical studies on canine cerebral amyloid angiopathy and senile plaques.

Amyloid protein was isolated from the cerebral meninges of 4 aged dogs with cerebral amyloid angiopathy. By immunoblot analysis, antiserum against synthetic oligo-peptide consisting of 1-28 amino acid of amyloid beta protein recognized prominent wide band ranging from 14 to 18 kilodalton (kd). When amyloid samples were solubilized by formic acid, the antiserum recognized lower molecular weight band ranging from 3 to 4 kd. Immunohistochemical studies on cerebral amyloid angiopathy and senile plaques were performed in 17 aged dogs. Anti-amyloid beta protein serum labeled amyloid deposits in cerebral vessel walls and senile plaques. Compact deposits of beta protein were detected in primitive or classical plaques. After using formic acid pretreatment, diffuse deposits of beta protein in the neuropil representing diffuse plaques were detectable. Classical and primitive plaques reacted with antiserum against glial fibrillary acidic protein, while not with antisera against alpha 1-antichymotrypsin, IgG and IgM. Amyloid deposits in the intestines of aged dogs examined, did not react with anti-amyloid beta protein serum.

Aging↗
PubMed1992

Impact of the advances in age on the gastrointestinal microflora of beagle dogs.

The gastrointestinal microflora of male beagle dogs in two different age groups; I) less than month 12 of age, and II) more than year 11 of age, was compared. No detectable difference occurred on the microflora of stomach, duodenum, jejunum, and ileum in both dogs. Large bowel (cecum, colon and rectum) microflora in both dogs yielded the different microbial populations. In all regions of large bowel, the levels of bacteroides, eubacteria, peptostreptococci, bifidobacteria, lactobacilli, and staphylococci in the elderly dogs were lower than those in the younger animals, whereas the numbers of Clostridium perfringens and streptococci in the elderly animals were higher than those in the youngers. The high incidence of lecithinase-negative clostridia was observed with advances in age, but not that of spiral shaped rods. The result of this study shows that the advances in age of beagle dogs yield some changes in the microbial population of large bowel in the animals.

Aging↗
PubMed1992

Glomerulopathy with IgA deposition in the dog.

In 100 dogs autopsied, glomerular IgA deposition was examined by the immunofluorescence technique and the histopathological features of glomeruli with IgA deposition were examined by light and electron microscopy. The incidence of the IgA deposition was age-related but there were no sex and breed predisposition. Deposition of IgA was observed mainly in mesangial areas in approximately a half (47%) of dogs examined. IgG, IgM and C3 often co-deposited. Histopathology of the glomeruli with IgA deposition indicated increase of mesangial cells, crescent formation, hemispherical deposits in paramesangial areas and glomerular sclerosis. Ultrastructurally electron dense substances positive for IgA deposited in mesangial and paramesangial areas. The examination to know the relation between the severity of IgA deposition and the number of mesangial cells or percent of the cells to total glomerular cells indicated that mesangial cells increased at the early stage of the disease and subsequently epithelial and endothelial cells proliferated as the increasing amount of IgA. Dogs suffering from enteritis or liver diseases showed high incidence of glomerular IgA deposition.

Animals↗
PubMed1992

Pentasomy X mosaic in two adult sisters with diabetes mellitus.

Pentasomy X mosaic in two adult sisters with non-insulin dependent diabetes mellitus is described. The younger sister had schizophrenia, and both were mentally retarded, but no apparent somatic abnormalities were found. Chromosome analyses revealed karyotype 45,X/46,XX/47,XXX/48,XXXX/49,XXXXX mosaic with a low frequency of aneuploidy on cultured peripheral lymphocytes and 46,XX on cultured skin fibroblasts in both sisters. The low frequency of X chromosome aberration may be responsible for the lack of somatic abnormalities and the long life in both sisters. The association of pentasomy X mosaicism and diabetes mellitus however appears to be coincidental.

Aneuploidy↗
PubMed1992

Measurements of CO2 diffusivity and buffering capacity in myoglobin solutions.

Diffusion processes of CO2 into or out of a thin layer of myoglobin (Mb) solution were followed by pH-sensitive fluorescence of 4-methylumbelliferone. Mb solutions were prepared by dissolving horse heart Mb at 0.1 to 4 mM in a modified Krebs solution containing NaHCO3 of 30 mM. Carbonic anhydrase was added to observe the diffusion-limited pH changes. The PCO2 in the layer were calculated as the numerical solution of a diffusion equation. For the simulation of the observed pH-time curves, the PCO2 changes were converted to the pH changes using a linear relation between logPCO2 and pH. The diffusion coefficients of CO2 and HCO3- (DCO2 and DHCO3) were determined as the optimum parameters to fit the calculated pH-time curves to the observed ones. Both the DCO2 and DHCO3 decreased exponentially as the Mb concentration was increased. At a physiological concentration of Mb in cardiomyocytes (0.2 mM) and at 37 degrees C, the DCO2 and DHCO3 values were 9.8 x 10(-5) and 16 x 10(-5) cm2.s-1, respectively. The buffer value (beta) was calculated as the slope of a pH-bicarbonate diagram by measuring the CO2 content and pH of the Mb solutions equilibrated with known PCO2 gases. The beta was found to increase with increasing Mb concentration with a value of 6.2 mEq.l-1.pH-1 at 0.2 mM.

Animals↗
PubMed1992

Enhancement by ubenimex (bestatin) of host resistance to Candida albicans infection.

Ubenimex is a low molecular weight microbial metabolite which has been demonstrated to have antitumor and immunomodulatory activities. In this study, the protective effect of ubenimex on Candida albicans infection was investigated in normal and immunosuppressed mice. In normal mice, treatment with ubenimex at 0.5, 5 and 25 mg/kg for 5 days prior to infection prolonged survival time in a dose-dependent manner. In immunosuppressed mice treated with a single dose of cyclophosphamide 4 days prior to infection, ubenimex treatment at 5 mg/kg for 5 days significantly increased the number of survivors. Ubenimex-treated mice had a significant increase in number of peritoneal exudate cells with neutrophils as well as enhanced functions, including phagocytosis and active oxygen production. These results suggest the potential usefulness of ubenimex as a prophylactic agent for the management of patients with opportunistic fungal infections.

Animals↗
PubMed1992

A novel antibody from rheumatoid arthritis patients.

A 106 base-pair length DNA sequence was isolated from rheumatoid synovium. Base sequence analysis showed this fragment to correspond to sequences already reported as the non-transcribed spacer of ribosomal DNA. Base sequence analysis also revealed that a fused protein has a unique five amino acid sequence. This five amino acid sequence was considered to be an epitope for an antibody. This antibody was named BUNGO antibody (BUNGO is the old name for Oita prefecture). An antigen peptide was synthesized chemically in accordance with the amino acid sequence of the epitope. Using this synthetic peptide, BUNGO antibody in serum was measured. Twelve of 32 patients (37.5%) with RA (rheumatoid arthritis) tested positive for the antibody. Five of 32 (15.6%) age and sex-matched control subjects were positive, indicating a significant difference from the RA group (chi 2 = 3.9, p < 0.05).

Adult↗
PubMed1992

A simple and reliable method for the detection and quantitation of the human T-cell leukemia virus type-I provirus in peripheral blood mononuclear cells of seropositive blood donors.

Human T-cell leukemia virus type I (HTLV-I) antibody detection has been widely used to screen HTLV-I carriers. Sometimes, however, it gives false positive or negative results. A demonstration of the HTLV-I provirus from patients' peripheral blood mononuclear cells (PBMC) should, therefore, give the crucial evidence for them being HTLV-I carriers. We established a simple and reliable method using the polymerase chain reaction (PCR) to detect one molecule of HTLV-I provirus in 100 x 10(3) PBMC, during which internal control primers for the human beta-globin gene were also employed in the same reaction tube to check the success of the amplification reaction. We can thus easily avoid any false negative judgement and quantitate the HTLV-I provirus in PBMC simply by diluting the sample before PCR. One ml blood was enough for ten or more determinations by PCR. Analysis of seropositive blood from donors demonstrated a wide range for the number of HTLV-I provirus in PBMC. The method could conveniently be used for quantitating HTLV-I proviruses and following up HTLV-I carriers to study the pathophysiology and mode of HTLV-I transmission.

Base Sequence↗
PubMed1992

Fecal and stomal bile acid composition after ileostomy or ileoanal anastomosis in patients with chronic ulcerative colitis and adenomatosis coli.

Fecal bile acids (FBA) were analyzed by gas-liquid chromatography in 29 patients [17 with ulcerative colitis (UC) and 12 with adenomatosis coli (AC)] and 5 healthy volunteers. Seven UC and 9 AC patients had undergone total colectomy and J-shaped ileal pouch-anal anastomosis (JAA). The mean daily FBA output was similar for JAA and terminal ileostomy patients (approximately 370 mg/day), and was about 1.5 times that of healthy Japanese volunteers (approximately 235 mg/day). The output of unconjugated bile acids, secondary bile acids, and 7-dehydroxylated bile acid was higher in JAA patients with UC than in terminal ileostomy patients, but there were no significant differences between the groups. The total fecal bacterial count in JAA patients was 10 times that in terminal ileostomy patients but was 1/10 of that in healthy volunteers. In patients with defunctioning high ileostomy, FBA output increased markedly (maximum, 3054 mg/day), and serum cholesterol levels were also significantly lower (P less than 0.05). These results suggest that after JAA the bile acid metabolism and fecal bacterial flora undergo more normalization than after terminal ileostomy.

Adenomatous Polyposis Coli↗
PubMed1992

[A case of hypersensitivity pneumonitis due to isocyanate exposure showing progression even two months after removal of the antigen].

A 68-year-old male developed dry cough and exertional dyspnea after handling paint spray containing isocyanates (TDI, MDI) for three months. Initially, the symptoms fluctuated according to whether he was at work or not. He was admitted to our hospital on February 7, 1990, because of progressive worsening of symptoms. In spite of admission to hospital and cessation of exposure to isocyanates, there was no improvement of symptoms. His chest X-ray film showed diffuse small nodular and reticular shadows. Transbronchial lung biopsy revealed thickening of the alveolar walls and formation of Masson's bodies associated with mononuclear cell infiltration in alveolar spaces. High titers of TDI-HSA and MDI-HSA specific IgG antibodies were detected by ELISA, and a high level of serum soluble IL2 receptor was also detected. From these results, we diagnosed hypersensitivity pneumonitis due to exposure to isocyanates. One week administration of prednisolone caused dramatic improvement of his symptoms, chest X-ray findings, and laboratory data. His clinical course and response to prednisolone therapy indicated that long-term steroid administration could not be avoided. The prolonged symptoms and the necessity for long-term steroid therapy are discussed.

Aged↗
PubMed1992

Dopaminergic modulation of the pressure-natriuresis response in rats.

OBJECTIVE: The present study was carried out to examine the involvement of dopamine in the pressure-natriuresis phenomenon which has been postulated as a major regulator of extracellular fluid volume and thereby arterial pressure. DESIGN: Dopaminergic modulation of the pressure-natriuresis response was studied in the innervated and denervated rat kidney, to allow a distinction between the effects of neural and extraneural dopamine. METHODS: The pressure-natriuresis response was studied in anesthetized Sprague-Dawley rats, in which neural and hormonal influences on the kidney were fixed by denervating the kidney and by intravenous infusion of aldosterone, hydrocortisone, vasopressin and norepinephrine. The innervation to the kidney remained intact in some experiments with the selective dopamine-1 antagonist SCH 23390. Urinary excretion of dopamine during the pressure-natriuresis response was also examined in the innervated and denervated rat kidney. RESULTS: Although infusion of dopamine at a dose of 2 micrograms/kg per min had no effect on the pressure-natriuresis response in rats in which neural and hormonal influences on the kidney were fixed, the slopes of the relations between urine flow, sodium excretion and mean arterial pressure in rats given 10 micrograms/kg per min dopamine were significantly greater than those found in the control rats. Renal plasma flow increased significantly in the dopamine-treated rats whilst glomerular filtration rate did not differ between the control and dopamine-treated rats. The dopamine-induced increase in the slope of pressure-natriuresis relationship and renal plasma flow were completely blocked by 0.5 micrograms/kg per min SCH 23390. However, infusion of SCH 23390 alone at 0.5 micrograms/kg per min did not significantly alter the pressure-natriuresis response in rats with either denervated or innervated kidney. In addition, urinary excretion of dopamine derived from neither neural nor extraneural origins was altered in parallel with variations in mean arterial pressure. CONCLUSION: These results suggest that exogenous administration of dopamine may affect the pressure-natriuresis response by altering the magnitude of arterial pressure-induced changes in tubular sodium reabsorption, via an action of dopamine-1 receptors. However, endogenous dopamine does not appear to be capable of modulating the pressure-natriuresis response.

Animals↗