Biomedical subjects

K Inui

Publications and source records attributed to K Inui.

At least 325 records · Page 18Linked to original sources

PubMed1993

Quantitative analysis of neuronal damage induced by tri-ortho-cresyl phosphate in Wistar rats.

A quantitative analysis of neuronal damage was performed on the fasciculus gracilis (FG) of the cervical spinal cord in male Wistar rats that received orally a single dose of tri-ortho-cresyl phosphate (TOCP) at 1500 mg/kg. FG tissues were sampled at 1, 2, and 3 weeks after treatment and examined histopathologically. Wallerian degeneration of myelinated nerve fibers was observed in FG at 2 weeks. Morphological changes were most evident at 3 weeks after treatment and the number of fibers was reduced. Ultrastructurally, axonal swelling due to the accumulation of cytoplasmic contents was observed near the node of Ranvier in the affected animals, indicating paranodal degeneration. Axonal atrophy and swelling in organophosphorus-induced delayed neuropathy (OPIDN) were evaluated quantitatively using a computer-assisted image analyzer. Morphometric examinations on semi-thin sections and frozen sections stained with Nauta's method were demonstrated to be useful for objective evaluation of OPIDN in the rat.

Animals↗

PubMed1993

The quality of mass screening for breast cancer by physical examination.

Mass screening for breast cancer using physical examination alone has been carried out since 1983 in Zentsuji, Kagawa Prefecture, Japan. Over a 7-year period, breast cancer was detected in 11 of a total 8,271 examinees, the detection rate being high at 0.13%. The detected cases included a few early-staged breast cancers, suggesting that mass screenings are of slight efficacy. Seven cases of interval cancer were found by breast self-examination after the mass screenings, supporting the value of breast self-examination. A relatively large number of interval breast cancers was detected in 1985 and 1986, when the rates of required further examination remained under 1%. The sensitivity and specificity of this screening were 61.1% and 94.5%, respectively, indicating a low sensitivity. These results suggest that the qualitative diagnoses made from the first screening by physical examination alone were often revealed to be false negatives. Therefore, the existing diagnosis should be employed in the first screenings. It is recommended that mammography be introduced to detect breast tumors which are nonpalpable or undetectable by physical examination alone.

Adult↗

PubMed1993

Nephrosialidosis: ultrastructural and lectin histochemical study.

The neuropathological findings in a Japanese male with nephrosialidosis are reported. Clinically, coarse face, psychomotor retardation, macular cherry-red spot and proteinuria were noted at 1 year and 7 months. He was diagnosed to have nephrosialidosis on the basis of a deficiency of alpha-neuraminidase activity in both lymphocytes and cultured skin fibroblasts, and of severe glomerular and tubular involvement on renal biopsy. He died of multiple organ failure at 8 years and 6 months. There were numerous vacuoles and storage materials in visceral organs, particularly in the glomerular and tubular epithelial cells of the kidney and Kupffer cells as well as hepatocytes in the liver. Neuropathological examination revealed severe neuronal storage in the selected part of the central nervous system: lower motor neurons of the brain stem and spinal anterior horn cells, as well as neurons in the basal nucleus of Meynert. In the peripheral nervous system, sympathetic ganglia were severely affected. There was little or no neuronal storage in the basal ganglia, cerebral cortex or cerebellum, and demyelination was not found. Electron microscopic examination showed fine wavy multilamellar structures in the spinal anterior horn cells or Zebra body-like structures in the neurons of the Meynert's basal nucleus. Lectin histochemistry was positive for wheat germ agglutinin, Ricinus communis agglutinin-1 and peanut agglutinin within distended neurons. We conclude that the neuropathological feature in nephrosialidosis is not specific except for the selectiveness of the anatomical sites of involvement. It shares some aspects found in other types of sialidosis or galactosialidosis.

Brain↗

PubMed1993

Arterial baroreflex inhibition by midbrain periaqueductal grey in anaesthetized rats.

Midbrain periaqueductal grey (PAG) provokes the defense reaction when stimulated. The present study was conducted to determine whether, and how, the PAG produces baroreflex inhibition, a feature characterizing the hypothalamic defense reaction. In chloralose-urethane anaesthetized rats, baroreflex vagal bradycardia and baroreflex hypotension were provoked by aortic depressor nerve stimulation. When the PAG was electrically stimulated baroreflex vagal bradycardia was remarkably suppressed; suppression of baroreflex hypotension was observed following bilateral vagotomy. In contrast, chemical stimulation of the PAG by D,L-homocysteic acid microinjection markedly suppressed baroreflex vagal bradycardia but only minimally suppressed baroreflex hypotension. These findings suggest that whereas overall PAG stimulation inhibits not only cardiac but also vascular components of baroreflexes, inhibition of the latter component either depends largely on activation of passing fibers or requires recruitment of a larger number of PAG cell bodies. PAG inhibition of baroreflex vagal bradycardia was not affected following spinal cord transection at C1, indicating that the inhibition was exclusively central in origin and not due to peripheral, prejunctional inhibition of vagal acetylcholine release by increased cardiac sympathetic nerve activities. The PAG inhibition of baroreflexes was greatly attenuated following electrolytic as well as chemical destruction of the parabrachial region. On the other hand, when the PAG was extensively lesioned, baroreflex inhibition produced by hypothalamic defense area stimulation was markedly diminished. PAG excitation thus causes powerful inhibition of arterial baroreflexes which is mediated by the parabrachial region; the PAG also mediates a major fraction of hypothalamic inhibition of the baroreflexes.

Anesthesia↗

PubMed1993

Effect of methylprednisolone and prostacyclin on bronchial perfusion in lung transplantation.

In an experimental investigation using modified unilateral lung transplantation in pigs, the effects of systemic administration of methylprednisolone and prostacyclin on bronchial mucosal blood flow were assessed. Laser Doppler velocimetry (LDV) and radioisotope studies using radiolabeled erythrocytes (RI) were employed to measure blood flow at the donor main carina and upper lobe carina after 3 hours of reperfusion. The recipient carina was used as a reference point. Five groups of 6 animals each were studied. Group I served as control. In group II, methylprednisolone (20 mg/kg) was administered to the recipient. In group III, prostacyclin (4 ng.kg-1.min-1) was given to the recipient, and in group IV, prostacyclin (100 micrograms intravenously) was administered to the donor. In group V, prostacyclin was given to the recipient and the donor animals as in groups III and IV, respectively. In group I, bronchial blood flow at the donor main carina was 37.6% +/- 2.2% (LDV) and 44.1% +/- 14.8% (RI) of reference blood flow. No significant differences were found between the controls and groups II, III, and IV. In group V, bronchial blood flow was markedly increased both at the donor main carina (LDV, 39.8% +/- 6.2%, p = 0.12; RI, 55.7% +/- 11.4%, p < 0.2) and the donor upper lobe carina (LDV, 65.8% +/- 5.4%, p < 0.05; RI, 76.8% +/- 21.3%, p < 0.2). We conclude that systemic administration of prostacyclin to the donor and recipient results in marked improvement of bronchial blood flow and may reduce the incidence of bronchial complications after lung transplantation.

Animals↗

PubMed1993

Decreased cellular toxicity of neomycin in a clonal cell line isolated from LLC-PK1.

We have previously shown in LLC-PK1 cells, that apical membrane enzyme activity was inhibited by aminoglycoside antibiotics (Am. J. Physiol. 254, C251-C257, 1988). In the present study, the relationship between the lethal cytotoxic effect of aminoglycoside and its effect on apical membrane enzyme was examined by establishing aminoglycoside resistant cells. A clonal cell line, LLC-PK1/NRa3, was isolated from parent LLC-PK1 cells in the presence of neomycin. Neomycin inhibited colony formation and increased the number of floating dead cells in parent LLC-PK1 cultures. In contrast, these cytotoxic effects of neomycin were negligible or less pronounced in NRa3 cells, indicating that NRa3 cells were more resistant to neomycin compared with the parent cells. The inhibitory effect of neomycin on apical enzyme activity was significantly weaker in NRa3 cells than in the parent cells. These results suggest that a common mechanism is involved in the aminoglycoside-induced reductions in the apical enzyme activity and in cell viability of LLC-PK1 cells.

Alkaline Phosphatase↗

PubMed1993

Effects of trehalose in preservation of canine lung for transplants.

The effect of trehalose, a non-reducing disaccharide which stabilizes and protects membranes, in the preservation of canine lungs was examined when Euro-Collins solution was basically used as a preservant. In group I, five lungs were perfused and preserved in an Euro-Collins solution modified by replacing the glucose with 35.0 g/L of trehalose. Five control lungs (group II) were perfused and preserved with Euro-Collins solution containing 35.0 g/L glucose. In both groups, no vasodilators were used. After preservation for 12 hours, left lung allotransplantation was performed. At 10, 40, 70, and 130 minutes after reperfusion, the right pulmonary artery was clamped for 10 minutes and four parameters were measured: arterial oxygen tension, mean pulmonary arterial pressure, peak inspiratory pressure, and wet/dry weight ratios. The transplanted lung was also examined histologically. At 10, 40, 70, and 130 minutes after reperfusion, oxygen-tension levels from group I were 263.2 +/- 19.2, 283.4 +/- 14.0, 277.5 +/- 19.9 and 264.9 +/- 26.2 mmHg, respectively. In group II, the corresponding values were 191.2 +/- 33.9, 188.0 +/- 40.3, 153.4 +/- 40.0 and 134.7 +/- 49.4 mmHg, respectively. At 70 and 130 minutes the difference were significant (p < 0.05). All transplanted lungs from group I showed normal histology, whereas four dogs in group II developed severe pulmonary edema and one had a partially edematous lung. These findings suggest that simple substitution of trehalose for glucose has a beneficial effect on preservation of canine lung for 12 hours.

Anesthesia↗

PubMed1993

Different clinical features in monozygotic twins: a case of 7q--syndrome.

We present male monozygotic twins who showed quite different clinical features. Blood chromosome analysis revealed 46,XY/46,XY,del(7) (q32-->qter) mosaicism in both twins. However, cultured skin fibroblasts from the twins showed different karyotypes. Twin 1, with a normal phenotype, had normal chromosomes and was 46,XY. Twin 2, on the other hand, had the characteristic manifestations of 7q- syndrome and chromosomes of 46,XY,del(7) (q32-->qter). DNA fingerprint analysis of their peripheral blood samples revealed the same pattern. However, DNA fingerprint patterns of cultured skin fibroblasts and buccal mucosal cells were different when a 7q terminal marker, probe g3, was used. These identical twins with discordant phenotypes can be explained by the occurrence of twinning and simultaneous erroneous mitosis. In addition, there might be a vascular communication which probably resulted in blood exchange and chromosomal mosaicism of the lymphocytes of the monozygotic twins.

Abnormalities, Multiple↗

PubMed1993

Dipeptide transporters in apical and basolateral membranes of the human intestinal cell line Caco-2.

The localization and transport characteristics of dipeptide transporters of the intestinal epithelial cell line Caco-2 were examined by measuring the intracellular accumulation and transcellular flux of Bestatin, a dipeptide-like anticancer agent. When added to the apical surface of Caco-2 monolayers grown on microporous membrane filters, Bestatin was accumulated in the cells and was transported unidirectionally to the basolateral side. The cellular uptake of Bestatin from the basolateral as well as from the apical surface was inhibited by excess dipeptides. Bestatin accumulation from the apical surface was dependent on the pH of the incubation medium with an optimal pH of 6.0, whereas uptake from the basolateral surface was insensitive to the medium pH. Kinetic parameters for Bestatin uptake also indicated that the basolateral and apical dipeptide transporters could be distinguished from each other. A sulfhydryl reagent, p-chloromercuribenzene sulfonate, inhibited Bestatin accumulation from both surfaces, although the inhibitory effect on the basolateral transport was greater than that on the apical transport. These findings suggest not only that dipeptide transporters exist on both the apical and basolateral membranes of Caco-2 cells but also that the basolateral dipeptide transporter is distinct from the apical H(+)-dipeptide cotransporter.

4-Chloromercuribenzenesulfonate↗

PubMed1993

Target site of inhibition mediated by midbrain periaqueductal gray matter of baroreflex vagal bradycardia.

1. Both electrical and chemical stimulation of the midbrain periaqueductal gray matter (PAG) inhibit baroreflex vagal bradycardia (BVB). The present study was designed to determine the target site of this inhibition about which little is known. Electrical stimulation of the PAG, in particular of its dorsal portion, markedly suppressed BVB provoked by electrical stimulation of the aortic depressor nerve (ADN; percentage of inhibition = 91.0 +/- 9.7%, mean +/- SD; n = 64). To identify the target site of the inhibition, several types of experiments were conducted in rats under chloralose-urethan anesthesia. 2. The inhibition was exclusively of central origin because inhibition of BVB by stimulation of the PAG was unchanged after transection of the spinal cord at the C1 level. According to Wall's method, we examined whether PAG stimulation affects BVB presynaptically by modulating the excitability of ADN terminals in the nucleus tractus solitarius (NTS). However, excitability changes of ADN terminals by the PAG stimulation were not demonstrated. 3. Vagal bradycardia evoked by microinjection of glutamate into the nucleus ambiguus (NA) region was markedly suppressed by the PAG (percentage of inhibition = 85.9 +/- 9.1%; n = 9), an indication that vagal cardiac preganglionic neurons at this site were subject to the inhibitory action of the PAG. Basal vagal tone due to ongoing preganglionic neuronal activity was also subject to inhibitory control by the PAG because basal heart rate was increased by stimulation of the PAG after either C1 transection or NTS lesion. 4. We found that PAG stimulation suppressed ADN-induced field potentials in the NA region (37.7 +/- 13.8% relative to the control; n = 9) but only slightly in the NTS region (95.8 +/- 15.2%; n = 16). In addition, unitary recordings revealed that ADN-evoked unitary responses of neurons in the NA region were suppressed by PAG stimulation, whereas NTS baroreceptor neurons, either ADN responsive or nonresponsive, were scarcely inhibited by PAG stimulation. 5. These findings suggest that the PAG inhibited BVB mainly at the vagal preganglionic cell level and not at the NTS interneuron level. The conclusion is in harmony with our previous reports that the target site of hypothalamic inhibition of BVB in rats is also the preganglionic neurons and that hypothalamic inhibition of BVB is mediated predominantly by the PAG.

Animals↗

PubMed1993

Altered sensitivities to potential inhibitors of cholesterol biosynthesis in Niemann-Pick type C fibroblasts.

Cultured fibroblasts from patients with Niemann-Pick disease type C (NP-C) are characterized by the lysosomal accumulation of unesterified cholesterol and the inability of low-density lipoprotein (LDL) to stimulate cholesterol esterification, in addition to impaired LDL-mediated down-regulation of LDL receptor activity and cellular cholesterol synthesis. Although a defect in the transport of cholesterol from lysosomes to other intracellular membrane sites has been suggested, it is unclear how cells regulate the levels of cellular sterols and whether their membrane cholesterol requirements are satisfied or not. We studied the esterification of exogenously added cholesterol, total levels of cellular cholesterol and cholesteryl ester, cholesterol synthesis from a two-carbon precursor, and sensitivities to potential inhibitors of cholesterol biosynthesis in proliferating NP-C cells. We observed the following: (a) esterification of [3H]cholesterol was decreased but the total amount of cellular cholesteryl ester was not decreased; (b) synthesis of cholesterol from [3H]acetate was increased; and (c) cells were hypersensitive to cholecalciferol, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, and were resistant to filipin, which binds to membrane sterols and presumably damages the membrane. The results indicate that NP-C cells depend on the cellular cholesterol synthetic pathway for their proliferation, but the plasma membrane sterols are presumably decreased. The altered sensitivities to potential inhibitors of cholesterol biosynthesis should be a useful marker for diagnosis and genetic studies.

Acetates↗

PubMed1993

p-Aminohippurate transport in rat renal brush-border membranes: a potential-sensitive transport system and an anion exchanger.

Transport mechanisms of p-aminohippurate (PAH) were investigated in rat renal brush-border membrane vesicles. The uptake of PAH was stimulated by an inside-positive membrane potential created by K+ and valinomycin. This potential-stimulated uptake of PAH was inhibited by various anion transport inhibitors and was saturable. In addition, PAH uptake in the presence of valinomycin was linearly increased in proportion to log[K+]out/[K+]in. On one hand, PAH uptake was stimulated by [14C]PAH/PAH or [14C]PAH/Cl- exchange, and the [14C]PAH/PAH exchange was insensitive to the membrane potential. The uptake by the exchanger was also inhibited by anion transport inhibitors, but the potential-stimulated uptake of PAH was more sensitive to furosemide and 4,4'-diisothiocyano-2,2'-disulfonic stilbene. On the contrary, [14C]PAH/PAH exchange was more sensitive to urate than the potential-stimulated uptake of PAH. These findings indicate that PAH is transported by two distinct transport systems in rat renal brush-border membranes, a potential-sensitive transport system and an anion exchanger.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1993

[Effect of MHS-G, an amino acids granule, on hepatic encephalopathy in portacaval anastomosis rats].

Using portacaval anastomosis (PCA) rats as a model with or without injection of ammonium acetate, we investigated the effects of MHS-G on the abnormalities of electroencephalogram (EEG) and brain amines metabolism in comparison with those of SF-1008C, a commercial nutritional preparation for hepatic failure. MHS-G (0.68 g/kg, p.o.) clearly improved both the abnormalities of EEG (such as reduction of amplitude, increasing delta wave distribution and decreasing beta wave distribution) and brain amines metabolism (such as increasing of Trp and DOPAC content) after injection of ammonium acetate. Moreover, MHS-G significantly increased branched chain amino acid concentrations and decreased aromatic amino acid concentrations in plasma and brain in comparison with water, and it significantly decreased the ammonia level in plasma in comparison with water and SF-1008C. These results suggest that MHS-G has a positive effect on abnormalities of EEG and amino acids metabolism in the plasma and brain of PCA rats.

Acetates↗

PubMed1993

Protective effect of N-acyl amino acids (NAAs) on cephaloridine (CER) nephrotoxicity in rabbits.

The protective effect of N-acyl amino acids (NAAs) against cephaloridine (CER)-induced nephrotoxicity was studied in rabbits. A large single intravenous dose of CER (more than 100 mg/kg) induced severe proximal tubular necrosis. Simultaneous treatment with several NAAs (at dosages of 100, 200 mg/kg, etc., i.v.), such as N-benzoyl-beta-alanine (NBBA), N-benzoyl-6-aminocaproic acid, and N alpha,epsilon-dibenzoyl-D,L-lysine, remarkably suppressed the histopathological damage in the kidney induced by CER. NAAs have generally low toxicity in laboratory animals (e.g., the LD50 of NBBA was more than 3,000 mg/kg, i.v. in rats), and NAAs were suggested to be good candidates for reducing the nephrotoxicity of CER and other beta-lactam antibiotics.

Alanine↗

PubMed1993

[Present world status and problems resolved in lung transplantation: from the surgical view].

We have summarized the results of international data from many institutes. In 1983 in Toronto, Canada, Cooper performed that first successful clinical case lung-transplantation. Subsequently, there have been more than 1,500 cases of lung transplantation. One reason for Cooper's success was the use of cyclosporin, the other was the performing of omentopexy. Among the total lung transplant cases, single lung transplant comprised 66%, bilateral sequential lung transplant comprised 26%, and en-blocdouble lung-transplant, (8%). Of the 1,540 recipients, the most common underlying of sease was emphysema (360 cases), followed by fibrosis (289 cases), cystic fibrosis (206 cases), alpha-1 antitripsin deficiency (210 cases) and rare diseases including pulmonary hypertension, lymphagiomyomatosis and sarcoidosis. The survival rate of all patients was 68% at 1 year, and 60% at two years.

Adolescent↗

PubMed1993

[Carrier and prenatal diagnosis of Duchenne and Becker muscular dystrophy by PCR methods].

The PCR methods for carrier and prenatal diagnosis of Duchenne and Becker muscular dystrophy are described. When a deletion of the dystrophin gene is detected in the proband, the deletion analysis is informative for prenatal diagnosis, and the quantitative PCR analysis of the concerned exons is necessary for carrier diagnosis. When a deletion is not detected, RFLPs analysis should be considered. We analyzed seven polymorphic makers (pERT87-15 combined with digestions with BamHI or XmnI, pERT87-8 combined with digestion with TaqI, and four CA repeat markers at the 5' end and the 3' untranslated regions of the dystrophin gene) by PCR methods. Every woman examined showed a heterozygous finding for at least one of these markers, making it possible to make carrier and prenatal diagnosis. However, it is important to keep in mind that a third of the patients are due to new mutations and that about 10% recombination rate, between the 5' and 3' ends of the dystrophin gene, can exist.

Dystrophin↗

PubMed1993

Expression of the differentiated phenotype of chondrocytes in newly synthesized acetabulum.

Human cartilaginous cells produce two types of proteoglycan monomers (PGI and PGII) distinguishable by their molecular size in density gradient centrifugation under dissociative conditions. In order to determine whether connective tissues on the sliding surface of the acetabulum on an endoprosthesis are able to differentiate into cartilaginous tissue, we made histological and biochemical analysis of the incorporation of 35S and the distribution of the molecular size of proteoglycans produced. Histologically, dense collagen fibers were observed both on weight-bearing and non-weight-bearing surfaces, but there was little evidence of cartilaginous metaplasia. Biochemical analysis, however, demonstrated that incorporation of 35S in newly synthesized glycosaminoglycan (GAG) was higher than that in non-cartilaginous tissues, suggesting that cartilaginous differentiation of mesenchymal tissues had occurred.

Acetabulum↗

PubMed1993

Effect of excess phenylalanine diet during pregnancy on fetal brain growth in rats.

The effects of 10 and 20% casein diets containing 7% phenylalanine (Phe) during pregnancy on fetal brain growth were examined in rats. Control pregnant rats were fed the casein diets ad libitum or in restricted amounts. Total food intakes during 21-day period in the Phe excess groups decreased to about 50% of those of the liberally fed control groups. In control rats given 10 and 20% casein diets, fetal brain weights (Y, mg) were significantly and hyperbolically correlated to total food intakes (g/21 days), conforming to the following equations: Y = -10283/X + 130.5 (n: 13, r = 0.89, p < 0.001) and Y = -4396/X + 130.4 (n: 15, r = 0.68, p < 0.005), respectively. Similar plots for rats fed 10 and 20% casein diets with Phe fell below these lines, meaning that fetal brain growth was impaired by both the decreased food intake due to excess Phe (nonspecific effect) and the toxicity of excess Phe per se (specific effect). Total amounts of RNA and protein and protein/DNA ratio decreased in the fetal brain from excess Phe dams, suggesting that protein synthesis of brain cells was disturbed. This may be partly due to the disruption of normal patterns of free amino acids observed in the fetal brains. Reduction of total DNA was also seen in fetal brain from excess Phe groups, meaning impaired proliferation. From above findings we concluded that proliferation and hypertrophy were impaired in fetal brain from excess Phe dams.

Amino Acids↗