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Hiroshi Kitamura

Publications and source records attributed to Hiroshi Kitamura.

81 records · Page 5Linked to original sources
PubMed2002

Peritubular capillary regression during the progression of experimental obstructive nephropathy.

Injury to the renal microvasculature may be a major factor contributing to the progression of renal disease. Although severe disruption of peritubular capillaries (PTC) could lead to marked tubulointerstitial scarring, elucidation of that process remains incomplete. This study investigated the morphologic changes in PTC and their likely regulation by vascular endothelial growth factor (VEGF) during the progression of tubulointerstitial injuries. Unilateral ureteral obstruction was induced in Wistar rats by ligation of the left ureter, and the kidneys were then collected at selected times. PTC lumina and the expression of VEGF and its receptor Flk-1 were immunohistochemically detected. Morphologic changes in PTC endothelial cells were examined by using Ki67 staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling, and electron-microscopic studies. In the first week of the disease period, immunohistochemical labeling of tubular VEGF intensified, with accompanying deformation and dilation of adjacent thrombomodulin (TM)-positive PTC lumina; an angiogenic response of endothelial cells was demonstrated with Ki67 and TM double-staining. During the subsequent 2 wk, tubular VEGF labeling decreased until it was virtually absent, an effect confirmed by Western blotting. Concomitantly, labeling of the VEGF receptor Flk-1 in PTC endothelial cells decreased and PTC lumina began to regress, demonstrating endothelial cell apoptosis (as detected in terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling and electron-microscopic studies). By the end of week 4, the numbers of TM-positive PTC lumina were significantly decreased in areas of marked tubulointerstitial scarring. These results suggest that PTC regression, involving an early, unsustained, angiogenic response followed by progressive endothelial cell apoptosis, could be a potential factor contributing to tubulointerstitial scarring in this unilateral ureteral obstruction model.

Animals↗
PubMed2002

Activation of cytomegalovirus in pig-to-primate organ xenotransplantation.

Xenotransplantation of porcine organs carries the risk of reactivation of latent virus in donor and recipient tissues as well as transmission of viruses between species. We have investigated the activation of baboon cytomegalovirus (BCMV) and porcine CMV (PCMV) in a pig-to-primate model of xenotransplantation. Tissues originating from a series of six swine-to-baboon composite thymokidney xenotransplants were investigated. Four immunosuppressed baboons died (survival range, 7 to 27 days) with the graft in situ. Increases in BCMV DNA copy numbers occurred in three (75%) of these baboons and was thought to be responsible for pneumonitis and the death of one animal. In two baboons, disseminated intravascular coagulation was successfully treated by graftectomy and discontinuation of immunosuppression. PCMV was upregulated in five of six xenografts (83%). PCMV infection was associated with ureteric necrosis in one xenograft. Although significantly increased in native tissues, low levels of BCMV and PCMV were also detected in tissues other than that of the native viral host species. The cross-species presence of CMV did not appear to cause clinical or histological signs of invasive disease. Thus, viral infections with clinical disease were restricted to tissues of the native species of each virus. Intensive immune suppression currently required for xenotransplantation results in a significant risk of reactivation of latent infections by BCMV and PCMV. It is not yet known whether viral DNA detected across species lines represents cellular microchimerism, ongoing viral infection, or uptake of free virus. The observation of graft injury by PCMV demonstrates that CMV will be an important pathogen in immunosuppressed xenograft recipients. Strategies must be developed to exclude CMV from porcine organ donors.

Animals↗
PubMed2002

Induction of Src-suppressed C kinase substrate (SSeCKS) in vascular endothelial cells by bacterial lipopolysaccharide.

We isolated cDNA of the mouse homologue of the src-suppressed C kinase substrate (SSeCKS) and analyzed the effects of lipopolysaccharide (LPS) injection on the tissue expression pattern of this protein. Northern blotting analysis showed that SSeCKS mRNA was expressed abundantly in the testis but at undetectable levels in other tissues of untreated control mice. Intraperitoneal administration of LPS strongly induced SSeCKS mRNA expression in the lung, heart, liver, spleen, kidney, lymph node, adrenal gland, and pituitary gland, as well as in the brain. In lung and spleen, the SSeCKS mRNA levels increased almost 10-fold at 1 hr after LPS injection and persisted at high levels until 4 hr. Both in situ hybridization and immunohistochemical studies revealed that LPS administration conspicuously elevated expression of SSeCKS mRNA and protein in vascular endothelial cells of several organs. Ectopic expression of SSeCKS caused loss of cytoplasmic F-actin fibers in the mouse endothelial cell line LEII. These results indicate that SSeCKS is one of the major LPS-responsive proteins and may participate in alteration of cytoskeletal architecture in endothelial cells during inflammation.

A Kinase Anchor Proteins↗
PubMed2002

Serum leptin levels during the periparturient period in cows.

Serum leptin concentrations were measured in antenatal and postnatal cows housed at two different locations. The mean serum leptin concentration was 9.2 +/- 0.6 ng/m l (n=22) in one group, and was slightly lower in the other (7.4 +/- 0.4 ng/ml, n=54), probably because of the different nutritional conditions between the two groups. There was no consistent variation in relation to the menstrual cycle and the periparturient period in both groups. Moreover, serum leptin concentrations during the periparturient period were independent of the number of delivery and the incidence of mastitis and milk fever. These results are quite different from those in rodents and human, suggesting the different regulatory mechanism of circulating leptin concentration in cows.

Animal Nutritional Physiological Phenomena↗
PubMed2002

Experimental and clinical studies on plasma leptin in obese dogs.

Leptin is a protein synthesized and secreted primarily by adipocytes, and the circulating leptin concentration is elevated in obese humans and rodents. Recently, we have established a sandwich enzyme-linked immunosorbent assay for canine leptin. In the present study, plasma leptin concentrations were measured in experimentally developed obese beagles and in clinically obese dogs. When 5 male beagles were given a high-energy diet for 3 months, all of them became obese and the plasma leptin concentration significantly increased from 2.4+/-1.2 to 4.9+/-0.9 ng/ml, positively correlating with body fat content estimated by the deuterium oxide dilution method (r=0.87). The leptin concentrations of plasma samples collected from 59 dogs in veterinary practices were compared with their body condition scores (BCS). The plasma leptin concentrations of obese dogs were 9.7+/-0.7 and 12.3+/-1.5 ng/ml at BCS=4 and BCS=5, respectively, which were significantly higher than those of optimal (BCS=3) dogs (2.7+/-0.3 ng/ml). There was no significant effect of sex and breed. A weak positive correlation (r=0.37) was found between the plasma leptin concentration and age, probably due to the lesser content of visceral fat in puppies younger than 1 year old. These results indicate that plasma leptin is a good index of adiposity in dogs regardless of breed, age and sex, and may be useful for quantitative assessment of obesity in small animal practice.

Animals↗
PubMed2002

Bacterial lipopolysaccharide induces mRNA expression of an IkappaB MAIL through toll-like receptor 4.

Molecule possessing ankyrin-repeats induced by lipopolysaccharide (MAIL) is a nuclear IkappaB protein recently identified as a molecule appearing in immunocompetent organs after administration of bacterial lipopolysaccharide (LPS). Participation of Toll-like receptor (TLR) 4, which is a major form of LPS receptors, in the LPS-induced MAIL expression was investigated. When a human myelomonocytic cell line U937 was treated with phorbol 12-myristate 13-acetate for 3 days, the LPS-induced MAIL expression was much potentiated in parallel with an increase in TLR4 expression. The MAIL induction was attenuated when the cells were treated with a neutralizing antibody against TLR4. The in vivo induction of MAIL in the spleen was smaller in mice having a missense mutation of the Tlr4 gene than in normal control mice. These results collectively indicate that TLR4 contributes, at least in part, MAIL induction after LPS stimulation.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Peritubular capillary injury during the progression of experimental glomerulonephritis in rats.

The functional and morphologic changes occurring in the peritubular capillaries (PTC) of the kidney during the progression of renal disease are not yet completely understood. In this study, the features of PTC disruption observed in a rat anti-glomerular basement membrane-induced glomerulonephritis (GN) model were characterized. Contributions to the progression of the disease made by other interstitial components, including ED-1-positive macrophages and CD3-positive T cells, were also investigated. Within 7 d of inducing GN, severe necrotizing glomerular injuries were observed. Thrombomodulin staining revealed that within 3 to 8 wk, there was a significant (P < 0.001) decline in the number of PTC, accompanied by a marked accumulation of macrophages, T cells, and fibrotic material. By the end of this period, most PTC were severely damaged or lost, and tubulointerstitial scarring was noted in the affected areas. Furthermore, PTC endothelial cell apoptosis occurred concomitantly, as shown by application of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling methods and electron microscopy. It was presumed that the PTC injury was mediated possibly by the infiltrating macrophages and T cells, which, together with destruction of the PTC structure, correlated significantly with the impairment of renal function. These findings suggest that PTC disruption and the subsequent regression of the capillary network may contribute to the development of the tubulointerstitial injury largely responsible for the renal dysfunction in progressive GN.

Animals↗
PubMed1999

Study of the pharmacokinetics of vancomycin in patients with impaired liver function.

Infections caused by methicillin-resistant Staphylococcus aureus pose a serious problem postoperatively. Patients with hepatic dysfunction can be considered to be more susceptible to infection. Since little is known about the effects of the severity of hepatic dysfunction on the pharmacokinetics of vancomycin, we studied the pharmacokinetics of vancomycin in preoperative patients with hepatic dysfunction, after the intravenous infusion of 500 mg. In patients with liver disease and normal renal function, an enhancement of renal clearance caused by a reduction in percent protein binding was canceled out by a reduction in non-renal clearance caused by liver dysfunction, resulting in liver disease having no effect on the total clearance of the drug. In patients with impaired liver and renal functions and/or obstructive jaundice, the unbound fraction of vancomycin increased, whereas the renal excretion of vancomycin was delayed. It should be noted that an excessive increase in blood vancomycin concentration may be brought about even with a conventional dose in patients with hepatic dysfunction.

Journal Article↗