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N Kashihara

Publications and source records attributed to N Kashihara.

71 records · Page 4Linked to original sources
PubMed1992

Influence of genetics on the nephritogenic potential of proteoglycans.

Nephritogenic potential of antibodies directed against one of the glomerular basement membrane (GBM) components, i.e., heparan sulfate-proteoglycan (HS-PG), was investigated in different strain of rats, i.e., Brown Norway, Lewis, Long Evans, and Sprague-Dawley. The rats were given two intravenous injections of anti-HS-PG antibody on days 1 and 3, and killed 2 to 8 weeks later. Before killing, blood and urine were collected for determination of anti-rabbit IgG levels and excretion of proteins, respectively. In addition, the right kidney was perfused with 125I-anti-rat IgG to quantitate the amount of immune-complexes present within the GBM. The tissues were processed for morphologic, autoradiographic, and immunofluorescent studies. The anti-HS-PG antibody was seen uniformly bound to GBM equally in all strains of rats. However, the protein-uric response was as follows: Brown Norway much much greater than Lewis much greater than Long Evans greater than Sprague Dawley. Also, the glomerular cells, monocytes in the glomerular capillaries, immunoreactivity of rat IgG and C3 frequency of subepithelial immune deposits, serum levels of anti-rabbit IgG, and the amount of 125I-anti-rat IgG bound to the GBM were proportionately increased among different strains of rats. The data suggest that the sustained presence of anti-HS-PG antibodies in the subepithelial aspect of the GBM with differential humoral response in the production of the antibody by the host most likely attributed to the variable glomerular damage in different strains of rats. Thus, it seems that the genetic makeup of a given strain of rat heavily influences the nephritogenic potential of an antibody and consequentially the outcome of the immune complex-mediated glomerular injury.

Animals↗
PubMed1992

[Study of preventive effect of 1-hexylcarbamoyl-5-fluorouracil (HCFU) or combination of HCFU and 2.5-di-O-acetyl-D-glucaro (1-4) (6-3) dilactone (SLA) after preservative operation against bladder cancer].

To treat superficial bladder cancer or invasive bladder cancer presenting as a solitary tumor, conservative therapy such as transurethral resection of bladder tumor or partial cystectomy has long been carried out. We studied the effect of 1-hexylcarbamoyl-5-fluorouracil (HCFU), and the effects of the combination of HCFU and 2.5-di-O-acetyl-D-glucaro-(1-4)(6-3) dilactone (SLA) which is an anti-beta-glucuronidase agent, for preventive therapy. In the patients treated with HCFU, the recurrence rate was 3.6% and 26.6% one year and two years, respectively, after conservative operation. In the patients treated with both SLA and HCFU, the recurrence rate was lower than in those treated with HCFU one year or more after conservative operation, and a long-term preventive effect was expected for nondrinkers.

Adult↗
PubMed1991

Effect of puromycin on metanephric differentiation: morphological, autoradiographic and biochemical studies.

Effect of aminonucleoside of puromycin (PAN) on metanephric development and proteoglycans (PGs) was investigated. Murine metanephric tissues, obtained on the thirteenth day of gestation, were exposed to PAN in a culture medium for one to seven days and processed for morphological, histochemical and immunofluorescent studies. For tissue autoradiographic and biochemical studies, kidneys were labelled with a precursor product of PGs, that is, [35S]-sulfate. A generalized decrease in the glomerular population along with swelling and deformation in the ureteric bud branches was observed. These changes were accompanied with a diminution in the total incorporated radioactivity and a reduction in the autoradiographic grains, especially over the tips of ureteric bud branches. Sepharose CL-4B chromatography revealed a major high molecular weight PG (Mr greater than 2.5 x 10(6], and a relative increase in the chondroitinase-ABC sensitive PGs. The media PGs were of relatively smaller size. Immunoprecipitation experiments with [35S]-methionine-labeled tissues and immunofluorescent studies revealed a significant decrease of PGs in metanephric tissues, while type IV collagen and laminin were relatively unaffected. Significant glomerular changes included failure in differentiation of the visceral epithelial foot processes, formation of villi and in maturation of glomerular basement membrane. The latter was seen as fragments of extracellular matrices interspersed among undifferentiated podocytes and had reduced staining with ruthenium red--a dye marker for the PGs. This deficiency of PGs was confirmed by electron microscopic autoradiography, where a reduction in the number of silver grains was observed. The fact that the PAN-induced cellular and extracellular alterations were associated with perturbances in biosynthesis of PGs, suggests that the morphogenetic regulators, that is, PGs play a vital role in various differentiation processes involved during metanephric development.

Animals↗
PubMed1990

Stimulation of urinary bladder tumorigenesis by carcinogen-exposed stroma.

There is evidence to suggest that control mechanisms, either growth-stimulatory, inhibitory or inductive, may play a role in carcinogenesis. To test the hypothesis that treatment of rat urinary bladder with carcinogen induces alterations in the stroma which result in modified epithelial-stromal interactions, experiments were conducted using a rat model specifically designed for the study. Following exposure of Fischer F344 rats in drinking water to the urinary bladder carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) for four weeks, bladders were removed and subjected to a brief detergent treatment to completely remove epithelium. The bladders without epithelium ("stroma" bladder) were heterotopically transplanted to syngeneic recipients. Four days later, the denuded mucosa surface was resurfaced with intraluminal instillation of urothelial cells, either untreated or treated with BHBN for six weeks (6w-BHBN) or 10 weeks (10w-BHBN). Examination at 12 weeks posttransplant of the "stroma" bladders that had received 6w-BHBN urothelial cells showed a higher tumor incidence of carcinoma in the BHBN-exposed "stroma" bladders as compared with the incidence in the carcinogen-unexposed "stroma" bladders (p less than 0.05). Examination at 18 weeks posttransplant showed 100% incidence of tumors in all "stroma" bladders irrespective of the lengths of BHBN exposure of urothelial cells. However, among the bladders that had received 6w-BHBN urothelial cells, carcinogen-exposed "stroma" bladders proved to be better "soil" for neoplastic cells to proliferate; the mean tumor volume as well as the mean total tumor volume per bladder were significantly higher than in the control "stroma" bladders (p less than 0.01 for each comparison). Similarly, among the bladders that had been resurfaced with 10w-BHBN urothelial cells, the mean total tumor volume per bladder was greater in the carcinogen-treated "stroma" bladders than in the controls (p less than 0.05). No proliferative or neoplastic changes were observed in the BHBN exposed "stroma" bladders which had been resurfaced with normal urothelial cells. Our data indicate that neoplastic growth of carcinogen treated urothelium is enhanced when such cells interact with the stroma which has also been exposed to carcinogen.

Animals↗
PubMed1990

Stimulation of stromal cell growth by normal rat urothelial cell-derived epidermal growth factor.

Primary cultured adult rat urothelial (RU) cells caused increased thymidine incorporation in rat bladder stromal (RS) cells in a coculture system. The concentrated conditioned medium derived from RU cell culture (CM-RU) also stimulated the growth of RS cells, and induced anchorage independent growth of NRK-49F cells. Since these activities were heat and acid resistant, we investigated whether epidermal growth factor (EGF) and/or transforming growth factors were the humoral factor(s) responsible. The immunodiffusion analysis of CM-RU gave a positive precipitin line with rabbit anti-rat EGF IgG but not with rabbit anti-rat transforming growth factor-alpha antibodies. The anti-rat EGF IgG inhibited CM-RU-stimulated thymidine incorporation into RS cells, whereas normal rabbit IgG did not. By immunofluorescent technique using rabbit anti-rat EGF antibodies, immunoreactive EGF was demonstrated in RU cells and the urothelial of cryoinjury-induced reparative hyperplasia. Immunofluorescent technique also demonstrated the presence of EGF receptors on the cell membrane of RU and RS cells, basal cells of normal rat urothelium, and cells of whole epithelial layers of reparative hyperplasia. These data strongly suggest that EGF or an EGF-like substance produced by RU cells and released into medium stimulates the growth of RS cells possibly mediated by EGF receptors.

Animals↗
PubMed1988

[A clinicopathologic study of primary malignant lymphoma of the thyroid with a report of six cases].

From 1977 to 1984, 500 patients with thyroid disease (426 females and 74 males) were seen at the Kure Kyosai Hospital. Among them 6 patients (1 female and 5 males; all older than 50 y) were found to have a primary malignant lymphoma of the thyroid. Histologically, two were identified as being SNC, two were D-Mx, one was a D-L, and the last an IBL (plasmacytoid), according to the Working Formulation. Three patients manifesting a high grade malignancy died within 6 months after the diagnosis. Thyroid autoantibodies were detected in four patients, and, histologically, three of the four had chronic thyroiditis. The relationship between primary malignant lymphoma of the thyroid and chronic thyroiditis is discussed.

Aged↗
PubMed1987

A case of postganglionic cholinergic dysautonomia.

A 24 year old female presented with signs and symptoms of postganglionic cholinergic autonomic dysfunction manifested by impaired lachrymation and salivation, mydriasis of the pupil, decreased gastrointestinal motility, atony of the bladder, and sweating and taste disturbance. Clinical and pharmacological studies confirmed that the abnormalities were restricted mainly to the postganglionic cholinergic autonomic systems. The titre of serum complement was low, antinuclear antibodies revealed a diffuse pattern, and anti SS-A antibody was positive, suggesting that this disorder was caused by an immune mechanism.

Adult↗
PubMed1987

[Experience in transurethral ureterolithotripsy using a rigid ureteroscope].

We report our experience of transurethral ureterolithotripsy using a rigid ureteroscope on 18 ureteral calculus patients between November, 1985 and July, 1986. The stones could be successfully removed in 3 of the 10 cases of upper ureteral calculi and in all 8 cases of lower ureteral calculi. In this series, transurethral ureterolithotripsy proved to be valuable for the lower ureteral calculus. However, the device still needs to be improved for upper ureteral calculi.

Adult↗
PubMed1984

[Indications of extracorporeal surgery (autotransplantation) for upper urinary tumors and renal calculi].

Renal preservation and cure of bilateral occurrence of renal tumors or stones as well as occurrence in solitary kidney put all urologists on the thorns of dilemma. Application of extracorporeal surgery resulting in autotransplantation of the kidney for such complicated cases seems useful. Case 1 was a bilateral renal Wilms' tumors in a 17-month-old boy, case 2 and 3 were undiagnosed tumors in renal pelvis and ureter. Extracorporeal surgery enables an accurate partial nephrectomy and yet helps to avoid not only the dissemination of tumor cells, but also undesired nephrectomy in case of benign origin. On the contrary, bilateral nephrectomy followed by dialysis or homo-transplantation will result in an immunosuppressive state and the radicality may only be temporary. Besides, the 5-year survival of dialysis therapy is in the range of 60-65%. Thus the indication of autotransplantation was signified in the tumor situation of case 1. For the 2nd and 3rd cases, this method seems to be the best in satisfying the dilemma in discussion. Likewise, the complicated renal calculi could be completely removed without further deterioration of renal function if they were extracorporeally treated and autotransplanted. We proved that 83% of the difficult stones can be completely removed under hypothermia in situ. For application of autotransplantation to the calculous disease, we feel observation of contraindication is essential for better results at this stage.

Adult↗
PubMed1983

[Clinical study on cefmenoxime (CMX) in urology].

Basic and clinical studies were made on Cefmenoxime (CMX), a new cephalosporin antibiotic, and the following results were obtained. The serum concentration of CMX was examined in four healthy adults after administration of 250 mg of CMX by intramuscular injection, intravenous injection and one-hour intravenous drip infusion (cross over). In the case of intramuscular injection, the peak value of 5.9 micrograms/ml was obtained 30 minutes after administration, and the half-life in serum was 1.41 hours. In the case of intravenous drip infusion, injection, a concentration value of 11.1 micrograms/ml on the average was obtained after 15 minutes of administration, and the half-life in serum was 1.26 hours. In the case of intravenous drip infusion, the concentration was 12.4 micrograms/ml upon completion of drip infusion, and CMX disappeared from serum at a half-life of 0.94 hour. The urinary recovery up to 6 hours was from 60 to 70% in each The efficacy rate of this preparation was 100% for 4 cases of acute simple cystitis. The efficacy rate of CMX was 70% for 10 cases of complicated urinary tract infection; the 3 cases in which CMX was not effective were patients with a residual catheter and Pseudomonas persisting or appearing as superinfection. It was noted that Serratia, which was resistant to the conventional cephalosporin antibiotics, became negative. No subjective side effects due to the administration of this preparation were observed. As for abnormal laboratory findings, a slight and transient rise in transaminases was observed in one case. On the basis of the above-mentioned results, it was concluded that CMX is an effective preparation for the treatment of urinary tract infections.

Adult↗
PubMedDate not supplied

Phenotypic changes of the mesangium in diabetic nephropathy.

In diabetic nephropathy there is accumulation of matrix proteins. Overproduction of these matrix proteins considered to be due to the phenotypic change of mesangial cell. In order to detect the phenotypic change of the mesangial cell, renal biopsy specimens from patients with diabetic nephropathy were stained with antibodies against various types of collagens and contractile-associated protein, caldesmon. Type III collagen was not stained in the glomerulus and type VI collagen showed mesangial pattern from normal controls. In diabetes, mesangial staining of type III collagen and increases in type VI collagen were observed in the mesangium. Increased mesangial staining of caldesmon was noted in the glomerulus from diabetic nephropathy in contrast to only vessel staining from normal controls. These results indicate that phenotypic changes are noted in the mesangium in diabetes. Expression of contractile-associated protein such as caldesmon, would serve as a useful marker to predict glomerulosclerosis.

Antibodies↗
PubMedDate not supplied

Malignant hypertension with a rare complication of pulmonary alveolar hemorrhage.

A 34-year-old Japanese male was admitted to Okayama University Hospital with severe hypertension, rapidly progressive renal failure, blurred vision, dyspnea and hemoptysis. Clinical diagnosis of malignant hypertension was given and antihypertensive therapy and hemodialysis were immediately started. Renal biopsy was performed on the sixth day in hospital to examine the underlying disease, such as microscopic form of polyarteritis, since the complaint of hemoptysis and pulmonary alveolar hemorrhage was noted by computed tomography of the lungs. Typical pathological changes of malignant hypertension, i.e. fibrinoid necrosis of the afferent arterioles and proliferative endoarteritis at the interlobular arteries were observed. There was no evidence of active necrotizing glomerulonephritis and crescent formation. Renal function was gradually recovered and pulmonary hemorrhage completely disappeared by treatment with antihypertensive agents. The authors report a case of malignant hypertension with a rare complication of pulmonary alveolar hemorrhage and speculate that it may be related to vascular injuries at the alveolar capillary level caused by malignant hypertension.

Adult↗
PubMedDate not supplied

Antisense oligonucleotides.

Antisense technology was developed to inhibit gene expression by utilizing an oligonucleotide complementary to the mRNA which encodes the target gene. There are a few possible mechanisms for the inhibitory effects of antisense oligonucleotides. Among them, degradation of mRNA by RNase H is considered to be the major mechanism of action for antisense oligonucleotides. This technique was originally used to elucidate the function of a target gene, but may also have therapeutic applications, provided it is designed carefully and properly.

Animals↗
PubMedDate not supplied

Caldesmon isoform associated with phenotypic modulation of mesangial cells.

Caldesmon (CaD) is a major calmodulin- and actin-binding protein distributed in smooth muscle cells (SMC) and nonmuscle cells. There are at least two high-molecular-weight CaD (h-CaD) isoforms and four low-molecular-weight CaD (l-CaD) isoforms produced by alternative splicing. Isoformal interconversion is associated with phenotypic modulations of vascular SMC. We investigated the CaD isoform in human and rat glomerular mesangial cells (MC) to characterize the phenotypic changes of MC involved in glomerular diseases. A Western blot analysis and reverse-transcription analysis using exon-specific primers revealed that one l-CaD isoform lacking exons 1, 3b and 4 was predominantly expressed in human cultured MC. The expression of this isoform was markedly enhanced in anti-Thy1.1 nephritis rats and streptozotocin-induced diabetic rats, while little expression was observed in the normal glomerulus. Isoformal interconversion did not occur during the phenotypic changes of MC. These data suggested that the activated MC resembled dedifferentiated SMC in terms of the CaD expression pattern, and that CaD is a useful marker of the phenotypic modulations of MC.

Animals↗
PubMedDate not supplied

Bcl-2 expression and apoptosis in nephrotoxic nephritis.

The product of the Bcl-2 proto-oncogene has been shown to prolong cell survival by preventing apoptosis in several cell lineages. To investigate the regulatory mechanisms of apoptosis in glomerulonephritis, we examined the expression pattern of the Bcl-2 protein together with cellular events in rat nephrotoxic nephritis. Bcl-2 protein and proliferating cell nuclear antigen were detected in glomeruli by immunohistochemistry. Morphologic changes of apoptosis were identified by electron and light microscopy and an in situ DNA nick end labeling method. The first (heterologous) phase began with significant neutrophil infiltration shortly after the injection of nephrotoxic serum. Both Bcl-2 expression and the number of proliferating cells in the glomeruli were at maximum at 24 h in the heterologous phase. Glomerular hypercellularity with an influx of macrophages and the number of apoptotic glomerular cells peaked on day 14 in the second (autologous) phase. Glomerulonephritis resolved after that. These results suggest that overexpression of the Bcl-2 protein may play a role in glomerular cell survival and exacerbation of glomerulonephritis. Apoptosis may occur as an active mechanism in the resolution of the autologous phase in nephrotoxic nephritis.

Animals↗