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Biomedical subjects

N Yoshimura

Publications and source records attributed to N Yoshimura.

At least 523 records · Page 29Linked to original sources

Killer cell systems of cynomolgus monkeys experimentally infected with HTLV-1.

The cell-mediated killer activity in cynomolgus monkeys, which were infected 2.5 yr previously with HTLV-1, was examined. With HTLV-1-infected autologous lymphoid cells as targets, HTLV-1-specific killer cells were not detected among PBL cells of infected monkeys, but in monkeys in which specific memory cells were found. These memory cells were converted to active specific killer cells by stimulation with mytomycin C (MMC)-treated HTLV-1 infected autologous cells in vitro. Target blocking by anti-HTLV-1-related Ag suggested that the target molecules recognized by the specific killer cells may be virus envelope glycoprotein gp 68 and other cellular Ag induced by HTLV-1 infection. In addition to the specific killer cells, NK cells that could kill not only NK-sensitive target cells but also target lymphoid cells with HTLV-1 Ag on their surface, were found in these monkeys. In vitro stimulation caused enhancement of NK cell activity as well as induction of antigen specific killer cells. These findings suggest that Ag-specific killer cells may work together with NK cells to eliminate HTLV-1-bearing T cells in vivo.

Animals↗

Olfactory bulb involvement in Pick's disease.

The olfactory bulbs and stalks were examined in a case of Pick's disease that showed numerous and widespread Pick bodies in the brain. Typical argyrophilic inclusions (Pick bodies) were found not only in many cells of the anterior olfactory nucleus by also in some mitral cells and tufted cells. In addition, neuronal loss and astrocytosis were evident. No neurofibrillary change or senile plaque were detected anywhere in these structures. Electron microscopy disclosed that there was no ultrastructural difference between Pick bodies in the olfactory bulb and those in the cerebral cortex or hippocampus. These data indicate that in Pick's disease mitral cells and tufted cells, as well as anterior olfactory nucleus cells, are affected by degeneration specific to Pick's disease.

Aged↗

Juvenile Parkinson's disease with widespread Lewy bodies in the brain.

A clinico-pathological case report on a case of juvenile Parkinson's disease (JPD) with widespread Lewy bodies (LBs) in the brain is presented with comparative morphological studies on two demented cases of "classical" Parkinson's disease (CPD) with disease onset at an older age. The clinical and histological pictures of this JPD case were typical of Parkinson's disease, excepting numerous Lewy bodies in the cerebrum. There were no neurofibrillary change nor senile plaques throughout the CNS. The distribution and histochemical and ultrastructural characters of the histological lesions (i.e., LBs) in the JPD and the two CPD cases were investigated and compared. The comparison showed no qualitative but only quantitative differences between the two types of Parkinson's disease. The present study also revealed that in CPD cases significant numbers of LBs could be present in the cerebral cortex, amygdaloid and claustrum. These lesions can be in part responsible for dementia in CPD.

Adult↗

Involvement of fibronectin in in vitro regeneration of retinal pigment epithelium.

Argon laser photocoagulation was placed on the confluent monolayer of cultured chick retinal pigment epithelial cells as a model of the regeneration process of retinal pigment epithelium after laser burn. The intense fibrillar net immunofluorescent pattern of fibronectin appeared on the burnt area from 2 h after the laser application, before the beginning of tissue reconstruction. Fibronectin was observed for several days, then became undetectable before the complete regeneration of retinal pigment epithelial cells. This indicates that fibronectin is involved in the early regeneration process of retinal pigment epithelium.

Animals↗

The effect of cyclosporine on mortality and renal function in living related pediatric kidney transplant recipients.

The outcome, incidence of acute rejection episodes, complications and cyclosporine (CyA) induced nephrotoxicity were studied in 10 pediatric kidney transplant recipients who were grafted from one-haplotype indentical parent with immunosuppression of CyA and prednisolone (Pred). Excellent patient and graft survival could be achieved in this population with low incidences of acute rejection or serious complications as when compared with the results of azathioprine (AZ) treated pediatric patients. With a mean follow-up of 12.9 months (range 1 to 50 months), the patient survival rate was 100 per cent and the graft survival rate was 100, 84, 84 and 84 per cent at 1, 2, 3 and 4 years post transplantation, respectively. Serum creatinine levels in the group were 0.97, 1.17, 1.14 and 1.2 mg/dl at 3, 6, 12 and 24 months post transplantation, respectively. The incidence of treated acute rejection episodes was 20 per cent (2 out of 10) in the CyA-treated children, whereas it was 53 per cent (9 of 17) in the Az-treated children. Five children who had undergone transplant surgery before they were 11 years old displayed linear growth in height after their transplantation. There have been no opportunistic infections, aseptic necrosis or peptic ulcers in this group and cyclosporine nephrotoxicity has not been a serious problem in the pediatric recipients. Only 10 per cent (1 out of 10) of the recipients displayed acute nephrotoxicity and only one recipient has converted from CyA + Pred to CyA + AZ + Pred (Three drug therapy) due to persistent nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A kidney transplant recipient with renal cell carcinoma derived from a native kidney.

A case of renal cell adenocarcinoma which originated from a left native kidney following kidney transplantation, with widespread metastases, including multiple bone and liver metastases, is presented herein. An extensive clinical investigation, including bone marrow biopsy, liver biopsy, abdominal computerized tomography, excretory urography and examination of the gastrointestinal tract failed to determine the site of the primary lesion in this patient. Examination at autopsy revealed a small adenocarcinoma of the left native kidney with lobulated nodular capsular invasion and metastases to the bone and liver.

Adult↗

Experience with 247 living related donor nephrectomy cases at a single institution in Japan.

There is currently much concern over the morbidity and mortality of donors undergoing nephrectomy for living related renal transplants. Between April, 1970 and July, 1986, 247 cases of living related renal transplants were performed at the Second Department of Surgery, Kyoto Prefectural University of Medicine. The average age of the donors was 50.3 +/- 9.7 years, 81 per cent of the donors being parents of the recipients. Minor abnormalities which did not affect the donors suitability were found in 71 cases. Nephrectomies were performed extraperitoneally in all cases. Peri-operative complications, including wound complications in 13 cases, urinary infection in 12 cases and pulmonary complications and arrhythmia in 4 cases, were considered to be minor in nature. A variety of renal function tests, carried out two weeks after nephrectomy revealed normal levels, although they had become slightly worse than those estimated pre-operatively. Long-term sequelae in the follow-up period from 18 months to 16 years and 2 months, was studied on 124 donors who answered questionnaires. Currently, there are 5 late deaths, none of which are directly related to the nephrectomy. Of the 124 donors, 85.5 per cent stated that there had been no change in their physical states following surgery. Pain or a feeling of discomfort at the wound site was reported by 10 donors (8.1 per cent) and hypertension was observed only in 3 (2.4 per cent). No major complication directly related to the donor nephrectomy was found, except for one case of incisional hernia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Contraction of urinary bladder by central norepinephrine originating in the locus coeruleus.

Studies were performed to elucidate the role of the locus coeruleus, which is rich in norepinephrine-containing cell bodies, in vesical function using alpha-chloralose anesthetized cats. Stimulation of the locus coeruleus caused contraction of the urinary bladder, which was not affected by transection of the bilateral hypogastric nerves, but blocked by intravenous administration of hexamethonium, a ganglion blocking agent. In animals with transected hypogastric nerves, the locus coeruleus-induced contraction was inhibited by intrathecal administration of phentolamine (alpha-blocker) and prazosin (alpha 1-blocker), but not affected by intrathecal sotalol (beta-blocker) or yohimbine (alpha 2-blocker). In animals treated with reserpine, the locus coeruleus-induced contraction was enhanced by intravenous application of L-dopa, a precursor of norepinephrine. These results suggest that norepinephrine derived from the locus coeruleus activated preganglionic neurons in the sacral intermediolateral nuclei via alpha 1-receptors, thereby producing urinary bladder contraction.

Animals↗

Effect of cyclosporine on the endocrine and exocrine pancreas in kidney transplant recipients.

In order to assess whether cyclosporine (CsA) affects the endocrine and exocrine pancreas, 105 patient courses comprised of 87 living related donor (LRD) and 18 cadaver donor (CAD) transplants treated with cyclosporine and prednisolone (Pred) were compared with the results of historical controls of 170 LRD and 10 CAD transplants treated with azathioprine (Az) and Pred. All of the recipients were followed for over 6 months after transplantation. There were no differences in age, sex, Broca index, family history, and preoperative evaluation on diabetic dispositions between the two treatment groups. The incidence of diabetes mellitus (DM) requiring insulin therapy was higher in CsA-treated recipients (18/105, 17.1%) than in Az-treated recipients (23/180, 12.8%; P less than 0.05), although both the daily Pred and cumulative doses of methylprednisolone (MP) at the onset of DM were significantly smaller in the CsA group than in the Az group (26.1 +/- 2.2 mg v 41.4 +/- 3.4 mg, P less than 0.01 and 3,086 +/- 626 mg v 7,133 +/- 1,129 mg, P less than 0.01, respectively). Diabetic patients with CsA showed higher levels of blood glucose (401 +/- 46 mg/dL), but lower amounts of urinary glucose (40 +/- 4.3 g/d) compared with patients treated with Az (239 +/- 31 mg/dL, and 61.4 +/- 4.6 g/d, respectively, P less than 0.05). In the CsA group, the onset of DM was related to high CsA plasma trough levels (greater than 350 ng/mL) in 23% of patients. Insulin could be withdrawn within 3 months in six of eight patients who had been converted from CsA to Az.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

The in vivo immunosuppressive action of suppressor cells from alloantigen-cyclosporine-treated mice and the capacity of spleen cells to release interleukins and gamma-interferon.

Antigen-nonspecific suppressor T cells were identified in spleens of mice rendered unresponsive by sensitization of allogeneic antigen in combination with cyclosporine (CsA) treatment. Suppressor cells were obtained from C57BL/6 (B6, H-2b) mice treated with a single i.p. injection of 1 x 10(7) allogeneic P815 (H-2d) cells combined with a five-day course of CsA, a group that did not show any cytotoxic activity of spleen cells against P815 targets. These noncytolytic spleen cells displayed suppressor activity on the induction of cytotoxic T (Tc) cells of normal lymphocytes against not only P815 stimulator (80.9% suppression, P less than 0.01, responder:additional cell ratio = 2.5:1) but also third-party BW5147 (H-2k) stimulator (68.2% suppression, P less than 0.01). The unresponsive state appears to be due to suppressor T (Ts) cells that are nonadherent to plastic or nylon-wool, 1500 rads-sensitive, and Thy-1-positive. Capacities of spleen cells from CsA-P815-treated mice to release cytokines (interleukin 1 [IL-1]), interleukin 2 [IL-2], interleukin 3 [IL-3], and gamma-interferon [gamma-IFN]) were examined. Spleen cells from CsA-P815-treated B6 mice displayed 84.1%, 91.7% and 90.8% inhibition (0.35 +/- 0.07 U/ml, 1.4 +/- 0.29 U/ml, and 7.0 +/- 0.9 U/ml) of IL-1, IL-2, and gamma-IFN production compared with normal mice (2.2 +/- 0.54 U/ml, 16.9 +/- 2.1 U/ml, and 76.0 +/- 3.1 U/ml, P less than 0.01), respectively. However, IL-3 production was significantly less inhibition (46.1%, 2.35 +/- 1.0 U/ml in CsA-P815-treated mice and 4.36 +/- 1.7 U/ml in normal mice) compared with other cytokines (IL-1, IL-2, gamma-IFN). Two systems were employed to assess the immunosuppressive efficacy of antigen-nonspecific Ts cells in vivo. First, adoptive transfer (i.p.) of spleen cells harvested from CsA-P815-treated mice ten days after treatment on 3 consecutive days (days 0, 1, 2) at a 3 x 10(7) cell dose into virgin B6 mice that were immunized with P815 cells (1 x 10(7), day 0) completely inhibited the development of Tc cells against P815 targets (5% specific cytolysis, effector:target ratio [E:T] = 200). The suppressor effect was immunologically nonspecific; adoptive transfer of Ts cells from CsA-P815-treated mice also abrogated the development of Tc cells against third=party BW5147 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Neuronal degeneration in the brain of the brindled mouse. Histochemical demonstration of decreased cytochrome oxidase activity in the cerebellum and brain stem.

In order to investigate the levels of cytochrome oxidase activity in neuronal mitochondria in the brain of the brindled mouse hemizygote (BM), the cerebella and brain stems from 12 pairs of brindled and normal littermates aged 13-16 days were examined. The diaminobenzidine method for light- and electronmicroscopic histochemistry was adopted. Light microscopy revealed that mitochondria in the normal cerebellum showed an intensely positive reaction to diaminobenzidine, whereas those in the BM cerebellum showed a very weak reaction indicating an evident reduction of cytochrome oxidase activity. Electron microscopy disclosed a diaminobenzidine-OsO4 product densely appearing on the inner membranes of most mitochondria in Purkinje cells in the normal cerebellum. However, it was very faint or absent in those in the BM cerebellum. The same was true in Golgi II cells, granule cells, glomeruli and brain stem nuclei, but the degree of reduction was not uniform among these structures. In conclusion, there is not only a generalized reduction of cytochrome oxidase activity but also a topographical predilection of areas showing a reduction of the enzyme in the BM cerebellum and brain stem. These facts may explain the pathogenesis of neuronal degeneration in the brain of the BM.

Animals↗