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Biomedical subjects

T Oka

Publications and source records attributed to T Oka.

At least 631 records · Page 35Linked to original sources

Developmental changes in the expression of HMG 2a protein.

The levels of HMG 2a chromosomal protein and its mRNA change during the post-hatched development of chicks were investigated. The contents of both HMG 2a and 2b proteins of liver, heart, brain, muscle and gizzard were abundant in the newly hatched chicks but their contents decreased significantly in those tissues of the 70-day-old chicks. The HMG 2a mRNA levels of liver, heart and brain in 70-day-old chick decreased to about 40% of those mRNA in the newly hatched chicks while the HMG 2a mRNA levels of muscle and gizzard in the 70-day-old chicks increased 5- and 3-fold, respectively. These results suggest that the decrease in the HMG 2a protein contents of the muscle and gizzard in the 70-day-old chicks may be largely due to the stimulation of HMG 2a protein degradation or the reduction of HMG 2a mRNA translation.

Animals↗

A novel immunosuppressant, IR-1116, which has a different biological mechanism from that of cyclosporine A.

The effects of an epifumagillol derivative, IR-1116, on human lymphocytes in vitro, mouse antibody production in vivo and rat renal and cardiac transplantation were investigated. IR-1116 suppressed the human primary mixed lymphocyte reaction (MLR) in a dose-dependent manner with a value of the dose required for 50% suppression of 0.32 microM. IR-1116 suppressed the antibody production by human B lymphocytes activated with pokeweed mitogen or Epstein-Barr virus, but did not affect the interleukin-2 production by human lymphocytes stimulated with phytohemagglutinin. Furthermore, IR-1116 did not have any effect on the proliferation of B or T lymphocytes. IR-1116 is thought to have a different mechanism from cyclosporine A (CsA). BALB/c mice were immunized by s.c. injection of bovine gamma-globulin (BGG) and then received IR-1116 or CsA by i.p. injection at a dose of 20 mg/kg every other day for 2 weeks. IR-1116 suppressed the production of serum antibodies against BGG as strongly as CsA. In this experiment, IR-1116 apparently showed no adverse effects, while CsA-treated mice suffered from diarrhea and appeared to be irritated. Histological studies showed that IR-1116 suppressed the formation of germinal centers in the spleen of immunized mice. Flow cytometric analysis showed that IR-1116 caused a reduction of B lymphocyte population in splenocytes. On the other hand, CsA caused a marked reduction of helper T lymphocyte population in splenocytes and thymocytes. Furthermore, the i.p. administration of IR-1116 prolonged the survival time in a rat renal allograft model and the vital period of grafted hearts in rats. Based on the above, IR-1116 seems to be a new type of immunosuppressant acting via novel mechanisms different from those of immunosuppressants such as CsA, a potent T lymphocyte suppressant.

Adult↗

En bloc kidney and whole pancreaticoduodenal transplantation with bladder drainage in the rat: microsurgical technique and outcome.

A microsurgical technique for en bloc kidney and whole pancreaticoduodenal transplantation with bladder drainage employing triple vascular anastomoses without the need for a vascular cuff is described. Nineteen combined isografts were performed using this technique in inbred male Lewis (RT1:I) rats with streptozotocin-induced diabetes. Six recipients died within 1 month from early complications (two from uremia, two from pancreatitis, one from bleeding, one from peritonitis); the other 13 survived more than 1 month after transplantation with both the pancreas and kidney grafts functioning. Four of the 13 rats died after 1 month (one from uremia secondary to an obstructed ureter, one from unexplained uremia, one from peritonitis after a biopsy, and one of unknown causes). The pancreas isografts of two animals were excised at 1 and 3 months to confirm dependence on the graft; both animals became hyperglycemic after graft pancreatectomy and had immediate declines of urine amylase activity to normal. One animal was sacrificed at 3 months to determine the insulin content of its native and transplanted pancreas; insulin was very low in the former and normal in the latter. The remaining rats survived with both grafts functioning for at least 6 months (normoglycemic, high urinary amylase levels, normal or near-normal plasma creatinine concentrations), before being sacrificed within the context of other experiments and for histological observations. Both the kidney and pancreas isografts were well preserved microscopically.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗

Cellular fibronectin on intraocular lenses explanted from patients.

We investigated the origin of fibronectin (FN) on five posterior and four anterior chamber explanted intraocular lenses (IOLs) using immunohistochemical methods. Cellular deposits (assumed to be macrophages) and fibrous or membrane-like proteinaceous deposits on the IOLs showed immunoreactivity to an antibody against cellular FN. These proteinaceous deposits were believed to be products of the cells that adhered to the IOLs.

Aged↗

Calcium pump expression in human bone and soft tissue tumours.

Ninety-one cases of human bone and soft tissue tumours were studied for calcium pump expression by strepto-avidin-biotin immunohistochemical staining with a monoclonal antibody against sarcoplasmic reticulum calcium-ATPase (mAb6F5). Two out of 5 cases of embryonal rhabdomyosarcoma, 1 out of 5 cases of biphasic synovial sarcoma, 4 of 4 cases of chordoma and all of 3 chondrosarcoma cases were positive for mAb6F5. Although this novel monoclonal antibody can be used as a marker of myogenic tumours, the present positive result for endoplasmic reticulum calcium-ATPase (calcium pump) in other tumours including chordoma, chondrosarcoma and synovial sarcoma indicates a wider immunoreactivity. The findings further suggest that intracellular calcium may play an important role in cell proliferation and/or differentiation.

Adult↗

Parachordoma: an ultrastructural and immunohistochemical study.

A case of parachordoma of the left calf in a 19-year-old Chinese female is reported. The tumour showed multinodular growth pattern and consisted of round or oval tumour cells with abundant eosinophilic cytoplasm and myxoid matrix. Tumour cells formed small nests and sometimes showed concentric arrangement. Physaliferous-like cells and undifferentiated spindle cells were occasionally observed among the cell nests. The myxoid matrix was positive for high-iron diamine stain, indicating the presence of chondroitin 4- and 6-sulphates and keratan sulphate. Ultrastructurally, well-developed rough endoplasmic reticulum, abundant intermediate filaments, microvillous cytoplasmic processes, pinocytic vesicles, and desmosome-like junctional structures were found. Tumour cells were positive for S-100 protein and vimentin, but negative for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, and desmin. These results are consistent with the definition of parachordoma as a soft tissue neoplasm consisting of cells with histology and ultrastructure similar to those of chordoma cells but with immunohistochemistry similar to that of chondroid tumour cells.

Adult↗

Different expression of calpain in skeletal muscle of Japanese quail (Coturnix coturnix japonica) lines selected for body weight.

Calpain activity was determined by western blot analysis of steady-state concentrations of m-calpain (calpain requiring millimolar Ca2+ for activation) and also by northern blot analysis of steady-state concentrations of mRNA encoding m-calpain in three lines of quail: a random-bred control line (RR) and two lines selected for body weight, one for increased body weight (LL) and another for decreased body weight (SS). The m-calpain activities in skeletal muscle were higher in the SS line and lower in the LL line. From western blot analysis, enzyme levels of calpain were almost the same for all three lines. At the level of gene expression, the mRNA concentration encoding m-calpain was higher in the LL and lower in the SS line. These results suggest that the regulation of calpain activity in skeletal muscle is a three-step process, regulation at the transcription level, regulation at the enzyme level, and regulation of the activation of calpain.

Animals↗

Morphological characterization of a new human epithelioid sarcoma cell line, ES020488, in vitro and in vivo.

A new human epithelioid sarcoma cell line (ES020488) was established from a cutaneous metastasis in 26-year-old man, and was morphologically characterized in vitro and in vivo by comparison with the original tumor. The ES020488 cells showed a male karyotype ranging from 39 to 83 chromosomes, with various abnormalities but no specific pattern. The cells were round, polygonal or spindle-shaped with abundant cytoplasm and round nuclei containing prominent nucleoli; they proliferated in a sheet-like pattern. Tumors transplanted into nude mice revealed essentially the same features as the original tumor. Both in vitro and in vivo, the cells immunohistochemically expressed vimentin, cytokeratin, and EMA, but not desmin and S-100 protein. Ultrastructural study revealed irregular or round nuclei containing abundant euchromatin and prominent nucleoli, many intermediate filaments running irregularly or around the nucleus, and a number of filopodia-like processes. ES020488 cells were thus proven to retain and exhibit the unique morphological characteristics of an epithelioid sarcoma both in vitro and in vivo. These cells are possibly derived from synovioblastic mesenchyme.

Adult↗

Gene expression and aging.

Considerable amount of data has accumulated during the past few years showing several changes in gene expression as a function of age. However, the basic mechanism of aging still remains poorly understood. In this review, we have mainly analysed the data pertaining to the hypothesis that aging is associated with genetic instability and have attempted further to highlight the gaps that need to be bridged in order to have a clear picture of the aging phenomenon. Extensive investigations employing new and novel approaches are needed in future to elucidate the intricately interwoven patterns of molecular control that underlie the various aspects of gene expression during aging.

Aging↗

Pontine-induced generalized suppression of postural muscle tone in a reflexively standing acute decerebrate cat.

In a reflexively standing acute decerebrate cat, the pontine tegmentum was electrically stimulated and the effects on postural muscle tone and locomotor movements evoked by stimulation of the mesencephalic locomotor region (MLR) were studied. A stimulating microelectrode was placed systematically at 1-mm increments throughout the pons (H - 2 to H - 10) at levels ranging from P0.0 to P6.5 dorsoventrally and mediolaterally from LR0 to L4 or R4. Another stimulating microelectrode was placed in the physiologically identified MLR. Stimuli delivered to the dorsomedial regions of the pontine tegmentum (P3 to P4, LR1.5 to 2.5, H - 4 to H - 6) resulted in simultaneous and bilateral suppression of tonic activities in the neck, lumbar back, forelimb and hindlimb muscles. The pontine inhibitory sites corresponded to the medial area of the central tegmental field (FTC) and the central area of the gigantocellular tegmental field (FTG), bilaterally. Effects of pontine induced suppression on those muscles were stimulus frequency and stimulus intensity-dependent and the effects persisted even after termination of the stimulation. With concomitant pontine stimulation, MLR-evoked locomotor movements were suppressed along with prolongation of the forelimb and hindlimb step cycles.

Animals↗

Ureteropelvic junction obstruction with renal pelvic calcification: a case report.

Calcification in the wall of the renal pelvis is rare. We report on a 65-year-old man with hydronephrosis secondary to ureteropelvic junction obstruction with renal pelvic calcification. Calcium deposit was found in the wall of the severely dilated renal pelvis. Pathological examination revealed a damaged and hyalinized fibrous renal pelvic wall and serum calcium level was normal. Thus, we speculated that this calcification was dystrophic. Chronic extensive dilatation with intermittent hemorrhage of the renal pelvic wall may have caused this dystrophic renal pelvic calcification.

Aged↗

Haemodynamic and neurohumoral changes in spontaneously hypertensive rats with aortocaval fistulae.

1. Our aim was to evaluate the effects of an aortocaval fistula (1 mm) on cardiorenal haemodynamics, cardiac hypertrophy and neurohumoral factors in spontaneously hypertensive rats and to compare the results with those observed in Wistar rats at 2 weeks after fistulae placement. Sham-operated spontaneously hypertensive rats and Wistar rats served as controls. 2. Heart weight was significantly increased in spontaneously hypertensive rats (34%) and in Wistar rats (43%) at 2 weeks after fistula creation. Left ventricular systolic pressure and dp/dtmax. were significantly decreased (both P < 0.01) in spontaneously hypertensive rats with fistulae which had higher left ventricular end-diastolic pressure than Wistar rats with fistulae (P < 0.01). Signs of circulatory congestion (ascites, tachypnoea, prostration) were observed only in the overloaded spontaneously hypertensive rats (45%). Cardiac index was comparably increased in both fistulae groups due to an increase in stroke index, since heart rate was not increased. 3. Fistulae placement decreased renal blood flow and kidney weight, and increased blood urea nitrogen to a greater degree in spontaneously hypertensive rats (all P < 0.05); serum creatinine levels were unaltered. Plasma noradrenaline concentration was increased in spontaneously hypertensive rats with fistulae (P < 0.05), whereas plasma renin activity was not changed. 4. Thus, spontaneously hypertensive rats with fistulae developed overt haemodynamic signs of high-output heart failure with frequent ascites and dyspnoea, whereas most of these findings were milder or absent in Wistar rats. This model provides an opportunity to evaluate the pathophysiological and pharmacological responses in high-output heart failure.

Animals↗

Apolipoprotein E metabolism in sciatic nerves of diabetic rats. Implication for diabetic neuropathy.

Apolipoprotein (apo) E secreted by macrophages plays an important role in nerve injury and repair. We investigated the disturbance of neural apo E metabolism in diabetic rats and its relation to diabetic neuropathy. In BB/W rats, genetically diabetes prone rats, the secretion of apo E from sciatic nerves was 3-fold greater than that in control rats. Furthermore, a similar enhancement of apo E secretion was observed in injured nerves of STZ-induced diabetic rats (2-fold) as compared with those of nondiabetic rats, and this was reversible with insulin treatment. Histological examination of the nerves revealed more extensive infiltration of mononuclear cells in the injured nerves of STZ-induced diabetic rats than in those of non-diabetic rats. This is consistent with the findings that chemotactic activities for mononuclear cells, which were released from injured nerves, were greater in the STZ-induced diabetic rats than in the non-diabetic rats. From these results we conclude that the recruitment of monocyte/macrophages into injured nerves is enhanced in diabetes, thereby causing derangement of neural apo E metabolism. These abnormalities might contribute to the development of diabetic neuropathy.

Adult↗

Residual 152Eu and 60Co activities induced by neutrons from the Hiroshima atomic bomb.

Specific activities of 152Eu:Eu in stone samples exposed to the Hiroshima atomic bomb were determined for 70 samples up to a 1,500-m slant range from the epicenter. The specific activities of 60Co:Co were also determined for six samples near the Hiroshima hypocenter. First, the 152Eu data were investigated to find out the directional dependence of neutron activation. Directional anisotropy was not definite; however, there was an indication that the activation in the west-southwest was lower than in other directions. Second, measured 152Eu and 60Co radioactivity data were compared with activation calculations based on DS86 neutrons. It is clearly shown that the measured data are lower than the calculation near the hypocenter and vice versa at long distances beyond 1,000 m. The calculated-to-measured ratios of 152Eu are 1.6 at the hypocenter, 1.0 at approximately 900 m, and 0.05 at a 1,500-m slant range. Present results indicate that systematic errors exist in the DS86 neutrons concerning the source-term spectrum, neutron transport calculations in air, and/or activation measurements.

Cobalt Radioisotopes↗

Aberrant expression of the p53 tumor suppressor gene in adult T-cell leukemia and HTLV-I-infected cells.

By immunoprecipitation analysis, enhanced p53 expression was detected in 3 of 4 adult T-cell leukemia (ATL) cell lines, 1 of 3 HTLV-I-infected cell lines and 1 of 5 fresh ATL samples, compared with phytohemagglutinin-stimulated peripheral blood lymphocytes. Among these 5 high expressers, p53 missense mutations were indicated in 2 ATL cell lines and 1 fresh ATL sample by extensive p53 cDNA and genomic DNA polymerase chain reaction single-strand conformation polymorphism analysis. No mutation was found throughout the entire coding region of the remaining 2 high expressers (1 ATL and 1 HTLV-I-infected cell lines) and low expressers of p53 (2 HTLV-I-infected cell lines). Tax oncoprotein expression was found in these 2 high p53 expressers in which p53 mutation was not present, but not in low p53 expressers or cells carrying this mutation. The levels of p53 mRNA were similar among the samples regardless of p53 levels. Posttranscriptional mechanisms other than missense mutation would thus appear to increase p53 in the Tax-expressing cells but not in cells containing undetectable levels of Tax. No complex formation between p53 and Tax was observed.

Adult↗

Local immunosuppressive therapy with monoclonal anti-T cell antibody on renal allograft survival in the rat.

Considerable interest in the experimental and clinical use of MoAbs as potential therapeutic agents in allograft rejection has been generated by the recent reports of striking prolongation. In this study we investigated the efficacy of the local administration of MoAb OX-19 which is directed to the rat CD5 equivalent, through the renal artery using a rat kidney transplant model, in order to develop a potent method for modifying rejection while minimizing the systemic side effects. Untreated Lewis rats (LEW, RT-1(1)) rejected Brown-Norway rat (BN, RT-1n) kidney at 7.8 +/- 0.2 days (n = 10). Mean survival time (MST) of recipients treated with OX-19 (75 micrograms/kg per day) as single bolus injections via the dorsal penile vein for 7 days was 7.0 +/- 0.2 days (n = 5, NS). LEW hosts receiving OX-19 (75 micrograms/kg per day) continuously for 7 days via a femoral vein by using an osmotic minipump (IV-treated group) showed a slight prolongation of graft survival (MST = 8.8 +/- 0.9 days, n = 5), but this was not statistically significant. On the other hand, local continuous intrarenal arterial infusion of OX-19 (75 micrograms/kg per day) for 7 days (RA-treated group) significantly prolonged the graft survivals (MST = 16.8 +/- 1.3 days, n = 8, P < 0.01). Histological examination of MoAb-treated LEW hosts on day 6 post-grafting revealed that kidney grafts from RA-treated hosts showed a slight tubular necrosis, but reduced mononuclear cell infiltration, whereas kidney grafts from IV-treated hosts displayed a severe mononuclear cell infiltration around the artery with interstitial oedema. Moreover, the local intrarenal administration of OX-19, even when the dose is delayed until day 4 after renal grafting, has a therapeutic effect for on-going acute allograft rejection (MST = 11.4 +/- 0.8 days, n = 8) compared with administration of OX-19 intravenously from day 4 after grafting (MST = 7.6 +/- 0.2 days, n = 5, P < 0.01) or with no treatment (MST = 7.8 +/- 0.2 days, P < 0.01). The phenotype of graft infiltrating cells (GIC) was investigated on day 6 post-grafting. There was a significantly lower percentage of cells positive for OX-19, OX-8, OX-26 (transferrin receptor), and OX-39 (IL-2 receptor) in the RA group than in the IV group.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Endogenous D-serine in rat brain: N-methyl-D-aspartate receptor-related distribution and aging.

Recently, a substantial amount of free D-serine has been demonstrated in rat brain, although it has long been presumed that D-amino acids are uncommon in mammals. The anatomical distribution and age-related changes in endogenous D-serine have been examined here to obtain insight into its physiological functions. Free D-serine exclusively occurs in brains, with a persistent high content from birth to at least 86 postnatal weeks. The patterns of the regional variations and the postnatal changes in brain D-serine are closely correlated with those of the N-methyl-D-aspartate (NMDA)-type excitatory amino acid receptor. Because D-serine potentiates NMDA receptor-mediated transmission by selective stimulation of the strychnine-insensitive glycine site of the NMDA receptor, it is proposed that D-serine is a novel candidate as an intrinsic ligand for the glycine site in mammalian brain.

Aging↗

Embryonic development and postnatal changes in free D-aspartate and D-serine in the human prefrontal cortex.

We have analyzed free chiral amino acids (aspartate and serine) in the human frontal cortex at different ontogenic stages (from 14 weeks of gestation to 101 years of age) by HPLC with fluorometric detection after derivatization with N-tert-butyl-oxycarbonyl-L-cysteine and o-phthaldialdehyde. Exceptionally high levels of free D-aspartate and D-serine were demonstrated in the fetal cortex at gestational week 14. The ratios of D-aspartate and of D-serine to the total corresponding amino acids were also high, at 0.63 and 0.27, respectively. The concentration of D-aspartate dramatically decreased to a trace level by gestational week 41 and then remained very low during all postnatal stages. In contrast, the frontal tip contained persistently high levels of D-serine throughout embryonic and postnatal life, whereas the D-amino acid content in adolescents and aged individuals was about half of that in the fetuses. Because D-aspartate and D-serine are known to have selective actions at the NMDA-type excitatory amino acid receptor, the present data suggest that these D-amino acids might play a pivotal role in cerebral development and functions that are related to the NMDA receptor.

Adolescent↗