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Biomedical subjects

N Nishimura

Publications and source records attributed to N Nishimura.

At least 163 records · Page 9Linked to original sources

Effects of cytokines on the growth of cultured rabbit renal cortical tubular cells.

The effects of various cytokines including interleukin-1 beta, -2, and -6, tumor necrosis factor-alpha, and granulocyte-macrophage colony stimulating factor on the DNA synthesis of cultured rabbit renal cortical tubular cells were investigated. Among these cytokines, it was found that only interleukin-1 beta could stimulate the DNA synthesis of cultured renal tubular cells, while interleukin-6 mildly suppressed the DNA synthesis of such cells. Interleukin-1 beta and -6 are produced by mesangial cells. The above results suggest that these cytokines may regulate the growth of tubular cells via the urinary flow in the nephron.

Animals↗

[Two cases of hemorrhagic shock and encephalopathy syndrome].

A 10-month-old male infant (case 1) and another male infant aged 1 year and 11 months (case 2) were admitted to our department because of fever, watery diarrhea and convulsion. On admission, they were unconscious and showed rigidity of the limbs. Laboratory examination revealed a marked increase in GOT and GPT, a decrease in platelet and antithrombin III and an increase in FDP. Metabolic acidosis was found by blood gas analysis. Brain CT showed an extensive area of low density in case 1, and low density centering on the cerebral basal ganglia and brainstem in case 2. Rotavirus was detected in case 2 by fecal examination. The clinical pictures in these cases closely resembled those of hemorrhagic shock and encephalopathy (HSE) reported by Levin et al. in 1983. The etiology of this disease is currently unknown, and its prognosis is poor. The relationship between this disease and rotavirus should be examined in future studies.

Brain Diseases↗

A new bioactive bone cement: its histological and mechanical characterization.

We have developed a bioactive bone cement using CaO-SiO 2-P 2O 5-CaF 2 glass powders and ammonium phosphate solution, and investigated its histological and mechanical characteristics in vivo. A bone defect was drilled in proximal metaphysis of the rat tibia and filled with the bioactive bone cement in paste form or polymethylmethacrylate (PMMA) bone cement in the dough state. The cements were allowed to harden in situ. Histological examination demonstrated direct bonding between the new cement and bone by 4 weeks. The bioactive bone cement did not degrade up to 24 weeks postimplantation. The inflammatory reaction to the bioactive bone cement was less intense than the reaction induced by PMMA. Changes in the mechanical properties of the cement in vivo were studied by implanting hardened cylindrical specimens of both types of cement into the hindlimb muscles of rats for 12 weeks. The compressive strength of the bioactive cement increased significantly after implantation, and reached 68 MPa in 1 week and 73 MPa in 4 weeks. These values were comparable to those of PMMA, and were maintained up to 12 weeks after implantation. This bioactive bone cement hardens in situ within a few minutes with negligible rise of temperature and can be easily handled as a paste for filling bone cavities of different shapes. In addition, this cement has good osteoconductive and bone bonding potential and fairly high mechanical strength. Therefore, this new cement could be used both as a bioactive bone cement and bone defect filler.

Animals↗

Immunohistochemical localization of metallothionein in the eye of rats.

In order to elucidate possible physiological roles of metallothionein (MT), we have studied immunohistological localization of MT in the eye of the rat, using an avidin-biotin peroxidase complex method. As a result, strong MT immunostaining was observed in the epithelium of the lens and cornea. In the retina, considerably strong MT immunostaining was observed in the pigment cell layer while the nerve fiber layer and inner plexiform layer showed weak MT staining. Glial cells in the optic nerve were found to have marked MT staining. The present result is consistent with the hypothesis that MT may be involved not only in activation of zinc enzymes and cell proliferation through supply of zinc ions, but also in a protective mechanism in the blood-retina barrier.

Animals↗

Hepatitis C virus infection in patients with chronic liver diseases.

Antibodies against hepatitis C (HCV) in 512 patients were measured by an enzyme immunoassay (Ortho-HCV ELISA). The frequency of anti-HCV was 80%, 86%, 85% in nonB (NB) chronic hepatitis (CH), cirrhosis (LC), hepatocellular carcinoma (HCC), respectively; 70%, 90% in alcoholic (AL) LC, HCC; 15%, 33%, 58% in hepatitis B (HB) CH, LC, HCC, respectively. Anti-HCV positive cirrhotics had a shorter survival time and earlier development of HCC than anti-HCV negative cirrhotics. The findings suggest that HCV is a major cause of NB chronic liver diseases and may play a pathogenetic role in AL and HB liver diseases.

Adult↗

Cell-kinetic analysis of pancreatic cancers in Syrian golden hamsters.

Cell-kinetic analysis of pancreatic cancers using bromodeoxyuridine (BrdU) was performed on four transplantable pancreatic ductal adenocarcinomas, which were experimentally induced by giving N-nitrosobis (2-hydroxypropyl) amine (BHP) to Syrian golden hamsters. The volume-doubling time (Td) of the tumor was 0.43, 1.03, 2.30, and 3.50 d for tumor lines J, D, B, and F, respectively. In the pulse-labeling study, the labeling index was 15.8, 23.3, 27.9, and 31.7, respectively. The most rapidly growing tumor line, J, unexpectedly showed the lowest BrdU-labeling index (LI). The further study of tumor using the cumulative-labeling method revealed that the duration of S phase (Ts), the generation time (Tg) and the growth fraction (GF) were 2 h, 14 h, and 90% for tumor J and 12 h, 37 h, and 85% for slowly growing tumor B, respectively. Cells of limited life span (CLLS) of these lines did not differ from each other. These results conclude that the marked difference of Tg between tumor lines J and B resulted in a distinction of their growth rates. The disagreement of Ts/Tg also lead to a reversion of LI between the two lines. Furthermore, LI of BrdU with one-point pulse labeling did not seem to be a sufficient indicator of the growth characteristics, at least, in the present experiment.

Adenocarcinoma↗

Localization of metallothionein in hair follicles of normal skin and the basal cell layer of hyperplastic epidermis: possible association with cell proliferation.

Metallothionein is a low-molecular-weight metal-binding protein. Although it is inducible by a variety of agents and ubiquitously present in many tissues, its physiologic functions are still not clear. The present study was undertaken to determine the possible functions of metallothionein in both the proliferation and differentiation of epidermal keratinocytes. Metallothionein was detected immunohistochemically in hair matrix cells of the bulb and cells of the outer root sheath of anagen hair follicles, but not in dermal papillae in normal skin in the back of mice. In hyperplastic epidermal tissue, induced by either a phorbol ester tumor promoter or cholera toxin, the basal cells of the interfollicular epidermis stained strongly for metallothionein. Elevated expression of mRNA of the metallothionein gene was also demonstrated when the skin was stimulated by agents that induced hyperplasia. Papillomas produced by two-stage carcinogenesis protocols also stained for metallothionein. These observations suggest that metallothionein is involved in the proliferation of epidermal keratinocytes.

Animals↗

Transient increase in renal epidermal growth factor content after unilateral nephrectomy in the mouse.

A sensitive enzyme-linked immunosorbent assay for mouse epidermal growth factor was established for measurement of the content of epidermal growth factor in the remaining kidney after uninephrectomy. In 5-week-old male mice, the renal epidermal growth factor content before uninephrectomy was 355 +/- 97 ng/g wet tissue with a 2.1-fold increase on the first day after uninephrectomy, whereafter it gradually decreased. In 15-week-old mature male mice, the renal epidermal growth factor content increased 1.7-fold on the first day after uninephrectomy. Immunohistochemical analysis showed that epidermal growth factor was present in the distal tubular cells and that the staining intensity was increased on the first day after uninephrectomy. During the course of compensatory renal growth, no significant alteration of epidermal growth factor content was observed in plasma or in the submaxillary gland. Our data suggest that the increase in renal epidermal growth factor content after uninephrectomy is due to an increased production of epidermal growth factor in the kidney itself. The significance of this phenomenon is discussed.

Animals↗

[Bladder replacement with sigmoid colon for bladder cancer].

From 1972 to 1989, 21 patients underwent bladder replacement with sigmoid colon after cystectomy for bladder cancer. A portion of sigmoid colon (about 15 to 20 cm) was isolated and anastomosed to the urethral stump. Then the ureters were implanted in the sigmoid colon via submucosal tunnels. There were 20 men and 1 woman, ranging in age from 24 to 71 years (average 51 years). Preoperative investigations showed that all the cases were free of metastasis. Five years survival rate was 60.7% and there was no operative mortality. There was urethral recurrence in one case and in that case postoperative histopathology revealed carcinoma in situ with tumor. All patients were able to void by themselves without any difficulty. Five patients complained mild incontinence at daytime and all patients had mild incontinence during deep sleep at night, but all of them could maintain their normal daily life like before. The major postoperative complications were: leak at the site of anastomosis (between sigmoid colon and urethra) in 6 cases, hydronephrosis in 2 cases, VUR in 2 cases and bladder stone in 1 case. The patients who underwent bladder replacement with sigmoid colon were well satisfied, because there were no external stoma and the patients could void by themselves. From now, we want to improve our operative method in order to avoid postoperative incontinence.

Adult↗

[The application of in vivo diffusion weighted magnetic resonance imaging to intracranial disorders].

We have developed a magnetic resonance (MR) spin echo method to obtain diffusion weighted imaging using motion-probing gradient (MPG) pulses in one or three orthogonal directions before and after a 180 degree pulse. Phantom models containing water and acetone, normal volunteers and patients with brain tumors, brain edema and infarction were examined. Experimental models of brain edema including triethyltin intoxication and cold injuries were also examined in Wistar rats. MRI was performed at a 1.0-T clinical machine or a 4.7-T experimental machine using spin echo pulse sequences with or without additional MPGs on one or three orthogonal axes. The one direction method was useful to define diffusion anisotropy of myelinated axonal fibers in white matter. Faster diffusion was detected in the white matter parallel to the direction of MPGs. On the other hand, slower diffusion was detected perpendicular to the direction of MPGs because the myelin sheath restricted water diffusion. The three orthogonal gradients method was useful to demonstrate the difference in the diffusion coefficients in various diseases due to its larger total gradient strength. The clear distinction between the cytotoxic edema, which revealed slower diffusion, and the vasogenic edema, which revealed faster diffusion, was demonstrated in the experimental models using diffusion weighted image. In the clinical cases, faster diffusion was demonstrated in the brain tumor and perifocal vasogenic edema, which was in agreement with the results in the experimental models of rats. Brain tumors such as low grade astrocytoma with microcysts and perifocal vasogenic edema have very wide extracellular space.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[The distribution of solutions in the epidural space].

In 21 patients the distribution within the epidural space of epidurally injected 99mTc-DTPA was assessed. The gamma emissions from the epidural space were measured externally with the patients in supine position by use of a gamma camera. The recordings over the patient's back were stored in digital computer for 60 min. The results were as follows; 1) The spread of the radionuclide was mainly to cephalad direction, and seldom crossed the L5 level to sacral region. 2) The solution injected in the epidural space would distribute to less resistant compartments and the spread depends on the power of injection, negative pressure in the high epidural space and capillary pressure. 3) The elimination half-life of the injected radionuclide was between 1 to 17 min depending on the region in the epidural space. 4) The solution injected in the epidural space may penetrate dura mater at the ink cuff area and local anesthetic agents may affect the spinal nerve roots in the subarachnoid space rather than at the extra-dural space. 5) With continuous infusion technique the diffusion and penetration of the local agent through the dura mater are facilitated and more profound anesthetic effects would be expected. In clinical practice the utilization of the continuous infusion method should be considered along with the bolus injection.

Adult↗

A bioactive glass powder-ammonium hydrogen phosphate composite for repairing bone defects.

Bioactive glass powder (AW-G) was made into a rigid compound by mixing with ammonium hydrogen phosphate and was evaluated as a bone-defect filler. The proximal metaphysis of the rat tibia was drilled and packed with (a) polymethyl-methacrylate (PMMA) bone cement, (b) AW-G powder, (c) AW-G powder with ammonium hydrogen phosphate (AW-G)-(A-P), or (d) nothing, as a control. The animals, with different implantation periods up to 24 weeks, were sacrificed and the defective sites were histologically analyzed. The results revealed direct bonding between the bone tissue and the (AW-G)-(A-P). The general inflammatory reaction of (AW-G)-(A-P) was less than that of PMMA bone cement. The compressive strength of (AW-G)-(A-P) implanted subcutaneously into rats was measured chronologically and deterioration did not occur during a period of 24 weeks. The rigidity increased to 1.6 times 6 months after implantation as compared with the initial value. This compound can be used as paste and is transformed into a rigid compound in about 4 min without noticeable elevation of the temperature. Thus, this (AW-G)-(A-P) composite can be used as a bone defect filler, and there is a possibility that it can even be used as a bone cement if higher rigidity can be attained.

Animals↗

Transforming growth factor beta-like activity in human hydrocele fluid.

In this study transforming growth factor beta (TGF-beta)-like activity in human hydrocele fluid was investigated. Inhibition of DNA synthesis of adult rat hepatocytes in primary culture and stimulation of colony formation of normal rat kidney (NRK) fibroblasts, clone 49F in soft agar were observed in all acidified hydrocele fluids and these activities were neutralized by the specific antibody raised against human native TGF-beta. In samples obtained from recurrent cases of hydrocele, TGF beta-like activity was observed in its active form (without acidification). These results suggest that human hydrocele fluid contains TGF beta-like activity and that the active form of TGF-beta in recurrent hydrocele fluid may be responsible for the recurrence of the disease even after repeated aspiration.

Animals↗

High cell density suspension culture of mammalian anchorage independent cells: oxygen transfer by gas sparging and defoaming with a hydrophobic net.

Gas sparging directly into the culture-broth is not done in cell culture, except when the gas flow rate is very small, because much foaming occurs. During screening of defoaming methods, foam was observed to be broken up effectively when it made contact with a net fabricated from hydrophobic materials. Providing a highly efficient oxygen supply to suspension culture was tried using the new defoaming method. In a 5 l reactor equipped with the foam-eliminating net fabricated with polysiloxane, oxygen was transferred at 21 mmole/l.h equivalent to a consumption rate of 1 X 10(8) cells/ml, even at a low oxygen gas flow rate of 0.1 cm/s corresponding to a fourth of the gas flow rate when foam leaked through the net. Perfusion culture of rat ascites hepatoma cell JTC-1 was successfully carried out in the 5 l scale culture system with the net and a hydrophobic membrane for cell filtration. The viable cell concentration reached 2.7 X 10(7) cells/ml after twenty-seven days, in spite of the nutrient-deficient condition of the lower medium exchange rate, that is, a working volume a day, and viability was maintained at more than 90%. In a 1.21 scale culture of mouse-mouse hybridoma cell STK-1, viable cell concentration reached 4 X 10(7) cells/ml. These results showed that oxygen transfer by gas sparging with defoaming was useful for high density suspension culture. A foam-breaking mechanism was proposed.

Animals↗

The effect of transforming growth factor-beta on the alkaline phosphatase activity in rabbit renal cortical tubular cell cultures.

The effect of various growth regulators including epidermal growth factor and transforming growth factor-beta on the alkaline phosphatase activity of rabbit renal cortical tubular cells has been investigated in a serum-free culture. As a result, it was found that transforming growth factor-beta, known to be a growth inhibitor of renal tubular cells, increased the alkaline phosphatase activity of the tubular cells dose-dependently and that cycloheximide blocked any increase in the activity of this factor. In contrast, epidermal growth factor decreased the alkaline phosphatase activity in the tubular cells.

Alkaline Phosphatase↗