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Biomedical subjects

T Sugisaki

Publications and source records attributed to T Sugisaki.

At least 73 records · Page 4Linked to original sources

[Six-month chronic subcutaneous toxicity study of cefodizime sodium in rats].

Six-month chronic subcutaneous toxicity study of cefodizime sodium (THR-221) in rats was carried out with dose levels of 3000, 1000, 300 and 100 mg/kg/day. The systemic change observed was slightly decreased spontaneous activity, which appeared only in a very few animals. At the injection site of the animals at 1000 and 3000 mg/kg/day, various cutaneous changes (subcutaneous retention of fluid, incrustation, loss of hair and perforation) were observed. The body weight gains of the males at 1000 and 3000 mg/kg/day were depressed from 1 month of administration onward, but the food consumption was not affected in any group. The water intakes at 1000 and 3000 mg/kg/day were increased. Hematological findings were signs of anemia, a slight decrease in red blood cell count or increases in platelet and/or reticulocyte counts in all THR-221 groups. At 3000 mg/kg/day, increases in white blood cell and neutrophil counts and a decrease in lymphocyte count were also observed. Plasma chemistry revealed decreases in total protein amount and, albumin (A) or globulin (G) amounts, and a decrease or increase in A/G ratio in all compound groups. Autopsy revealed dilation of the cecum and hematoma, dark red spots and yellowish brown spots in the subcutaneous tissue at the injection site in all THR-221 groups. Hypertrophy of the spleen was also noted at 300-3000 mg/kg/day. Changes in organ weights were a decrease in liver weight in all compound groups and an increase in spleen weight at 3000 mg/kg/day. Microscopically, the following were observed: brown granules or hyaline droplets in the epithelium of renal tubules; hemorrhage and inflammatory changes in the subcutaneous tissue at the injection site; and an increased number of lymphocytes or granulocytes in the spleen and bone marrow. Urinalysis and ocular and auditory tests showed no changes related to THR-221. From the present results, the toxicologically non-effective doses of THR-221 are considered to be 300 mg/kg/day for male rats and more than 1000 mg/kg/day for female rats.

Anemia↗

Confronting cisternae in pituitary gland thyrotrophs of congenitally hypothyroid mice.

Confronting cisternae were found in pituitary thyrotrophs of congenitally hypothyroid mice. These confronting cisternae rapidly reverted back to ordinary rough endoplasmic reticulum following thyroxine administration. Confronting cisternae were not observed in the thyrotrophs of euthyroid control mice. Our results strongly suggest that confronting cisternae are a peculiar form of rough endoplasmic reticulum which appears under certain conditions of enhanced cellular metabolism.

Animals↗

Alteration of cerebral ganglioside metabolism in developing Snell dwarf mice.

The ganglioside metabolism of the Snell dwarf cerebrum was examined on postnatal days 15 and 20, by monitoring the rate of incorporation of radioactivity into each ganglioside species from tritiated N-acetyl-D-mannosamine. It was found that the turnover rate of the GM3 ganglioside was reduced throughout the entire period of development, resulting in retardation of A pathway metabolism which becomes abundant during late cerebral development. In addition, the turnover rate of the GM4 species, which is considered related to myelin formation, was also found to be reduced throughout the entire period of cerebral development.

Animals↗

Presence of a somatomedin-C-immunoreactive substance in the central nervous system: immunohistochemical mapping studies.

Somatomedin C (SMC; insulin-like growth factor I) is thought to mediate the effects of growth hormone (GH) mainly on skeletal growth. SMC is produced in the liver but its production by various other fetal tissues including the brain, suggests a local regulatory role rather than a general one. A substance cross-reacting with recombinant human SMC (rSMC) was localized in the central nervous system (CNS) of the normal control and Snell dwarf mice by the unlabeled antibody peroxidase-antiperoxidase technique. rSMC-immunoreactive substance (rSMC-IRS) was found in the neuronal cells of forebrain structures. These included the caudate nucleus/putamen, hippocampus, thalamus, hypothalamus, globus pallidus and amygdala. No positive cells were found in the cerebral cortex. Investigation of the dwarf brain showed rSMC-IRS distributed in identical areas of the brain, although the intensity of the staining of rSMC-IRS was found to be weaker than that of the positive cells in the normal brain. Moreover, the number of positive cells was found to be less than in the normal brain. After treatment with bovine GH for 3 days the reduced number of positive cells and weaker staining in the cerebral sections of the dwarf mice did not change. Thus, rSMC may represent another peptide which is common to both the endocrine and the nervous system, with a potential neurotransmitter/neuromodulator function in the CNS.

Animals↗

Oncofetal expression of glutathione S-transferase placental form in human stomach carcinomas.

The content of glutathione S-transferase placental form (GST-pi) was immunohistochemically analyzed in 100 cases of human stomach carcinoma of various histological types and compared with the content in the stomach mucosa of the human fetus, infant and adult. High levels of GST-pi content were demonstrated in all stomach carcinomas except for signet ring cell carcinomas. High levels were also present in surface mucous cells and glandular cells of the stomach from a fetus aged 18 weeks, whereas only the parietal cells of fundic glands in the adult stomach showed slight staining for GST-pi. These results indicate that the phenotypic expression of GST-pi in human stomach carcinoma is oncofetal in character.

Adenocarcinoma↗

Retarded growth of the suprachiasmatic nucleus and pineal body in dw and lit dwarf mice.

The suprachiasmatic nucleus (SCN) and the pineal body in 3 types of inherited hormone-deficient mice, the dw, lit and hyt mice were examined by morphological, morphometric and biochemical techniques. In the dw and lit mice the SCN was underdeveloped. In the ventral part of the SCN, where most of the retinal fibers appeared to terminate, both cell number and cell size were decreased, although the size of the SCN was unaltered. In addition, the pineal bodies of both mice were morphologically underdeveloped and showed low levels of N-acetyltransferase activity. In contrast, the hyt SCN was comparable to the normal controls in every respect. The hyt pineal was well developed and showed levels of enzyme activity comparable to the controls. However, in all the deficient mice, the optic nerve appeared to be normal in morphological and biochemical studies. These results suggest that the underdevelopment of the pineal body, the reduced levels of spontaneous locomotion and the indistinct diurnal periodicity of the dw and lit mice might be related to the retarded neuronal growth of the SCN, and that growth hormone likely is indispensable for the development of the SCN.

Animals↗

Spermatogenesis in Snell dwarf, little and congenitally hypothyroid mice.

The status of spermatogenesis in Snell dwarf, little and congenitally hypothyroid mice was studied. In all of these mice with a hormone deficiency the seminiferous tubules were smaller in size and contained fewer spermatogonia, spermatocytes, spermatids and spermatozoa than did those of normal control mice. There was no substantial difference in the Johnsen score between the hormone-deficient mice and normal control mice, but the former had underdeveloped seminiferous tubules with a corresponding paucity of germ cells, which may be partly responsible for the infertility of these mice. In the present study, growth hormone and thyroxine were administered separately to growth hormone-deficient and thyroxine-deficient mice, respectively. Such replacement therapy brought about an increase in cell counts of the seminiferous tubules and in sperm counts in both groups.

Animals↗

Stimulatory effects of growth hormone and thyroxine on the concentration of gangliosides in the Snell dwarf cerebrum.

The concentration of gangliosides in the Snell dwarf mouse cerebrum was monitored from postnatal day 5 to day 40. In the dwarf cerebrum, the concentration of total gangliosides increased up to postnatal day 20 and then stopped, whereas in the control cerebrum, it continued to increase up to postnatal day 40. At postnatal day 40, the ganglioside level in the dwarf cerebrum was 70% of that in the control cerebrum. Among the ganglioside species, the concentrations of GM4, GM2, GM1, GD1a, GD3, GD1b, GT1b, and GQ1b were significantly lower in the dwarf cerebrum than in the controls at postnatal day 40. The reduced concentrations of ganglioside species GM2, GD1a, GD3, GD1b, and GQ1b were completely restored by administration of bovine growth hormone (GH) during the first 20 days of postnatal life. The reduced concentration of the GM1 and GM4 species were most efficiently restored by administration of bovine GH plus thyroxine (T4) during the second 20 days of postnatal life. These results indicate that the lower ganglioside concentrations in the dwarf cerebrum can be elevated by hormone therapy and that there exist distinct GH and T4 actions on the enzymes participating in ganglioside metabolism.

Animals↗

An immunocytochemical and electron microscopic study of the hyt mouse anterior pituitary gland.

The hyt mutant mouse used in this study has a hypoplastic thyroid gland and is characterized by retarded somatic growth, very low to undetectable levels of plasma thyroxine (T4), and increased levels of plasma thyroid-stimulating hormone (TSH). This congenital hypothyroid mouse is therefore an ideal model for studying the effects of thyroid hypofunction on the adenohypophysis. The anterior pituitary of the hyt mouse appeared less granular than that of the normal control when viewed by light microscopy, owing to a decrease in the population of somatotrophs. Many cells, in various stages of transformation into 'thyroidectomy cells', were recognized by the appearance of the characteristic granules and dilated rough endoplasmic reticulum. In some cases, the enlarged rough endoplasmic reticulum also contained spherical electron-dense secretory granules. In addition there were many cells undergoing mitosis and these were identified as thyrotrophs by their characteristic granules. Administration of T4 during the first 40 days of life prevented the abnormal changes in the hyt anterior pituitary. A reduction in immunoreactive thyrotrophin-releasing hormone (TRH) levels was seen in the median eminence of the hyt mouse. Treatment with T4 restored this to normal, suggesting that the reduced TRH content of the hypothalamus of the mutant mouse may be due to T4 deprivation.

Animals↗

[A study of the antineoplastic activity of K18].

K18 is a new drug produced by a combination of Melphalan and human immunoglobulin. K18 produced an inhibitory effect on the proliferation of human gastric and colon cancer transplanted in to nude mice. Also, combination effects of K18 with MMC and 5-FU were recognized in the same system. In a study of distribution after K18 administration, the accumulation and retention of this drug in the tumor region were observed. In the case of Melphalan administration, these phenomena were not observed. The antitumor activity of tumor homogenate was evaluated using a colony-forming assay with KB cells. As to the Melphalan-treated group, a four-hour homogenate reduced the number of colonies but a 48-h one did not. In the K18-treated group, the four-hour homogenate decreased the number slightly and the decrease became obvious with 48-h homogenate. In cell cycle analysis using K18 or Melphalan administration, gathering of S-phase cells was observed, but these changes appeared later with K18 than with Melphalan. This result showed that the effect of K18 was produced by the alkylating activity of Melphalan which was combined with immunoglobulin. For clinical application, K18 was administered to cancer patients at a dose of 60-90 mg every day. Two cases of good response were achieved. No side effect was observed. This remarkable efficacy and low degree of side effects in clinical application is probably due to the higher affinity and accumulation of K18 in the tumor region. K18 is a useful new drug for clinical application alone, or in combination with other chemotherapeutic drugs.

Animals↗