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Biomedical subjects

T Sugisaki

Publications and source records attributed to T Sugisaki.

At least 55 records · Page 3Linked to original sources

Stimulatory effects of exogenous thyroid hormone and growth hormone on sn-glycerol-3-phosphate dehydrogenase activity in the genetic-hypothyroid mutant mouse cerebellum: restricted to the second 20 days of postnatal life.

We recently reported that by postnatal day 40 the activity of sn-glycerol-3-phosphate dehydrogenase (GPDH) was significantly depressed in the cerebellum of genetic-hypothyroid mutant mice. This mutant mouse-GPDH combination was used in the present study to define the critical time period during which thyroid hormone (T4) and growth hormone (GH) are essential for maturation of Bergmann glial cells. Our findings are that (a) induction of GPDH activity in the Bergmann glial cell is dependent on T4, (b) T4 is most effective when administered during the second 20 days of postnatal life, (c) the effect of GH on GPDH activity is complementary to or synergistic with that of T4, and (d) Bergmann glial cells and radial glial fibers of the mutant mice contain immunoreactive GPDH following various hormonal treatments. These results suggest that T4 is indispensable for the maturation of Bergmann glial cells.

Animals↗

Induction of glomerular injury by singlet oxygen.

The role of the reactive oxygen species (ROS) in the induction of tissue injury has been well documented. Regarding glomerular injury, the focus of past studies has been on superoxide, hydrogen peroxide, hydroxyl radical and C10-. However, whether singlet oxygen, an exceptionally reactive oxygen metabolite, may cause glomerular lesions has not been investigated. In the present study we documented the effects of locally generated singlet oxygen in the kidney. To generate singlet oxygen, kidneys were perfused with the pigment pheophorbide a, which was followed by exposure to light. One hour after irradiation, severe morphological damage of the glomerular cell had developed. Extensive deposits of fibrin and accumulation of platelets were seen in the glomerular capillary lumina. By contrast, kidneys not exposed to light showed no, or only minimal, abnormalities. Glomerular injury was not inhibited by pretreatment with superoxide dismutase. These results suggest that singlet oxygen produced by pheophorbide a by photodynamic reaction leads to tissue injury in vivo.

Animals↗

[Involvement of allergic mechanism in minimal change nephrotic syndrome (MCNS)].

In this study we evaluated the involvement of allergic mechanisms in patients with adult onset MCNS (17 cases) by measuring serum IgE levels and RAST scores to house dust 1 (H.D.1), house dust 2 (H.D.2), Dermatophagoides farinae (D.f.), Dermatophagoides ptenonyssinus (D.p.). Out of the 17 cases, three cases showed high levels of IgE (more than 1000 IU/ml) and the mean level of serum IgE was 877 IU/ml before treatment. All cases were treated with steroid and/or cyclophosphamide. After the treatment, all cases returned to remission. The level of IgE decreased to the normal range in four out of seven cases which had shown high levels of IgE before treatment. RAST was carried out on seven of the 17 cases. RAST scores for D.f. and D.f. were found to be positive in three cases, but these became negative in two cases after treatment. In five cases relapsed, the all cases showed to have the increased level of serum IgE and two of four cases which were examined RAST score showed to have the increased RAST score for D.f. and D.p. Thus, the data indicated that allergic mechanism, especially against D.f. and D.p. antigen, seemed to play one of the factors in the pathogenesis of MCNS.

Adolescent↗

[Effect of exercise on rats with renal injury].

Effect of exercise on rats with renal injury was studied. Nephritis was induced in rats by injection of anti-GBM antibody followed by ligation of a branch of the left renal artery after nephrectomy of the right kidney. Moderate daily treadmill exercise was forced on these experimental rats for ten weeks. Sedentary nephritic rats that received the same treatment described above served as controls. The sedentary nephritic rats suffered progressively increasing proteinuria during the time course of the experiment, whereas the nephritic rats with daily treadmill exercise experienced less proteinuria. Mild proteinuria was induced by daily treadmill exercise forced on non-nephritic rats that had received only nephrectomy of the right kidney, but no NTS injection. Light microscopy and immunofluorescence microscopy revealed severe glomerular injury in the sedentary nephritic rats, however, less glomerular injury was seen in nephritic rats with treadmill exercise. Serum cholesterol level was higher in the sedentary rats than in the rats with daily treadmill exercise. The results suggest that daily exercise by nephritic rats will not aggravate renal injury.

Animals↗

Composition of immune deposits present in glomeruli of NZB/W F1 mice.

This paper describes the results of experiments designed to investigate the composition of immune complexes present, in the form of immune deposits, in glomeruli of NZB/NZW F1 mice. Granular deposits of mouse IgG were present along the glomerular capillary walls of 6- to 12-month-old mice. Disappearance of mouse IgG from glomerular deposits, indicating a dissociation of immune complexes, was observed following incubation of kidney sections with an excess of mouse IgG, mouse Fc fragments, rat IgG, and rat Fc fragments, but not with human and rabbit Cohn fraction-II (FII), DNA, nucleohistone, and PBS. Antinuclear antibody activity in mouse sera or in glomerular eluates was removed by absorption with mouse IgG or mouse Fc fragments, rat IgG or rat Fc fragments, DNA, and nucleo-histone, but not by absorption with human or rabbit FII. These results suggest that the IgG antinuclear antibodies present in the sera and in glomerular deposits possess rheumatoid factor (RF) activity. In other experiments, kidney sections were incubated with various concentrations of pepsin, which digests the Fc portion of the IgG. After digestion, the sections were washed and stained for mouse IgG, IgG F(ab')2, and IgG Fc. At concentration of 10 micrograms/ml, pepsin completely removed IgG and IgG Fc, whereas faint IgG F(ab')2 deposits persisted in glomerular deposits. At the concentration of 1 microgram/ml, deposits of mouse IgG, F(ab')2, and Fc persisted, while F(ab')2 was observed bound to nuclei of glomerular cells. At the pepsin concentration of 0.1 microgram/ml or 0.01 microgram/ml, IgG F(ab')2 was bound to the nuclei of glomerular and tubular cells, indicating that the digestion of the Fc portion of IgG had released F(ab')2 with nuclear reactivity from glomerular deposits. The solubilization of mouse IgG from glomerular immune deposits with mouse IgG and the demonstration that pepsin digestion releases mouse F(ab')2 with nuclear reactivity are consistent with the interpretation that the immune deposits present in glomeruli of NZB/NZW F1 mice contain complexes formed by antinuclear IgG and IgG RF. These two antibodies probably cross-react and form multilayer aggregates which contribute to the formation of immune deposits.

Animals↗

The lowering effect of probucol on plasma lipoprotein and proteinuria in puromycin aminonucleoside-induced nephrotic rats.

Hyperlipidemia associated with nephrotic syndrome was treated with probucol and the changes in plasma lipoprotein lipid concentration and urinary protein excretion were examined in puromycin aminonucleoside-induced nephrotic rats. Rats made nephrotic exhibited severe hyperlipidemia with increases in all major lipoprotein fractions. Probucol treatment of nephrotic rats significantly lowered plasma triglyceride (TG), cholesterol (Ch) phospholipid (PL) and apoprotein B associated with very-low-density and low-density lipoprotein and Ch and PL in high-density lipoprotein (HDL). Malondialdehyde (MDA) associated with the lipoproteins was significantly elevated in nephrotic rats and probucol treatment also lowered MDA concentration in all major lipoproteins. In control rats probucol moderately, but significantly, reduced plasma TG and HDL-Ch concentrations. Proteinuria associated with nephrosis was decreased significantly by treatment with probucol. Probucol treatment did not affect blood urea nitrogen and plasma creatinine levels. A significant positive correlation existed between the amount of protein excreted in urine and the plasma lipid concentrations in all nephrotic rats, suggesting that the hypolipidemic effect of probucol may attenuate proteinuria associated with nephrosis. These results suggest that probucol may be a favorable treatment for hyperlipidemia associated with nephrotic syndrome.

Animals↗

Analysis of ultrastructural immune deposits in passive heymann nephritis by double-staining methods with electron microscopy.

In this study, we located and quantitated the ultrastructural glomerulus-bound immunoglobulins of passive Heymann nephritis from 10 min through 64 days using the double immunogold staining method. At the early stage (10 min to 21 days), rabbit IgG was found predominantly comparing rat IgG. With time (from 21 days to 32 days), rat IgG increased, although rabbit IgG was almost the same as at the early stage. At the late stage (64 days), rat IgG was predominantly found in all of the dense deposits on the glomerular basement membrane, whereas rabbit IgG was decreased. Thus, the double staining method was useful to analyze the composition of the immune complex and also to elucidate the immunopathogenesis of immune complex-mediated glomerulonephritis.

Animals↗

Genetic hypothyroid mice: normal cerebellar morphology but altered glycerol-3-phosphate dehydrogenase in Bergmann glia.

The present study was undertaken to investigate the effects of thyroid deficiency on cerebellar development with mouse endocrine genetic models. Four types of mutant mice, the growth hormone- and thyroid hormone-deficient Snell dwarf mouse (dw/dw), the growth hormone-deficient little mouse (lit/lit), the primary hypothyroid mouse (hyt/hyt), and the congenital genital goiter mouse (cog/cog) were analyzed for expression of the glial enzyme marker glycerol-3-phosphate dehydrogenase (GPDH) and several other marker proteins. GPDH expression, as determined by enzyme activity and Northern blot analysis, was reduced by about 50% in the cerebellum and brainstem of the three hypothyroid mutant mice. No reduced expression was found in any region of the brain of the growth hormone-deficient lit/lit mutant. Visualization of GPDH by immunohistology showed that the immunoreactive enzyme was strikingly reduced in the Bergmann glial cells of dw/dw, hyt/hyt, and cog/cog mutant mice, particularly in the radial glial processes. To evaluate the specificity of the effect on GPDH expression, we also examined the expression of the glial cell-specific S-100 protein by immunohistology. In all mutant cerebella, both the intensity and pattern of staining of the Bergmann glial cells were indistinguishable from that of normal controls, suggesting that the Bergmann glial cells are morphologically normal in the hypothyroid mice. The morphology of the Purkinje cell neurons was similarly visualized by immunohistology using an antiserum specific for the microtubule-associated proteins. Surprisingly, the morphology of the Purkinje cell dendritic arborization also appeared unaltered in the hypothyroid mice. The results suggest that the morphological development of the mouse cerebellum is relatively unaffected by hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Two cases of renovascular hypertension detected by 2-D Doppler method].

Renovascular hypertension is most frequent causes of secondary hypertension. Although angiography of renal artery is reliable procedure for the diagnosis of the renovascular hypertension, it is expensive and invasive. We report two cases which become possible to make diagnosis of the renovascular hypertension by measurement of velocity of segmental or interlobar artery using 2-D color Doppler method. Case 1: 39 year-old male was hospitalized because of hypertension (200/130 mmHg). Ccr was 82 ml/min. 2-D Doppler test demonstrated that the Vmax, the Vmin and the Vmin/Vmax of the right segmental artery were 40 cm/sec., 24 cm/sec. and 0.60, respectively. The Vmax, the Vmin, and the Vmin/Vmax of the left segmental artery were 42 cm/sec., 22 cm/sec. and 0.52, respectively. Renal angiography shows right renovascular stenosis. After percutaneous transluminal angioplasty, the blood pressure became normal and Vmin/Vmax ratio of the right segmental artery was down to 0.52. Case 2: 46 year-old male was hospitalized because of chronic renal failure (Ccr: 14.6 ml/min) and uncontrollable hypertension. 2-D Doppler test demonstrated that the Vmax, the Vmin, the Vmin/Vmax ratio and the acceleration of the right segmental artery were 10 cm/sec., 6 cm/sec., 0.62 and 1.7 m/sec.2, respectively. The Vmax, the Vmin, the Vmin/Vmax ratio and the acceleration of the left interlobar artery were 8 cm/sec., 5 cm/sec., 0.63 and 0.8 m/sec.2, respectively. Renal angiography shows bilateral renovascular stenosis. Thus, the elevated value of Vmin/Vmax ratio (over 0.6) (mean value: 0.43 +/- 0.08, when Ccr is over 70 ml/min, whereas 0.32 +/- 0.11, when Ccr is under 30 ml/min) and decreased acceleration (under 2.0 m/sec. 2) of the segmental or the interlobar artery seems to be helpful for the diagnosis of renovascular hypertension.

Adult↗

Factors contributing to cerebral hypomyelination in the growth hormone-deficient little mouse.

We attempted to delineate the events leading to hypomyelination in the brain of the little mouse, a promising murine model of isolated growth hormone deficiency. At 20 days of age, the mutant mouse brain weighed less than its normal counterpart, and this difference in brain weight persisted. Increase in CNPase activity was found to be suppressed in the cerebrum throughout the developmental stage, but not in the other parts of the brain. Differences in cerebral DNA content between the little and normal mice first became apparent on the 10th day of age. Thereafter, the rate of increase in the little brain consistently lagged behind the normal. [3H]Thymidine incorporation into the DNA fraction in vivo on the 7th day of age, when glial cell proliferation in the normal cerebrum is most active, was approximately half that of the controls in all parts of the little brain. These findings indicate that the hypomyelination of the mutant cerebrum might result from reduced oligodendroglial proliferation due to growth hormone deficiency.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

[Clinical signification of localization of S protein and late components in the skin from lupus patients].

We studied frozen tissue of lesional skin and normal-appearing skin from SLE patients and DLE patients by immunofluorescence. S-protein and late components (C5, C7, C9) were localized at the dermal-epidermal junction of the lesional skin from SLE and DLE patients. All specimens of normal-appearing skin from patients with SLE were free of deposits of S-protein and late components. These results suggest that late components may play a role in the development of skin lesions of SLE and DLE.

Adult↗

Electrocardiogram studies on cancer patients treated with OK-432, a streptococcal preparation with potent biological response modifier activities.

The present study was performed to see if OK-432, a useful anticancer agent with potent biological response modifier activities, induces effects on heart due to its nature as a streptococcal preparation. Examination of electrocardiograms of cancer patients treated with a variety of doses and routes of OK-432 has revealed that none of 266 patients examined showed any significant change in electrocardiograms (ECGs) after OK-432 treatments, regardless of their pretreatment heart conditions (normal or abnormal ECGs). Furthermore, these patients did not develop any detectable antibodies against heart muscle, either in serum or deposited on heart tissue. Experimentally, antibodies reactive with human heart tissue became detectable in the sera of rabbits immunized with streptococci in complete Freund's adjuvant, confirming the previous reports. However, the repeated injections of OK-432 without the adjuvant did not induce any detectable antibodies. These results indicate that OK-432 can be used for treating cancer patients with little fear of possible side effects on the heart.

Adult↗

Generation of oxygen radicals and formation of fibrin thrombi in glomerular capillaries of rats with nephrotoxic nephritis.

This paper describes the results of experiments designed to investigate the role of oxygen radicals in the pathogenesis of rat experimental glomerulonephritis. Generation of oxygen radicals was induced by phorbol ester in rats with Masugi nephritis, aminonucleoside nephrosis and streptozotocin-induced diabetes mellitus. Marked formation of fibrin thrombi was observed in the glomerular capillaries during the heterologous phase of Masugi nephritis, but not during the autologous phase. Induction of fibrin thrombi was also seen in nephrotic rats which had received the aminonucleoside, puromycin, but not in diabetic rats. These results suggest that in Masugi nephritis, oxygen radicals may be related to the formation of fibrin thrombi. Neutrophils seem to be of importance in the pathogenesis of such lesions.

Animals↗

Restoration of microcephalic cerebrum with hypomyelination in the growth hormone-deficient mouse (lit): stimulatory effects of GH restricted to the first 20 days of postnatal life.

We administered bovine growth hormone to the Little (lit), a promising model of isolated growth hormone deficiency, during the first and second 20 days after birth. Positive results were obtained only when bovine growth hormone was given during the first 20 days of postnatal life. We observed a distinct increase in cerebral weight, DNA content, and 2',3'-cyclic nucleotide 3'-phosphohydrolase activity. The latter administration of bovine growth hormone was ineffective. These data prove that growth hormone has an independent action on cerebral development, apart from the complementary or synergistic action of thyroid hormones, and that the administration of exogenous growth hormone led to increased myelinogenesis through its stimulatory effects on glial proliferation, as evidenced by the increase in cerebral DNA content.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Reduced vasoactive intestinal polypeptide immunoreactivity in the pituitaries of hormone-deficient mutant mice.

The prolactin-producing cells of the bovine anterior pituitary were found to contain a vasoactive intestinal polypeptide (VIP) immunoreactive substance, thus suggesting a role for VIP in the regulation of prolactin release. The pituitaries of the dw and lit strains of mutant mice, congenitally deficient in prolactin-producing cells, and hyt mice, which were found to have reduced numbers of prolactin-producing cells, showed a markedly reduced VIP immunoreactivity. Hypothalamic VIP immunoreactivity, however, was found to be unchanged in the three strains of mutant mice, indicating that the high concentration of VIP in the hypothalamus does not derive from the adenohypophysis through retrograde flow. The deficiency in the mutant mice seems to be due to the lack of prolactin target cells in the pituitary.

Animals↗