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Biomedical subjects

S Okuda

Publications and source records attributed to S Okuda.

At least 109 records · Page 6Linked to original sources
PubMed1995

Localization of transforming growth factor-beta and latent transforming growth factor-beta binding protein in rat kidney.

TGF-beta plays an important role in maintaining the renal histological structure, and glomerular and tubular function. TGF-beta is usually secreted in a biologically inactive or latent form with high molecular weight by normal cells. The latent form of TGF-beta is composed of three distinct components: (a) mature TGF-beta (b) TGF-beta latency associated peptide (LAP) (c) latent TGF-beta binding protein (LTBP). LTBP plays a central role in the assembly, secretion and activation of TGF-beta 1. Most cells secrete a large latent TGF-beta with LTBP, while the other cells secrete a small latent TGF-beta without LTBP. However, the precise localization of TGF-beta and LTBP in the kidney is still not known. In the present study, we used the reverse transcription in combination with polymerase chain reaction (RT-PCR) to investigate the precise localization of TGF-beta 1 and LTBP in the microdissected glomeruli, renal tubules and arterioles. Our findings showed that TGF-beta 1 mRNA was detected in all nephron segments, glomeruli, and arterioles. On the other hand, LTBP mRNA was present in the glomeruli and arterioles, while it was absent in every segment of the renal tubules. Moreover, the immunohistochemical study of LTBP showed that the LTBP protein was localized on the glomeruli and arterioles but not on the renal tubules at the same localization as LTBP mRNA. These results indicate that the tubular epithelial cells secrete the small latent TGF-beta 1, while glomerular cells secrete the large latent TGF-beta 1, suggesting that they both have different structures and thus potentially different biological functions.

Animals↗
PubMed1995

Isolation and identification of adenosine triphosphoribosyl nicotinamide adenine dinucleotidephosphate from Azotobacter vinelandii.

A novel type of pyridine nucleotide, containing two adenosine triphosphate ribose residues rather than one, was isolated from Azotobacter vinelandii strain O. The nucleotide was shown to be 2"- or 3"-(2'-phosphoadenosine-5'-diphosphoribosyl)nicotinamide adenine dinucleotide phosphate, in which 2'-phospho-5'-diphosphoadenosylribose was glycosidically linked to the NADP at position 2' or 3' of the nicotinamide mononucleotide moiety. The ATPribosylNADP did not show coenzyme activity for yeast glucose 6-phosphate dehydrogenase, nor was it cleaved by Neurospora crassa NAD(P) glycohydrolase, indicating that the biological properties conferred on the beta-NADP molecule were largely modified by the attachment of the ATP-ribose group.

Adenosine Triphosphate↗
PubMed1995

Cellular immunity in hemodialysis patients: a quantitative analysis of immune cell subsets by flow cytometry.

Immune cell subsets, when measured by two-color flow cytometry in a population of 129 hemodialysis patients, showed significant variance from normal values. Lymphopenia, decreased absolute counts, and altered percentage values of immune cells were found. Increased proportions of CD3+, T cell receptor (TCR) alpha beta + cells and CD4+ T lymphocytes were present. An abnormally high percentage of a subset of activated TCR alpha beta + cells (alpha beta + DR+) was also seen in hemodialysis patients. The proportion of B lymphocytes was found to be significantly lower as compared with controls. Relative values for TCR gamma delta+cells, both for activated (gamma delta + DR+) and nonactivated (gamma delta + DR-) subsets, as well as for CD8+ lymphocytes and natural killer cells did not vary from those of normal controls. Also, the CD4+/CD8+ ratio showed no significant change. Analysis of absolute counts of the investigated immune cell populations revealed significantly decreased numbers for the majority of subsets, as a result of the preexisting lymphocytopenia, characteristic of end-stage renal disease. We conclude that profound quantitative alterations of immune cells, including TCR+T cells subsets, exist in hemodialysis patients. These account, at least in part, for the immune dysregulation associated with chronic renal failure.

B-Lymphocyte Subsets↗
PubMed1995

Influence of a high salt diet on glomerular injury and the preventive effects of amiloride in adriamycin nephropathy.

The effects of a high salt diet on glomerular hypertrophy and sclerosis were examined in a focal glomerular sclerosis rat model. Sprague-Dawley rats were injected twice with Adriamycin (ADR, 2.5 mg/kg body weight) and then divided into 3 groups: (1) ADR rats fed a 1% sodium chloride (NaCI) diet (control ADR rats); (2) ADR rats fed an 8% NaC1 diet (ADR-NaC1 group), and (3) ADR rats fed a 10% sodium bicarbonate (NaHCO3) diet (the ADR-NaHCO3 group), and were then observed for 8 weeks. There were no differences in the blood pressure levels between the control ADR and ADR-NaC1 groups. The urinary protein excretion was significantly less in the ADR-NaC1 and ADR-NaHCO3 groups than in the control ADR group. However, a progressive increase in the blood urea nitrogen and serum creatinine associated with extensive glomerular sclerosis and hypertrophy was only observed in the ADR-NaC1 group. An increase in the glomerular diameter preceded the development of glomerulosclerosis in this group. Furthermore, a daily administration of amiloride, a Na+/H+ exchanger inhibitor, to the ADR-NaC1 rats prevented the development of glomerular hypertrophy and sclerosis. These results therefore suggest that the aggravated effect of a high salt diet on glomerular sclerosis may be related to glomerular hypertrophy which is associated with the stimulation of the Na+/H+ exchanger.

Amiloride↗
PubMed1995

[Growth factors in tubular cells].

Tubular cells are a major source of growth factors in the kidney, while the growth factors may play a crucial role for maintaining the histological structure or functions of renal tubulus. EGF, IGF-1 and HGF are important for the development of tubular segment, renal hypertrophy, regeneration after acute tubular necrosis and renal cyst formation. In contrast, TGF-beta is closely related to tubulo interstitial fibrosis. Since the tubulo interstitial lesions determine the progression or prognosis of the renal diseases, the regulation of these growth factors may be needed for the prevention of the irreversible tubular injury or for the regeneration of tubular cells.

Animals↗
PubMed1995

Matrix-associated latent TGF-beta with latent TGF-beta binding protein in the progressive process in adriamycin-induced nephropathy.

BACKGROUND: A progressive increase in latent transforming growth factor-beta (TGF-beta) secretion from diseased tissue was revealed in our previous work using adriamycin (ADR)-nephropathy (Kidney Int 45:525-36, 1994). Latent TGF-beta is composed of mature TGF-beta and latency-associated peptide (LAP) with or without latent TGF-beta-binding protein (LTBP). LTBP has been reported to contribute to either matrix-association or activation of latent TGF-beta. LTBP also seems to play a key role in the renal lesions of this model. The present study was designed to show the secretion of latent TGF-beta with LTBP and the location of LTBP in renal tissue in ADR-nephropathy. EXPERIMENTAL DESIGN: The renal cortical tissue specimens were sampled at Weeks 4, 8, and 16 after the injection of ADR or saline (control) for cortical tissue culture and immunohistology. TGF-beta in the conditioned medium was assayed by immunoprecipitation and bioassay using mink lung epithelial cells. An immunohistochemical study was performed to examine the localization of LTBP, ED-1-positive macrophages, and extracellular matrix proteins including laminin, fibronectin, and collagen type I and type III. RESULTS: A TGF-beta bioassay revealed a progressive increase in latent TGF-beta secretion from the cortex of diseased kidney. Free LTBP and LTBP-LAP complex with mature TGF-beta were immunoprecipitated by anti-LTBP Ab from the cortical culture medium. An immunohistochemical study using anti-LTBP Ab demonstrated that LTBP localization was restricted to the glomeruli and the arterioles in the control cortex. In the ADR rats at Week 4, a faint deposition of LTBP was observed in the interstitium around the glomeruli. At Week 8 or 16, LTBP was accumulated in the sclerosing glomeruli or fibrous interstitium, where ECM proteins and infiltrating ED-1-positive macrophages were intensely located. CONCLUSIONS: Our results indicated that latent TGF-beta with LTBP was localized in association with the extracellular matrix in the sclerotic and fibrotic tissue in this model. Matrix-associated latent TGF-beta with LTBP may thus play an important role in the progressive process of glomerulosclerosis and interstitial fibrosis in ADR-nephropathy.

Animals↗
PubMed1995

Ameliorative effects of tea catechins on active oxygen-related nerve cell injuries.

Active oxygen species are suggested to be concerned with various senile disorders. Tea catechins, (+)catechin (CA), (-)epicatechin (EC) and (-)epigallocatechin gallate, are polyhydroxy-fravan derivatives from tea leaves and have been proposed to possess active oxygen scavenging effect. Tea catechins protected the cultured newborn-mouse cerebral nerve cells from death induced by glucose oxidase. The protective potency of (-)epigallocatechin gallate was weaker than those of EC and CA. Learning ability of mice was assessed by a step-down-type passive avoidance test, and memory impairment of mice was achieved by intracisternal injection of glucose oxidase or cerebral ischemia induced by 10 min occlusion of the common carotid arteries. Intracisternal injection of EC improved the memory impairment induced by intracisternal glucose oxidase, and i.v. injection of CA or EC improved that induced by the cerebral ischemia. CA and EC depressed carrageenin-induced edema in rat hind paw, but (-)epigallocatechin gallate did not. These results suggest that tea catechins ameliorate the injuries or impairments induced by active oxygens through scavenging intracellular active oxygens, and might become useful for protecting human from senile disorders such as dementia.

Animals↗
PubMed1995

[Two siblings of familial amyotrophic lateral sclerosis with multisystemic degeneration characterized by mild involvement of the middle root zone of the posterior column, Clarke's nuclei and spinocerebellar tract].

The aim of this study is to clarify the clinicopathological characteristics of the multisystem degeneration seen in two male siblings with familial amyotrophic lateral sclerosis (FALS). A similar neurological disorder affected their elder sister and paternal uncle, but not their parents. The older brother (case 1) developed muscular weakness at 50 years of age and the younger brother (case 2), at 42 years of age. The duration of illness was 19 months in case 1 and 31 months in case 2. The clinical picture was the common (suspended) form in case 1 and the pseudopolyneuritic form in case 2. Pyramidal tract sign was obscure in both cases and cerebellar sign, sensory disturbance, sphincter disturbance and oculomotor palsy were not observed in either case. Neuropathological examination revealed similar findings in the two cases: 1) marked loss of lower motor neurons in the spinal anterior horn and motor nuclei of the lower brain stem in both cases, with neuronal loss of Onuf's nuclei in case 2; 2) very mild involvement in Clarke's nuclei, the dorsal and ventral spinocerebellar tracts and the middle root zone of the posterior column; 3) relatively well preserved Betz cells in the upper motor cortex with the appearance of a few macrophages, and mild changes in the pyramidal tract of the spinal cord; and 4) mild degenerative changes in the pallidoluysian system and the dentatorubral system. The most characteristic pathological findings common to both cases were the extremely mild involvement of the middle root zone of the posterior column, Clarke's nuclei and spinocerebellar tracts. The pattern of lower motor neuron system degeneration paralleled the development of clinical features. Genetic studies demonstrated no mutations in exons 1, 2 and 4 of Cu/Zn-binding superoxide dismutase gene. We emphasized the existence of mild involvement of middle root zone of posterior column, Clarke's nuclei and spinocerebellar tract in FALS with multisystemic degeneration.

Adult↗
PubMed1995

[CT and MRI: what you see and don't see].

CT and MRI have become indispensable methods for the diagnosis of stroke or the investigation for the disease. The use of these auxiliary diagnostic procedures, especially of MRI, has made possible the accurate diagnosis of lesions of the posterior cranial fossa. The flow void in MRI has made it feasible to infer severe stenosis or occlusion of the main arteries before undertaking angiography. The silent stroke or white matter abnormalities in the vicinity of the lateral ventricle observed in CT or MRI have become a serious clinical problem and these are generally considered risk factors for stroke. Obviously, CT and MRI have proven effective in this area, yet their findings do not always make it readily possible to infer the nature of cerebral arteries involved. Recently, here have been attempts to classify infarcts in the region of perforating branches of the middle cerebral artery. With the diversification of therapeutic approaches for stroke in the days to come, the effort to encourage such insight on the basis of non-invasive testing will be increasingly important.

Brain↗
PubMed1994

[Blood pressure change and syncope during leg phlebography].

Although syncope attacks such as black-out, faint consciousness, and cold sweat are sometimes experienced during leg phlebography, no study of their incidence and mechanism has been reported. We measured blood pressure noninvasively by using a Finapress with ECG monitor during overall examinations (21 cases, 33 limbs; male 8, female 13) following anamnesis. Age, sex, and past history of drug, syncope, leg phlebography, and other diseases were determined. All examinations were done in the upright position. Three cases (14.3%) and four limbs (12.1%) showed syncope attacks during leg phlebography. Syncope occurred after steps taken for the evaluation of venous return in two limbs, during infusion of contrast medium in one, and after infusion in the other. In all cases, the systolic blood pressure measurement during syncope was below 80 mmHg, and the sudden decrease of both systolic blood pressure (-83.0 +/- 22.0 mmHg) and heart rate (-29.5 +/- 5.0/min) suggested vasovagal reaction as a mechanism of syncope. Other causes of syncope including anaphylaxy, hyperventilation syndrome, seizure, and arrhythmia (except for bradycardia) were not found. There were also significant changes in blood pressure and heart rate in the nonsyncope group during leg phlebography that seemed to trigger vasovagal excitation. Premedication, contrast media, and position might be important factors and should be discussed further.

Adult↗
PubMed1994

Cytologic examination of pancreatic juice for differential diagnosis of benign and malignant mucin-producing tumors of the pancreas.

BACKGROUND: A new clinical type of pancreatic tumor, the mucin-producing tumor, has been recognized recently. However, it is not always easy to distinguish benign from malignant tumors preoperatively. In this study, three different methods of differentiating mucin-producing tumors of the pancreas were compared. METHODS: Endoscopic ultrasonography, endoscopic retrograde pancreatography, and cytologic examination of pancreatic juice were performed in 14 patients who had mucin-producing pancreatic tumors (11 carcinomas and 3 adenomas). Pancreatic juice was collected endoscopically without papillotomy. RESULTS: The sensitivity, specificity, and overall accuracy of endoscopic ultrasonography were 82%, 90%, and 79%, respectively; those of endoscopic retrograde pancreatography were 91%, 91%, and 86%; and those of cytologic examination were 91%, 100%, and 93%. CONCLUSION: Cytologic examination of pancreatic juice was the best of these three methods for differentiating benign from malignant mucin-producing pancreatic tumors.

Adenocarcinoma, Mucinous↗
PubMed1994

Diagnosis of colorectal tumors by the endoscopic Congo red-methylene blue test.

The endoscopic Congo red-methylene blue test was performed on 51 tumors of the large intestine. Results revealed that colorectal adenocarcinomas and adenomas bleached the Congo red and methylene blue sprayed over their surface and so appeared in sharp contrast to the bluish red mucosa of unaffected areas. No bleaching of the dyes was observed on the surface of non-neoplastic polyps. Moderately differentiated adenocarcinomas, submucosal or advanced cancers, and adenomas with severe atypia bleached the dyes most frequently. Thus this test facilitates early detection of colorectal tumors.

Adenocarcinoma↗
PubMed1994

Tandem mass spectrometry for characterization of unsaturated disaccharides from chondroitin sulfate, dermatan sulfate and hyaluronan.

Fast atom bombardment tandem mass spectrometry has been used in the characterization of non-, mono-, di- and trisulfated disaccharides from chondroitin sulfate, dermatan sulfate and hyaluronan. The positional isomers of the sulfate group of mono- and disulfated disaccharides were distinguished from each other by both positive- and negative-ion fast atom bombardment tandem mass spectra, which gave sufficient information characteristic of the isomers. The anomeric isomers of nonsulfated disaccharides were characterized by the technique in the positive-ion mode. This fast atom bombardment collision induced dissociation mass spectrometry/mass spectrometry technique was also applied successfully to the characterization of trisulfated disaccharide.

Carbohydrate Conformation↗
PubMed1994

Two cases of urogenital malignancies in male patients undergoing maintenance haemodialysis.

We report two cases of urogenital malignancies, prostatic cancer in a 72-year-old man and urinary bladder carcinoma in a 50-year-old man, that developed during maintenance haemodialysis. The former patient responded to hormonal therapy with diethylstilboestrol and is still alive on maintenance haemodialysis, but the latter patient did not respond to treatment, being past cure in the far advanced stage. There are few clinical symptoms suggesting the existence of urogenital malignancies in dialysis patients and screening methods such as urine cytology or roentgenology must be restricted because of extremely reduced urine volume. However, the high incidence of urogenital malignancies in such patients is well recognized. Screening examinations with ultrasonography and/or CT scan following digital rectal examination or testing for serum prostate-specific antigen should be performed at least every 6 months.

Aged↗
PubMed1994

Inhibitory effects of antihypertensive drugs on mesangial cell proliferation after anti-thymocyte serum (ATS)-induced mesangiolysis in spontaneously hypertensive rats.

The effects of antihypertensive drugs on mesangial cell proliferation were studied in spontaneously hypertensive rats (SHR) with anti-thymocyte serum (ATS)-induced glomerulo-nephritis. Rats were treated with either enalapril (Group 1), nifedipine (Group 2), or reserpine + hydrochlorothiazide + hydralazine (Group 3), or were untreated (Group 4). The animals were sacrificed 2, 4 and 7 days after ATS injection and the glomerular cell number and degree of mesangial area expansion were examined. A marked, similar decrease in glomerular nuclear cell number (NC) due to severe mesangiolysis was observed in all of the groups on day 2. Thereafter, an increase in NC reflecting mesangial cell proliferation after mesangiolysis occurred in Group 4 on days 4 and 7. In Group 1 and 2, the NC was significantly smaller than that in Group 4 on days 4 and 7, indicating suppression of mesangial cell proliferation. In Group 3, however, the number of NCs did not differ from that in Group 4 on days 4 and 7, indicating a lack of such suppression by conventional antihypertensive drugs. The degree of mesangial area expansion (MS) showed the same pattern as mesangial cell proliferation. That is, the rapid increases in MS seen in Group 4 on days 4 and 7 were apparently suppressed in Groups 1 and 2, but not in Group 3. Our in vivo observations that both an angiotensin converting enzyme (ACE) inhibitor and a calcium channel blocker suppress mesangial cell proliferation and mesangial area expansion suggest that these agents have practical implications in the treatment of mesangial proliferative glomerular diseases through the suppression of excess mesangial cell proliferation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Arachidonic acid: toxic and trophic effects on cultured hippocampal neurons.

Arachidonic acid (20:4) is a component of membrane lipids that has been implicated as a messenger both in physiological and pathophysiological processes, including ischemic injury and synaptic plasticity. In order to clarify direct trophic or toxic effects of arachidonic acid on central neurons, primary cultures of rat hippocampal neurons were exposed to arachidonic acid under chemically-defined conditions. Arachidonic acid present in the culture medium at concentrations over 5 x 10(-6) M showed profound toxicity, whereas at lower concentrations (10(-6) M) it significantly supported the survival of hippocampal neurons. These effects were not mimicked by oleic acid (18:1) or palmitic acid (16:0). The toxic action of 10(-5) M arachidonic acid was markedly and significantly prevented by a lipoxygenase inhibitor nordihydroguaiaretic acid (10(-6) M). AA861 and baicalein (each at 10(-6) M), a selective inhibitor for 5- and 12-lipoxygenase, respectively, also showed a significant protective effect, whereas cyclooxygenase inhibitor indomethacin (10(-5) M) had no effect. The toxic action was also prevented by an antioxidant alpha-tocopherol (10(-6) M), but not by superoxide dismutase (100 U/ml) or catalase (200 U/ml). The trophic effect of 10(-6) M arachidonic acid was not suppressed by the treatments listed above. At lower concentrations (10(-7)-10(-6) M), arachidonic acid promoted neurite elongation, which was not inhibited by nordihydroguaiaretic acid or indomethacin. Overall, arachidonic acid has both trophic and toxic actions on cultured hippocampal neurons, part of which involves its metabolism by lipoxygenases. The mechanisms and the physiological significance of these effects are discussed.

Animals↗