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Biomedical subjects

S Mori

Publications and source records attributed to S Mori.

At least 199 records · Page 11Linked to original sources
PubMed2000

Intracavernous sinus ectopic adrenocorticotropin-secreting tumours causing therapeutic failure in transsphenoidal surgery for Cushing's disease.

BACKGROUND: The major cause of surgical failure in the treatment of Cushing's disease lies in unsuccessful identification of adenomas. In the present study, we investigated the pathogenesis of negative exploration in transsphenoidal surgery for Cushing's disease by analyzing neuro-imaging studies, endocrinological examination and selective venous sampling. METHODS: Thirty patients with ACTH-dependent Cushing's syndrome that met the endocrinological criteria for Cushing's disease were treated by transsphenoidal microsurgery. Depending on positive or negative identification of adenomas during the surgery, selective adenomectomy, partial hypophysectomy or subtotal hypophysectomy was performed. FINDINGS: All nine patients who underwent selective adenomectomy showed endocrinological remission and did not need any hormone replacement therapy. Of the 12 patients who underwent partial hypophysectomy, 11 showed normalization of hypercortisolism but seven needed permanent replacement of hydrocortisone. Four patients underwent subtotal hypophysectomy because no adenoma could be identified in spite of detailed exploration, and three of them showed remission but with permanent requirements of hydrocortisone and other pituitary hormones. Five patients, whose hypercortisolism persisted after initial surgery, underwent total hypophysectomy as secondary transsphenoidal surgery, and only one of them showed endocrinological remission. Of the six patients with surgical failure, four were thought to be rare cases in whom the ACTH-secreting tumours may have occurred ectopically in the cavernous sinus without direct contact with the pituitary gland. Endocrinologically, these four patients showed a low or no response to corticotropin releasing hormone (CRH) stimulation, and for three of them, radiation therapy to the sellar region including the cavernous sinus was effective for persistent hypercortisolemia. INTERPRETATION: Recognition of an ectopic intracavernous sinus ACTH-secreting tumour as a pathological entity for Cushing's disease may not only enhance the diagnostic accuracy but also be important for determining the optimal surgical mode for persistent Cushing's disease.

Adenoma↗
PubMed2000

Marked decrease in plasma apolipoprotein A-I and high density lipoprotein-cholesterol in a case with Werner syndrome.

The patient was a 39-year-old Japanese male with a body height of 160 cm and weight of 48 kg who was diagnosed as Werner syndrome of homozygote for mutation 4. His plasma total cholesterol (TC), triglycerides (TGs), high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-I (apo A-I) levels were 7.2, 2.1, 1 mmol/l and 128 mg/dl, respectively. During the clinical course of treatment of this patient, his plasma levels of HDL-C and apo A-I declined drastically to levels of as low as 0.2 mmol/l and 10 mg/dl, respectively, with concurrent reciprocal increase in plasma TG levels. Plasma HDL-C, apo A-I and TG levels gradually returned to original values. Lipoprotein lipase activity and mass in post-heparin plasma were markedly low when the apo A-I and HDL-C levels decreased to 10 mg/dl and 0.21 mmol/l, respectively, and these values improved when the apo A-I and HDL-C levels returned to more normal values of 106 mg/dl and 0.94 mmol/l, respectively. The result of direct sequence of the exon 3 and 4, and the promoter region of the apo A-I gene of the patient revealed no single nucleotide changes. These results suggest that in the present patient, impaired hydrolysis of TGs in TG-rich lipoproteins, is due at least in part to a decreased LPL enzyme level, reduced the formation of nascent HDL, resulting in unusually low plasma levels of HDL-C and apo A-I.

Adult↗
PubMed2000

Increased atherogenesis in Otsuka Long-Evans Tokushima fatty rats before the onset of diabetes mellitus: association with overexpression of PDGF beta-receptors in aortic smooth muscle cells.

The mechanism of diabetic macroangiopathy was studied from the view point of phenotypic change of arterial smooth muscle cells (SMC). Otsuka Long-Evans Tokushima fatty (OLETF) rat, an animal model of non-insulin dependent diabetes mellitus (NIDDM), develops spontaneous persistent hyperglycemia after the age of 18 weeks. Medial SMC in OLETF rats expressed more platelet-derived growth factor (PDGF) beta-receptor and fibronectin at the protein level than those from control, Long-Evans Tokushima Otsuka (LETO) rats, not only after but also before the onset of diabetes mellitus. Cultured SMC from OLETF rats more strongly responded specifically to the mitogenic stimuli of PDGF-AB and PDGF-BB and also expressed PDGF beta-receptor more intensely compared with those from LETO rats. PDGF is known to be the main contributor to the intimal thickening induced by balloon catheter injury, which is one of several forms of arterial injuries. Intimal thickening of carotid arteries in OLETF rats after balloon catheter injury increased compared with that in LETO rats before the onset of diabetes mellitus. In in vitro culture system, fibronectin synthesis was stimulated by transforming growth factor-beta1(TGF-beta1) in SMC from OLETF rats, but not in those from LETO rats, suggesting that SMC from OLETF rats respond to TGF-beta1. These results indicate that overexpression of PDGF beta-receptor and fibronectin in medial SMC plays an important role in the accelerated intimal thickening before the onset of diabetes mellitus in OLETF rats.

Animals↗
PubMed2000

Decrease in triglyceride accumulation in tissues by restricted diet and improvement of diabetes in Otsuka Long-Evans Tokushima fatty rats, a non-insulin-dependent diabetes model.

With respect to the connection between triglyceride (TG) and non-insulin-dependent diabetes mellitus (NIDDM), previous reports have shown that TG accumulation in the liver and muscle is one of the causes of insulin resistance, and TG accumulation in pancreatic islets induces impairment of pancreatic beta-cell function. This experiment examined the relationship between an amelioration of hypertriglyceridemia (HTG), a decrease in TG accumulation in tissues, and an improvement of NIDDM by food restriction. In this experiment using Otsuka Long-Evans Tokushima fatty (OLETF) rats developing NIDDM and Long-Evans Tokushima Otsuka (LETO) rats as controls, sequential changes in body weight and TG content in tissue were measured and biochemical blood tests, an insulin euglycemic clamp test, and histopathologic examination of the pancreas and liver were performed. OLETF rats were allocated to a food-satiated group (satiated) or 30% food-restricted group (restricted). As a result, several findings were more evident in the restricted group than in the satiated group: (1) reductions in body weight and intraabdominal fat weight, decreases in plasma TG, insulin, and glucose levels, a decrease in the TG secretion rate, and an increase in plasma lipoprotein lipase (LPL) activity, (2) decreases in the TG content in the liver, pancreas, and muscle, (3) improvement of the glucose infusion rate (GIR), and (4) a marked reduction of TG accumulation in the liver and pancreatic islets on histopathologic examination. These results indicate that the improved HTG caused a reduction in TG accumulation in the liver and muscle, thereby improving insulin resistance. Moreover, the decrease in TG accumulation in pancreatic islets suggests an improvement of pancreatic beta-cell function.

Animals↗
PubMed2000

Comparison of human cytomegalovirus DNA polymerase activity for ganciclovir-resistant and -sensitive clinical strains.

Previously, we found that a ganciclovir (GCV)-resistant clinical human cytomegalovirus (HCMV) isolate had an amino acid substitution at codon 501 (Leu --> Phe) in the delta-region C of the DNA polymerase gene. DNA polymerases have now been (partially) purified from both the GCV-resistant and sensitive parental strains and the activity of DNA polymerase and 3'-5' exonuclease compared. With respect to DNA polymerase activity, the Michaelis constant (Km) and maximum velocity (Vmax) of the GCV-resistant strain for the DNA template were lower than those of the GCV-sensitive strain. With respect to 3'-5' exonuclease activity, the Km and Vmax of the GCV-resistant strain for the DNA substrate in the presence of ammonium sulfate were lower than those of the GCV-sensitive strain, while being similar in the absence of ammonium sulfate. Although the polymerase activity of the two strains showed almost the same sensitivity for the different polymerase inhibitors, the 3'-5' exonuclease activity of the GCV-resistant strain was more resistant to these inhibitors than that of the GCV-sensitive strain.

Antiviral Agents↗
PubMed2000

Antiviral activity of NMSO3 against respiratory syncytial virus infection in vitro and in vivo.

NMSO3, a sulfated sialyl lipid was evaluated for its efficacy against respiratory syncytial virus (RSV) and other myxovirus infections in cell culture. The median effective concentration (50% effective concentration, EC(50)) of NMSO3 against replication of the Long strain of RSV in HEp-2 cells was 0.2 and 0.32 microM by optical ELISA and the plaque reduction method, respectively. On the other hand, the corresponding values for ribavirin were 10.5 and 11.2 microM, respectively. NMSO3 showed potent activity against other laboratory strains as well as fresh clinical isolates of RSV, and the average EC(50) was similar to that for Long strain. NMSO3 exhibited minimal cytotoxicity against HEp-2, MDCK, HMV-2 and Vero cells for which the median cytotoxic concentration (CC(50)) was more than 685 microM. The selectivity index [SI=(CC(50) for HEp-2/EC(50))] of NMSO3 for RSV exceeded 2978 and that of ribavirin was 6. The EC(50) of NMSO3 against influenza virus (FluV) A (H3N2) was 23.8 by the MTT method using HMV-2 cells, and 17.8 microM by the TCID(50) method using MDCK cells. NMSO3 did not inhibit replication of influenza B virus, parainfluenza virus type 2 and canine distemper virus at 103 microM. NMSO3 inhibited RSV infection of HEp-2 cells when it was added between 0 and 1.5 h after virus infection. By a temperature shift experiment during the period of contact between the virus and cells, NMSO3 inhibited both the binding of RSV to the cells and its penetration into the cells. Prophylactic and therapeutic efficacy of NMSO3 against RSV infection in cotton rats was examined. Intraperitoneal administration of 100 mg/kg per day of NMSO3 to cotton rats from 1 day before or 1 h after to 3 days after the RSV infection, once a day every day, decreased the RSV titer in lungs to 10(-1.26) to 10(-1.63) compared to the control rats which were infected with RSV and left untreated.

Animals↗
PubMed2000

The cat neostriatum: relative distribution of cholinergic neurons versus serotonergic fibers.

The distribution of choline acetyltransferase (ChAT)-containing neurons and serotonin (5-HT)-containing nerve fibers in the cat neostriatum was investigated by use of immunohistochemical techniques. Both ChAT- and 5-HT-staining techniques were applied to alternate brain sections, thereby allowing a precise comparison of the distribution pattern of ChAT-immunopositive cells (ChAT cells) and 5-HT-immunopositive fibers (5-HT fibers). In the neostriatum, ChAT cells were strongly stained throughout their cell bodies and proximal (first-order) dendrites. The majority of them were multipolar cells with a soma diameter of 20-50 microm (long axis)x10-30 microm (short axis). In the caudate nucleus, ChAT cells were evenly and diffusely distributed except for the dorsolateral region of its rostral half, in which latter region they were distributed in loosely formed clusters. In the rostral portion of the putamen, the density of ChAT-cell distribution was like that in the medial region of the caudate nucleus. In contrast, this distribution was more dense in the caudomedial region of the putamen, adjacent to the globus pallidus. 5-HT fibers in the neostriatum were dark-stained, of quite fine diameter (<0.6 microm), and they contained small, round varicosities (diameter, usually 0.5-1.0 microm, but some >1.0 microm). Such 5-HT fibers were distributed abundantly throughout the caudate nucleus and putamen. In the rostrocaudal portion of the caudate nucleus, their density was high in its dorsal and ventral components, and low in the middle component. Throughout the putamen, 5-HT fibers were distributed homogeneously in the mediolateral and dorsoventral directions. In the caudal portion of the putamen adjacent to the globus pallidus, the 5-HT fibers had a higher density while maintaining their homogenous distribution pattern. In the two main divisions of the striatum, the so-called 'patch' (acetylcholinesterase (AChE)-poor) and 'matrix' (AChE-rich) compartments, there was a near-even distribution of 5-HT fibers and terminals. The above results suggest that the 5-HT-dominated, raphe-striatal pathway is optimally arranged for modulating the activity of both the intrinsic and the projection neurons of the neostriatum.

Acetylcholine↗
PubMed2000

Species specificity of barnacle settlement-inducing proteins.

We previously isolated a larval settlement-inducing protein complex (SIPC) from adult extracts of the barnacle, Balanus amphitrite using a nitrocellulose membrane settlement assay. In the present study, we found that the extracts of other adult barnacles, Megabalanus rosa and Balanus eburneus, also induced the settlement of B. amphitrite cyprids although the inductive activity was slightly lower than that of conspecific extracts. Furthermore, we examined reactivity to anti-SIPC antibody in adult extracts from six species of Japanese barnacles other than B. amphitrite, brine shrimp and eight marine sessile organisms besides barnacles. The results showed that all barnacles examined contained SIPC-like proteins with slightly different molecular weight, while the other animals did not react to the antibody by immunoblot analysis. These findings suggest that species specificity in settlement-inducing proteins of barnacles is not so strict, but these proteins are characteristic to barnacle species.

Animals↗
PubMed2000

Japanese population data for two STR loci, HumTPO and HumLPL.

The two short tandem repeat (STR) systems, HumTPO and HumLPL, were investigated in blood samples obtained from approximately 800 unrelated Japanese individuals living in seven geographically different areas of Japan. Neither deviation from a Hardy-Weinberg equilibrium nor significant difference between the allele distributions was found among the seven Japanese populations in the two STR systems. These findings indicate that there is a general uniformity for both the STR loci in the Japanese population.

Journal Article↗
PubMed2000

Cloning of inulin fructotransferase (DFA III-producing) gene from Arthrobacter globiformis C11-1.

A gene encoding an inulin fructotransferase (DFA III-producing) [EC 2.4.1.93] from Arthrobacter globiformis C11-1 was cloned and the nucleotide sequence was determined. The cloned fragment contained a 1353 bp open reading frame. The initiation codon was estimated to be an unusual codon, GTG. The gene encoded a signal peptide (40 amino acid residues) for secretion. The molecular mass of the native enzyme was calculated as 43,400 Da from the sequencing data. The deduced amino acid sequence of the enzyme had 74.0 % homology with that of inulin fructotransferase (DFA III-producing) from Arthrobacter sp. H65-7. It also had 45.1% homology with that of inulin fructotransferase (DFA I-producing) [EC 2.4.1.200] from Arthrobacter globiformis S14-3. The enzyme produced in the culture supernatant of an Escherichia coli clone was purified to the electrophoretically homogeneous stage. The N-terminal amino acid sequence of the cloned enzyme secreted in the broth was the same as that of the native enzyme from A. globiformis C11-1. Therefore, on this enzyme, it is estimated that the cleavage sites by the signal peptidase for secretion of A. globiformis C11-1 and E. coli JM109 are the same.

Journal Article↗
PubMed2000

Two dioxygenase genes, Ids3 and Ids2, from Hordeum vulgare are involved in the biosynthesis of mugineic acid family phytosiderophores.

A cDNA clone, Ids3 (iron deficiency-specific clone 3), was isolated from an Fe-deficient-root cDNA library of Hordeum vulgare. Ids3 encodes a protein of 339 amino acids with a calculated molecular mass of 37.7 kDa, and its amino acid sequence shows a high degree of similarity with those of plant and fungal 2-oxoglutarate-dependent dioxygenases. One aspartate and two histidine residues for ferrous Fe binding (Asp-211, His-209, His-265) and arginine and serine residues for 2-oxoglutarate binding (Arg-275, Ser-277) are conserved in the predicted amino acid sequence of Ids3. Ids3 expression was rapidly induced by Fe deficiency, and was suppressed by re-supply of Fe. Among eight graminaceous species tested, Ids3 expression was observed only in Fe-deficient roots of H. vulgare and Secale cereale. which not only secrete 2'-deoxymugineic acid (DMA), but also mugineic acid (MA) and 3-epihydroxymugineic acid (epiHMA, H. vulgare), and 3-hydroxymugineic acid (HMA, S. cereale). The Ids3 gene is encoded on the long arm of chromosome 4H of H. vulgare, which also carries the hydroxylase gene that converts DMA to MA. Moreover, the Ids2 gene, which is the plant dioxygenase with the highest homology to Ids3, is encoded on the long arm of chromosome 7H of H. vulgate, which carries the hydroxylase gene that converts MA to epiHMA. The observed expression patterns of the Ids3 and Ids2 genes strongly suggest that IDS3 is an enzyme that hydroxylates the C-2' positions of DMA and epiHDMA, while IDS2 hydroxylates the C-3 positions of MA and DMA.

Amino Acid Sequence↗
PubMed2000

Abnormalities of cAMP signaling in affective disorders: implication for pathophysiology and treatment.

OBJECTIVE: During the last decade, much attention has been given to the role of signal transduction pathways in affective disorders. This review describes the possible role of the cAMP signaling in such disorders. METHODS: Among the components of cAMP signaling, this review focuses on the cAMP-dependent phosphorylation system. We analyzed the basic components of the cAMP-dependent phosphorylation system and the preclinical evidence supporting their involvement in the biochemical action of antidepressants and mood stabilizers. The clinical data available until now, concerning the possible link between the cAMP-dependent phosphorylation system and the pathophysiology of affective disorders, are also reviewed. RESULTS: The studies herein presented demonstrated that the levels and the activity of cAMP-dependent protein kinase are altered by antidepressants and mood stabilizers. Furthermore. these medications are able to modify the phosphorylation state, as well as the levels of some of the cAMP-dependent protein kinase substrates. More recently, clinical studies have reported abnormalities in the cAMP-dependent phosphorylation system in both peripheral cells and the postmortem brain of patients with affective disorders. CONCLUSIONS: Overall, these studies support an involvement of cAMP signaling in affective disorders. The precise knowledge of the findings has the potential to improve the understanding of pharmacotherapy and to provide directions for the development of novel biochemical and genetic research strategies on the pathogenesis of affective disorders.

Antidepressive Agents↗
PubMed2000

Argyrophilic nucleolar organizer regions (AgNORs) in mucosal epithelium under experimental denture bases in rats.

The purpose of this study was to evaluate changes in the argyrophilic nucleolar organizer region (AgNOR) counts in mucosal epithelium induced by continuous or intermittent compressive pressure exerted through experimental denture bases and to examine the relationships between the AgNOR count, histopathological changes and the intensity of the pressure under denture bases. Continuous or intermittent compressive pressure exerted through the denture bases was applied to the hard palate of the molar region in rats. A morphometric analysis of AgNORs was performed in denture-supporting tissue 3 days and 1, 2, 4, 8, 12 and 20 weeks after the denture insertion. From the results of this study, it was found that non-pressure contact of the denture bases with palatal tissues did not change the AgNOR count. The AgNOR count was decreased by continuous or intermittent compressive pressure, and then recovered to almost the same level as with the non-pressure contact at 20 weeks following a decrease of the pressure. The AgNOR counts in the epithelium under the denture bases were revealed to be related to the histopathological changes in the denture-supporting tissues and the intensity of the pressure under the denture bases.

Acrylic Resins↗
PubMed2000

Expression of apoptotic signaling proteins in leukoplakia and oral lichen planus: quantitative and topographical studies.

Although the pathogenesis of leukoplakia has been unclear, carcinogenic transformation is postulated to result from alterations of apoptotic signal transduction proteins in epithelial cells. The pathogenesis of oral lichen planus (OLP) has also been unclear, but apoptotic changes of the epithelial cells in OLP have been reported. In the present study, we used a histochemical approach to describe human keratinocyte-expression of several apoptotic signaling proteins in leukoplakia, in OLP, and in normal oral mucosa as a control. Mucosal biopsies from patients with leukoplakia (n=13), OLP (n=10), and normal oral mucosa (n=9) were frozen, sectioned and immunostained with monoclonal antibodies to wild-type (wt) tumor suppressive protein p53, cyclin-dependent kinase inhibitor p21WAF1/CIP1 and the oncoproteins MDM2, and Bcl-2. Apoptosis was assessed in all cases by the TUNEL method. MDM2 and Bcl-2 expression in keratinocytes were quantitatively greater in leukoplakia than in OLP. Wt-p53 and p21WAF1/CIP1 expression was quantitatively greater in keratinocytes in OLP than in leukoplakia. Keratinocyte maturation appeared histologically normal in OLP, even though wt-p53 and p21WAF1/CIP1 were expressed in these cells. Altered keratinocyte maturation was seen in leukoplakia lesions expressing MDM2 and Bcl-2. No significant difference for the number of apoptotic epithelial cells was observed between leukoplakia and OLP, in spite of the divergent outcomes of the apoptotic signaling proteins.

Adult↗
PubMed2000

Human herpesvirus 8-associated solid lymphomas that occur in AIDS patients take anaplastic large cell morphology.

Human herpesvirus type 8 (HHV-8; Kaposi's sarcoma-associated herpesvirus) is a recently isolated human herpesvirus frequently identified in Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Here we report three cases of HHV-8-bearing solid lymphomas that occurred in AIDS patients (Cases 1-3). All three patients were homosexual men presenting extranodal masses in the lungs (Case 1) or skin (Cases 2 and 3), together with the presence of Kaposi's sarcoma (Case 1), primary effusion lymphoma (Case 2), or multicentric Castleman's disease (Case 3). These solid lymphomas exhibited anaplastic large cell morphology and expressed CD30, corresponding to the recent diagnostic criteria of anaplastic large cell lymphoma (ALCL). The chromosomal translocation t(2;5)-associated chimeric protein p80NPM/ALK was not observed in any of these cases. HHV-8 was detected in all of these cases by polymerase chain reaction, immunohistochemistry of HHV-8-encoded ORF73 protein, and in situ hybridization of T1.1. Epstein-Barr virus was detected only in Cases 2 and 3 by in situ hybridization. It is interesting that inoculation of a cell line obtained from a primary effusion lymphoma cell in Case 2 to severe combined immunodeficiency mice produced HHV-8-positive and Epstein-Barr virus-negative tumors in inoculated sites. These tumor cells exhibited phenotypes of ALCL that were identical to the subcutaneous tumor cells of this particular patient. These findings clearly show that HHV-8 can associate with solid lymphomas and that it can take anaplastic large cell morphology. Those lymphomas should be distinguished from the classical ALCL as were defined by the revised European-American classification of lymphoid neoplasms even though morphology and a part of immunophenotype mimic that of classical ALCL.

Adult↗
PubMed2000

Donor lymphocyte infusion for treatment of life-threatening respiratory syncytial virus infection following bone marrow transplantation.

We describe two patients who developed respiratory syncytial virus (RSV) pneumonia after BMT. One died of RSV pneumonia after three courses of steroid pulse therapy. Surprisingly, RSV antigen was identified in the bronchoalveolar lavage fluid (BALF) obtained post mortem. Steroid pulse therapy might have suppressed anti-RSV immunity, leading to persistent RSV infection for more than 1 month. The other patient received donor lymphocyte infusions (DLI) for relapsed plasma cell leukemia, while having active RSV pneumonia. His respiratory condition improved after DLI, and RSV antigen disappeared in BALF and nasal swabs. DLI might be effective in cases of life-threatening RSV pneumonia.

Acute Disease↗
PubMed2000

Myopericarditis caused by cyclophosphamide used to mobilize peripheral blood stem cells in a myeloma patient with renal failure.

Cyclophosphamide (CPA) is widely used for peripheral blood stem cell mobilization, and a dose adjustment of CPA in the presence of renal failure has not been suggested. However, we describe a myeloma patient with renal failure (serum creatinine 4.2 mg/dl, creatinine clearance 11.2 ml/min) receiving CPA 2 g/m2 for 2 days, who developed unexpectedly severe toxicity, including myopericarditis and prolonged myelosuppression. The serial serum concentrations of CPA metabolites were persistently much higher than those in a myeloma patient with normal renal function. We consider, therefore, that the dose of CPA should be reduced in the presence of severe renal failure when used as high-dose therapy or to mobilize peripheral blood stem cells.

Adult↗