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Biomedical subjects

S Inoue

Publications and source records attributed to S Inoue.

At least 415 records · Page 23Linked to original sources
PubMed1999

Structure-activity relationship of hydroxamate-based inhibitors on membrane-bound Fas ligand and TNF-alpha processing.

Both Fas ligand (FasL) and tumor necrosis factor-alpha (TNF-alpha) are type II integral membrane proteins. Recently, we have reported that FasL is processed to a soluble form by an unknown metalloproteinase at the cell surface and some hydroxamate matrix metalloproteinase (MMP) inhibitors inhibit the processing similar to the case observed with TNF-1alpha. We studied the inhibitory effects of various hydroxamate MMP inhibitors on FasL and TNF-alpha processing in order to characterize the processing enzymes using human FasL cDNA transfectants and LPS-stimulated THP-1 cells. It turned out that (1) the P1' group of hydroxamates was very important for the selective inhibitory activity toward TNF-alpha and FasL processing, (2) P1' 3-phenylpropyl group was favorable for the inhibition of FasL processing, and (3) P1' isobutyl and isopropyl groups were favorable for that of TNF-alpha processing. These differences in sensitivity to inhibitors imply that (1) membrane-bound FasL and TNF-alpha might be processed by distinct metalloproteinases, (2) the S1' site of FasL processing enzyme differs from that of MMP-1 and MMP-9, but appears to be similar to that of MMP-3, and (3) the S1' site of TNF-alpha processing enzyme is smaller than that of FasL processing enzyme. These results would be helpful in designing a more selective inhibitor.

Humans↗
PubMed1999

[Left ventricular relaxation in lone atrial fibrillation and atrial fibrillation with heart disease].

Atrial fibrillation with organic heart disease shows a steady value for the time constant of left ventricular isovolumetric relaxation (TC), whereas left ventricular contractility varies from beat to beat. However, there is no report on left ventricular relaxation in lone atrial fibrillation. This study assessed left ventricular relaxation in 5 patients with lone atrial fibrillation, 3 with ischemic heart disease and one with hypertrophic cardiomyopathy. Left ventricular pressure was recorded at 3 msec intervals, with a high fidelity micromanometer-tipped catheter. Maximal positive dP/dt (dP/dtmax) and TC of isovolumetric left ventricular relaxation period [P(t) = (P0-P infinity) exp (-t/TC) + P infinity] were measured as indices of left ventricular contractility and left ventricular relaxation, respectively. Correlation coefficients of dP/dtmax and TC versus the ratio of the preceding to the pre-preceding RR-interval (RR2/RR1) were calculated. A good correlation was found between dP/dtmax and RR2/RR1 in all patients (r = 0.71-0.84, p < 0.0001). No correlation between TC and RR2/RR1 was found in patients with atrial fibrillation with organic heart disease, but a good correlation was found between TC and RR2/RR1 in patients with lone atrial fibrillation (r = 0.74-0.95, p < 0.0001). The correlation between TC and RR2/RR1 is well preserved in lone atrial fibrillation. The mechanism of the variation of TC with the RR2/RR1 interval in lone atrial fibrillation may be similar to the change of TC in postextrasystolic potentiation, which is attributed to the change of intracellular Ca2+ concentration. Absence of correlation between TC and RR2/RR1 interval may indicate that left ventricular relaxation is disturbed in patients with atrial fibrillation with organic heart disease.

Aged↗
PubMed1999

[Incidence of recurrence after hepatic resection and prophylactic hepatic arterial infusion chemotherapy for liver metastases from colon cancer].

We studied recurrence after hepatic resection and prophylactic hepatic arterial infusion chemotherapy for liver metastases from colon cancer, retrospectively. Eighty-six patients underwent curative hepatic resection for liver metastases, and 41 of them received arterial infusion chemotherapy. Eight patients (20%) developed only remnant liver metastases, 6 patients (15%) had hepatic and extrahepatic recurrences, and 10 patients (24%) developed only extrahepatic recurrences. Regional therapy including hepatic resection for residual liver metastases should be indicated for recurrences after hepatic arterial infusion chemotherapy.

Antineoplastic Agents↗
PubMed1999

[Ultrasonogram of carotid artery in endoarterectomy patients].

Ultrasonograms of the carotid artery were compared with the intraoperative finding of atheroma plaque in terms of stenosis, fragility, ulceration and calcification. Soft type, intermediate type and these mixed type plaques were fragile plaques in almost all cases. All hard type plaques were tough plaques. The detection of stenosis and calcification was satisfactory, however that of ulceration was not sufficient. The stenotic lesions frequently existed in bilateral carotid arteries and the intima was easy to become thick even after the endoarterectomy. The ultrasonogram was thought to be the essential study for the carotid artery lesions.

Aged↗
PubMed1999

[Application of measuring 99mTc-MAG3 plasma clearance based on one-compartment model (MPC method) to renal transplantation].

Measurement of 99mTc-MAG3 plasma clearance (CLmag) based on one-compartment model (MPC method) was applied to renal transplantation and evaluated for the factors which might affect the calculated results, especially concerning renal depth. Correlation coefficient of CLmag between MPC method using real renal depth and Russell or Bubeck single sampling method was good (r = 0.852 or 0.876, respectively). Regression equation between MPC method and Russell method was y = 1.044x - 3.0 and was more closer to y = x than that between MPC method and Bubeck method. CLmag of MPC method calculated by estimated renal depth from the abdominal thickness was also similar to that by real renal depth. Even if the fixed renal depth, 4 cm, was applied, the coefficient and regression equation between MPC method and Russell method were r = 0.884 and y = 1.004x - 10.2. In conclusion, MPC method is applicable to the evaluation of renal transplants. Though measuring renal depth is best, calculation with fixed renal depth of 4 cm might be practically acceptable.

Adult↗
PubMed1999

Disappearance of complete atrioventricular block after chemotherapy for malignant lymphoma: a case report.

A 77-year-old man with malignant lymphoma presented with dizziness and exertional dyspnea. Physical examination revealed marked bradycardia (36 beats/min). Twelve-lead electrocardiography showed complete atrioventricular block with narrow QRS escape beats. Gallium scintigraphy demonstrated significant abnormal uptake in the heart. Transesophageal echocardiography showed a thick interatrial septum with increased echogenecity. He underwent chemotherapy under external temporary pacing with a suspected diagnosis of complete atrioventricular block secondary to cardiac invasion of malignant lymphoma. Atrioventricular conduction progressively improved and the complete atrioventricular block disappeared. He is currently well and has required no cardiac pacing for 6 months. We conclude that complete atrioventricular block may be reversible in some patients with malignant lymphoma, even in the elderly.

Aged↗
PubMed1999

Is sedation necessary for demented patients under infiltration anesthesia?

BACKGROUND: Sedation for intraoperative patients under infiltration anesthesia is often used, however, disadvantages of sedation for demented patients may sometimes exceed its advantages because some of the demented patients are already apathetic about their surroundings. The authors prospectively investigated whether sedation for alert or demented patients receiving surgery under infiltration anesthesia is useful and safe for intraoperative management. METHODS: Sixty patients undergoing irrigation and drainage of chronic subdural hematoma under infiltration anesthesia were divided into four groups. Patients in Group A were non-sedated alert patients. Patients in Group B were non-sedated demented patients. Patients in Group C were sedated alert patients. Patients in Group D were sedated demented patients. Intraoperative variables, adverse effects, and the postoperative satisfaction represented by five-point score were recorded. RESULTS: The heart rate in group A during operation was significantly faster than the control value. The postoperative satisfaction score in group A was significantly lower than any other groups. A patient in group D required a nasal airway to improve respiration during operation. CONCLUSIONS: These results suggest that there is no evidence to show that advantages of sedation for demented surgical patients under infiltration anesthesia excel the disadvantages although sedation for alert patients may be an effective and rational conduct in intraoperative management.

Aged↗
PubMed1999

[Accuracy of clinical prediction of survival for terminally ill cancer patients].

Accurate estimation of survival is vital for effective palliative care. To verify the value of clinical prediction of survival (CPS), a prospective study was performed on 150 terminally ill cancer patients. The CPS was highly correlated with actual survival (AS), but the accuracy was not significantly superior to the prediction by performance status alone. Serious pessimistic error, defined as AS was at least 28 days and twice as long as CPS, was recognized in 13%, while serious optimistic error, defined as AS was less than 28 days and half as long as CPS, in 15%. The frequency of serious error was not significantly different by physicians' experiences, patients' age, sex, primary disease, and metastatic locations, but was significantly higher in cases with better performance status. Also, unexpected changes resulting in death were experienced in 42% of another 186 cases. The main underlying causes were pneumonia, bleeding, heart failure, intestinal perforation, cerebrovascular disease, hepatic/renal failure, hypoglycemia, sepsis and electrolyte imbalance. Clinical prediction was not sufficiently reliable and must be further improved.

Aged↗
PubMed1998

Increased uncoupling protein-2 and -3 gene expressions in skeletal muscle of STZ-induced diabetic rats.

Streptozotocin (STZ)-induced diabetic animals are vulnerable to cold stress. Uncoupling proteins (UCPs) play an important role in regulating thermogenesis. We investigated the gene expressions of UCPs in brown adipose tissue (BAT), white adipose tissue (WAT), liver and gastrocnemius muscle of STZ-diabetic rats using Northern blot. UCP-1, -2 and -3 mRNA expressions in BAT were all remarkably lower in STZ-diabetic rats than those in control rats. Both UCP-2 and -3 gene expressions in gastrocnemius muscle were substantially elevated in STZ-diabetic rats and insulin treatment restored UCP gene expressions to normal levels. These results suggest that in STZ-diabetic rats, the overexpression of UCP-2 and UCP-3 in skeletal muscle provides a defense against hypothermogenesis caused by decreased UCPs in BAT.

Adipose Tissue, Brown↗
PubMed1998

Ultrastructure of familial amyloid polyneuropathy amyloid fibrils: examination with high-resolution electron microscopy.

The ultrastructure of familial amyloid polyneuropathy (FAP) amyloid fibrils was examined with high-resolution electron microscopy and immunolabeling. Sural nerve biopsies from FAP (Met 30) patients as well as control tissues were prepared for thin-section observations. Extracellular spaces in the vicinity of myelinated and unmyelinated peripheral nerves were found to be filled with amyloid fibrils as well as with deposits of an "amorphous" material. The fibril was composed of a surface layer and a core. The surface layer was made up of heparan sulfate proteoglycan and was externally associated with a loose assembly of 0.5- to 1-nm-wide filaments. The core was a microfibril-like structure in which amyloid P component was enclosed in a tight helical structure by chondroitin sulfate proteoglycan. Immunogold labeling showed that the peripheral fine filaments were composed of transthyretin. The dimensions of the transthyretin filament suggest that its basic unit is a modified monomer. The deposited amorphous material was a mixture of individual components of the fibril. These results suggest that the main body of FAP amyloid fibrils is similar to that of recently observed fibrils of experimental murine AA and hemodialysis-associated amyloid as well as of connective tissue microfibrils. The differences in the fibrils of these various types of amyloid are in the peripheral filaments which are composed of a protein specific to each type of amyloid.

Amyloid↗
PubMed1998

Mg2+ binding and catalytic function of sphingomyelinase from Bacillus cereus.

The modes of Mg2+ binding to SMase from Bacillus cereus were studied on the basis of the changes in the tryptophyl fluorescence intensity. This enzyme was shown to possess at least two binding sites for Mg2+ with low and high affinities. The effects of Mg2+ binding on the enzymatic activity and structural stability of the enzyme molecule were also studied. The results indicated that the binding of Mg2+ to the low-affinity site was essential for the catalysis, but was independent of the substrate binding to the enzyme. It was also indicated that the alkaline denaturation of the enzyme was partly prevented by the Mg2+ binding, whereas no significant protective effect was observed against the denaturation by urea. The pH dependence of the kinetic parameters for the hydrolysis of micellar HNP and mixed micellar SM with Triton X-100 (1:10), catalyzed by SMase from B. cereus, was studied in the presence of a large amount of Mg2+ to saturate both the low- and high-affinity sites. The pH dependence curves of the logarithm of 1/Km for these two kinds of substrates were similar in shape to each other, and showed a single transition. On the other hand, the shapes of the pH dependence curves of the logarithm of kcat for these two kinds of substrates were different from each other. The pH dependence curve for micellar HNP showed three transitions and, counting from the acidic end of the pH region, the first and third transitions having tangent lines with slopes of +1 and -1, respectively. On the other hand, the curve for mixed micellar SM with Triton X-100 showed one large transition with a slope of +1 (the first transition) and a very small transition (the third transition). On the basis of the present results and the three-dimensional structure of bovine pancreatic DNase I, which has a primary structure similar to that of B. cereus SMase, we proposed a catalytic mechanism for B. cereus SMase based on general-base catalysis.

Animals↗
PubMed1998

Expressed emotion of families and negative/depressive symptoms in schizophrenia: a cohort study in Japan.

This study investigated whether the Expressed Emotion (EE) status of families is associated with an increased risk of negative and depressive symptoms in schizophrenia. The subjects were 52 schizophrenic patients from mental hospitals in Kochi, Japan, who satisfied the DSM-III-R or ICD-9 criteria for schizophrenia. The Japanese version of the Camberwell Family Interview was administered to 73 key relatives of the patients within 2 weeks after admission. A certified rater evaluated the EE's status of each family, using an audiotaped interview and its transcript. Using cohort study design, the subjects were followed for 9 months after their discharge and were monitored for negative and depressive symptoms. Trained psychiatrists who were blind to the EE status of the patients' households administered the Brief Psychiatric Rating scale (BPRS) at discharge, and 9 months after discharge. Repeated-measures analyses of variance showed that EE effects were significant in Emotional withdrawal in all subjects, Depressive mood and Total depressive symptoms in non-relapsers. A multiple regression analyses revealed that EE's effect was significant only in Depressive mood in non-relapsers controlling confounding factors. In non-relapsers in positive symptoms, high EE families could make patients depressed. EE's effect on negative symptoms remains to be established.

Adolescent↗
PubMed1998

Molecular cloning, localization, and developmental expression of mouse brain finger protein (Bfp)/ZNF179: distribution of bfp mRNA partially coincides with the affected areas of Smith-Magenis syndrome.

Bfp (brain finger protein) is a member of the RING finger protein family, which is highly expressed in the brain. We have previously shown that one copy of the human bfp gene, mapped at 17p11.2, was actually deleted in six of six Smith-Magenis syndrome (SMS) patients. Now we have isolated the mouse bfp cDNA. Using in situ hybridization and immunohistochemistry, the distribution of mouse bfp mRNA and protein was identified especially in neural cells of the cerebral cortex, hippocampus, lateral amygdaloid nucleus, and ventromedial hypothalamus. In primary culture of the whole brain in a neonatal mouse, the Bfp protein was detected in both neuron and glial cells, and its subcellular localization was predominantly in the nucleus, but some amounts were also found in the cytoplasm. The bfp mRNA was also expressed strongly in the marginal zone of brain vesicles, optic stalk, and cartilage primordium, which are part of the critical tissues frequently involved in SMS patients, and in such tissues as nasal epithelium and primordium of follicles in a 13. 5-dpc embryo. Subsequently, its amount in the developing brain further increased during embryogenesis, reaching the highest level in the adult brain. These findings suggest a possibility that Bfp might be involved in the pathogenesis of Smith-Magenis syndrome as a regulator protein related to neural differentiation and function.

Abnormalities, Multiple↗
PubMed1998

Molecular cloning of a novel RING finger-B box-coiled coil (RBCC) protein, terf, expressed in the testis.

RING finger is a variant zinc finger motif present in a new family of proteins including transcription regulators. Here, utilizing the polymerase chain reaction with degenerate primers, we isolated a genomic DNA fragment containing the RING finger motif. Using this fragment as a probe, we have identified a novel cDNA from rat testis library. Then, the human homologue of the terf cDNA was also isolated from a testis library. This gene was designated testis RING finger protein (terf) because the corresponding transcripts were detected almost exclusively in the testis by Northern blot analysis. Both cDNAs encode an open reading frame of 477 amino acids sharing high homology (74% identity at the protein level) between two species. The terf contains an N-terminal RING finger domain, one B-box domain, middle coiled-coil domain, and a C-terminal domain, belonging to the RING finger-B box-coiled coil (RBCC) family. Several RBCC proteins, such as PML, TIF1alpha and RFP, have transformation capabilities when found in chromosomal translocations. Among the members of the RBCC family, the terf shares highest homology (40% identity at the protein level) with RFP that is expressed only in the testis in normal tissues. Structural similarity raises the possibilities that the terf gene might be also involved in carcinogenesis or cell transformation.

Amino Acid Sequence↗
PubMed1998

Identification of free deaminated sialic acid (2-keto-3-deoxy-D-glycero-D-galacto-nononic acid) in human red blood cells and its elevated expression in fetal cord red blood cells and ovarian cancer cells.

Chemical studies have shown the occurrence of the deaminated sialic acid 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN) in paired samples of blood obtained from mothers and newborns of healthy human individuals. Most of the KDN was found in red blood cells, although low levels were detected in mononuclear cells. No N-glycolylneuraminic acid was detected. Unexpectedly, nearly all of the KDN in fetal cord and matched maternal red blood cells was present as the free sugar and comparatively little occurred conjugated or as cytidine 5'-KDN phosphate. The amount of free KDN in fetal newborn red blood cells was 2.4-fold higher than in red blood cells from the mothers or from healthy nonpregnant women. Free KDN was also identified in normal human ovaries, in ovarian tumors, and in ascites cells obtained from ovarian cancer patients. Importantly, as in fetal cord red blood cells, a distinguishing feature of KDN expression in ovarian tumor cells was an elevated level of free KDN compared with normal controls. A positive correlation was found between an increase in the ratio of free KDN/N-acetylneuraminic acid in ovarian adenocarcinomas and the stage of malignancy. This was particularly evident in tumor cells isolated from the ascites fluid. The central importance of these new findings is 2-fold. First, they show that free KDN is a minor but ubiquitous sialic acid in human red blood cells and that its elevated expression in red blood cells from fetal cord blood compared with maternal red blood cells may be developmentally related to blood cell formation during embryogenesis. Second, the enhanced expression of KDN in ovarian cancer cells suggests that this sialic acid, like the alpha2,8-linked polysialic acid glycotope, may be an oncofetal antigen in these tumors and thus could be an "early warning" signal for onset of disease and/or a marker for detection of recurrence of disease. These new findings highlight the importance of elucidating the role that KDN and KDN-containing glycoconjugates may play in normal development and malignancy.

Adenocarcinoma↗
PubMed1998

Nuclear translocation and increased expression of Bax and disturbance in cell cycle progression without prominent apoptosis induced by hyperthermia.

Effects of hyperthermia at 42.5 degreesC for 6 h on cell survival, cell cycle progression, and the localization and expression levels of Bcl-2 and Bax, as well as the association between Bcl-2 and Bax in human lung cancer cells were investigated. Untreated human lung cancer cells, though immortalized, expressed Bax unlike peripheral lymphocytes with low Bax expression. Bcl-2 was localized only in the cytoplasm in all the cell lines tested, whereas Bax was localized in the cytoplasm and/or nucleus; (1) only in the nucleus in three cell lines, (2) either in the nucleus or the cytoplasm in three cell lines, (3) in both the nucleus and the cytoplasm in one cell line, and (4) only in the cytoplasm in three cell lines. Of 10 cell lines examined, 6 had a low sensitivity to hyperthermia with a viability of 50% or more, and four cell lines had a high sensitivity to hyperthermia with a viability of less than 50% regardless of cell type. In cell lines highly sensitive to hyperthermia, Bax was localized in the nucleus. Hyperthermia increased the cellular level of Bax, but not Bcl-2, and reduced the association between Bcl-2 and Bax expression in PC-10 cells. Although the Bax level increased, hyperthermia induced only mild apoptosis and caused prominent cell cycle disturbance, especially in the S and G2M phases. Thus, hyperthermia at 42.5 degreesC for 6 h had cytostatic effect as well as caused mild apoptosis. Interestingly, during 3 h of hyperthermia, Bax translocated from the cytoplasm to the nucleus, whereas Bcl-2 remained in the cytoplasm. These results raise the possibility that Bax may lose its function as the inducer of apoptosis by translocating into the nucleus or have an unknown role in the nucleus.

Apoptosis↗
PubMed1998

Promoter analysis of mouse estrogen-responsive finger protein (efp) gene: mouse efp promoter contains an E-box that is also conserved in human.

The estrogen-responsive finger protein (efp) containing a RING finger motif has been identified as an estrogen-responsive gene in human and mouse. Here, we have characterized the basal promoter region of the mouse efp gene. The promoter lacks the TATA motif, and transcription initiation sites are found at positions -38T, -64A and -73C from the translation initiation site. Deletion analysis of the 5'-flanking region using Jyg-Mc(B) mouse breast cancer cells indicates that the sequence encompassing from -139 to -1 has a basal transcription activity. This region is GC-rich in both mouse and human promoters, and the E-box is precisely matched on the sequence alignment. A mutation experiment with E-box shows that the E-box is functionally active. An electrophoretic mobility shift assay using Jyg-Mc(B) nuclear extracts shows that a transcription factor, USF-1 binds to the E-box in the mouse efp promoter. It has been shown that the E-box in the human efp promoter is indispensable for basal transcriptional activity and binds USF-1. These findings suggest that the mouse efp promoter is regulated by a similar mechanism to that of the human. In mouse, however, we have not found a negative regulatory region that is present in human promoter.

Animals↗