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Biomedical subjects

H Katagiri

Publications and source records attributed to H Katagiri.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Monitoring of plasma concentration of low molecular weight heparin--comparative evaluation with chromogenic and clotting assays].

The efficacy of low molecular weight heparin (LMWH) in the treatment of thrombosis is increasing interest in its clinical potential. However, the measurement of in vitro anticoagulant activities of LMWH has been controversial for its appropriate clinical dose. The study has been carried out to compare two methods for measurement of anti-factor Xa activity of LMWH (fragmin). One is 'HEPTEST' recently developed as a new clotting assay method and the other is an authentic chromogenic assay using S-2222. The coefficients of variation in intra-assay were 1.87-2.75% in clotting assay, and 0.61-0.89% in chromogenic assay. The sensitivity to detect minimum concentration was 0.02 IU/ml in clotting assay, and 0.04 IU/ml in chromogenic assay. The correlation between two methods was good (r = 0.935), whereas clotting assay has been revealed as a very simple rapid method. LMWH (fragmin) with 75 IU/kg/day was administered to three patients with coagulopathy; two disseminated intravascular coagulopathy (DIC) and one veno-occlusive disease (VOD). Hemostatic abnormalities have been improved serially after treatment in all patients. During treatment, the plasma concentration of LMWH was measured, showing 0.05-0.23 IU/ml in DIC and 0.02-0.10 IU/ml in VOD. These results suggest that measurement of plasma concentration of LMWH using the easy and rapid clotting assay method as 'HEPTEST' is clinically useful for monitoring to detect clinical dose of LMWH for DIC and thrombosis.

Anticoagulants↗
PubMed1998

Clinical results of nonsurgical treatment for spinal metastases.

PURPOSE: In contrast with many analyses of surgical treatment for spinal metastases, there have been only a few recent well-documented publications assessing nonsurgical treatment. This paper is a study of the outcome of nonsurgical therapy for metastatic tumors of the spine. METHODS AND MATERIALS: One hundred and one patients with spinal metastases were treated with radiation therapy and/or chemotherapy without surgical intervention between 1990 and 1995, in prospective analysis, and had follow-up for more than 24 months. This study included 59 men and 42 women with a mean age of 61 years (range: 14 to 81). Mean follow-up periods were 11 months for patients dying of the disease and 53 months for the survivors. Neurological status, pain relief, functional improvement, and cumulative survival rate were assessed. RESULTS: Of the total treated, 67 patients (66%) were evaluated as being neurologically stable or improved after treatment. Pain relief was achieved in 67%, and 64% showed functional improvement. Primary lesion responsiveness to nonsurgical therapy influenced the survival, neurological recovery, pain control, and function. Neurological findings before therapy were useful in predicting ambulatory status after treatment. CONCLUSION: Nonsurgical treatment was often successful when primary tumors had responsiveness to radiation therapy and/or chemotherapy. We found this to be evident even when neurological deficits were found, particularly in lumbar spines. Spinal metastases of tumors with less responsiveness, unless patients were neurologically intact, responded poorly to therapy. Most of the patients who were successfully treated enjoyed relief lasting nearly until death. Their functional ability was limited by general debility, rather than by local tumor regeneration.

Adolescent↗
PubMed1998

Facilitation of long-term potentiation and memory in mice lacking nociceptin receptors.

The peptide nociceptin (also named orphanin FQ) acts in the brain to produce various pharmacological effects, including hyperalgesia and hypolocomotion. The nociceptin receptor uses guanine-nucleotide-binding proteins to mediate the inhibition of adenylyl cyclase, the activation of potassium channels and inhibition of calcium channels. It has been shown using knock-out mice that the nociceptin receptor is not required for regulation of nociceptive responses or locomotion activity, but modulates the auditory function. Here we show that mice lacking the nociceptin receptor possess greater learning ability and have better memory than control mice. Histological analysis revealed the expression of both the nociceptin precursor and the nociceptin receptor in the hippocampus, thought to take part in aspects of learning and memory. Moreover, the receptor-deficient mice showed larger long-term potentiation in the hippocampal CA1 region than control mice, without apparent changes in presynaptic or postsynaptic electrophysiological properties. These results show that the loss of the nociceptin receptor results in a gain-of-function mutation in both the memory process and the long-term potentiation mechanism in CA1, perhaps as a result of altered intracellular signal transduction systems in neurons.

Animals↗
PubMed1998

Role of JTT-501, a new insulin sensitiser, in restoring impaired GLUT4 translocation in adipocytes of rats fed a high fat diet.

JTT-501 is an insulin-sensitising compound with an isoxazolidinedione rather than a thiazolidionedione structure. Sprague-Dawley rats fed a high fat diet for 2 weeks were used as an animal model of insulin resistance, and JTT-501 was administered for the final week of the diet. An euglycaemic glucose clamp study showed that the glucose infusion rate (GIR) required to maintain euglycaemia was 57% lower in rats fed a high fat diet than in control rats, and that JTT-501 treatment restored the reduction in GIR produced by the high fat diet. To explain the mechanisms underlying the effects of a high fat diet and JTT-501 treatment, epididymal fat pads were excised and used in the analysis of insulin action. The high fat diet caused: (1) a 58% decrease in insulin receptor substrate-1 (IRS-1) content with a 58% decrease in IRS-1 tyrosine phosphorylation; (2) reductions of 56% and 73% respectively in insulin-induced maximal PI 3-kinase activation in anti-phosphotyrosine and anti-IRS-1 antibody immunoprecipitates; (3) a 46% reduction in the glucose transporter protein, GLUT4 content and, consequently, (4) severely impaired insulin-induced GLUT4 translocation to the plasma membrane and glucose uptake in adipocytes. JTT-501 treatment restored appreciably the protein content and tyrosine phosphorylation level of IRS-1. Insulin-stimulated PI 3-kinase activation was also restored in anti-phosphotyrosine and anti-IRS-1 antibody immunoprecipitates. As reflected by these improvements in insulin signalling, JTT-501 treatment improved considerably insulin-induced GLUT4 translocation to the plasma membrane as well as insulin-induced glucose uptake. However, JTT-501 had no effect on the decrease in GLUT4 content produced by the high fat diet. These observations suggest that JTT-501 enhances insulin signalling and may be effective in reducing insulin resistance.

Adipocytes↗
PubMed1998

Diaphragm function during sighs in awake dogs after laparotomy.

Pulmonary complications after upper abdominal surgery are usually ascribed to temporary postoperative impairment of diaphragm function, which may not originate from intrinsic, structural injury but from reflex inhibition of diaphragm contractility. Spontaneous breathing is interrupted periodically by sighs, even after upper abdominal surgery. If postoperative dysfunction of the diaphragm arises from a reflexic inhibition, then the sigh should temporarily override the inhibition and restore normal diaphragm function. We implanted sonomicrometer and electromyogram transducers chronically in six dogs by laparotomy, then directly measured length, shortening, and electromyogram activity of costal and crural diaphragm segments, parasternal intercostal, and transversus abdominis muscles an average of 8.7 (range, 1-16) d later during resting tidal breathing and sighs. In each animal we analyzed a sequence of breaths, including a sigh, when costal or crural diaphragm contractility was abnormal. With each sigh, the shape and amplitude of costal and crural diaphragm segmental shortening improved abruptly, from 0.9 and 1.4% of baseline length (% LBL) during resting breathing to 12.1 and 11.1% LBL, respectively, during sighs. The sighs were compared to CO2-stimulated breaths of equivalent tidal volume, which did not show either pattern or amplitude of shortening equivalent to sighs. We conclude that diaphragm dysfunction after laparotomy arises from a reflex inhibition, which is overridden abruptly to return diaphragm function briefly to normal during each spontaneous sigh.

Abdominal Muscles↗
PubMed1998

Magnetometric evaluation for the effect of chrysotile on alveolar macrophages.

Alveolar macrophages are thought to play an important role in fibrogenesis due to asbestos exposure. In this experiment, we evaluated the effect mainly by unique magnetometry and also by conventional methods such as lactate dehydrogenase (LDH) activity measurement and morphological observations. Alveolar macrophages obtained from Syrian golden hamsters by bronchoalveolar lavages were exposed 18 hours in vitro to Fe3O4 as an indicator for magnetometry and chrysotile for experiments. A rapid decrease of the remanent magnetic field, so called "relaxation", was observed after the cessation of an external magnetic field in macrophages phagocytizing Fe3O4 alone, while relaxation was delayed in those concurrently exposed to chrysotile. Since relaxation is thought due to the cytoskeleton-driven random rotation of phagosomes containing iron oxide particles, chrysotile is considered to interfere with the cytoskeletal function of macrophages. Release of LDH from chrysotile-exposed macrophages into the medium was recognized, but it was not significantly higher than the controls. Apoptosis was negligible in macrophages exposed to chrysotile by the DNA ladder detection, the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling method and morphological observations. Electron microscopical examinations revealed early necrotic changes in macrophages exposed to chrysotile. These findings indicate that cell magnetometry detects impaired cytoskeletal function due to in vitro exposure to chrysotile.

Animals↗
PubMed1998

Altered expression levels and impaired steps in the pathway to phosphatidylinositol 3-kinase activation via insulin receptor substrates 1 and 2 in Zucker fatty rats.

To elucidate the mechanism of obesity-related insulin resistance, we investigated the impaired steps in the processes of phosphatidylinositol (PI) 3-kinase activation through binding with insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) in liver and muscle of Zucker fatty rats. The expressions of IRS-1 and IRS-2 were shown to be downregulated in both liver and muscle in fatty rats (hepatic IRS-1, 83%; hepatic IRS-2, 45%; muscle IRS-1, 60%; muscle IRS-2, 78%), resulting in decreased tyrosine phosphorylation in response to insulin stimulation. Despite the decrease in the tyrosine phosphorylation levels of hepatic IRS-1 and IRS-2 being mild to moderate, associated PI 3-kinase activities were dramatically decreased in fatty rats (IRS-1, 14%; IRS-2, 10%), which may suggest alteration in the sites of phosphorylated tyrosine residues of hepatic IRS-1 and IRS-2. In addition, we demonstrated that the expressions of p85alpha and p55alpha regulatory subunits of PI 3-kinase were reduced (p85alpha, 67%; p55alpha, 54%), and that the p50alpha regulatory subunit was markedly upregulated (176%) in the livers of fatty rats without apparent alterations in expressions of the catalytic subunits p110alpha and p110beta. These alterations may reflect the obesity-related insulin resistance commonly observed in human NIDDM.

Albumins↗
PubMed1997

Role of the C terminus in histamine H2 receptor signaling, desensitization, and agonist-induced internalization.

To evaluate the role of the histamine H2 receptor C terminus in signaling, desensitization, and agonist-induced internalization, canine H2 receptors with truncated C termini were generated. Wild-type (WT) and truncated receptors were tagged at their N termini with a hemagglutinin (HA) epitope and expressed in COS7 cells. Most of the C-terminal intracellular tail could be truncated (51 of 70 residues, termed T308 mutant) without loss of functions: cAMP production, tiotidine binding, and plasma membrane targeting. In fact, the T308 mutant produced more cAMP than the WT when cell-surface expression per cell was equivalent. Pretreatment of cells with 10(-5) M histamine desensitized cAMP productions via WT and T308 receptors to similar extents. Incubation of cells expressing WT receptors with 10(-5) M histamine reduced cell-surface anti-HA antibody binding by approximately 30% (by 30 min, t1/2 approximately 15 min), but did not affect the Bmax of tiotidine in membrane fractions, which represents total receptor amounts, suggesting that WT receptors were internalized from the cell surface. In contrast, no internalization was observed with T308 receptors following histamine treatment. A mutant with a deletion of the 30 C-terminal amino acids, termed T329, was functional but was as potent as the WT in terms of cAMP production. Apart from being desensitized by histamine, the internalization of the receptor was indistinguishable from that of the WT. Internalization was observed in the T320 but not in T313 mutant, narrowing the region involved in internalization to that between Glu314 and Asn320 (ETSLRSN). Of these seven residues, either Thr315, Ser316, or both, were replaced with Ala. Thr315 and Ser316 are conserved among species. The mutation at Thr315 (but not that at Ser316) abolished internalization. Taken together, these results demonstrate that Thr315 is involved in agonist-induced internalization. Furthermore, the finding that T308 receptors were desensitized in the absence of internalization suggests that internalization and desensitization are meditated by independent mechanisms.

Amino Acid Sequence↗
PubMed1997

Oligomer formation of histamine H2 receptors expressed in Sf9 and COS7 cells.

A histamine H2 receptor, which had been mutated at its glycosylation site and tagged at its N-terminus with an HA tag (HA-H2 receptor), was expressed in Sf9 cells and COS7 cells. Immunoprecipitation and immunoblotting of HA-H2 receptors with alphaHA antibody revealed four bands of 31.5 +/- 2.5 kDa, 59.0 +/- 6.0 kDa, 80.5 +/- 4.5 kDa and 120 kDa. These bands were also detected by immunoblot using anti-H2 receptor serum (C-terminus). In addition, H2 receptors without the HA-tag coimmunoprecipitated with HA-tagged H2 receptors devoid of the 51 C-terminal amino acids, via immunoprecipitation with alphaHA antibody, when the two receptors were coexpressed. These results suggest that H2 receptors are present as receptor oligomers and that the C-terminal portion is not involved in the formation of these oligomers.

Animals↗
PubMed1997

Insulin receptor substrate (IRS)-2 is dephosphorylated more rapidly than IRS-1 via its association with phosphatidylinositol 3-kinase in skeletal muscle cells.

Insulin receptor substrate (IRS)-2 is structurally and functionally similar to IRS-1. Indeed, stimulation with insulin or insulin-like growth factor I led to the rapid tyrosine phosphorylation of both IRS-1 and IRS-2, which in turn activated phosphatidylinositol (PI) 3-kinase in L6 cells and rat skeletal muscle. However, IRS-2 was rapidly dephosphorylated (3-10 min after the addition of insulin/insulin-like growth factor I), whereas IRS-1 phosphorylation continued for at least 60 min. The time courses of the PI 3-kinase activity associated with IRS-1 and IRS-2 paralleled the tyrosine phosphorylation of these proteins. Preincubation with sodium orthovanadate, an inhibitor of protein tyrosine phosphatase, blocked the rapid dephosphorylation of IRS-2, suggesting the involvement of tyrosine phosphatase. The activation of PI 3-kinase apparently plays an important role in the rapid dephosphorylation of IRS-2, as IRS-2 dephosphorylation was inhibited markedly by suppressing PI 3-kinase activity with wortmannin or overexpression of the dominant negative p85 subunit of PI 3-kinase, which cannot bind the p110 catalytic subunit. In addition, platelet-derived growth factor stimulation prior to insulin stimulation decreased IRS-associated PI 3-kinase and significantly inhibited the dephosphorylation of IRS-2. Taken together, these observations suggest that IRS-2 plays a unique role in mediating the signals from the insulin receptor to downstream molecules and that this effect is more transient than that of IRS-1. Tyrosine phosphatase and IRS-associated PI 3-kinase activity thus contribute to the rapid dephosphorylation of IRS-2.

Androstadienes↗
PubMed1997

Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor epsilon 1 or epsilon 2 subunit.

1. We have explored the effects of targeted disruption of the N-methyl-D-aspartate (NMDA) receptor epsilon 1 or epsilon 2 subunit gene on NMDA receptor-mediated excitatory postsynaptic currents (NMDA EPSCs) and long-term potentiations (LTPs) at the two types of synapse in mouse hippocampal CA3 pyramidal neurons: those formed by the commissural/associational (C/A) and fimbrial (Fim) inputs. 2. Electrophysiological experiments were performed in hippocampal slices prepared from both wild-type and epsilon 1- or epsilon 2-disrupted mice using extracellular and whole-cell patch recording techniques. To assess the epsilon 1, epsilon 2 and zeta 1 subunit expression at cellular levels, we performed non-isotopic in situ hybridization with digoxigenin-labelled cRNA probes. 3. We could record EPSCs in response to the stimulations to either of the C/A and Fim afferents from a single CA3 pyramidal neuron. The epsilon 1, epsilon 2 and zeta 1 subunits were expressed together in individual CA3 neurons. 4. The epsilon 1 subunit disruption selectively reduced NMDA EPSCs and LTP in the C/A-CA3 synapse without significantly affecting those in the Fim-CA3 synapse, whereas the epsilon 2 subunit mutation diminished NMDA EPSCs and LTP in the Fim-CA3 synapse with no appreciable functional modifications in the C/A-CA3 synapse. 5. These results suggest that NMDA receptors with different subunit compositions function within a single CA3 pyramidal cell in a synapse-selective manner.

Animals↗
PubMed1997

Co-localization of glucokinase with actin filaments.

A portion of glucokinase appeared to be co-localized with actin filaments in the cytoplasm of cultured rat hepatocytes incubated with 25 mM glucose. When liver- or islet-type glucokinase was transiently expressed in COS-7 cells, the expressed glucokinase was also co-localized with actin filaments in the cytoplasm of these transfected cells. Although co-localization of glucokinase with actin filaments was not clearly demonstrated in the pancreatic beta-cell line MIN6, islet glucokinase was found to be present in both the nucleus and the cytoplasm, though predominantly in the nucleus. These findings suggest that subcellular localization of glucokinase, including co-localization with actin filaments, may have an important physiological role in metabolic regulation.

Actins↗
PubMed1997

p85alpha gene generates three isoforms of regulatory subunit for phosphatidylinositol 3-kinase (PI 3-Kinase), p50alpha, p55alpha, and p85alpha, with different PI 3-kinase activity elevating responses to insulin.

Phosphatidylinositol 3-kinase (PI 3-kinase) is stimulated by association with a variety of tyrosine kinase receptors and intracellular tyrosine-phosphorylated substrates. We isolated a cDNA that encodes a 50-kDa regulatory subunit of PI 3-kinase with an expression cloning method using 32P-labeled insulin receptor substrate-1 (IRS-1). This 50-kDa protein contains two SH2 domains and an inter-SH2 domain of p85alpha, but the SH3 and bcr homology domains of p85alpha were replaced by a unique 6-amino acid sequence. Thus, this protein appears to be generated by alternative splicing of the p85alpha gene product. We suggest that this protein be called p50alpha. Northern blotting using a specific DNA probe corresponding to p50alpha revealed 6.0- and 2.8-kb bands in hepatic, brain, and renal tissues. The expression of p50alpha protein and its associated PI 3-kinase were detected in lysates prepared from the liver, brain, and muscle using a specific antibody against p50alpha. Taken together, these observations indicate that the p85alpha gene actually generates three protein products of 85, 55, and 50 kDa. The distributions of the three proteins (p85alpha, p55alpha, and p50alpha), in various rat tissues and also in various brain compartments, were found to be different. Interestingly, p50alpha forms a heterodimer with p110 that can as well as cannot be labeled with wortmannin, whereas p85alpha and p55alpha associate only with p110 that can be wortmannin-labeled. Furthermore, p50alpha exhibits a markedly higher capacity for activation of associated PI 3-kinase via insulin stimulation and has a higher affinity for tyrosine-phosphorylated IRS-1 than the other isoforms. Considering the high level of p50alpha expression in the liver and its marked responsiveness to insulin, p50alpha appears to play an important role in the activation of hepatic PI 3-kinase. Each of the three alpha isoforms has a different function and may have specific roles in various tissues.

Amino Acid Sequence↗
PubMed1997

Prostaglandin levels of primary bone tumor tissues correlate with peritumoral edema demonstrated by magnetic resonance imaging.

BACKGROUND: Several reports have shown peritumoral edema accompanying primary bone tumors demonstrated by magnetic resonance imaging (MRI). However, the mechanism of this inflammatory reaction is still unclear. The authors postulated that the reaction was caused by some chemical mediators including prostanoids, because several investigators have observed that some types of bone tumors synthesize prostanoids. Therefore, the authors compared MRI findings and tumor prostaglandin (PG) levels. METHODS: The subjects were 29 patients with primary bone tumor or tumor-like conditions: chondroblastoma (n = 5); chondrosarcoma, including rare variants (n = 8); giant cell tumor (n = 6); osteochondroma (n = 5); osteoblastoma (n = 2); Ewing's sarcoma (n = 2); and eosinophilic granuloma (n = 1). T1- and T2-weighted spin echo images were obtained in all but one patient before surgery. The tumor concentration of prostaglandin E2, 6-keto-PGF1 alpha, and thromboxane B2 were measured by radioimmunoassay. RESULTS: MRI distinctly showed bone marrow edema in 9 and soft tissue edema in 12 of the 28 patients examined. These findings were significantly correlated with the PG levels. Moreover, the PG levels were correlated with the histologic classifications (P < 0.001). In particular, the chondroblastomas showed prominent concentrations of PGs compared with other cartilaginous tumors or giant cell tumors. CONCLUSIONS: Although peritumoral edema accompanying benign and malignant bone tumors is not necessarily related to one single pathophysiologic mechanism, these results suggest that PG production was an important cause of the inflammatory reaction that was revealed by MRI. Recognition of this phenomenon is advantageous not only for strict diagnostic purposes but also for understanding the characteristic features of individual primary bone tumors.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Screening of patients with maternally transmitted diabetes for mitochondrial gene mutations in the tRNA[Leu(UUR)] region.

To investigate the prevalence and clinical characteristics of diabetes mellitus caused by mitochondrial gene mutations in the tRNA[Leu(UUR)] region, a known 'hot spot' for pathogenic mutations, we screened 440 diabetic patients with diabetic mothers for 11 mitochondrial gene mutations reported in mitochondrial neuromuscular disorders; nucleotide pairs (np) 3250, 3251, 3252, 3254, 3256, 3260, 3271, 3291, 3302 and 3303 in addition to an A to G transition at np 3243. The dot-blot hybridization method using 32P-labelled sequence-specific oligonucleotides as probes was used. One subject carrying a T to C transition at np 3271 and seven carrying the A to G transition at np 3243 were identified, while none of the other diabetic patients screened had these mutations in the tRNA[Leu(UUR)] region. The patient with the 3271 mutation, a 39-year-old male, had excellent glycaemic control with diet alone and had neither hearing impairment nor symptoms suggesting mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Thus, among patients with maternally transmitted diabetes, the prevalence of the 3271 mutation was approximately one-seventh that of the 3243 mutation, and other mutations are even more rare in the mitochondrial tRNA[Leu(UUR)] region.

Adult↗
PubMed1997

Use of adriamycin-impregnated methylmethacrylate in the treatment of tumor metastases in the long bones.

Internal fixation or endoprosthetic replacement of a long bone metastatic lesion was performed using adriamycin-containing bone cement (methylmethacrylate) after resection or curettage of the lesion in 25 patients (27 limbs). Survival rate, limb function, and local recurrence rate were retrospectively evaluated in this patient cohort. Survival rate was 53% at 12 months and 30% at 24 months, which was better than in previous reports. One patient showed local recurrence radiographically. Postoperatively, none of the patients developed infection, delayed wound healing, myelo-suppression attributed to adriamycin, and 74% of the patients were able to walk outdoors.

Adolescent↗
PubMed1997

Malignant hemangioendothelioma of the left calcaneus associated with fever and hematological abnormalities.

A case of malignant hemangioendothelioma of the left calcaneus associated with unique system manifestations is reported here. The severe toxic manifestations included: high fever, anemia, leukocytosis, coagulation abnormalities, and other signs. Because of poor response to many antibiotic regimens, the confusion of diagnosis, and severe coagulation abnormalities with clinical signs that the life of the patient was endangered, below the knee amputation was performed. Pathological studies revealed a malignant hemangioendothelioma. A review of the case suggests that the signs and symptoms were possibly due to an immune response to the tumor rather than to secondary infection, although the latter possibility cannot be completely excluded.

Adult↗