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Biomedical subjects

H Murakami

Publications and source records attributed to H Murakami.

At least 199 records · Page 11Linked to original sources
PubMed1999

The role of amino acids surrounding tyrosine 1062 in ret in specific binding of the shc phosphotyrosine-binding domain.

We investigated the role of the I-E-N-K-L (amino acids 1057-1061) sequence amino-terminal to Tyr1062 in Ret for binding of the Shc phosphotyrosine-binding (PTB) domain. Substitution of Ser for Ile1057 (I1057S), Ala for Asn1059 (N1059A), or Pro for Leu1061 (L1061P) in this sequence significantly decreased the transforming activity of Ret with the multiple endocrine neoplasm type 2A (MEN2A) mutation as well as the binding affinity of Shc to it in vivo and in vitro, indicating that these three amino acids play a role in Shc binding. In addition, as the RET protooncogene is translated as three isoforms of 1114 amino acids (Ret 51), 1106 amino acids (Ret 43), and 1072 amino acids (Ret 9) that differ from one another in the sequence carboxyl-terminal to Tyr1062, we examined whether these sequence differences influence the binding affinity of Shc to Ret. As a result, we found that the transforming activity of Ret 43 isoform with the MEN2A mutation and the binding affinity of Shc to it were very low, although the consensus sequence for the binding of the Shc PTB domain is conserved in the Ret 43 isoform. This finding suggested that the sequence carboxyl-terminal to Tyr1062 in Ret could also influence the binding affinity to Shc.

3T3 Cells↗
PubMed1999

Aromatase and sex steroid receptors in human vena cava.

Among sex steroids, especially estrogen metabolism has been considered to play a role in the function and pathology of human veins. We investigated the expression and activity of the estrogen-producing enzyme aromatase and estrogen receptor (ER) in human vena cava to assess possible in situ biosynthesis of estrogens and their modes of action. We first examined aromatase expression by immunohistochemistry in human inferior vena cava obtained from 29 autopsy cases (11 males, 18 females, 63.6 +/- 3.0 years old). We then semiquantitated the level of aromatase mRNA by reverse transcriptase-polymerase chain reaction in 24 cases and aromatase activity by 3H-water assay in 15 cases to examine whether or not and in which cell types aromatase was expressed. We also studied alternative use of multiple exon 1s of its gene and immunolocalization of 17beta-hydroxysteroid dehydrogenase type I (17beta-HSD I), which converts estrone produced by aromatase to estradiol, a biologically active estrogen and ER. Aromatase and 17beta-HSD I immunoreactivity were both detected in smooth muscle cells (SMC) of the media in all the cases and in endothelial cells (EC) in 20 and 22 cases, respectively. ER immunoreactivity was detected in SMC of vena cava in 21 cases. The amount of aromatase mRNA was significantly greater in the cases utilizing 1c (I.3) or 1d (P.II) of exon 1 (9 cases, 191.1 +/- 26.3 attomol/ng total RNA) than those utilizing 1b (I.4) as the promoter (14 cases, 50.6 +/- 13.0 attomol/ng total RNA) (p < 0.01). Significant correlation (p < 0.05) was observed between the amount of aromatase mRNA and aromatase activity in 15 cases examined. No significant correlation was detected between the amount of aromatase mRNA or aromatase labeling index and the ER status. These results suggest that estrone and estradiol are produced in the human vena cava and that their production is mediated by aromatase and 17beta-HSD I, respectively but not all of these locally synthesized estrogens may not work directly in situ.

17-Hydroxysteroid Dehydrogenases↗
PubMed1999

Serum leptin levels and bioelectrical impedance assessment of body composition in patients with Graves' disease and hypothyroidism.

We investigated whether thyroid status modulates serum leptin concentrations and body composition as determined by bioelectric impedance analysis (BIA). The percent body fat mass (%FM) in male Graves' disease was significantly lower than that in age- and sex- matched normal subjects, at the levels of 11.4+/-6.4% (mean+/-SD) vs 19.9+/-9.2% for men (n=12, P<0.05) but not for women (22.6+/-7.6% vs 24.9+/-13.1%, n=28). In contrast, in female hypothyroidism (n=11) %FM was significantly higher than that in normal subjects (32.9+/-11.5%, P<0.01). Among other body composition parameters, the percentage of body water (%BW), and lean body mass (LBM) were significantly lower in hypothyroid patients, and the ECM (extracellular mass)/BCM (body cell mass) ratio was significantly (P<0.0001) increased in Graves' disease which was the result of marked depletion of BCM with concomitant expansion of ECM. The serum leptin levels were significantly decreased in male Graves' patients (2.3+/-0.7 ng/ml, P<0.05), whereas in female Graves' patients (8.8+/-5.9 ng/ml) and patients with hypothyroidism (9.5+/-7.6 ng/ml), the levels were not different from those of normal controls matched for BMI or %FM. There was a positive correlation between serum leptin levels and %FM in female Graves' patients (r=0.635, P=0.001) and in hypothyroid patients (r=0.801, P=0.014) but not in male Graves patients. There was no significant relationship between serum leptin levels and thyroid hormones, TRAb, or TSAb. In euthyroid obese subjects there was a positive relationship between serum leptin levels and serum TSH levels (r=0.37, P<0.01). These results suggest that hyperthyroidism is characterized by the decreased fat mass and serum leptin levels in men, but female patients appear to be resistant to the effect of thyroid hormones. Together with previous reports, thyroid status has a minor role in the regulation of serum leptin levels.

Adult↗
PubMed1999

Probable lymphocytic hypophysitis diagnosed by short-term serial computed tomography and gallium-67 scintigraphy--case report.

A 61-year-old female presented with headache, malaise, and left oculomotor nerve paralysis. Computed tomography (CT) demonstrated a diffuse pituitary mass and enlarged pituitary stalk with homogeneous contrast enhancement. Her symptoms gradually resolved without treatment. Gallium-67 scintigraphy showed abnormal uptake in the pituitary lesion. Serial CT every 2 weeks after admission showed homogeneous contrast enhancement and shrinking of the pituitary mass to a normal size 12 weeks after the onset. The final diagnosis was lymphocytic adenohypophysitis without biopsy. Recurrence has not been observed for 8 years after discharge. The patient did not need hormone replacement therapy. Histological examination is not always necessary to diagnose probable lymphocytic adenohypophysitis with the characteristic feature of rapid onset, abnormal gallium-67 uptake in the lesion, and resolution of symptoms in the acute stage with shrinking of the lesion on neuroimaging.

Female↗
PubMed1999

[The role of protein kinases and phosphatases in erythroid colony formation of elderly].

Using H-7, HA1001, FK506, cyclosporin A (CsA) and okadaic acid (OA), which are protein kinase and phosphatase inhibitors, we examined qualitative changes in hematopoietic precursor cells due to aging from the viewpoint of the role of protein kinases and phosphatases. Though H-7 and OA suppressed erythroid colony formation both in the elderly (age: 72-92, median: 86) and the young (age: 22-39, median: 29), no change due to aging was noted. HA1001 did not affect erythroid colony formation either in the elderly or the young. Erythroid colony formation was enhanced by FK506 and CsA in the young, however, erythroid colony formation was suppressed in the elderly. Similar examinations using cell fractions of non-T, non-macrophage, non-T + T, and CD34 positive cells were performed in both groups. Enhancement of erythroid colony formation in the young and suppression in the elderly by FK506 using unseparated MNC disappeared after removal of T cells. Enhancement of colony formation in the young and suppression of colony formation in the elderly were recovered when T cells were added again. The effects of FK506 and CsA on erythroid colony formation were thought to be the results of T cell inactivation, and the different sensitivity to FK506 and CsA in the elderly and young seemed to be the result of changes in the control mechanisms of hematopoiesis, such as the regulation of cytokine production by T cells, caused by aging.

Adult↗
PubMed1999

[Concomitant mitral valvuloplasty and fenestrated total cavopulmonary connection: a case report].

A seven-year-old boy with tricuspid atresia successfully underwent a fenestrated total cavopulmonary connection and mitral valvuloplasty. Preoperative cardiac catheterization showed a mean pulmonary artery pressure of 16 mmHg. Pulmonary arteriography showed poor development of the branches (PA index: 180). Echocardiography revealed mild to moderate mitral valve incompetence due to prolapse of anterior leaflet. Mitral valve was exposed through the trans-septal approach. The excess chorda length was tucked into a longitudinal split in the top of the posterior papillary muscle. Then wedge resection of the redundant segment of the anterior leaflet and bilateral annuloplasty were performed. Finally, a total extracardiac cavopulmonary anastomosis with a 6 mm fenestration was completed. Postoperative clinical course was uneventful, and he is doing well with no recurrence of mitral incompetence 1 year after the operation.

Child↗
PubMed1999

[Clinical effects of combination therapy with cefozopran and tobramycin for severe infections in patients with hematologic diseases].

We studied clinical effect of a combination therapy with cefozopran (CZOP) and tobramycin (TOB) for infections in 80 patients with hematologic diseases in 15 institutes. Combined doses with CZOP 2 g and TOB 60-90 mg twice a day had been given intravenously. Of the 80 patients, 61 patients (42 with acute leukemia, 10 with malignant lymphoma, 3 with aplastic anemia, 2 with chronic myeloid leukemia, 2 with multiple myeloma, and 2 with myelodysplastic syndrome) were evaluable. Those consisted of 6 patients with septicemia, 49 with suspected septicemia, 3 with pneumonia, and 3 with other infections. Clinical efficacy by the treatment was excellent in 24, good in 17, fair in 9, and poor in 11 patients, and the overall efficacy rate including excellent and good was 67.2%. Microbiologically, 5 of the 6 patients with septicemia (1 coagulase negative Staphylococcus, 2 S. pneumoniae, 1 S. oralis, and 1 E. coli) were responded. The efficacy rate in patients with severe granulocytopenia showing 100/microliter or lesser neutrophil counts during the drug administration was 57.1% (12/21). Side effects and abnormal changes of clinical laboratory findings were observed in 5 patients, and 16 patients, respectively, but most of them were mild. The findings above suggested that the combination therapy with CZOP and TOB is useful as an empiric therapy for severe infections in patients with hematologic diseases.

Adult↗
PubMed1999

[Midterm results of bilateral enlargement of the aortic valve ring for valve replacement].

From 1989, 4 patients underwent bilateral enlargement of the aortic valve ring for valve replacement. Age at the operation ranged from 2 to 8 (mean 6) years; body weight ranged from 14.9 to 25.4 (mean 19.0) kg. This procedure enabled us to implant a prosthesis 3 to 4 sizes larger (19 to 23 mm) than that measured with the native aortic annulus (13 to 17 mm). There was no late death and no cardiac event over a mean follow-up period of 6.2 years. Pressure gradient across the prosthesis measured by echocardiography was 40 mmHg in 1 patient who underwent aortic valve replacement with the use of 19 mm St. Jude Medical valve at 2 years of age. There was no significant pressure gradient in other 3 patients. All patients showed normal left ventricular function. We conclude that bilateral enlargement of the aortic valve ring for valve replacement has provided good midterm results with no mortality and no cardiac event.

Aortic Valve↗
PubMed1999

[A surgical case of right coronary artery-right atrial fistula complicated with postoperative myocardial infarction].

We report a 10-year-old girl with a right coronary artery-right atrial fistula and aneurysm formation. The proximal orifice was closed from the inside of the aneurysm, and the distal orifice through the right atrium under cardiopulmonary bypass. On the 9th postoperative day, myocardial infarction developed due to thrombosis in the fistula stump and the dilated coronary artery. Thrombosis may have been induced by postoperative dehydration and inadequate anticoagulant therapy. It is important to minimize a fistula stump and to strictly administer postoperative anticoagulant therapy.

Arterio-Arterial Fistula↗
PubMed1999

Implication of expression of GDNF/Ret signalling components in differentiation of bone marrow haemopoietic cells.

Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) mediate their actions through a unique multicomponent receptor system composed of Ret receptor tyrosine kinase and glycosyl-phosphatidylinositol-linked cell surface proteins (designated GFRalpha-1 and GFRalpha-2). In the present study, expression of these signalling components in the process of differentiation of haemopoietic cells was investigated. Ret was expressed at variable levels in normal and malignant cells of the myelomonocyte lineage. Immunohistochemical analysis of human and mouse tissues revealed that Ret expression was increased in intermediate mature myeloid cells such as promyelocytes and myelocytes and decreased in mature granulocytes and monocytes. Consistent with this observation, when THP-1 monocytic and HL-60 promyelocytic leukaemia cells expressing Ret were differentiated toward macrophages or granulocytes by treatment of 12-O-tetradecanoylphorbol-13-acetate (TPA) or all-trans retinoic acid (RA), Ret expression strikingly decreased during differentiation. Expression of GDNF, NTN, GFRalpha-1 and GFRalpha-2 was undetectable in THP-1 and HL-60 cells as well as in bone marrow haemopoietic cells. In contrast, bone marrow stromal cells appeared to express GDNF, GFRalpha-1 and GFRalpha-2 but not Ret. These findings suggested that the interaction between stromal cells and Ret-expressing haemopoietic cells in the bone marrow microenvironment may play a role in the differentiation of myelomonocyte-lineage cells through activation of the GDNF/Ret signalling pathway.

Animals↗
PubMed1999

Adrenomedullin in monocytes and macrophages: possible involvement of macrophage-derived adrenomedullin in atherogenesis.

Macrophages secrete a variety of growth factors, cytokines and vasoactive peptides, which are related to the progression of atherosclerosis. Adrenomedullin (ADM) is a potent vasodilator peptide and inhibits proliferation and migration of vascular smooth muscle cells. In this study, we investigated the production and secretion of ADM by monocytes and macrophages by Northern blot analysis, RIA and immunocytochemistry. Northern blot analysis showed that ADM mRNA was expressed in human monocytes obtained from peripheral blood and monocyte-derived macrophages. The expression level of ADM mRNA in monocyte-derived macrophages was about five times higher than that in monocytes. Treatment with lipopolysaccharide (100 ng/ml) for 24 h increased ADM mRNA expression levels in both monocytes and monocyte-derived macrophages. The levels of immunoreactive ADM in the media of monocyte-derived macrophages were about three times higher than that of monocytes (0. 718+/-0.046 fmol/24 h/10(5) cells, n=8 compared with 0.259+/-0.018 fmol/24 h/10(5) cells, n=8; mean+/-S.E.M., P<0.01). The secretion was also increased by treatment with lipopolysaccharide. Immunocytochemistry showed positive ADM immunostaining in macrophages in atherosclerotic lesions of human aorta obtained at autopsy. ADM secreted from activated macrophages may play an inhibitory role in atherogenesis.

Adrenomedullin↗
PubMed1999

[Autoimmune neutropenia accompanied by Tolosa-Hunt syndrome].

A 47-year-old woman presented with severe neutropenia accompanied by diplopia and orbital pain. Her bone marrow was normal except for the absence of segmented neutrophils. Because the administration of granulocyte colony-stimulating factor (G-CSF) at a dose of 1 microgram/kg/day was not sufficiently effective and neutropenia developed, the patient was admitted to our hospital. Physical examination revealed painful ophthalmoplegia and hypoalgesia in the first region of trigeminal nerve, suggestive of Tolosa-Hunt syndrome. Severe neutropenia was observed in both peripheral blood and bone marrow, together with mild anemia and thrombocytopenia. The life span of red cells and platelets was shortened. High PAIgG levels, a positive Coombs test, and a positive test for anti-NA1 antibody suggested that blood cells were being destroyed by an autoimmune mechanism. Corticosteroid hormone therapy preceded by the administration of G-CSF at 5 micrograms/kg/day was effective for both neutropenia and in improving the patient's neurological findings.

Autoimmune Diseases↗
PubMed1999

Infectious complications during remission induction therapy in 577 patients with acute myeloid leukemia in the Japan Adult Leukemia Study Group studies between 1987 and 1991.

The Japan Adult Leukemia Study Group analyzed infectious episodes in 577 patients with acute myeloid leukemia during remission induction therapy between 1987 and 1991. 542 patients (93.9%) experienced at least one infectious episode, 121 (21.0%) had microbiologically documented infection; there was clinically documented infection in 184 (31.9%) and unexplained fever in 237 (41.1%). Among 121 microbiologically documented infections, bacteremia/fungemia was observed in 68, pneumonia in 33, and other types of infections in 20. Among the bacteremia/fungemia, gram-negative bacteria accounted for 41.2% (Pseudomonas aeruginosa was the most common), gram-positive bacteria for 39.7%, fungi for 16.2% (Candida spp. being most frequent), and polymicrobial for 2.9%. The most frequent isolates among pneumonia were Pseudomonas aeruginosa and Aspergillus. A total of 70 patients (12.1%) died during remission induction. Mortality of 68 patients with bacteremia/fungemia was 26.5%; in these patients, mortality with concomitant pneumonia increased to 41.4%; without pneumonia, mortality was 15.4% (P < 0.05). Mortality according to the isolated microbes was 17.2% for gram-negative bacteria, 25% for gram-positive bacteria, and 54.5% for fungi. Mortality of 113 patients with pneumonia (33 microbiologically documented and 80 clinically documented), 20 with other microbiologically documented infections, 104 with other clinically documented infections, and 237 with unexplained fever was 25.7%, 5.0%, 5.8%, and 5.1%, respectively.

Acute Disease↗
PubMed1999

A chronic myelogenous leukemia-like myeloproliferative disorder accompanied by T-cell lymphoblastic lymphoma with chromosome translocation t(8;13)(p11;q12): a Japanese case.

A 40-year-old male patient presented with leukocytosis and mild splenomegaly. Bone marrow aspirate showed myeloid hyperplasia and eosinophilia resembling chronic myelogenous leukemia in the chronic phase. Cytogenetic examination of bone marrow cells revealed an unusual karyotype, t(8;13)(p11;q12), in 20/20 metaphases. Not the BCR/ABL, but the ZNF198/FGFR1 chimeric mRNA was detected by reverse transcription-polymerase chain reaction. Since 1992, 12 patients with a similar atypical myeloproliferative disorder with T-cell non-Hodgkin's lymphoma or eosinophilia, associated with a t(8;13) translocation in both bone marrow and lymph node specimens, have been described. The present case is an additional one that should be classified into this new clinicopathologic entity.

Adult↗
PubMed1999

Regulated permeability of tight junctions by E-cadherin in rat submandibular gland acini.

We examined the relationship between E-cadherin (E-CD), protein kinase C (PKC) and assembly of the tight junction (Tj) in rat submandibular gland acinar cells. The junctional complex of the acinar cells was double-labeled with anti-ZO-1 antibody and anti-E-CD antibody. When Ringer's solution was intraductally injected into the main duct, ZO-1 labels were highly concentrated at the Tj zone, and the adherens junction (Aj) was exclusively labeled by E-CD. In addition, the Tj was impermeable to microperoxidase. Neither intraductal injection of anti-E-CD antibody solution nor infusion of carbachol produced labels for ZO-1 at the Tj zone, although these proteins were occasionally intermixed at the Aj zone. In these cases, the Tj was permeable to microperoxidase. Intraductal injection of anti-E-CD antibody solution with PKC agonist, resulted in a reduction of E-CD labels in the Aj zone, while the ZO-1 was labeled exclusively in the Tj zone. In this case, Tj was impermeable to microperoxidase. These results suggest that E-CD plays a major role in mediating intercellular physical adhesion, and that PKC may be active in signaling the pathway activated by E-CD-mediated cell-cell adhesion.

Animals↗
PubMed1999

Ulnar nerve compression secondary to ulnar artery true aneurysm at Guyon's canal.

UNLABELLED: This article presents a case of ulnar nerve compression at the Guyon's canal caused by a true aneurysm of the ulnar artery secondary to blunt trauma. The duration of follow-up was one year. SETTING: Hospitalized care. A 27-year-old man who worked in an office fell on to a gravel path landing on his out-stretched right hand. Decompression of the ulnar nerve was made by simple ligation of the damaged artery and resection of aneurysm. MEASURES: Histological examination. The sensory symptoms disappeared two days after the operation. At one year after surgery, the patient was completely asymptomatic. There was no residual cold intolerance. Simple ligation of the damaged artery and resection of aneurysm resulted satisfactory. It seemed to be a safe method in this case. Ulnar nerve compression due to a true aneurysm of the ulnar artery in the Guyon's canal is rarely described in the literature.

Adult↗