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Biomedical subjects

H Kishimoto

Publications and source records attributed to H Kishimoto.

At least 91 records · Page 5Linked to original sources
PubMed1998

Brain imaging of affective disorders and schizophrenia.

We review recent findings in human brain imaging, for example, which brain areas are used during perception of colors, moving objects, human faces, facial expressions, sadness and happiness etc. One study used fluorine-18-labeled deoxyglucose positron emission tomography (PET) in patients with unipolar depression and bipolar depression, and found hypometabolism in the left anterolateral prefrontal cortex. Another study reported increased regional cerebral blood flow in the amygdala in familial pure depressive disease. Using 11C-glucose PET, we reported that the glutamic acid pool was reduced in cortical areas of the brain in patients with major depression. We also found that the thalamic and cingulate areas were hyperactive in drug-naive (never medicated) acute schizophrenics, while the associative frontal, parietal, temporal gyri were hypoactive in drug-naive chronic schizophrenics. Brain biochemical disturbances of schizophrenic patients involved glutamic acid, N-acetyl aspartic acid, phosphatidylcholine and sphingomyelin which are important chemical substances in the working brain. The areas of the thalamus and the cingulate which become hyperactive in acute schizophrenic patients are important brain areas for perception and communication. The association areas of the cortex which become disturbed in chronic schizophrenia are essential brain areas in human creativity (language, concepts, formation of cultures and societies) and exist only in human beings.

Bipolar Disorder↗
PubMed1998

Requiring higher doses of erythropoietin suggests pregnancy in hemodialysis patients.

BACKGROUND/AIMS: Pregnancy in hemodialysis (HD) patients tends to be diagnosed late because of its infrequency and the lack of validity of urine pregnancy tests, and because these patients tend to have menstrual irregularities. The outcome is influenced by pregnancy-related anemia. We investigated the characteristics of pregnancy-related anemia and whether it is a useful diagnostic clue to pregnancy in HD patients. METHODS: We retrospectively investigated six pregnancies of 5 HD patients (mean age 30 years), including 4 patients treated with recombinant human erythropoietin (rHuEpo) and a transfusion-dependent patient with two pregnancies in the pre-rHuEpo era. RESULTS: The mean duration of HD was 6 years, the mean duration of the patients' marriages at the time of pregnancy was 6 years, and the mean gestational age at diagnosis was 11 weeks and 4 days. The progression of anemia (an 8% decrease in the hematocrit) was detected by 8 weeks of gestation in all patients. The prepregnancy hematocrit was stable in 5 pregnancies, facilitating the detection of changes, but during one of the pregnancies of the transfusion-dependent patient the hematocrit was low and was influenced by the transfusions. The amount of rHuEpo required to attain a target hematocrit of 30% increased gradually or rapidly until delivery. CONCLUSIONS: The progression of anemia or hyporesponsiveness to rHuEpo was a useful early diagnostic clue to pregnancy in HD patients. However, the prepregnancy hematocrit should be stabilized with rHuEpo, so that decreases can be easily detected. The precise mechanisms of hyporesponsiveness to rHuEpo, which progressed during pregnancy and subsided after delivery, remain to be clarified.

Adult↗
PubMed1998

A placebo-controlled, single-blind study to determine the appropriate alendronate dosage in postmenopausal Japanese patients with osteoporosis. The Alendronate Research Group.

Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate) is a potent inhibitor of bone resorption. The efficacy and safety of 36 weeks of treatment with alendronate were evaluated in Japanese women with osteoporosis, osteoporotic osteopenia or artificial menopause. The bone mineral density (BMD) of the lumbar vertebrae, markers of bone and calcium metabolism and clinical symptoms were monitored. A total of 113 randomly selected patients with osteoporosis or osteopenia were enrolled in the study, of whom 12 were excluded from the analyses because of lack of data. As a result, 101 patients were evaluated for the safety of the drug. Since eight patients were excluded from the efficacy analysis, 93 were evaluated. The incidence of adverse effects in the placebo (P), alendronate 2.5 mg/day (L) and alendronate 10 mg/day (H) groups increased with increasing dose of alendronate, being 6.1, 14.3 and 18.2%, respectively. The most common adverse effects were gastrointestinal symptoms, none of which was serious. Lumbar BMD increased after 36 weeks of drug administration to 5.21%, 5.64% and -0.90% in the L, H and P groups, respectively (P < 0.001, L vs. P and H vs. P). Serum alkaline phosphatase activity, serum osteocalcin and urinary deoxypyridinoline excretion were significantly decreased in a dose-related manner. Serum calcium and phosphorus were also significantly decreased after alendronate administration. Serum intact PTH was transiently increased. The present results indicate that alendronate effectively decreases bone turnover in a dose-related manner and increases lumbar BMD at a dosage of 2.5 mg/day, the lowest dose used in this study, in Japanese patients with osteoporosis.

Adult↗
PubMed1998

[A case report: inhaled nitric oxide improves respiratory function in an infant with pulmonary hypertension].

Nitric oxide (NO) was administered to an infant in a near fatal crisis of pulmonary hypertension after total correction of double outlet right ventricle. Inhaled NO of 4 parts per million reduced pulmonary arterial pressure (PAP) and increased tidal volume during pressure limit ventilation. Both respiratory system compliance and resistance were improved with NO inhalation. There was a significant negative correlation between mean PAP and respiratory system compliance. We speculated that a reduction in PAP with NO inhalation resulted in the improvement of respiratory function. He was successfully weaned from mechanical ventilation.

Double Outlet Right Ventricle↗
PubMed1998

QT interval prolongation in the patients receiving maintenance hemodialysis.

QT prolongation is associated with a poor prognosis in patients with various diseases. The pathogenesis of the long QT syndrome is not well understood and little is known about the QT interval in the patients receiving maintenance hemodialysis. We evaluated changes in the QTc interval and investigated factors that contribute to its prolongation in 42 patients receiving maintenance hemodialysis. We also examined the association between the QTc interval and ventricular arrhythmias on 24-h ambulatory electrocardiograms. Comparison of standard 12-lead electrocardiograms of 42 patients and of 30 healthy controls matched for age and sex showed that the QTc interval in the patients was significantly prolonged (432.6 +/- 24.9 vs 402.0 +/- 21.0 ms, p <0.001). Multivariate analysis using stepwise multiple regression identified diabetes mellitus and the ejection fraction measured by echocardiography as independent risk factors for QTc prolongation. The QTc interval was significantly prolonged in patients with complex VPCs (couplets or salvos) (n = 13, 447.9 +/- 14.4 ms) on 24 h ambulatory ECG compared with simple VPCs (none or occasional) (n = 29, 425.6 +/- 25.8 ms) (p = 0.03). In conclusion, the QTc interval was prolonged in patients receiving maintenance hemodialysis and QTc prolongation was associated with complex VPCs. Decreased myocardial contractility and diabetes mellitus contributed to QTc prolongation.

Arrhythmias, Cardiac↗
PubMed1998

[Bisphosphonates: pharmacology and use in the treatment of osteoporosis].

Bisphosphonates are attractive antiresorptive drugs for osteoporosis. The only compound available in Japan is the first-generation bisphosphonate, etidronate. Etidronate adsorbes to the surface of hydroxyapatite crystals, and can slow bone mineralization and inhibit bone resorption. It has a narrow therapeutic window between these two actions, so that long-term continuous administration is not feasible. The intermittent use of etidronate produces a positive effect on bone mass. But the response varies directly with the rate of bone turnover at baseline. In high turnover osteoporosis there could be a gain in bone mass, but it reaches a plateau after 2 to 3 years. In normal or low turnover osteoporosis bone mass is stabilized but does not increase. However, the long-term effect of bisphosphonates on bone strength is not known.

Diphosphonates↗
PubMed1998

[A case of leiomyosarcoma of the jejunum with postoperative hepatic encephalopathy].

We report a case of leiomyosarcoma of the jejunum with postoperative hepatic encephalopathy. A 60-year-old man was operated for tumor of the abdomen. He was diagnosed as leiomyosarcoma of the jejunum with disseminated peritoneal metastasis, but no liver metastasis and cirrhosis. A palliative resection of the jejunum was performed. After operation, disturbance of orientation and apraxia with electroencepharographic abnormality and hyperammonemia developed. He was diagnosed as hepatic encephalopathy without lesion of the liver, and died 11 months after surgery. We consider that the portosystemic shunt and bleeding from the digestive tract due to invasion of metastatic lesions caused hepatic encephalopathy.

Hepatic Encephalopathy↗
PubMed1997

Requirements for peptide-induced T cell receptor downregulation on naive CD8+ T cells.

The requirements for inducing downregulation of alpha/beta T cell receptor (TCR) molecules on naive major histocompatibility complex class I-restricted T cells was investigated with 2C TCR transgenic mice and defined peptides as antigen. Confirming previous results, activation of 2C T cells in response to specific peptides required CD8 expression on the responder cells and was heavily dependent upon costimulation provided by either B7-1 or ICAM-1 on antigen-presenting cells (APC). These stringent requirements did not apply to TCR downregulation. Thus, TCR downregulation seemed to depend solely on TCR/peptide/interaction and did not require either CD8 or B7-1 expression; ICAM-1 potentiated TCR downregulation, but only with limiting doses of peptides. TCR downregulation was most prominent with high affinity peptides and appeared to be neither obligatory nor sufficient for T cell activation. In marked contrast to T cell activation, TCR downregulation was resistant to various metabolic inhibitors. The biological significance of TCR downregulation is unclear, but could be a device for protecting T cells against excessive signaling.

Animals↗
PubMed1997

Negative selection in the thymus includes semimature T cells.

The thymic medulla plays a key role in negative selection (self-tolerance induction) and contains differentiated T cells en route to the extrathymic environment. However, being relatively mature, medullary T cells are thought to be beyond the stage of tolerance induction. This paradox is resolved by the finding that medullary T cells (CD4+8- thymocytes) comprise two distinct subsets. Medullary thymocytes expressing a fully mature (HSAlo) phenotype are strongly resistant to tolerance induction, whereas cells with a semimature (HSAhi) phenotype are tolerance susceptible. These findings suggest that the differentiated T cells reaching the medulla from the cortex remain sensitive to tolerance induction for a brief period before acquiring a fully mature tolerance-resistant phenotype. The semimature subset of medullarsy T cells displays unique requirements for tolerance induction; depending upon the conditions used, tolerizing these cells can involve either a Fas (CD95)-dependent or a Fas-independent pathway.

Animals↗
PubMed1997

Signal transduction via the CD38/NAD+ glycohydrolase.

The human cell surface CD38 molecule is a 46-kDa type-II transmembrane glycoprotein with a short N-terminal cytoplasmic domain and a long Cys-rich C-terminal extracellular one. We previously demonstrated that an ecto-form NAD+ glycohydrolase (NADase) activity induced by all-trans retinoic acid in HL-60 cells is due to the extracellular domain of CD38. In the present study, we investigated a possible signal transduction mediated through CD38 in the retinoic acid-differentiated HL-60 cells with anti-CD38 monoclonal antibodies (mAbs). The addition of selected anti-CD38 mAbs to the cells induced rapid tyrosine phosphorylation of the cellular proteins with the molecular weights of 120,000, 87,000 and 77,000; the phosphorylated 120-kDa protein was identified as the c-cbl proto-oncogene product, p120c-cbl. Furthermore, the phosphorylated p 120c-cbl associated with the 85-kDa subunit of phosphatidylinositol 3-kinase. To determine the relationship between the amino acid sequence responsible for the NADase activity and epitopes recognized by the stimulatory mAbs, we produced its carboxy-terminal deletion mutants in COS-7 cells. The mutants with less than 15 amino acids deleted from the carboxyl terminus of the 300-amino acid wild-type molecule still maintained NADase activity, but those with more than 27 amino acids deleted did not. Introduction of site-directed mutation of a cysteine residue (Cys275), located in the 273-285 sequence, completely abolished the NADase activity. These CD38 mutants were also used for an epitope mapping of anti-CD38 mAbs. All the epitopes recognized by the mAbs inducing the tyrosine phosphorylation were mapped on the same Cys275-containing sequence of 273-285. Thus, the discrete carboxy-terminal sequence not only plays a key role in its ecto-NADase activity, but also contains the epitopes of the agonistic anti-CD38 mAbs for the transmembrane signaling. We also found that the agonistic mAbs markedly potentiate superoxide generation induced by the stimulation of G protein-coupled chemotactic receptors. Our results suggested that the stimulation of CD38 might generate an accessory signal(s) to enhance the G protein-mediated signaling, probably though the protein-tyrosine phosphorylation.

ADP-ribosyl Cyclase↗
PubMed1997

Clinical trial of prophylactic endoscopic variceal ligation for esophageal varices.

Endoscopic variceal ligation is an effective therapy for variceal bleeding, and use of the method has recently been increasing. We evaluated the clinical usefulness of prophylactic endoscopic variceal ligation. Twenty-two patients with enlarged, tortuous varices and "red color signs" were selected. These patients were treated with ligation therapy alone and the varices were eradicated, i.e., reduced to small, straight varices without red color signs. Ligation therapy was withdrawn if the general condition of the patient worsened or if the varices could not be removed by suction. Follow-up endoscopy was performed every 4 months, and another ligation was performed if there were recurrent varices or variceal bleeding. The total reduction rate was 86.4%, and eradication required two sessions of therapy and 30 days of hospitalization on average. Complications included esophageal injury in 1 patient and treatment-induced bleeding in 1 patient; both complications were easily controlled. No variceal bleeding occurred after the eradication. There was no mortality due to gastrointestinal bleeding during the median follow-up period of 346 days. Prophylactic endoscopic variceal ligation made it possible to prevent fatal variceal bleeding with a minimum risk of complications, suggesting that this could be an alternative method for the prevention of first-time variceal bleeding.

Adult↗
PubMed1997

Endoscopic resection of rectal carcinoid tumors using aspiration lumpectomy.

BACKGROUND AND STUDY AIMS: Although carcinoid tumors have malignant potential, complete resection can be curative if the lesion is located within the submucosal layer. In this study, we evaluated the effectiveness of endoscopic aspiration lumpectomy for the treatment of small rectal carcinoid tumors. PATIENTS AND METHODS: Eight patients with rectal carcinoid tumors less than 10 mm in diameter and located within the submucosa were treated by aspiration lumpectomy. It was confirmed that none of the patients had any metastatic lesions before treatment. The procedure was carried out using an endoscope with a cylinder attached to the tip and a Teflon tube along its outer axis. The lesion was aspirated into the cylinder, grasped by a snare passed through the tube, and then resected. RESULTS: All lesions were excised completely, without any complications. The resected specimens were circular, with the lesions located in the center of the surrounding mucosa. The diameter of the specimens (mean +/- SD) was 18.3 +/- 6.2 mm. All tumors were histologically typical, and the lateral and bottom margins of the specimens were free of tumor cells. No recurrences or distant metastases were found in any of the patients during the mean observation period of 13.3 months. CONCLUSIONS: We conclude that aspiration lumpectomy is a useful and safe technique for the treatment of small rectal carcinoid tumors contained within the submucosa.

Carcinoid Tumor↗
PubMed1997

Hypersensitivity to mosquito bites conceals clonal lymphoproliferation of Epstein-Barr viral DNA-positive natural killer cells.

In order to clarify the relationship between Epstein-Barr (EB) virus and hypersensitivity to mosquito bites (HMB), and to search for the mechanism which induces EB virus-associated lymphoproliferative diseases, we investigated patients with HMB, using hematological, immunological and virological techniques. Among 5 cases of HMB, CD56+ cells had proliferated and CD3+ cells were diminished in 4 cases. Although anti-EB virus antibody titers were not consistent with chronic active EB virus infection, EB viral DNA was detected in the peripheral blood mononuclear cells in all 5 cases. Moreover, EB viral DNA-positive cells had proliferated monoclonally in 4 cases, and biclonally in 1 case. It was proved that most of the EB viral DNA existed in natural killer (NK) cells through polymerase chain reaction analysis. These findings suggest that the basis of HMB may be clonal lymphoproliferation of EB viral DNA-positive NK cells and this hematological abnormality may induce the characteristic symptoms of HMB. In some cases, the proliferating NK cells can metamorphose into leukemic cells, and hemophagocytic syndrome, which has been assumed to be a complication of HMB, may then occur.

Adolescent↗
PubMed1997

Antitumor effect of transcatheter oily chemoembolization for hepatocellular carcinoma assessed by computed tomography: role of iodized oil.

The efficacy of transcatheter oily chemoembolization (TOCE) was evaluated in 82 patients with unresectable hepatocellular carcinoma (HCC) by computed tomography more than 6 months after TOCE. A doxorubicin in oil emulsion (DOE) was administered to 42 cases and an epirubicin in oil emulsion (EOE) was administered to 40 cases. No significant differences were found in the patient background characteristics between the DOE-treated group and the EOE-treated group. Tumor regression of more than 50% of the product of two dimensions was observed in 26 DOE-treated cases and in 25 EOE-treated cases at 1 year or more after TOCE. No difference in antitumor effect was observed between DOE and EOE, although a sufficient dose per tumor volume would be required to manifest an antitumor effect on hepatocellular carcinoma.

Antibiotics, Antineoplastic↗
PubMed1996

Differing roles for B7 and intercellular adhesion molecule-1 in negative selection of thymocytes.

To ensure self tolerance, immature thymocytes with high binding affinity for self peptides linked to major histocompatibility complex (MHC) molecules are eliminated in situ via apoptosis (negative selection). The roles of two costimulatory molecules, B7-1 and intercellular adhesion molecule-1 (ICAM-1), in negative selection was examined by studying apoptosis of T cell receptor transgenic CD4+8+ thymocytes cultured with specific peptides presented by MHC class I-transfected Drosophila cells. When coexpressed on these cells, B7-1 and ICAM-1 act synergistically and cause strong class 1-restricted negative selection of thymocytes. When expressed separately, however, B7-1 and ICAM-1 display opposite functions: negative selection is augmented by B7-1, but is inhibited by ICAM-1. It is notable that B7-1 is expressed selectively in the thymic medulla, whereas ICAM-1 is expressed throughout the thymus. Because of this distribution, the differing functions of B7-1 and ICAM-1 may dictate the sites of positive and negative selection. Thus, in the cortex, the presence of ICAM-1, but not B7-1, on the cortical epithelium may preclude or reduce negative selection and thereby promote positive selection. Conversely, the combined expression of B7-1 and ICAM-1 may define the medulla as the principal site of negative selection.

Amino Acid Sequence↗