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T Kitamura

Publications and source records attributed to T Kitamura.

At least 109 records · Page 6Linked to original sources
PubMed2001

Cholesterol requirement for cation-independent mannose 6-phosphate receptor exit from multivesicular late endosomes to the Golgi.

The regulation of endocytic traffic of receptors has central importance in the fine tuning of cell activities. Here, we provide evidence that cholesterol is required for the exit of cation-independent mannose 6-phosphate receptor (CI-MPR) from the endosomal carrier vesicle/multivesicular bodies (ECV/MVBs) to the Golgi. A previously established Chinese hamster ovary cell mutant, LEX2, exhibits arrested ECV/MVBs in which CI-MPR and lysosomal glycoprotein-B (lgp-B) are accumulated. The abnormal accumulation of CI-MPR within the ECV/MVBs in LEX2 cells was corrected in a post-translational manner by the supplementation of medium with cholesterol. Furthermore, it was shown that, by expression cloning using LEX2 mutant, the introduction of the NAD(P)H steroid dehydrogenase-like protein, an enzyme involved in the later stage of cholesterol biosynthesis, allows the exit of CI-MPR from the MVBs to the Golgi and reduces the number of arrested ECV/MVBs in LEX2 cells. The recovery of the exit transport of CI-MPR from the ECV/MVBs was associated with the restoration of the normal cellular free cholesterol level and segregation between CI-MPR and lgp-B, both of which had been localized at the internal small vesicles of the arrested ECV/MVBs. By contrast, the restoration of cholesterol failed to correct the defective processing of endocytosed LDL to a degradative compartment in LEX2 cells. These results suggest that cholesterol is required for ECV/MVB reorganization that drives the sorting/transport of materials destined for the Golgi out of the pathways towards lysosomes.

Animals↗
PubMed2001

Role of MgcRacGAP/Cyk4 as a regulator of the small GTPase Rho family in cytokinesis and cell differentiation.

To identify the key molecules that regulate differentiation of hematopoietic cells, we carried out retrovirus-mediated functional screening for cDNAs whose expression suppresses IL-6-induced differentiation of mouse myeloid leukemic M1 cells. From this screening, we obtained a full length cDNA encoding a mouse homologue of human MgcRacGAP. Overexpression of the anti-sense MgcRacGAP profoundly inhibited IL-6-induced macrophage-differentiation of M1 cells. On the other hand, overexpression of the full-length form of MgcRacGAP alone enhanced macrophage differentiation of M1 cells in response to IL-6, and induced macrophage differentiation of HL-60 leukemic cells. To determine how this protein regulates differentiation and proliferation, an antibody against MgcRacGAP was prepared. Immunohistochemical studies revealed that MgcRacGAP mainly localizes in the nucleus in interphase, accumulates on the mitotic spindle in metaphase, and is condensed in the midbody during cytokinesis. Overexpression of an N-terminal domain deletion mutant, which lacks the ability to localize to the midbody through association with tubulins, or a GAP-inactive mutant resulted in the formation of multinucleated cells in HeLa cells as well as in hemopoietic cells. Interestingly, MgcRacGAP in the midbody was phosphorylated probably on serine and threonine residues. These results indicate that MgcRacGAP regulates cytokinesis and cellular differentiation as a regulator of Rho family of GTPase and suggest that this process is controlled by some serine/threonine kinases.

Animals↗
PubMed2001

Case report: Hypoechoic area as an ultrasound finding suggesting subserosal invasion in polypoid carcinoma of the gall bladder.

Ultrasound studies have demonstrated the gall bladder wall to consist of two or more (usually three) layers. Gall bladder tumours with neither a thinned nor split outermost hyperechoic layer are confined to the mucosa or muscle layer, or have only invaded the shallow subserosa. Differentiation of these two types of tumour has posed difficulties. We report a case of polypoid gall bladder carcinoma invading the shallow subserosa with a thickened outermost hyperechoic layer but a hypoechoic area in the deeper part of the tumour. Ultrasound and pathological correlation in this case demonstrated that the hypoechoic area represented an adenocarcinoma invading the subserosa accompanied by abundant fibrosis.

Adenocarcinoma, Papillary↗
PubMed2001

Functional role of endogenous endothelin-1 in congestive heart failure treated with angiotensin II receptor antagonist.

Interactions between angiotensin (ANG) II and endothelin (ET)-1 receptor transduction pathways have been unclear in congestive heart failure (CHF). Therefore the objects of this study are, in CHF, whether production of ET-1 is modulated by ANG II and/or whether hemodynamic effects of endogenous ET-1 are modulated by ANG II. Twelve dogs were randomly assigned to two groups: untreated (n = 6) and treated with ANG II type 1 (AT1) receptor antagonist (TCV116, 1.5 mg/kg/d) (n = 6). After rapid ventricular pacing (240 bpm) for 4 weeks, plasma and cardiac ET-1 levels were compared between the two groups. Acute hemodynamic effects of a nonspecific ET(A&B) receptor antagonist, TAK044 (3 mg/kg plus 3 mg/kg/h i.v.) were examined in both groups by a conductance catheter and a micromanometer. After 4 weeks of pacing, plasma and cardiac tissue ET-1 levels were elevated in both groups to a similar degree. In the group treated with TCV116, TAK044 produced an increase in stroke volume and a decrease in total systemic resistance; heart rate was unchanged. The time constant of left ventricular (LV) relaxation was significantly decreased. The slope of LV end-systolic pressure-volume relation (E(ES)) was increased (p < 0.05), indicating an increased LV contractility. Thus endogenous ET-1 produces an arterial vasoconstriction and impairs LV contractility and relaxation in CHF with AT1 receptor antagonism. These hemodynamic responses to TAK044 in CHF treated with TCV116 were similar in untreated CHF. These results suggest that the production of ET-1 and the cardiac effects of endogenous ET-1 in CHF may be unaffected by ANG II acting through AT1 receptors.

Angiotensin Receptor Antagonists↗
PubMed2001

Diagnostic reliability and accuracy of pathological grief and psychiatric disorders among Japanese psychologists and psychology students.

The present study examined the reliability and accuracy of diagnoses regarding pathological grief and other psychiatric disorders using a case vignette design. Two Japanese psychologists (Ph.D. and M.A. levels) and five graduate students in psychology participated. Analysis suggests that psychologists and psychology students can reliably apply the diagnostic criteria for pathological grief and other psychiatric disorders.

Adult↗
PubMed2001

[Efficiency of bispectral index in anesthetic management of a patient with hypothyroidism].

A 72-year-old, female patient with severe hypothyroidism underwent tracheostomy using deltopectral flap. During the anesthetic management, we assessed the hypnotic level using the bispectral index and regulated the dose of general anesthetics to maintain the bispectral index at about 50. The general anesthetics caused a marked cardiovascular depression, but the condition was treatable with the intravenous administration of dopamine. Using these methods, we could anesthetize this patient safely without a prolonged awakening time from general anesthesia. Although the anesthetic requirement for patients with hypothyroidism is generally thought to be decreased, there is no practical index by which we can estimate the optimal dose of anesthetic agents for these patients. This case report shows that the assessment of the hypnotic level by the bispectral index can be utilized as an efficient index to determine the optimal dose of general anesthetics for patients with hypothyroidism.

Aged↗
PubMed2001

Decrease in platelet count during saturation diving.

BACKGROUND: The change in platelet count (PC) occurring during saturation diving has rarely been discussed. We set out to clarify the details of this change in PC, and its relationship with: i) the storage depth and duration of the saturation dive, and ii) the presence of decompression bubbles. METHODS: In a total of 42 divers, the change in PC was measured in 8 simulated saturation dives (1992-1998) using a Deep Diving Simulator with decompression procedures based on the modified DUKE-GKSS schedule. Blood samples were taken before the dive, at the bottom (twice), during decompression, on surfacing, and about 1 wk after surfacing. Decompression bubbles were examined by ultrasonic M-mode echocardiography. RESULTS: PC (mean +/- SD x 10(4) x microl(-1)) was 23.9 +/- 4.85, 24.9 +/- 4.9, 24.2 +/- 4.8, 19.2 +/- 4.4*, 20.1 +/- 4.5*, 25.0 +/- 5.1 on the occasions listed above (*= p < 0.05 vs. pre-dive). The PC showed no correlation with either storage depth or dive duration. Decompression bubbles were detected during decompression in only 2 divers (4.8%), and the bubbles disappeared immediately after surfacing. In these 2 divers the decreases in PC values from baseline to the middle of decompression and on surfacing were 2 and 2.7 x 10(4) x microl(-1), and 3.4 and 1.7 x 10(4) x microl(-1) respectively. No diver complained of decompression sickness. CONCLUSION: The magnitude of the decrease in PC (< 5 x 10(4) x microl(-1)) and the time to recover to the pre-dive value (< 1 wk) suggests that changes in PC during saturation diving should not cause any clinical problems. The mechanisms underlying the decrease in PC remain unclear.

Adult↗
PubMed2001

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (1)--Single oral and intravenous dose toxicity studies in rats].

A single oral dose toxicity study of Cefmatilen hydrochloride hydrate (S-1090) and a single intravenous dose toxicity study of its sodium salt (S-1090-Na) were conducted in rats. One dose level of 2000 mg potency/kg was set in both studies. Single oral dose toxicity study of S-1090 No deaths occurred. Diarrhea occurred on the dosing day and slightly soft feces lasted until 6 days after administration. These changes were considered to result from changes of intestinal flora induced by the antibiotic activity of S-1090. Reddish-brown feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet) were also observed until the next day after administration. Body weights increased favorably, and no S-1090-related pathological changes were observed. The oral lethal dose of S-1090 was estimated to be more than 2000 mg potency/kg. Single intravenous dose toxicity study of S-1090-Na No deaths occurred. The rats showed characteristic clinical signs such as hypoactivity, abnormal gait and hypopnea immediately after dosing, and some rats showed prone position or paleness of eyeballs and ear auricles in due course. These signs disappeared by 4 hr after administration. Slightly soft feces and reddish-brown feces were observed much the same as in the orally-treated rats. Body weights increased favorably. In the pathological examinations, slight cecal enlargement and increased basophilia, dilatation and calcification of the renal tubules in the kidney were observed. The intravenous lethal dose of S-1090-Na was estimated to be more than 2000 mg potency/kg.

Administration, Oral↗
PubMed2001

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (3)--One- and three-month repeated oral dose toxicity studies in rats].

One- or three-month repeated oral dose toxicity studies of Cefmatilen hydrochloride hydrate (S-1090) in rats were conducted. Doses were set at 80, 200, 500 and 1250 mg potency/kg/day in the one-month toxicity study, and 100, 300 and 1000 mg potency/kg/day in the three-month toxicity study. Body weights increased favorably and no deaths occurred in all treated groups of both studies. The changes observed in both studies were soft feces, abdominal distention, increased food and water consumption, decreases of urine volume and pH, and a decrease of blood neutrophils in almost all treated groups, reddish-brown feces (due to chelated products of S-1090 and its decomposition products with Fe3+ in the diet) in groups dosed at 300 mg potency/kg or more, and a lower mature granulocyte ratio in the bone marrow in groups dosed at 1000 mg potency/kg or more. In necropsy, cecal enlargement with a large amount of muddy content was observed in all treated groups of both studies. In the three-month toxicity study, elevated drug-metabolizing enzyme activities were noted in the liver of the males in the 1000 mg potency/kg group. These changes were slight except for the cecal enlargement and the rats recovered well with drug withdrawal. Since no toxicologically significant changes were noted in either study, the NOAEL of S-1090 was estimated to be 1250 mg potency/kg/day in the one-month toxicity study and 1000 mg potency/kg/day in the three-month toxicity study.

Administration, Oral↗
PubMed2001

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (4)--One- and three-month repeated oral dose toxicity studies in dogs].

One- or three-month repeated oral dose toxicity studies of Cefmatilen hydrochloride hydrate (S-1090) were conducted in beagle dogs. Doses were set at 25, 100 and 400 mg potency/kg/day in both studies. In both studies, no deaths occurred, and reddish-brown feces (due to chelated products of S-1090 and its decomposition products with Fe3+ in the diet) were observed in all treated groups. A transient excretion of reddish urine was observed in the 400 mg potency/kg group and a slight increase in plasma irons was also observed in the 100 and 400 mg potency/kg groups of both studies. However, as no changes suggesting anemia or hepatic injury were noted in these groups, the change of plasma irons was considered to have no toxicological significance. Plasma S-1090 concentrations increased in a manner less than dose-proportional in both studies. In the one-month toxicity study, no toxicologically significant changes, including the above findings, were noted, so the NOAEL was assessed to be 400 mg potency/kg/day. In the three-month toxicity study, urinalysis in the 400 mg potency/kg group revealed a positive reaction to occult blood and erythrocytes in sediments. In the pathological examinations, submucosal edema, hemorrhage, inflammatory cell infiltration and occasionally focal mucosal thickening were observed in the urinary bladder of the 400 mg potency/kg group. The cystisis was considered to result from chronic stimulation with the metabolite(s) of S-1090 in urine, and the reversibility was demonstrable upon one-month drug withdrawal. From these results, the NOAEL of S-1090 in the three-month toxicity study was assessed to be 100 mg potency/kg/day.

Administration, Oral↗
PubMed2001

[Anesthetic management of a hyper-obese patient by target-controlled infusion (TCI) of propofol and fentanyl].

We gave total intravenous anesthesia to an over-100% hyper-obese patient using target-controlled infusion (TCI) of propofol and fentanyl. To keep him asleep, we maintained his BIS in a range of 40 to 60 by adjusting the target concentration of propofol. For the target concentration of fentanyl, we chose 2 ng.ml-1 at incision and 1.6 ng.ml-1 during the operation. At the patient's emergence from anesthesia, his estimated blood concentration of propofol was 1.51 micrograms.ml-1 and his BIS was 80. The relationship between BIS value and effect-site concentration of propofol was almost the same as that assessed in ordinary adults of a normal weight. We conclude that the estimated concentration of propofol is a good indicator of the effect of propofol and that TCI is a useful technique in obese patients as well as in ordinary adults.

Adult↗
PubMed2001

[Anesthetic management for gastrojejunostomy in a patient with hemiplegia and recurrent laryngeal nerve palsy].

A 70-year-old man who had undergone a low anterior resection for primary rectal cancer 9 years before complained of anorexia, hemiplegia, and recurrent laryngeal nerve palsy. The anorexia was caused by duodenal stenosis due to swollen lymph nodes, the hemiplegia was caused by a metastatic brain tumor, and the recurrent laryngeal nerve palsy was caused by metastases of the cancer to the mediastinal space. Metastases were also found in the bilateral lungs, liver, ureter, and cervical vertebra. In choosing the anesthesia for the gastrojejunostomy to improve the malnutrition of this patient, we decided, on the basis of the patient's full stomach, malnutrition, hypovolemia, hemiplegia, cerebral compression, recurrent laryngeal nerve palsy, renal dysfunction, and respiratory dysfunction, to use thoracic epidural anesthesia rather than spinal anesthesia or general anesthesia. Thoracic epidural anesthesia could provide sufficient analgesia, and the operation was uneventful. In anesthetic management of an end-stage patient undergoing a palliative operation like this, we should consider the purpose of the operation, its complications, and further complications which may be induced by anesthesia in order to plan out an anesthetic regimen unlikely to lead to harmful events in perioperative period.

Aged↗
PubMed2001

[Epidemiological study of depression in Japan].

Recent epidemiological studies in Western countries have been carried out using either questionnaires or diagnostic structured interviews. Use of these instruments enhances the reliability and validity of epidemiological diagnoses and of transcultural comparisons. In Japan, psychiatric epidemiology is still in the 'neonatal' stage. A very limited number of studies have used a structured interview or operational diagnostic criteria. In these studies, the prevalence of Major Depression was surprisingly high, particularly in younger age groups. As in reports from Western countries, the prevalence was about twice as high among women as among men. In addition, some researchers have focused on depression in elderly or adolescent populations or in medical outpatients. However, such studies have all been of a small sample size. Studies with large samples are therefore required.

Adolescent↗
PubMed2001

Polymorphisms of two fucosyltransferase genes (Lewis and Secretor genes) involving type I Lewis antigens are associated with the presence of anti-Helicobacter pylori IgG antibody.

Helicobacter pylori attach to the gastric mucosa with adhesin, which binds to Lewis b (Le(b)) or H type I carbohydrate structures. The Secretor (Se) gene and Lewis (Le) gene are involved in type I Le antigen synthesis. The present study was performed to investigate the possibility that Se and Le gene polymorphisms alter the risk of H. pylori infection. Two hundred thirty-nine participants were genotyped for Se and Le and tested for the presence of anti-H. pylori IgG antibodies. Using the normal gastric mucosa from 60 gastric cancer patients, we assessed immunohistochemically whether type I Le antigen expression depended on the Se and Le genotypes. The H. pylori infection rate was positively associated with the number of Se alleles (se/se group, 45.1%; Se/se group, 64.6%; and Se/Se group, 73.3%) and negatively associated with the number of Le alleles (le/le group, 76.4%; Le/le group, 68.3%; and Le/Le group, 55.6%). When the subjects were classified into three groups [low risk, (se/se, Le/Le) genotype; high risk, (Se/Se, le/le), (Se/Se, Le/le), and (Se/se, le/le) genotypes; moderate risk, other than low- or high-risk group], the odds ratio relative to the low-risk group was 3.30 (95% confidence interval, 1.40-7.78) for the moderate-risk group and 10.33 (95% confidence interval, 3.16-33.8) for the high-risk group. Immunohistochemical analysis supported the finding that Se and Le genotypes affected the expression of H. pylori adhesin ligands. We conclude that Se and Le genotypes affect susceptibility to H. pylori infection.

Adult↗
PubMed2001

[The effects of the fat component of propofol solution of ketogenesis during propofol anesthesia].

To examine the effects of the fat component in propofol solution on the fat metabolism during propofol anesthesia, we measured the urine ketone body (UKB) and blood concentrations of 3-hydroxybutyrate (3-OHBA) and glucose. The anesthesia was maintained with propofol, fentanyl, and vecuronium. Infusion fluid without glucose was used while we measured the concentration of 3-OHBA. UKB was detected only when the concentration of 3-OHBA was more than 400 mumol.ml-1. The blood concentration of 3-OHBA increased in proportion to the total amount of propofol solution, while UKB did not show any such relationship. Furthermore, the rate of increase of 3-OHBA was larger in the group whose concentration of 3-OHBA was higher than the normal range. The blood concentration of glucose ranged within the normal fasting level. There were no cases who needed special treatment for hyperketonemia in this study. We concluded that 3-OHBA was a more sensitive indicator of ketogenesis than UKB, and that ketogenesis was accelerated both by propofol anesthesia with the lipidemic solution of propofol and by fasting before surgery. The acceleration of ketogenesis was especially marked in the patients with hyperketonemia.

3-Hydroxybutyric Acid↗
PubMed2001

[A case of ovarian cancer with metastatic tumor in the liver with paclitaxel and carboplatin systemic chemotherapy was very effective].

An 82-year-old woman was admitted to the Dept. of Obstetrics and Gynecology, Yamanashi Medical University to try to identify the origin of a liver metastatic tumor. CT examination revealed a small tumor located adjacent to the uterine cervix in a cul-de-sac. With biopsy using MR, it was clearly shown histologically that the origin of the tumor was the ovary. Systemic chemotherapy with paclitaxel and carboplatin was selected as the most reasonable treatment for this case because of the patient's age. After 6 courses of this chemotherapy, the tumor in the cul-de-sac disappeared and the tumor in the liver decreased markedly. Furthermore, no severe side effects were seen during this treatment. This result indicated that systemic chemotherapy with paclitaxel and carboplatin is effective and safe in cases of advanced ovarian cancer.

Adenocarcinoma↗
PubMed2001

[Anesthetic management using propofol and fentanyl for transrectal ultrasound-guided prostatic biopsy].

We prospectively evaluated the efficiency of the anesthetic management using propofol and fentanyl for the transrectal, ultrasound-guided, prostatic biopsy. In the anesthetic management for the transrectal, ultrasound-guided, prostatic biopsy, it is required to obtain enough muscle relaxation of the anal sphincter for placing the transrectal ultrasound probe and to secure immobilization of the patient during the prostatic biopsy. Eight patients undergoing the transrectal, ultrasound-guided, prostatic biopsy participated in this study. Without premedication, anesthesia was induced using fentanyl (100 micrograms) and target-controlled infusion of propofol with an estimated blood concentration of 3 micrograms.ml-1. We obtained both sufficient muscle relaxation of the anal sphincter and complete immobilization of the patient during the prostatic biopsy in all patients. Moreover, this anesthetic management assured short awakening time from anesthesia and low incidence of adverse effects. From these results, we conclude that the anesthetic management using propofol and fentanyl for the transrectal, ultrasound-guided, prostatic biopsy is efficient and practical.

Aged↗