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Biomedical subjects

T Ito

Publications and source records attributed to T Ito.

At least 199 records · Page 11Linked to original sources

Repeated thalamic haemorrhage: case report and review of the literature.

Recurrence of thalamic haemorrhage has rarely been reported. A 70-year-old woman had recurrent thalamic haemorrhage five-times during a period of 6 years. The first, second and fifth haemorrhages were located in the right thalamic region, and the third and fourth haemorrhages in the left thalamic region. Cranial computed tomography and magnetic resonance imaging revealed no abnormal lesion. After the first, second, and third haemorrhage with medical treatments, the patient recovered her functional ability or was at least capable of self-care at home. However, after the fourth and fifth haemorrhage, with medical therapy the patient's prognosis was severe disability. In this case, systemic blood pressure was normalized without antihypertensive agents after the first attack. However, there was an episode of sudden hypertension at each attack. Although the mechanism of rebleeding has not been clarified, rebleeding might be associated with changes of cerebral circulation following the previous haemorrhage.

Aged↗

Decreased plasma activity of antithrombin or protein C is not due to consumption coagulopathy in septic patients with disseminated intravascular coagulation.

We investigated whether depressed plasma antithrombin and protein C activity, considered as a specific finding of disseminated intravascular coagulation (DIC), is due to consumption coagulopathy in septic patients with DIC. An analysis of hemostatic parameters was performed in 139 septic patients (68 with DIC and 71 without DIC). Plasma activity of antithrombin and protein C tended to be significantly decreased in septic patients with DIC but not in those without DIC (p < 0.001). However, when the septic patients were classified into three groups according to the albumin (or choline esterase) level, no significant differences in antithrombin activity or protein C activity were observed between the patients with and without DIC in any of the subgroups. Notably, neither the plasma activity of antithrombin nor protein C was decreased even in septic patients with DIC who had normal plasma levels of albumin (or choline esterase). No significant correlation was observed between plasma levels of thrombin-antithrombin complex (TAT) and antithrombin activity, or between plasma levels of TAT and protein C activity either in septic patients with DIC or without DIC. It is reasonable to conclude that the markedly reduced plasma activity of antithrombin and protein C is not due to consumption coagulopathy in septic patients with DIC.

Aged↗

Effects of 5-HT(4) receptor agonists, cisapride and mosapride citrate on electrocardiogram in anaesthetized rats and guinea-pigs and conscious cats.

The purpose of this study was to examine the arrhythmogenic potential of 5-HT4 receptor agonists, cisapride and mosapride citrate (mosapride) in vivo. In anaesthetized rats, cisapride at intravenous infusion of 10 and 30 mg/kg/hr for 1 hr prolonged the electrocardiographic RR and QT intervals, whereas at 3 mg/kg/hr, it prolonged the RR interval without affecting the QT interval. Mosapride at 30 mg/kg/hr for 1 hr slightly, but not significantly, prolonged the QT interval. In anaesthetized guinea-pigs, cisapride at intravenous infusion of 0.3, 1 and 3 mg/kg over 15 min. prolonged the RR interval (18-44%), QT interval (18-42%) and the corrected QT interval (QTc; 8-19%). Mosapride at 3, 10 and 30 mg/kg over 15 min. little affected the QTc although at 30 mg/kg, it slightly prolonged the RR and QT intervals. With repeated oral administrations of 30 mg/kg twice a day for 7 days, cisapride prolonged the QT interval (11-35%) and QTc (11-32%) at the 3rd and 7th days in conscious cats. In addition, cisapride depressed the ST segment in two out of five cats. Mosapride at 60 mg/kg twice a day for 7 days did not affect the QT interval or QTc in cats. The maximal plasma concentrations of mosapride and its main metabolite (a des-4-fluorobenzyl-mosapride) at the 7th day in cats were 9.4+/-2.8 microM and 2.5+/-0.3 microM , respectively, being 100 and 30-60 times higher than those in man given therapeutic doses (Sakashita et al. 1993a&b). These results indicate that mosapride has little arrhythmogenic potential.

Anesthesia↗

Solution structure of the PX domain, a target of the SH3 domain.

The phox homology (PX) domain is a novel protein module containing a conserved proline-rich motif. We have shown that the PX domain isolated from the human p47phox protein, a soluble subunit of phagocyte NADPH oxidase, binds specifically to the C-terminal SH3 domain derived from the same protein. The solution structure of p47 PX has an alpha + beta structure with a novel folding motif topology and reveals that the proline-rich motif is presented on the molecular surface for easy recognition by the SH3 domain. The proline-rich motif of p47 PX in the free state adopts a distorted left-handed polyproline type II helix conformation.

Amino Acid Motifs↗

Modulation of the expression of the Cip/Kip family of cyclin-dependent kinase inhibitors in foetal developing lungs of hamsters.

We examine the cell proliferation activity and expression of cyclin-dependent kinase inhibitors of the Cip/Kip family, p21Cip1, p27Kip1 and p57Kip2, in foetal hamster lungs to determine the expression patterns of the cyclin-dependent kinase inhibitors and to clarify the relationship between expression of the cyclin-dependent kinase inhibitors and lung development. Foetal hamster lungs on gestational days 12.5-16 (the day of birth) and adult lungs were fixed in 4% paraformaldehyde. Frozen sections were immunostained for the cyclin-dependent kinase inhibitors, and examined by immunostaining for Ki-67 and bromodeoxyuridine to determine the proliferation activity of the foetal lungs. During the foetal period, cell proliferation activity, as analysed by Ki-67 or bromodeoxyuridine labelling, decreased with development of the lung. In contrast to the gradual decrease of cell proliferation activity, cells with p27Kip1 immunoreactivity increased with development. On the other hand, p21Cip1-positive cells were most prominent around gestational day 14.5, while after birth positive cells decreased markedly. A few p57Kip2-positive cells were detected in the bronchiolar epithelium on gestational day 14.5. Western blotting analyses confirmed these immunostaining patterns. Thus, the levels of the cyclin-dependent kinase inhibitors of the Cip/Kip family are modulated in the lungs during the foetal period, and each shows a unique expression pattern. The cyclin-dependent kinase inhibitors may play roles not only in regulating cell proliferation activity but also in regulating other functions such as differentiation in the lung during the foetal period.

Aging↗

Human homologues of the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C.

BACKGROUND: Asymmetric cell division in the Caenorhabditis elegans embryos requires products of par (partitioning defective) genes 1-6 and atypical protein kinase C (aPKC), whereas Cdc42 and Rac, members of the Rho family GTPases, play an essential role in cell polarity establishment in yeast and mammalian cells. However, little is known about a link between PAR proteins and the GTPases in cell polarization. RESULTS: Here we have cloned cDNAs for three human homologues of PAR6, designated PAR6alpha, beta and gamma, comprising 345, 372 and 376 amino acids, respectively. The PAR6 proteins harbour a PDZ domain and a CRIB-like motif, and directly interact with GTP-bound Rac and Cdc42 via this motif and with the aPKC isoforms PKCiota/lambda and PKCzeta via the N-terminal head-to-head association. These interactions are not mutually exclusive, thereby allowing the PAR6 proteins to form a ternary complex with the GTPases and aPKC, both in vitro and in vivo. When PAR6 and aPKC are expressed with a constitutively active form of Rac in HeLa or COS-7 cells, these proteins co-localize to membrane ruffles, which are known to occur at the leading edge of polarized cells during cell movement. CONCLUSION: Human PAR6 homologues most likely play an important role in the cell polarization of mammalian cells, by functioning as an adaptor protein that links activated Rac and Cdc42 to aPKC signalling.

Amino Acid Sequence↗

Diverse gene expression and function of semaphorins in developing lung: positive and negative regulatory roles of semaphorins in lung branching morphogenesis.

BACKGROUND: Previously, we reported that Sema3A, one of the secreted repulsive axon guidance molecules, CRMP (collapsin response mediator protein)-2, a putative intracellular signalling molecule for Sema3A and Sema3A receptor neuropilin-1 are expressed in the developing lung. Sema3A inhibits branching morphogenesis of embryonic lung in organ culture. RESULTS: We examined the gene expression of Sema3A, Sema3C, Sema3F and their receptors, NP-1, NP-2 and plexin-A1 by in situ hybridization. Transcripts of all six genes were detected in mouse lung from embryonic day E11.5 to E17.5, and displayed highly specific spatiotemporal distributions. The distribution of the receptor genes was detected in patterns which were consistent with known receptor usage of the semaphorins. In contrast to Sema3A, we found that the other class 3 semaphorins, Sema3C and Sema3F, stimulated branching morphogenesis. This stimulatory effect of Sema3C or Sema3F was accompanied by a moderate increase in the incorporation of bromodeoxyuridine (BrdU) into DNA in the terminal epithelial cells. CONCLUSION: The coordinated expression patterns of different semaphorins and their receptors, together with the specific activities affecting branching morphogenesis, suggest that the semaphorins act as both positive and negative regulators of branching morphogenesis in the developing lung.

Animals↗

Rapidly destructive arthropathy of the hip in haemophilia.

The aetiology of rapidly destructive arthropathy is still being debated. We report a 48-year-old male haemophiliac who exhibited hip arthropathy that was similar to rapidly destructive arthropathy. The hip joint was destroyed 6 months after the onset of symptoms. Results of clinical and laboratory examinations did not show any features of neuropathic, inflammatory or septic arthropathy, except for coagulopathy. Magnetic resonance imaging revealed an expansive joint capsule with synovial proliferation in the affected hip joint. Total hip arthroplasty was carried out successfully with total resection of the synovial tissue and joint capsule. A histological examination revealed bone necrosis, nonspecific inflammation, haemosiderosis and synovial hypertrophy. The recurrent bleeding into the hip joint induced pronounced inflammation with synovial proliferation and acute destruction of bony tissue.

Hemophilia A↗

Serotonergic neurones in the dorsal raphe nucleus that project into the medial preoptic area contain oestrogen receptor beta.

Serotonin is involved in female sexual behaviour in which the medial preoptic area (MPA) has a pivotal role. The present study used immunohistochemistry, in situ hybridization and retrograde transport analysis to investigate whether serotonin neurones in the dorsal raphe nucleus (DRN) of females projecting into the MPA contained oestrogen receptor alpha or beta. The projection of serotonin neurones from the DRN to the MPA was confirmed using the microinjection of Fluoro-Gold (FG), a fluorescent retrograde tracer, into the MPA of ovariectomized (OVX-group) and OVX-rats treated with oestradiol benzoate (E2-group). A number of serotonin neurones in the DRN were labelled with FG, indicating that these serotonin neurones in DRN project their terminals into the MPA. FG-labelled serotonin neurones expressed ERbeta mRNA in the DRN, and the number of the serotonin neurones containing ERbeta mRNA between the OVX-group and the E2-treated group was not significantly different. Serotonin neurones in the DRN did not express ERalpha-immunoreactivity. Since previous findings showed that the density of serotonin-immunoreactive fibres and the concentration of serotonin within the MPA was significantly lower in the E2-group than the OVX-group, our present observations suggested that the regulatory effects of E2 on the serotonergic neurone system in the MPA may be via ERbeta within the serotonin-containing cells in the DRN of female rats.

Animals↗

Postoperative detection of alpha-fetoprotein mRNA in blood as a predictor for metastatic recurrence of hepatocellular carcinoma.

BACKGROUND: We tested for the presence of alpha-fetoprotein (AFP) mRNA by using nested RT-PCR in the peripheral blood of hepatocellular carcinoma (HCC) patients who had undergone curative surgery, and investigated the occurrence of intrahepatic and/or extrahepatic metastasis thereafter, to reveal the optimal timing of blood sampling for the prediction of metastatic recurrence. METHODS: Twenty-nine patients with HCC, who had been operated on were analyzed with RT-PCR at several points during the clinical course, and examined for metastatic recurrence for 3-28 months (mean = 18.7 months) after surgery. RESULTS: The presence of AFP mRNA before surgery was significantly correlated with the tumor size (P = 0.017). Metastatic recurrence was associated with the postoperative detection of AFP mRNA (P < 0.001), but not with the preoperative and/or perioperative detection. Furthermore, AFP mRNA was detected in some cases that showed low serum AFP levels at recurrence. The recurrence-free period after the detection of AFP mRNA varied from 1 to 12 months. CONCLUSIONS: The postoperative detection of AFP mRNA is useful for the prediction of metastatic recurrence, and long-term follow up with this method should be conducted.

Adult↗

Effects of vitamin B12 on bright light on cognitive and sleep-wake rhythm in Alzheimer-type dementia.

The present study investigated the effects of vitamin B12 (VB12) on circadian rhythm in Alzheimer-type dementia (ATD). Twenty-eight ATD patients were treated with bright light therapy (BLT) for 8 weeks. For the latter 4 weeks, half were treated with VB12 with BLT (BLT + VB12). We evaluated the cognitive state with Mini-Mental State Examination and the circadian rhythm with actigraphy after the fourth and eighth week. After the first 4 weeks BLT improved the circadian rhythm disturbances and cognitive state especially in the early stage of ATD. Although the latter 4 week-BLT caused no significant effects on the circadian rhythm; BLT + VB12 improved the vigilance level during the daytime. These results suggest that VB12 has some efficiency to enhance vigilance for ATD patients.

Aged↗

Primary signet-ring cell carcinoma of the urinary bladder inducing renal failure.

A case of primary signet-ring cell carcinoma of the urinary bladder that was found to have induced renal failure is the second such case reported in the world. Primary signet-ring cell carcinoma of the urinary bladder is a rare histologic variant of adenocarcinoma. The patient died of distant metastasis 8 months after undergoing total cystectomy. The neoplasm had a high stage at diagnosis, so the prognosis was very poor. To improve the prognosis, earlier diagnosis and establishing a regimen of chemotherapy is necessary.

Carcinoma, Signet Ring Cell↗

M1 prostate cancer with a serum level of prostate-specific antigen less than 10 ng/mL.

BACKGROUND: M1 prostate cancer, which is invasive, is usually associated with a serum level of prostate-specific antigen (PSA) greater than 10 ng/mL, but cases are occurring where the serum PSA level is less than this. The present study investigated the clinical and pathologic characteristics of these cases of M1 prostate cancer. METHODS: Between April 1989 and March 1998, 167 cases of M1 prostate cancer were diagnosed by transrectal needle biopsy and eight of these with a serum PSA level less than 10 ng/mL were investigated. The patients' ages ranged from 57 to 79 years (median, 73) and the serum PSA levels ranged from less than 4.0 to 9.8 ng/mL. In all cases except one, the distal metastasis was to bones only. All cases had received hormonal therapy as the initial therapy. Immunostaining of PSA, chromogranin A, neuron-specific enolase, carcinoembryonic antigen and vimentin were performed in five of the eight cases. RESULTS: Four cases were poorly differentiated, two were undifferentiated, one was a mixture of poorly differentiated and undifferentiated and one case was moderately differentiated. Of the five cases in the immunohistochemical study, three cases with an undifferentiated carcinoma component showed negative staining reactions for PSA and all cases were positive for carcinoembryonic antigen. Four of the patients died of prostate cancer. In two of these four cases, hormonal therapy was ineffective, but systemic chemotherapy and irradiation therapy had been moderately effective. The overall 3-year survival rate was 33.3%. CONCLUSIONS: The cases of M1 prostate cancer with a serum PSA less than 10 ng/mL are almost always poorly differentiated or undifferentiated and have a poor prognosis compared with the usual M1 prostate cancer. Because hormonal therapy is ineffective in these cases, systemic chemotherapy and irradiation therapy should be chosen as the initial therapy.

Aged↗

Acquisition of susceptibility to hepatitis C virus replication in HepG2 cells by fusion with primary human hepatocytes: establishment of a quantitative assay for hepatitis C virus infectivity in a cell culture system.

Hepatitis C virus (HCV) replicates in human and chimpanzee hepatocytes. To characterize the nature of HCV and evaluate antiviral agents, the development of an HCV replication system in a cell culture is essential. We developed a cell line derived from human hepatocytes by fusing them with a hepatoblastoma cell line, HepG2, and obtained several clones. When we tested the clones for their ability to support HCV replication by nested RT-PCR, we found 1 clone (IMY-N9) that was more susceptible to HCV replication than HepG2. The negative-strand HCV RNA was detected in IMY-N9 by strand-specific RT-PCR, and viral RNA was identified in culture supernatant during the culture. Then we monitored HCV RNA titers in IMY-N9 and HepG2, respectively, by real-time detection PCR throughout the culture. A significant increase in the HCV RNA titer was observed only in IMY-N9. Serial passages of HCV culture supernatant were shown in the culture system. Furthermore, we tested several infectious materials for viral infectivity by monitoring HCV RNA titers and/or 50% tissue culture infectious dose (TCID50) of HCV on IMY-N9. In each material, HCV showed various growth patterns and a different TCID50 even though the PCR titer in each material was identical. The results showed that HCV in each material served various growth patterns and different TCID50 even though PCR titer in each material was identical. This cell line is useful for estimating viral activity and for studying cellular factors that may be necessary to HCV replication in human hepatocytes.

Cell Fusion↗

Remnant-like particles cholesterol is higher in diabetic patients with coronary artery disease.

Diabetes mellitus (DM) has been well known to be one of the risk factors of coronary artery disease (CAD). Recently, remnant-like particles cholesterol (RLP-C) has been reported to be associated with CAD. However, few studies reported the association of RLP-C level with CAD in subjects with DM. To investigate the effects of presence or absence of DM on the association between RLP-C and CAD, we compared the RLP-C level in 142 male patients with CAD and 123 male subjects without CAD (non-CAD), including 44 and 38 DM patients, respectively. RLP-C was significantly higher in CAD than non-CAD (P <.05). RLP-C and RLP-C/plasma-triglyceride (TG) ratio in CAD with DM were higher than CAD without DM (P <.01, P <.05), and non-CAD with DM (P <.001, P <.05). There was positive correlation between RLP-C and plasma-TG in non-CAD without DM (r =.44, P <.01), non-CAD with DM (r =.56, P <.001), CAD without DM (r =.81, P <.0001), and CAD with DM (r =.75, P <.001). After excluding the hypertriglyceridemic patients (>200mg/dL), RLP-C/plasma-TG ratio was significantly higher in CAD with DM than CAD without DM (P <.001) and non-CAD with DM (P <.05). These results suggest that increased RLP-C to plasma-TG may be associated with CAD in middle-aged diabetic male subjects.

Blood Glucose↗

Progesterone stimulates the expression of aminopeptidase A/angiotensinase in human choriocarcinoma cells.

In human placenta aminopeptidase A (APA), a principal enzyme that converts angiotensin II to angiotensin III, seems to be involved in angiotensin II metabolism during pregnancy. In this study, we investigated the possible effects of progesterone and estrogen on APA mRNA and protein levels in choriocarcinoma cells as a model for placenta. By RNase protection assay, progesterone induced higher APA mRNA levels than estrogen at the same concentration. Progesterone exhibited dose-dependent stimulation of APA mRNA, 1.8-fold increase at 10(-6) m for 24 h treatment. Progesterone at 10(-6) m increased APA mRNA levels within 12 h and in time-dependent fashion up to 24 h. Fluorescence-activated cell sorting analysis and measurements of APA activities revealed the induction of APA protein by progesterone. Expression of progesterone receptors (PR) and glucocorticoid receptors (GR) were determined in these cells by RT-PCR, which suggested that the progesterone's actions might be displayed through PR and/or GR. These findings may serve as a useful model to study the effects of progesterone on angiotensin II metabolism in placenta, although the physiological validity of these studies remains to be clarified.

Aminopeptidases↗