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Biomedical subjects

T Kitamura

Publications and source records attributed to T Kitamura.

At least 307 records · Page 17Linked to original sources

Single and repeated elective abortions in Japan: a psychosocial study.

Despite its social, legal and medical importance, termination of pregnancy (TOP) (induced abortion) has rarely been the focus of psychosocial research. Of a total of 1329 women who consecutively attended the antenatal clinic of a general hospital in Japan, 635 were expecting their first baby. Of these 635 women, 103 (16.2%) had experienced TOP once previously (first aborters), while 47 (7.4%) had experienced TOP two or more times (repeated aborters). Discriminant function analysis was performed using psychosocial variables found to be significantly associated with either first abortion or repeated abortion in bivariate analyses. This revealed that both first and repeated aborters could be predicted by smoking habits and an unwanted current pregnancy while the repeated aborters appear to differ from first aborters in having a longer pre-marital dating period, non-arranged marriages, smoking habits, early maternal loss experience or a low level of maternal care during childhood. These findings suggest that both the frequency of abortion and its repetition have psychosocial origins.

Abortion, Induced↗

Cytokine receptors: structures and signal transduction.

The characteristic features of cytokines are functional pleiotropy and redundancy. Each cytokine is produced by a variety of cell types and acts on a wide range of target cells and tissues. Many cytokines have overlapping biological activities in the same cells. It was originally thought that each cytokine has a specific receptor and a unique signal transduction system. However, extensive studies on cytokines and their receptors revealed that many cytokines share receptor subunits and signal transduction system, and that biological functions of a single cytokine can vary depending on the status of the cells. Therefore, it is important to know the structure and function of cytokine receptors to understand the pleiotropy and redundancy as well as specificity of cytokines. Among signal transduction pathways, recently identified Jak/STAT pathway, which connects activation of the receptor complexes and transcription of various genes directly, would give us further insights in the mechanisms of cytokine action.

Animals↗

[Balloon-occluded arterial infusion chemotherapy in treatment of the patients with locally recurrent carcinoma of the cervix who previously received radiation therapy].

Nine patients with locally recurrent carcinoma of the cervix were treated with balloon-occluded arterial infusion chemotherapy (BOAI) in order to secure high concentrations of antitumor agents. All the patients had previously received radiation therapy for squamous cell carcinoma of the cervix. Recurrence was diagnosed by cytology and/or biopsy, or CT. Either cisplatin 100 mg/body and doxorubicin hydrochloride 40 mg/body or cisplatin 50-100 mg/body and pirarubicin 40-60 mg/body were infused after the bilateral internal iliac arteries had been occluded using balloon catheters. As the largest diameter of the tumors on CT increased, the mean survival after BOAI decreased. The mean survival of 4 patients with no detectable masses on CT was 45 +/- 30.7 months. In 5 patients, neurological complications, subcutaneous and/ or skin reactions of the buttock, or necrosis of the uterus developed. The neurological complications were damage to the sciatic nerve at the level of S1 or S2. Our study suggests that BOAI therapy may lead to a high complication rate in patients with locally recurrent carcinoma of the cervix who previously received radiation therapy, although long-term survival can be expected in patients with no detectable masses on CT.

Antineoplastic Combined Chemotherapy Protocols↗

[SMANCS-TAE combined with PEI in the treatment for hepatocellular carcinoma].

From January 1996 to August 1997, 24 patients with advanced hepatocellular carcinoma (HCC) equal to or more than 2 cm (mean +/- SD; 4.1 +/- 3.0 cm) in main tumor diameter were treated by SMANCS-TAE (20 cases) or SMANCS-TAI (4 cases) combined with PEI. Six cases had solitary lesion, 16 cases had multiple lesions, and 2 cases had massive lesions. After this combination therapy, 21 of 24 cases had complete tumor necrosis. During 3 to 19 months follow up period, 12 cases had cancer-free survival (SMANCS-TAI; 3 cases), and 9 cases had tumor recurrences (3 cases were local recurrences and 6 cases involved new lesions). Two cases died of hepatic infarction and cancer death, however, the remaining 22 cases were surviving. SMANCS-TAE combined with PEI is useful treatment for advanced large or multiple HCC lesions in patients who are poor surgical risks.

Aged↗

[Surgical or medical castration with LH-RH analogue for prostatic cancer].

Since the discovery by Huggins and Hodges that androgen deprivation therapy is effective for prostatic cancer, surgical castration or the administration of exogenous estrogen has been the mainstay of treatment for advanced prostatic cancer. However, surgical castration is refused by some patients because of psychological impact and estrogen therapy is reported to be associated with significant morbidity and mortality. The chronic administration of superactive analogue of LHRH has been shown to suppress markedly gonadal steroidogenesis. Medical castration with LHRH analogue has been demonstrated to be safe and effective in patients with advanced prostatic cancer. But the traditional surgical castration still remains as another powerful option, because it is more excellent in the points of compliance and cost-benefit than a monthly injection of expensive LH-RH analogue.

Antineoplastic Agents, Hormonal↗

Liver regeneration, liver cancers and cyclins.

Accumulating evidence has revealed that malignant cell growth is regulated by complex mechanisms involved in genetic and epigenetic factors. Among human cancers, cancer in the liver (hepatocellular carcinoma (HCC)) is characterized by the evidence that it is usually based on chronic liver diseases such as liver cirrhosis or chronic hepatitis, in which the liver is persistently regenerating following hepatic injury. This raises the possibility that repeated hepatocyte proliferation may cause disorder of genes that are regulating the cell cycle in hepatocytes, thus causing HCC. In this article, recent studies focusing on liver regeneration and cancer are reviewed from the viewpoint of the cell cycle that is regulated by cyclin and the associated proteins.

Carcinoma, Hepatocellular↗

Hepatic and renal expression of senescence marker protein-30 and its biological significance.

A novel rat hepatic protein was detected and isolated, the amount of which is downregulated in an androgen-independent manner with ageing. This protein was designated as senescence marker protein-30 (SMP30). Senescence marker protein-30 turned out to be identical to a hepatic calcium-binding protein called regucalcin (RC). This review gives an overview of SMP30 in its structure, expression and possible physiological function(s). A hypothetical role of SMP30 in ageing and calcium homeostasis is also discussed.

Aging↗

Development of a novel selective amplifier gene for controllable expansion of transduced hematopoietic cells.

To overcome the low efficiency of gene transfer into hematopoietic cells, we developed a novel system for selective expansion of transduced cells. To this end, we constructed a chimeric cDNA (GCRER) encoding the fusion protein between the granulocyte colony-stimulating factor receptor (G-CSFR) and the hormone-binding domain (HBD) of the estrogen receptor (ER) as a selective amplifier gene. Use of the intracellular signaling pathway of G-CSFR was considered to be appropriate, because G-CSF has the ability not only to stimulate the neutrophil production, but also to expand the hematopoietic stem/progenitor cell pool in vivo. To activate the exogenous G-CSFR signal domain selectively, the estrogen/ER-HBD system was used as a molecular switch in this study. When the GCRER gene was expressed in the interleukin-3 (IL-3)-dependent murine cell line, Ba/F3, the cells showed IL-3-independent growth in response to G-CSF or estrogen. Moreover, the Ba/F3 cells transfected with the Delta(5-195)GCRER, whose product lacks the extracellular G-CSF-binding domain, did not respond to G-CSF, but retained the ability for estrogen-dependent growth. Further, murine bone marrow cells transduced with the GCRER or Delta(5-195)GCRER gene with retroviral vectors formed a significant number of colonies in response to estrogen, as well as G-CSF, whereas estrogen did not stimulate colony formation by untransduced murine bone marrow cells. It is noteworthy that erythroid colonies were apparently formed by the bone marrow cells transduced with the GCRER gene in the presence of estrogen without the addition of erythropoietin, suggesting that the signals from the G-CSFR portion of the chimeric molecules do not preferentially induce neutrophilic differentiation, but just promote the differentiation depending on the nature of the target cells. We speculate that when the selective amplifier genes are expressed in the primitive hematopoietic stem cells, the growth signal predominates and that the population of transduced stem cells expands upon estrogen treatment, even if some of the cells enter the differentiation pathway. The present study suggests that this strategy is applicable to the in vivo selective expansion of transduced hematopoietic stem cells.

Animals↗

Typing of urinary JC virus DNA offers a novel means of tracing human migrations.

Although polyomavirus JC (JCV) is the proven pathogen of progressive multifocal leukoencephalopathy, the fatal demyelinating disease, this virus is ubiquitous as a usually harmless symbiote among human beings. JCV propagates in the adult kidney and excretes its progeny in urine, from which JCV DNA can readily be recovered. The main mode of transmission of JCV is from parents to children through long cohabitation. In this study, we collected a substantial number of urine samples from native inhabitants of 34 countries in Europe, Africa, and Asia. A 610-bp segment of JCV DNA was amplified from each urine sample, and its DNA sequence was determined. A worldwide phylogenetic tree subsequently constructed revealed the presence of nine subtypes including minor ones. Five subtypes (EU, Af2, B1, SC, and CY) occupied rather large territories that overlapped with each other at their boundaries. The entire Europe, northern Africa, and western Asia were the domain of EU, whereas the domain of Af2 included nearly all of Africa and southwestern Asia all the way to the northeastern edge of India. Partially overlapping domains in Asia were occupied by subtypes B1, SC, and CY. Of particular interest was the recovery of JCV subtypes in a pocket or pockets that were separated by great geographic distances from the main domains of those subtypes. Certain of these pockets can readily be explained by recent migrations of human populations carrying these subtypes. Overall, it appears that JCV genotyping promises to reveal previously unknown human migration routes: ancient as well as recent.

Adult↗

Plus- and minus-stranded hepatitis G virus RNA in liver tissue and in peripheral blood mononuclear cells.

Hepatitis G virus (HGV), which was recently identified, is a single, plus-stranded RNA virus that is thought to replicate via minus-stranded RNA, but no information is available about the distribution of either plus- (genomic) or minus- (replicative) stranded HGV RNAs in HGV infected patients. We, therefore, tested the serum, liver tissue, and peripheral blood mononuclear cells (PBMCs) of six hepatitis patients with HGV infection for the presence of plus- and minus-stranded HGV RNA. The RT-nested PCR was used with primers derived from 5'-noncoding region of the genome. Before RT-PCR analysis, the 3'-termini of RNA specimens were chemically modified to discriminate between plus- and minus-stranded HGV RNA. Plus-stranded HGV RNA was detected in the serum and liver tissue of all six patients and in the PBMCs of five patients. Minus-stranded RNA was detected in the liver tissue of all six patients, in the serum of two patients, and in the PBMCs of one patient. In summary, the detection of minus-stranded HGV RNA in liver tissue may indicate that HGV replicates in the liver.

Flaviviridae↗

Differences of the primate flocculus and ventral paraflocculus in the mossy and climbing fiber input organization.

Potential sources of cerebellar cortical afferent fibers were identified in the vestibular ganglion, medulla oblongata, pons, and cerebellar nucleus of seven anesthetized Macaca fuscata after local injections of wheat germ agglutinin-conjugated horseradish peroxidase or Fast Blue into the flocculus (FL) or ventral paraflocculus (VP). There were differences in the sources of mossy fibers to the FL and VP. Labeled neurons, after injections into the FL, were located mainly in the ipsilateral vestibular ganglion, bilaterally in the vestibular and prepositus hypoglossal nuclei, nucleus reticularis tegmenti pontis, and the central part of the mesencephalic reticular formation including the raphe nuclei. Labeled neurons were rarely seen in the pontine nuclei after injections into the FL. By contrast, after injections into the VP, numerous labeled neurons were located in the contralateral pontine nuclei, but relatively few in the vestibular nuclei bilaterally. Sources of climbing fibers to the FL and VP were completely contralateral to the injection side. After the injection into the FL and VP, labeled neurons were located in the dorsal cap, ventrolateral outgrowth, and ventral part of the medial accessory olivary nucleus. The projections from these three olivary areas were generally consistent with a zonal pattern of terminations in the FL and VP. The present results are consistent with a hypothesis that the FL is mainly involved in the control of vestibulo-ocular reflex and that the VP is mainly involved in the control of smooth pursuit eye movements.

Afferent Pathways↗

Thirteen-week subchronic toxicity study of thiamphenicol in F344 rats.

A 13-week subchronic toxicity study of thiamphenicol (TAP) was performed in F344 rats. The minimum lethal dose was estimated to be greater than 10 g/kg body weight, when a single dose of 4-10 g/kg of TAP was given orally. In the subchronic toxicity study, groups of 12 F344 rats of each sex were given solutions containing 0 (control), 125, 250 and 500 ppm of TAP as their drinking water ad libitum for 13 weeks. Body weight gain was significantly suppressed in both sexes of the 250 and 500 ppm groups. Slight suppression of erythropoiesis was observed in the highest-dose group along with slightly reduced spermatogenesis in the testes of the males. In addition, spermatogranulomas were found in the epididymis of both middle- and highest-dose groups. The no observed adverse effect level (NOAEL) was concluded to be 125 ppm (daily doses of 9.0 mg/kg in males and 11.6 mg/kg in females). From the above described results, doses of 250 and 125 ppm were selected as appropriate for a 2-year carcinogenicity study.

Animals↗

Bruton's tyrosine kinase regulates apoptosis and JNK/SAPK kinase activity.

Mast cells derived from Bruton's tyrosine kinase (Btk)-defective xid or btk null mice showed greater expansion in culture containing interleukin-3 (IL-3) than those from wild-type (wt) mice. Although the proliferative response to IL-3 was not significantly different between the wt and xid mast cells, xid and btk null mast cells died by apoptosis more slowly than their wt counterparts upon IL-3 deprivation. Consistent with these findings, the apoptosis-linked c-Jun N-terminal kinase/stress-activated protein kinase (JNK) activity was compromised in these btk-mutated cells upon Fc(epsilon)RI crosslinking or upon stimulation with IL-3 or with stem cell factor. p38 activity was less severely, but significantly, affected by btk mutation, whereas extracellular signal-regulated kinases were not affected by the same mutation. Btk-mediated regulation of apoptosis and JNK activity was confirmed by reconstitution of btk null mutant mast cells with the wt btk cDNA. Furthermore, growth factor withdrawal induced the activation and sustained activity of JNK in wt mast cells, while JNK activity was consistently lower in btk-mutated mast cells. These results support the notion that Btk regulates apoptosis through the JNK activation.

Agammaglobulinaemia Tyrosine Kinase↗

Analysis of prognostic factors in stage IIB-IVA cervical carcinoma treated with radiation therapy: value of computed tomography.

PURPOSE: To define the influence of the tumor size measured by computed tomography (CT) and lymph node involvement detected by CT in patients treated with radiation therapy for Stage IIB-IVA carcinoma of intact uterine cervix. METHODS AND MATERIALS: This was a retrospective analysis of 233 patients with uterine cervical cancer managed with both external irradiation and high-dose-rate intracavitary brachytherapy (HDR-ICR) at Kanagawa Cancer Center. The results were analyzed for the end points of absolute survival (AS), disease-free survival (DFS), pelvic control (PC), and central control (CC). The parameters of stage, CT-measured anterior-posterior (AP) cervix size, and CT-detected lymph node metastases were evaluated using univariate and multivariate analysis. RESULTS: The stage, AP cervix size, and lymph node involvement were significant pretreatment factors in univariate analysis with respect to AS, DFS, PC, and CC. Multivariate analysis confirmed that significant risk was associated with certain prognostic parameters. Those in terms of AS, in order of decreasing significance, were lymph node involvement, AP cervix size, age, and total HDR-ICR dose. When DFS was studied, lymph node involvement and AP cervix size were demonstrated to have a significant effect. Stage and lymph node involvement significantly affected PC. CONCLUSION: Because the International Federation of Gynecological Obstetrics staging system fails to incorporate important prognostic information about tumor volume and lymph node involvement, CT-detected lymph node metastases as well as CT-measured cervix size should be determined as complementary additional prognostic measures.

Adult↗

Interaction of Nck-associated protein 1 with activated GTP-binding protein Rac.

Bacterially expressed glutathione S-transferase fusion proteins containing Rac1 were used to identify binding proteins of this Rho family GTPase present in a bovine brain extract. Five proteins of 85, 110, 125, 140 and 170 kDa were detected, all of which were associated exclusively with guanosine 5'-[gamma-thio]triphosphate-bound Rac1, not with GDP-bound Rac1. The 85 and 110 kDa proteins were identified as the regulatory and catalytic subunits respectively of phosphatidylinositol 3-kinase. Several lines of evidence suggested that the 125 kDa protein is identical with Nck-associated protein 1 (Nap1). The mobilities of the 125 kDa protein and Nap1 on SDS/PAGE were indistinguishable, and the 125 kDa protein was depleted from brain extract by preincubation with the Src homology 3 domain of Nck to which Nap1 binds. Furthermore, antibodies to Nap1 reacted with the 125 kDa protein. Nap1 was co-immunoprecipitated with a constitutively active form of Rac expressed in Chinese hamster ovary cells. The observation that complex formation between activated Rac and PAK, but not that between Rac and Nap1, could be reproduced in vitro with recombinant proteins indicates that the interaction of Nap1 with Rac is indirect. The 140 kDa Rac-binding protein is a potential candidate for a link that connects Nap1 to Rac. The multimolecular complex comprising Rac, Nap1 and probably the 140 kDa protein might mediate some of the biological effects transmitted by the multipotent GTPase.

Animals↗

Diagnosis of carcinoma in situ of the pancreas by peroral pancreatoscopy and pancreatoscopic cytology.

BACKGROUND: Most pancreatic carcinomas are unresectable at the time of diagnosis, but recently the diagnosis of carcinoma in situ of the pancreas has become possible. This diagnosis can be made by the detection of cancer cells in pancreatic juice and the radiographically demonstrated lack of a mass lesion. It has greatly improved the effectiveness of surgery. Carcinoma in situ remains within the pancreatic ductal epithelium and has not yet invaded the parenchyma. However, it has often been difficult to locate carcinoma in situ by conventional diagnostic methods, such as ultrasonography, endoscopic ultrasonography, computed tomography, and endoscopic retrograde pancreatography. METHODS: Peroral pancreatoscopy and a new method of cytodiagnosis, pancreatoscopic cytology, were used to analyze 11 patients with carcinoma in situ of the pancreas, 10 with disease in the main duct of the pancreas and 1 with disease in the branch ducts. The results of pancreatoscopic cytology were compared with those of conventional pancreatic juice cytology. RESULTS: Under peroral pancreatoscopy, carcinoma in situ of the pancreas in the main duct appeared as papillary mucosa, irregular mucosa, or nodular mucosa. Using pancreatoscopic cytology, cancer cells were obtained from all the lesions, allowing a more thorough analysis than pancreatic juice cytology. CONCLUSIONS: Peroral pancreatoscopy and pancreatoscopic cytology are useful for locating and diagnosing carcinoma in situ of the pancreas.

Aged↗