Biomedical subjects
Publications and source records attributed to T Kitamura.
We report a case of a nerve sheath ganglion of the ulnar nerve at the canal of Guyon. This case involved a ganglion which was confined to the epineurium of the ulnar nerve. and it was completely excised without any damage to the nerve fiber. A nerve-sheath ganglion is rare, but it should be considered in the differential diagnosis of any tumor which is causing neural disturbance.
AIMS/HYPOTHESIS: To investigate whether proinsulin C peptide influences sympathetic nerve activity directly or indirectly through parasympathetic nerve activity. METHODS: The proliferative response of splenic lymphocytes to Concanavalin A (ConA response) which is known to be suppressed by subjection of rats to footshock or intracerebroventricular injection of corticotropin-releasing factor through sympathetic nerve activation was measured. Effect of C peptide alone or before subjection to footshock or injection of corticotropin-releasing factor was examined. RESULTS: Intraperitoneal injection of C peptide was without effect on the basal ConA response, while subjection to footshock or injection of corticotropin-releasing factor lowered it. In contrast, prior injection of C peptide obviated the footshock and corticotropin-releasing factor-induced suppression of the response. When given intracerebroventricularly, C peptide was also effective at much smaller doses. Prior injection of atropine cancelled the C-peptide effects. CONCLUSION/INTERPRETATION: Our results indicate that C peptide counteracts the sympathetic nerve-mediated suppression of splenic lymphocyte proliferation in an atropine-sensitive manner. Thus, C peptide probably activates the parasympathetic nervous system through the afferent mechanism, that in turn antagonizes the sympathetic nerve-mediated suppression of splenic lymphocyte functions.
UNLABELLED: Recently, a new and highly effective method termed suppressive subtractive hybridization (SSH) has been introduced to clone differentially expressed mRNAs. Genes expressed in androgen-independent but not in androgen-dependent tumors, and vice versa, are obviously significant to delineate the mechanisms of androgen dependency/independency of these tumors. Mouse mammary cancer (Shionogi carcinoma-115) has been extensively used to analyze the mechanism of androgen-dependent cancer growth. METHODS: We cloned androgen-independent and androgen-dependent Shionogi carcinoma-115 specific mRNAs by the SSH method. Cloned sequences were compared with known sequences using NCBI BLAST across the Internet. Two clones were positive for cDNA insert when androgen-independent cDNA was used as tester cDNA, while no clones were positive using the androgen-dependent tester cDNA. One of the former was mouse protein kinase C beta-II while the other was a new DNA sequence. Mouse protein kinase C beta-II mRNA and the new mRNA were shown to be differentially expressed by RT-PCR analysis in androgen-independent but not androgen-dependent Shionogi carcinoma. Two mRNA species differentially expressed in androgen-independent but not androgen-dependent Shionogi carcinoma were cloned by the SSH method. The significance of these mRNAs for androgen-dependency/independency of Shionogi carcinoma should be explained in future studies.
Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system caused by a ubiquitous human polyomavirus designated as JC virus (JCV). JCVs in the brain of PML patients (PML-type JCVs) contain various regulatory regions generated from the archetypal regulatory region during persistence in the patients. We determined the complete DNA sequences of 2 PML-type isolates and 5 archetype isolates. Amino acid sequences of individual viral proteins were deduced from complete DNA sequences, and were compared among 16 isolates (6 PML types and 10 archetypes). From the data obtained, we concluded that PML-associated amino acid changes did not occur in the viral proteins of PML-type JCVs.
BACKGROUND: Undertreatment of depression appears widespread but the available literature is limited to North American and European countries. We aimed to examine the treatment received by patients with major depression in Japan and to elucidate any predictor of their treatment level. METHODS: A naturalistic, prospective follow-up study of an inception cohort of subjects with mood disorders was undertaken in psychiatric departments of 13 university hospitals, those of six general hospitals, three mental hospitals and one community mental health center from all over Japan. A total of 95 patients without any prior antidepressant treatment were diagnosed with major depression according to DSM-IV and were followed up every month until treatment termination and every 6 months thereafter. RESULTS: The follow-up information was available in 98 to 97% of the cohort. The proportion of patients receiving less than 125 mg/day of imipramine or equivalent reached 69% (95% CI: 58-78%) at 1 month and 67% (95% CI: 54-77%) at 6 months. A few clinical variables were significantly associated with inadequate antidepressant prescription but altogether they explained only 5 to 14% of the variance observed. CONCLUSIONS: Japan was no exception to the other industrialized countries in its less than optimal provision of treatment to major depression and its lack of explanatory predictors for this common practice.
STAT5 is activated in a broad spectrum of human hematologic malignancies. We addressed whether STAT5 activation is necessary for the myelo- and lymphoproliferative disease induced by TEL/JAK2 using a genetic approach. Whereas mice transplanted with bone marrow transduced with retrovirus expressing TEL/JAK2 develop a rapidly fatal myelo- and lymphoproliferative syndrome, reconstitution with bone marrow derived from Stat5ab-deficient mice expressing TEL/JAK2 did not induce disease. Disease induction in the Stat5a/b-deficient background was rescued with a bicistronic retrovirus encoding TEL/JAK2 and Stat5a. Furthermore, myeloproliferative disease was induced by reconstitution with bone marrow cells expressing a constitutively active mutant, Stat5a, or a single Stat5a target, murine oncostatin M (mOSM). These data define a critical role for Stat5a/b and mOSM in the pathogenesis of TEL/JAK2 disease.
A potent retrovirus packaging cell line named Platinum-E (Plat-E) was generated based on the 293T cell line. Plat-E is superior to existing packaging cell lines regarding efficiency, stability and safety. The novel packaging constructs utilized in establishment of Plat-E ensure high and stable expression of viral structural proteins. Conventional packaging constructs made use of the promoter of MuLV-LTR for expression of viral structural genes gag-pol and env, while our packaging constructs utilized the EF1alpha promoter, which is 100-fold more potent than the MuLV-LTR in 293T cells in combination with the Kozak's consensus sequence upstream of the initiation codon resulting in high expression of virus structural proteins in Plat-E cells. To maintain the high titers of retroviruses under drug selection pressure, we inserted the IRES (internal ribosome entry site) sequence between the gene encoding gag-pol or env, and the gene encoding a selectable marker in the packaging constructs. Plat-E cells can stably produce retroviruses with an average titer of 1 x 107/ml for at least 4 months. In addition, as we used only the coding sequences of viral structural genes to avoid inclusion of unnecessary retrovirus sequences in the packaging constructs, the probability of generating the replication competent retroviruses (RCR) by recombination can virtually be ruled out.
Somatic mutation of the FLT3 gene, in which the juxtamembrane domain has an internal tandem duplication, is found in 20% of human acute myeloid leukemias and causes constitutive tyrosine phosphorylation of the products. In this study, we observed that the transfection of mutant FLT3 gene into an IL3-dependent murine cell line, 32D, abrogated the IL3-dependency. Subcutaneous injection of the transformed 32D cells caused leukemia in addition to subcutaneous tumors in C3H/HeJ mice. To develop a FLT3-targeted therapy, we examined tyrosine kinase inhibitors for in vitro growth suppression of the transformed 32D cells. A tyrosine kinase inhibitor, herbimycin A, remarkably inhibited the growth of the transformed 32D cells at 0.1 microM, at which concentration it was ineffective in parental 32D cells. Herbimycin A suppressed the constitutive tyrosine phosphorylation of the mutant FLT3 but not the phosphorylation of the ligand-stimulated wild-type FLT3. In mice transplanted with the transformed 32D cells, the administration of herbimycin A prolonged the latency of disease or completely prevented leukemia, depending on the number of cells inoculated and schedule of drug administration. These results suggest that mutant FLT3 is a promising target for tyrosine kinase inhibitors in the treatment of leukemia.
BACKGROUND: Aspirin is known to cause adverse effects, including gastric mucosal injury, and to retard gastric wound healing. Growth factors including hepatocyte growth factor (HGF), epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) have been shown to play an important role in the repair of gastric mucosal injury. AIM: To employ the cultured gastric epithelial cell model to elucidate the effects of aspirin, as well as several growth factors (HGF, EGF and IGF-I), on gastric wound repair. METHODS: Isolated rabbit gastric epithelial cells (92% mucous cells) were cultured in F-12 medium and formed a complete monolayer cell sheet in 48 h. A wound with a cell-free area of constant size (2 mm2) was then created and the wound repair process was monitored by measuring wound size every 12 h. Proliferating cells were detected by BrdU staining. Effects of aspirin (8 mM), HGF (10 ng/mL), EGF (10 ng/mL) and IGF-I (30 ng/mL) were assessed. RESULTS: Aspirin significantly retarded wound healing, but simultaneous addition of growth factors significantly accelerated wound repair compared with aspirin alone. Growth factors reversed the aspirin-induced inhibition of cell proliferation. CONCLUSION: Growth factors, including HGF, EGF and IGF-I, reversed the aspirin-induced inhibition of wound repair through their cytoprotective effects on gastric epithelial cells.
The hepatotoxic effects of alcohol have been described in detail, but factors responsible for its hepatotoxicity have only partially been characterized. For example, it is known that chronic ethanol ingestion increases hepatotoxicity and produces fatty liver, hepatitis and cirrhosis. However, acute ethanol consumption reduces endotoxin hepatotoxicity. It now appears that Kupffer cells participate in several aspects of these phenomena. Previously, most studies on the effects of alcohol on liver function have focused chiefly on the hepatocyte. Recently, attention has been directed towards the effect of ethanol ingestion on Kupffer cell function, which is stimulated by gut-derived endotoxins (lipopolysaccharides) via mechanisms dependent on increased gut permeability and the possible relationship between Kupffer cells and alcohol-induced liver injury. Here we will review new evidence for the proposal that Kupffer cells and endotoxins play a pivotal role in hepatotoxicity following alcohol exposure, based on studies using the continuous intragastric enteral feeding model developed by Tsukamoto and French and an acute model developed by us.
BACKGROUND: Vascular endothelial growth factor (VEGF) exerts its actions on the microvasculature, by interacting with specific endothelial cell receptors, and thus, contributes to angiogenesis and growth in many tumours. METHODS: Using nested reverse-transcription-polymerase chain reaction, we examined the biopsy specimens of 14 patients with human hepatocellular carcinoma (HCC) and cirrhosis, for the expression of hepatic VEGF, and the VEGF receptors KDR and fit-1. To avoid the influence of hypoxia or ischaemia induced by surgical manipulation, we used biopsy specimens of the liver instead of resected specimens. RESULTS: Vascular endothelial growth factor mRNA expression was detected in the tumour portion of the specimens in 13 of 14 patients (93%), and in the corresponding non-tumour portion of the specimens in eight patients (57%; P= 0.08). No differences were found between the tumour portion and the corresponding non-tumour portion in relative concentrations of VEGF mRNA. However, mRNA expression of the VEGF receptors, KDR and fit-1, was detected in 14 (100%) and 11 (79%) of the tumour portions, respectively, and in four (29%) and five (36%) of the corresponding non-tumour portions, respectively (chi2 test: KDR, P< 0.01; fit-1, P= 0.08). The relative concentration of KDR mRNA in the tumour portions was significantly higher than in the non-tumour portions (Mann-Whitney U-test: P<0.001) but no differences were detected for fit-1. CONCLUSIONS: KDR mRNA is significantly overexpressed in HCC lesions and could be associated with the angiogenesis and tumour growth induced by VEGF.
The competency of psychiatric patients to give informed consent is important in respecting patients' decisions as well as protecting patients from undue exploitation. A total of 176 members of the Japanese Society of Psychiatry and Neurology gave a clinical judgment in a questionnaire of competency in five case transcriptions. Their interrater reliability of competency judgment was slight (generalized kappa 0.31). Clinicians' global judgment of patients' competency was not reliable, but it may be improved by the use of a structured interview.
Amendment of the Mental Health and Welfare Law in Japan will limit admission for medical care and protection only for those individuals who are incapable of giving consent to admission. This is a first in the history of the Japanese mental health legislation. By reviewing the law and psychiatric literature, it is argued that: (i) informed consent is a legal transaction that embodies the idea of an individual's right to autonomous decision-making in medical settings; (ii) health professionals have a duty to protect those individuals who cannot decide medical matters because of lack of capacity to do so; (iii) some patients are marginally incompetent so assessment of their competency is essential in protecting patients' civil rights; (iv) in order for a competency assessment to be reliable (and hence fair) the method should be psychometrically sound; (v) at the same time, in order for a competency assessment to be valid, the structure of a competency assessment should match the patient's psychological, cultural, and social background; and (vi) because informed consent is a process rather than a cross-sectional event, a competency assessment should be performed in everyday practice. The use of a brief and semistructured interview to assess patients' competency to give informed consent may meet all of the requirements described.
The present study investigates the differences in public attitudes towards the mentally ill in Bali (Indonesia) and Tokyo (Japan), the former being a non-industrialized society and the latter an industrialized society in Asia. Seventy-seven residents of Bali and 66 residents from Tokyo were examined by a devaluation-discrimination measure and a self-assessment questionnaire to gauge their reactions to five imaginary case study vignettes consisting of three cases of schizophrenia, one case of a depressive episode, and one case of obsessive-compulsive disorder. Balinese respondents had significantly lower devaluation-discrimination measure scores, indicating a more favorable global attitude towards persons with a history of psychiatric treatment than did respondents in Tokyo. However, the extent to which people were prejudicial against mental patients in the two societies varied with the kinds of mental disorders, with Balinese having a more positive attitude to schizophrenics but more negative to depressive and obsessive-compulsive patients.
A structured interview was used to examine the 1-year incidence and prevalence of depression among 116 first-year university students. While 24 of the subjects (20.7%) met the Diagnostic and Statistical Manual of Mental Disorders 4th ed. (DSM-IV) criteria for Major Depressive Episode (MDE), 62 (53.4%) met the Diagnostic and Statistical Manual of Mental Disorders 3rd ed. Revised (DSM-III-R) criteria for MDE, and 27 (23.3%) also met the Research Diagnostic Criteria (RDC) for Major Depressive Disorder (MDD) for the 12 months prior to the interview. Moreover, 23 of the subjects (19.8%) had onset of the DSM-IV criteria for MDE, 54 (46.6%) had onset of the DSM-III-R criteria for MDE, 24 (20.7%) had onset of the RDC for MDD, during the same time period. These high rates of depression may be explained by the students' difficulties in and by their readjustment after entering university.
A 64-year-old man suffered from hypertensive syncope and was admitted to Branch Hospital, Faculty of Medicine, The University of Tokyo. On admission he had no symptoms; however, two renal cysts of about 5 cm in diameter were found in his left kidney. Cystofiberscopy with a thin optical fiberscope was performed in addition to puncture and cystography. Cytology revealed class I, but the wall surface of the lower cyst was uneven, fluid-filled, colloid-like and white-gray compared with that seen in the upper cyst. It was diagnosed as renal cell carcinoma (RCC) and left nephrectomy was performed (5 cm in diameter, RCC, papillary tubular, common, clear cell subtype, G2>G1, INF beta, pT2, pMx, pV0, ew(-)).
BACKGROUND: Alpha1-adrenoceptors are highly concentrated in the urethral smooth muscles and may play an important role in the contraction of this area. However, detailed examinations of age-related changes of the properties of urethral smooth muscle have rarely been undertaken. METHODS: The contractile properties of urethras from young non-parous and old parous female beagles were determined with a urethral function study, macroscopic autoradiography for urethras using [3H]-labeled tamsulosin and morphometry of the urethral muscles. RESULTS: The antagonistic effect (pA2) of prazosin for norepinephrine was 7.76+/-0.13 in young dogs and 7.62+/-0.06 in aged dogs. The specific binding of [3H]-tamsulosin (a relatively selective alpha1A-adrenoceptor antagonist) was recognized diffusely in proximal urethras with in vitro autoradiography. The density of binding in smooth muscles was approximately 60 and 40% in circular longitudinal layers, respectively, for both dogs. CONCLUSIONS: The female canine urethra had alpha1A, and alpha1L-adrenoceptors. No age-related changes were seen in the function of the proximal urethra, distribution of alpha1-adrenoceptor binding sites and smooth muscle densities.
OBJECTIVE: To clarify the clonality of bilateral tumours by genetic analysis of bilateral renal cell carcinomas (RCCs) using the VHL gene, which is inactivated in approximately 60% of RCCs and which plays a causal role in the development of most cases of nonpapillary RCC. PATIENTS AND METHODS: The study included 20 patients; seven had von Hippel-Lindau disease, three had papillary RCC and 10 had nonpapillary RCC. Paraffin-embedded blocks of tumour tissue were obtained from two of the three patients with papillary RCC and from nine of 10 with nonpapillary disease; all three exons of VHL were examined by direct sequencing. RESULTS: As reported previously, no VHL mutations were found in papillary tumours. However, in five of the nine nonpapillary cases, VHL mutations were identified in tumours on one or both sides. Three of the tumours had the same mutation on both sides, confirming a common origin. In the remaining two patients, the mutation status differed between the sides, confirming a bilateral primary origin. The former cases were characterized by a relatively large tumour on one side and multiple tumours on the other. CONCLUSIONS: In nonpapillary RCC multiplicity may suggest a metastatic origin. Such genetic information will be useful in treating and following patients with bilateral renal tumours.