Biomedical subjects

T Fukazawa

Publications and source records attributed to T Fukazawa.

At least 91 records · Page 5Linked to original sources

PubMed1996

[University education in geriatrics. Present status and future plans of universities regarding the development of a program in geriatrics].

Because the number of people who reach an advanced age has been increasing at an unprecedented rate in Japan, geriatricians are expected to play a central role in health care for the elderly. However, only 16 out of 80 medical schools (20 percent) now have departments of geriatrics for undergraduate education. To develop undergraduate education in the field of geriatrics, a survey was sponsored by the Research Projects on Aging and Health (Health Science Research Grant the Ministry of Health and Welfare of Japan). A questionnaire regarding the present status and future plans of the university about a program in geriatrics, was sent to deans of medical faculties or vice-presidents of medical schools. The questionnaire included questions about current status and future plans regarding undergraduate geriatric education, the presence of a department or clinic of geriatrics, educational requirements in the field of geriatrics, opportunities for practice, institutions of practice, research on geriatrics, and other suggestions. The response rate was 93.7 percent (74/79). Departments or clinics of geriatrics had been established in 15 institutions (20.3 percent) and were planned in 18 (24.3 percent). Undergraduate education in geriatrics was considered necessary in 73 schools (98.7 percent) and indispensable as an obligatory subject in 56 (75.7 percent). Clinical practice was considered more important and effective than lectures in 50 schools (63.3 percent). Coordinated lectures on basic biomedical gerontology (such as mechanism of aging) and geriatric medicine for chronic degenerative diseases such as senile dementia were considered essential to the curriculum. In practicing geriatrics, experience in providing medical care to aged patients as well as social support and a welfare system for the aged is emphasized. Institutions, nursing homes, and geriatric hospitals outside medical schools be easily accessible. It was generally agreed that geriatrics should be taught in advanced classes. In conclusion, medical schools in Japan regard undergraduate education in geriatrics as necessary and agree on the optimal curriculum, but it is not universally implemented.

Education, Medical, Undergraduate↗

PubMed1996

[University education in geriatrics. Opinions of teaching staff on undergraduate education in gerontology and geriatric medicine].

Undergraduate education in gerontology and geriatric medicine has become more important because of a progressive increase in the aged population. To assess curricula in geriatric medicine and to survey the opinions of teaching staffs as to the ideal curriculum, a questionnaire was sent to professors of gerontology and geriatric medicine at 14 medical schools. Responses were obtained from all 14 professors. In all medical schools, students are given lectures in the fifth or sixth year, or both. The total number of hours for the lectures varied from a few hours to 40 hours, and contents of the lectures varied between schools. Medical staffs pointed out that little time is allocated to geriatric medicine. They also emphasized the importance of bedside teaching.

Curriculum↗

PubMed1996

[Undergraduate teaching of geriatric medicine in western countries--literature review].

To help plan for the future of undergraduate education in geriatric medicine in Japan, we reviewed the literature concerning undergraduate teaching of geriatric medicine in western countries. Undergraduate teaching in geriatric medicine in the UK is well developed: 22 of 25 universities have a full department of geriatric medicine. Training in geriatric medicine is mandatory in almost all universities. In contrast, geriatric medicine is an elective in most universities in the US. There is a shortage of geriatric medicine faculty in the US, which is similar to the situation in Japan. Clinical and basic research in geriatric medicine and gerontology should be encouraged to attract persons into this field.

Education, Medical, Undergraduate↗

PubMed1996

[University education in geriatrics--present status and future prospects of gerontology and geriatrics education in pathology].

The increase in the number and proportion of the elderly in Japan over the last 30 years has been faster than that in any other country. One of the measures we are compelled to take to deal with this drastic change in medicosocial circumstances is reform of the medical school curriculum. However, the necessary reforms are being implemented slowly and are still insufficient. We surveyed the present status of gerontology and geriatrics education in pathology, and the understanding, interest, and opinions on this matter among professors of pathology. Questionnaires were sent to 148 professors of pathology in 80 medical schools. Responses were received from 84 professors (57%) at 64 medical schools (80%). Of the 11 medical schools with a department of geriatrics 10(90%) included gerontology in the curriculum. In contrast, 43(80%) of the 53 remaining schools did not include gerontology in the curriculum, although education in geriatrics and gerontology has been given as part of pathology lectures in almost all medical schools. Many professors want to establish a department of geriatrics in their school, but feel it will be difficult because of lack of money and higher priority given to other fields. As other hindrances, most of the respondents noted the lack of money and higher priority given to other fields. As other hindrances, most of the respondents noted the lack of a good textbook of gerontology, ambiguity in the concept of the field, and the immaturity of gerontology as a science. Another major problem noted was uncertainty regarding the status of geriatrics as a clinical specialty. One professor mentioned that promotion of aging research would be the best way to solve these problems.

Education, Medical, Undergraduate↗

PubMed1996

[Distribution of EIA reactive values and serum antibody titers of Chlamydia trachomatis urethritis and cervicitis at the first visit].

Among 120 non-gonococcal male urethritis, 83 were found to be Chlamydia trachomatis (CT) positive by Chlamydiazyme with 2 to 5 times repeated urethral swab collection during pre-treatment period. Among 97 female partner of male CT urethritis, 76 were CT positive by the same repeated specimen collection from cervix. In the 83 male CT urethritis and the 76 female CT cervicitis, EIA reactive values by Chlamydiazyme and serum CT antibody titer by FA at the first visit were investigated. The EIA reactive values of cervicitis were lower than those of urethritis. There was no case of "CT negative at the first visit and positive at repeated detection" in male urethritis. 3 case of "CT negative at the first visit and CT positive at repeated detection" were experienced among females who were the partner of male CT urethritis. The sensitivity of Chlamydiazyme was found to be enough to decide presence or absence of CT by single specimen collection in male urethritis but not enough in female cervicitis. It could be assumed that by the improved sensitivity of CT detection, CT detection rate would be raised among female cervicitis but not in male urethritis. Positive rate CT serum antibody were 63.9% in male urethritis and 100% in female cervicitis. The clinical value of CT antibody detection might be not as detection method of CT infection in progress, but as non-invasive screening for CT infection up to the present, namely the risk factor of STD, especially in females in whom detection of CT is not complete.

Antibodies, Bacterial↗

PubMed1996

[A case of chronic bromvalerylurea intoxication with episodic neurological manifestations such as optic neuropathy ophthalmoplegia and ataxia].

A 28-year-old man presented with a bilateral visual loss of acute onset, and was diagnosed as having optic neuropathy by an ophthalmologist. It disappeared spontaneously within 2 months. A visual loss at the left side relapsed ten months later, followed by a dysarthria, horizontal defective saccade, ataxia, and mild weakness of four extremities, which also subsided within one month only by multi-vitamin therapy. These signs recurred episodically with characteristic clinical features of dysarthria, horizontal ophthalmoplegia, defective saccade, ataxia, and weakness, during the next year. Clinical features mimicked those of various neurological disorders, especially multiple sclerosis, Wernicke encephalopathy, brainstem encephalitis, Fisher syndrome, disorders of amino acid metabolism and episodic ataxia. Tablets of bromvalerylurea were incidentally found at the bedside and bromides were detected in his sera. Drugs containing bromides are now easily available without prescription, so we should keep the intoxications of those drugs in mind in facing undiagnosed patients with various episodic neurological symptoms.

Adult↗

PubMed1996

[MRI changes in spontaneous intracranial hypotension].

We report MRI changes in a spontaneous intracranial hypotension(SIH). The patient was 29-year-old woman, who developed headaches in upright position, nausea, and vomiting preceded by pressure feeling of ears. Neurological examination was unremarkable except for hyperreflexia in the lower extremities. Lumbar punctures revealed very low opening pressure, a mild elevated CSF protein and a mild pleocytosis. No evidence of underlying systemic or neoplastic diseases was noted. The brain and cervical MRI showed diffuse and continuous pachymeningeal enhancement with gadolinium. Her symptoms gradually improved within two months without any treatment, and follow-up MRI showed resolution of the abnormalities within five months. The dural enhancement with gadolinium seen in the SIH should be kept in mind in case of hypertrophic pachymeningitis of unknown etiology, and be differentiated from such diseases as hypertrophic pachymeningitis associated with infectious, neoplastic diseases or sarcoidosis.

Adult↗

PubMed1995

T cell activation-dependent association between the p85 subunit of the phosphatidylinositol 3-kinase and Grb2/phospholipase C-gamma 1-binding phosphotyrosyl protein pp36/38.

Tyrosine phosphorylation of cellular proteins is an early and an essential step in T cell receptor-mediated lymphocyte activation. Tyrosine phosphorylation of transmembrane receptor chains (such as zeta and CD3 chains) and membrane-associated proteins provides docking sites for SH2 domains of adaptor proteins and signaling enzymes, resulting in their recruitment in the vicinity of activated receptors. pp36/38 is a prominent substrate of early tyrosine phosphorylation upon stimulation through the T cell receptor. The tyrosine-phosphorylated form of pp36/38 is membrane-associated and directly interacts with phospholipase C-gamma 1 and Grb2, providing one mechanism to recruit downstream effectors to the cell membrane. Here, we demonstrate that in Jurkat T cells, pp36/38 associates with the p85 subunit of phosphatidylinositol 3-kinase (PI-3-K p85) in an activation-dependent manner. Association of pp36/38 with PI-3-K p85 was confirmed by transfection of a hemagglutinin-tagged p85 alpha cDNA into Jurkat cells followed by anti-hemagglutinin immunoprecipitation. In vitro binding experiments with glutathione S-transferase fusion proteins of PI-3-K p85 demonstrated that the SH2 domains, but not the SH3 domain, mediated binding to pp36/38. This binding was selectively abrogated by phosphopeptides that bind to p85 SH2 domains with high affinity. Filter binding assays demonstrated that association between pp36/38 and PI-3-K p85 SH2 domains was due to direct binding. These results strongly suggest the role of pp36/38 in recruiting PI-3-K to the cell membrane and further support the idea that pp36/38 is a multifunctional docking protein for SH2 domain-containing signaling proteins in T cells.

Adaptor Proteins, Signal Transducing↗

PubMed1995

The SH3 domain-binding T cell tyrosyl phosphoprotein p120. Demonstration of its identity with the c-cbl protooncogene product and in vivo complexes with Fyn, Grb2, and phosphatidylinositol 3-kinase.

Previously, we have identified p120 as a Fyn/Lck SH3 and SH2 domain-binding protein that is tyrosine phosphorylated rapidly after T cell receptor triggering. Here, we used direct protein purification, amino acid sequence analysis, reactivity with antibodies, and two-dimensional gel analyses to identify p120 as the human c-cbl protooncogene product. We demonstrate in vivo complexes of p120cbl with Fyn tyrosine kinase, the adaptor protein Grb2, and the p85 subunit of phosphatidylinositol (PI) 3-kinase. The association of p120cbl with Fyn and the p85 subunit of PI 3-kinase (together with PI 3-kinase activity) was markedly increased by T cell activation, consistent with in vitro binding of p120cbl to their SH2 as well as SH3 domains. In contrast, a large fraction of p120cbl was associated with Grb2 prior to activation, and this association did not change upon T cell activation. In vitro, p120cbl interacted with Grb2 exclusively through its SH3 domains. These results demonstrate a novel Grb2-p120cbl signaling complex in T cells, distinct from the previously analyzed Grb2-Sos complex. The association of p120cbl with ubiquitous signaling proteins strongly suggests a general signal transducing function for this enigmatic protooncogene with established leukemogenic potential but unknown physiological function.

Adaptor Proteins, Signal Transducing↗

PubMed1995

Spinocerebellar ataxia 1 (SCA1) in the Japanese: analysis of CAG trinucleitide repeat expansion and instability of the repeat for paternal transmission.

SCA1 is caused by expansion of an unstable CAG triplet repeat in a novel gene located on the short arm of chromosome 6. In 126 Japanese individuals from 12 pedigrees with SCA1, studies were done to determine if they carried this mutant gene. All the affected and pre-symptomatic individuals, determined by haplotype segregation analyses, carried an abnormally expanded allele with the range of 39-63 repeat units. This repeat size inversely correlated with the age at onset. However, contrary to reported results, size of the repeat did not correlate with gender of the transmitting parent. Therefore, the CAG triplet repeat instability on paternal transmission is not likely to be fundamental to SCA1.

Adolescent↗

PubMed1995

Macrophage inflammatory protein-1 alpha in the cerebrospinal fluid of patients with multiple sclerosis and other inflammatory neurological diseases.

The level of macrophage inflammatory protein-1 alpha (MIP-1 alpha), a newly discovered cytokine of chemokine family, was determined in cerebrospinal fluid (CSF) from 18 patients with multiple sclerosis (MS) and from control patients with other neurological disorders by an enzyme-linked immunosorbent assay (ELISA). The concentration of MIP-1 alpha in CSF was significantly elevated in MS in relapse (4.4 pg/ml) compared with non-inflammatory neurological disease control samples (0.3 pg/ml) (p < 0.0002). These concentrations in MS patients correlated well with leukocyte cell counts and protein content in CSF (r = 0.845, p < 0.0001; r = 0.853, p < 0.0001, respectively). In other inflammatory neurological disorders such as Behçet's disease and HTLV-1 associated myelopathy, significantly increased CSF levels of MIP-1 alpha were also observed. Chemokines are reported to play an important role in an early event of inflammation such as lymphocyte traffic. This report is the first study which confirmed the involvement of a chemokine in MS and other inflammatory neurological disorders.

Adult↗

PubMed1995

CAG repeat expansion of Machado-Joseph disease in the Japanese: analysis of the repeat instability for parental transmission, and correlation with disease phenotype.

Machado-Joseph disease (MJD) is caused by abnormal expansion of an unstable CAG repeat in a novel gene locating on chromosome 14q32.1. We analysed this CAG repeat polymorphism with 66 Japanese MJD patients. All the patients were selectively associated with abnormal expansion of the CAG repeat. Repeat length of the mutant allele did not overlap that of normal allele and closely correlated with not only age at onset but also with clinical phenotypes. CAG repeat size is apparently related to a wide variety of phenotypic presentations in MJD.

Adult↗

PubMed1995

Spinocerebellar ataxia 1 (SCA1) in the Japanese in Hokkaido may derive from a single common ancestry.

Spinocerebellar ataxia 1 (SCA1) is caused by expansion of an unstable CAG triplet repeat located on the short arm of chromosome 6. Precise mapping has shown a positional relationship to closely linked markers in the order of D6S109-D6S274-D6S288-SCA1-AM10GA-D6S89+ ++-EDN1 from centromere to telomere. The haplotype which cosegregated with the disease was determined in 12 Japanese pedigrees with SCA1. Although the alleles of the SCA1 haplotype varied from pedigree to pedigree, depending on the distance from the SCA1 locus, the affected and presymptomatic subjects carried the same alleles at D6S288 and D6S274. All the families with SCA1 had migrated from either Miyagi or Yamagata Prefectures, neighbouring areas in the Tohoku District, the northern part of Honshu which is the main island of Japan. It seems highly likely that SCA1 in the Japanese, at least those residing in Hokkaido, derives from a single common ancestry.

Chromosome Mapping↗

PubMed1995

Erdheim-Chester disease and slowly progressive cerebellar dysfunction.

A 59 year old woman developed pronounced thirst, increased water intake, and increased urinary output followed by slowly progressive cerebellar symptoms. Brain MRI showed abnormal hyperintensity on T2 weighted studies in the region of both dentate nuclei without atrophy of the cerebellum or the brainstem. A 99mTC diphosphonate bone scan showed bone lesions in the distal parts of both femurs as well as distal and proximal parts of both tibias. The diagnosis of Erdheim-Chester disease was made by bone biopsy. This is the first case of Erdheim-Chester disease presenting as a slowly progressive cerebellar syndrome and diabetes insipidus, and also showing high signal lesions in deep cerebellar nuclei on MRI. Skeletal surveys are indicated for patients with otherwise unexplained slowly progressive cerebellar symptoms.

Bone Diseases↗

PubMed1995

Visual function in patients with optic neuritis associated with acute transverse myelopathy in multiple sclerosis.

The authors reviewed the records of 20 patients with optic neuritis, all of whom were diagnosed as having clinically definite multiple sclerosis (MS). They were classified into two subgroups: Group A, consisting of 9 patients who had shown acute transverse myelopathy (ATM); and Group B, 11 patients without ATM. Four patients (44%) in Group A had complete visual loss, but none in Group B. Six patients (67%) in Group A had less than 0.1 visual acuity in the affected eye, but only 2 patients (18%) in Group B. Four patients in Group A showed evidence of anticardiolipin antibodies. While both groups were diagnosed as having clinically definite MS, there were differences between them in the clinical features. We assume that the patients with ATM may constitute a different subgroup among MS patients.

Acute Disease↗

PubMed1995

[Sepsis].

Explore the source record for details and available documents.

Humans↗

PubMed1994

The effect of mutant beta 2-microglobulins on the conformation of HLA-B27 detected by antibody and by CTL.

The arthritis-predisposing HLA-B27 consists of a heavy chain, a small peptide, and the monomorphic beta 2-microglobulin (beta 2-m). CTLs and a mAb, Ye-2, which recognize the complex with specificities both for the heavy chain and for the peptide, are available. The beta 2-m is in noncovalent association with the heavy chain at multiple points and is exchangeable with free beta 2-m outside of the complex. The purpose of our experiments was to test whether mutant beta 2-m capable of modulating HLA-B27 activity could be created. Eighteen recombinant mutants of the human beta 2-m were experimentally generated. In 14 of these, mutations were at or near residues that are either contact residues or interface residues with the heavy chain. Relative to the parent beta 2-m, two-thirds of the mutants showed reduced ability to exchange into HLA-B27 complexes. However, at least four of them induced more than 80% decrease in Ye-2 Ab reactivity. Two mutants were able to induce a minor decrease in susceptibility to lysis by four CTL clones. One of the CTL clones was autoreactive. Two of the CTL clones were specific for HLA-B27 cells experimentally infected with arthritis-causing Yersinia enterocolitica. These results indicate that certain beta 2-m residues play an indirect role in peptide presentation, although they are not directly associated with the peptide residues.

Amino Acid Sequence↗

PubMed1994

Rapid T-cell receptor-mediated tyrosine phosphorylation of p120, an Fyn/Lck Src homology 3 domain-binding protein.

Tyrosine phosphorylation of cellular proteins is the earliest identifiable event following T-cell antigen receptor (TCR) stimulation and is essential for activating downstream signaling machinery. Two Src-family protein-tyrosine kinases, the TCR-associated p59fyn (Fyn) and the CD4/8-associated p56lck (Lck), have emerged as the likely mediators of early tyrosine phosphorylation in T cells. Here, we show direct binding of a 120-kDa TCR-induced phosphotyrosyl polypeptide, p120, to glutathione S-transferase fusion proteins of the Src homology 3 (SH3) domains of Fyn, Lck, and p60src (Src) but not other proteins. While binding of p120 to Fyn SH2 domain was phosphotyrosine-dependent as expected, its binding to the SH3 domain was independent of tyrosine phosphorylation, as shown by lack of competition with a phosphotyrosyl competitor peptide. In contrast, an SH3-specific proline-rich peptide completely abolished p120 binding to SH3. p120 was tyrosine-phosphorylated within 10 sec following stimulation of Jurkat cells with anti-CD3 monoclonal antibody, with maximal phosphorylation at 30 sec. Importantly, p120 was found associated with Fyn and Lck proteins in unstimulated Jurkat cells and served as an in vitro substrate for these kinases. These results provide evidence for a role of the SH3 domains of Fyn and Lck in the recruitment of early tyrosine-phosphorylation substrates to the TCR-associated tyrosine kinases.

Amino Acid Sequence↗