Biomedical subjects
Publications and source records attributed to N Hirayama.
The title compound, [1aS-(1a alpha, 8a alpha, 8b alpha)]-6-amino-1, 1a,2,8,8a,8b-hexahydro-8a-methoxy-1,5-dimethyl-8-methyleneazirino [2',3':3,4]pyrrolo[1,2-a]indole-4,7-dione, C15H17N3O3, is a derivative of the mitomycins, which are antitumor antibiotics. The quinone O atoms deviate significantly from the least-squares plane of the quinone ring.
The use of ELISA for the potency test of inactivated rabies vaccines for animal use was evaluated. Sandwich ELISA was developed, using monoclonal antibodies which enabled to recognize the glycoprotein (G-protein) of rabies virus and showed a protective effect in mice. Soluble G-protein which displays an ELISA activity but a low immunogenicity was removed by gel filtration before ELISA was carried out. The ELISA titres of the first fraction of vaccines separated by gel filtration were correlated with the neutralizing antibody titres of vaccinated guinea-pigs. Our results suggest that the ELISA titres of the first fraction of vaccines separated by gel filtration reflected the protective G-protein contents for the in vitro potency test of rabies vaccines compared with the current in vivo test.
Adrenomedullin has a potent vasodilating effect comparable to that of calcitonin gene-related peptide. To investigate the pathophysiologic role of endogenous adrenomedullin, we determined sequentially the plasma adrenomedullin level in 15 consecutive patients with acute myocardial infarction (AMI). Plasma adrenomedullin was higher immediately after the onset of AMI and decreased gradually; plasma levels during the 3-week period after the AMI were higher than plasma levels in 15 healthy control subjects (p < 0.001), with higher levels in patients with congestive heart failure than in patients without congestive heart failure throughout the period of the study (p < 0.05). Plasma adrenomedullin was positively correlated with pulmonary capillary wedge pressure, pulmonary arterial pressure, right atrial pressure, and heart rate in the early stage of AMI. These findings suggest that the elevation of plasma adrenomedullin is related to the retention of body fluid volume, the enhancement of sympathetic activity, and/or the elevation of pressure in pulmonary vascular beds. Adrenomedullin may act against excessive vasoconstrictors increased in AMI.
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A structure-based pharmaceutical database for drug interactions has been developed. This database is based on the ISIS/Desktop and the Microsoft Access relational database system for Windows. Data of Japanese accepted name, molecular formula, molecular weight, CAS registry number, therapeutic category index code, structural formula, Japan ethical drugs code, side effects information, drug interactions information were taken from "Japanese Accepted Names for Pharmaceuticals 1992", "Drugs in Japan Ethical Drugs 1993" and "Drug Intelligence Reinforce".
A series of (E)-4-(2-[[3-(indol-5-yl)-1-oxo-2-butenyl]amino]phenoxy)butyric acid derivatives was prepared, and the derivatives were demonstrated to be potent inhibitors of steroid 5 alpha-reductase in the rat prostate. The structure-activity relationships were as follows. An alpha-branched alkyl or benzyl substituent of proper size at position 1 of the indole is crucial for optimal enzyme inhibitory activity. N-Methylation of the amide NH resulted in complete loss of activity. Thus, coplanarity of the benzene ring and amide moiety is essential for such activity. Among the compounds prepared, (E)-4-(2-[[3-[1-[bis(4-fluorophenyl)methyl]indol-5-yl]-1-oxo-2- butenyl]-amino]phenoxy)butyric acid (57, KF18678) was one of the most potent compounds (rat prostate 5 alpha-reductase IC50 = 3.3 nM).
The function of the Fc receptors gamma chain (FcR gamma) for the expression of the T cell receptor (TCR) complex and for T cell development, especially for T cells localized in epithelia, was investigated by analyzing FcR gamma-deficient mice. In wild-type mice, CD8 alpha alpha + beta -TCR alpha beta + T cells of intestinal intraepithelial lymphocytes (i-IEL) utilized CD3 zeta homodimers and zeta-FcR gamma heterodimers, whereas CD8 alpha alpha + beta -TCR gamma delta + i-IEL used zeta-FcR gamma and FcR gamma homodimers in the TCR complex. On the other hand, these T cells in FcR gamma-deficient mice contained only zeta homodimers. The surface expression of the TCR complex was reduced in CD8 alpha alpha + beta -i-IEL and dendritic epidermal T cells (DETC) in these mice, whereas the development of these T cells was normal. The degree of reduction appeared to depend on the expression level of FcR gamma. In contrast to these populations, TCR gamma delta + intraepithelial T cells in reproductive organs (r-IEL) were dramatically decreased, suggesting that the development of r-IEL is FcR gamma-dependent, probably due to the predominant usage of FcR gamma homodimers in the TCR complex. These results indicate that the FcR gamma chain contributes differently to the TCR expression and to the development of T cells localized in epithelia.
A new set of recombinant inbred (RI) strain SMXA consisting of 26 substrains was established between SM/J and A/J. The history of the SMXA RI strains and their genetic profile covering 158 genetic marker loci are reported. From the strain distribution pattern among SMXA RI strains, the chromosomal location of salivary and tear protein genes Spe1-r, Spe1-s, Spe2, and Tpe1 were newly determined.
Two cases of intraaortic balloon entrapment were presented. In patient 1, urokinase was injected into the gas driver lumen of the intraaortic balloon catheter, then it could be removed. In patient 2, the intraaortic balloon was removed retrogradely through the left axillary artery. If the entrapped intraaortic balloon is encountered, it is effective to try a clot-lysis method initially, followed by a surgical approach through a left axillary artery.
Jak3 is a tyrosine kinase mediating cytokine receptor signaling through the association with the common gamma chain of the cytokine receptors such as IL-2, IL-4, IL-7, IL-9, and IL-15. Unlike other members of the Jak family, the expression of Jak3 is highly restricted in hematopoietic cells. To elucidate in vivo function of Jak3, Jak3-deficient mice were generated by homologous recombination. Mice homozygous for Jak3 null mutation showed severe defects, specifically in lymphoid cells. B cell precursors in bone marrow, thymocytes, and both T and B cells in the spleen drastically decreased, although these defects were significantly recovered as aging occurred. Peripheral lymph nodes, NK cells, dendritic epidermal T cells, and intestinal intraepithelial gamma delta T cells were absent. Normal number of hematopoietic stem cells in bone marrow from Jak3-deficient mice and the similar capability to generate myeloid and erythroid colonies as wild-type mice indicated specific defects in lymphoid stem cells. Furthermore, the abnormal architecture of lymphoid organs suggested the involvement of Jak3 in the function of epithelial cells. T cells developed in the mutant mice did not respond to either IL-2, IL-4, or IL-7. These findings establish the crucial role of Jak3 in the development of lymphoid cells.
A method for detecting wild-type canine parvovirus (CPV) strains which contaminate vaccines for dogs has been developed by PCR. PCR primers which distinguish vaccine strains from the most common, recent strains of wild-type CPV in many countries, including Japan and the United States, were developed. This PCR is based on the differences in nucleotide sequences which determine the two antigenic types of this virus. CPV vaccine strains derived from antigenically old-type virus prevalent in former times were not detected by PCR with differential primers. Detection sensitivity of PCR was 100- to 10,000-fold higher than that of the culture method in Crandell feline kidney cells.
A case of intra-aortic balloon pumping (IABP) entrapment in which the ruptured catheter could be removed through the left axillary artery was reported. A 68-year-old man was admitted with persistent chest pain, and because of his poor cardiac condition, an IAB catheter was inserted by the Seldinger technique. During attempted extraction of the IAB catheter resistance was encountered and it turned out to be entrapped. Then a guide-wire was passed through the IAB lumen to the left axillary artery, the artery was exposed, and the tip of the guide-wire and IAB catheter were led to the arteriotomy site. After the balloon was dissected, the IAB catheter could be removed through the axillary artery. Finally, left femoro-left branchial artery bypass was performed with e-PTFE graft because of the arterial injury and ischemia of the involved arm. The patient recovered from this episode.
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In 1993, thirteen strains (8.7%) of M. chelonae were isolated from bronchoalveolar lavage fluid (BALF) obtained by bronchoscopy of 150 patients in Tachikawa-sogo (T) hospital, where the same automated disinfection machine was commonly used for cleaning, sterilization and disinfection of fiberbronchoscope and fibercolonoscope except 3 bronchoscopes disinfected by gas sterilization. Since January 1994, manual cleaning and sterilization has been applied for bronchoscope, and thereafter no strain of M. chelonae was isolated from BALF of 55 patients in the T hospital. While only one strain (3%) of M. chelonae was isolated from BALF of 33 patients in Ota (O) hospital, but many strains of M. chelonae were isolated from intestinal fluid obtained by fibercolonoscopy of the patients. Manual method of cleaning and disinfection was performed for both bronchoscopes and colonoscopes in the O hospital from the beginning. Based on these results, it was suggested that M. chelonae are commonly present in the colon (intestine) of normal persons. Thus colonoendscope may be often contaminated with the organism and subsequently the automated disinfecting machine may also be contaminated with the organism which is resist and against usual disinfection procedure, and resulted in bronchoscope contamination. If the presence of M. chelonae in intestinal tract is not rare, bile duct may be naturally infected with the organism. A case of cholecystitis and cholangitis caused by M. chelonae, which has not been reported previously, was found in the T hospital.
We conducted a survey on nontuberculous mycobacteria (NTM) isolated in association with colonscopy at two hospitals. NTM was isolated from the fluid-phase of colonic contents in 17.6% of the specimens obtained at hospital A and in 46.3% at hospital B. The rate of isolation from the preexamination suction fluid was 9.5% and 43.3% at hospital A and B, respectively. Tap water samples from both hospitals were examined and proved to be free from contamination with NTM. The mycobacterial species isolated at hospital A were M. chelonae subsp. abscessus, M. chelonae subsp. chelonae, M. fortuitum, and M. gordonae. M. chelonae subsp. abscessus was the only mycobacterial species isolated at hospital B. M. avium complex was not isolated at either hospital. By an additional procedure to cleans and decontaminate the endoscopes by suction with Maskin ethanol solution, the incidence of isolation of NTM from the fluid-phase of colonic contents was significantly reduced. None of the patients from whom NTM was isolated exhibited positive signs of colonic NTM infection by the endoscopic examination and non had any underlying diseases which might induce immune suppression. We suspect that most of the NTM isolates have originated from the contaminated endoscope. In conclusion, when a colonscopic examination is carried out in suspicion of NTM disease in intestine, it is essential to reassess the possibility of mycobacterial contamination of the colonscopes and implement appropriate steps for cleansing and sterilization of them.
zeta and eta chains of the T cell antigen receptor (TCR) complex and the gamma chain of Fc receptors (FcR gamma) constitute a family of proteins important for the expression of, and signal transduction through, these receptors in hematopoietic cells. In zeta-deficient mice, TCR expression was reduced in most T cells. By contrast, CD8 alpha alpha + TCR-gamma/delta + intestinal intraepithelial lymphocytes in these mice expressed a normal level of TCR. Biochemical analysis of the TCR complex in these cells from zeta-deficient as well as normal mice revealed the predominant usage of FcR gamma. Furthermore, gamma/delta + T cells in epithelia of the skin and female reproductive organs from zeta-deficient mice also showed relatively high TCR expression, indicating the usage of FcR gamma. These observations demonstrate the preferential usage of FcR gamma by gamma/delta + T cells localized in epithelia of normal mice.
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The human Fc gamma RI gene encodes for a high-affinity Fc gamma receptor that plays pivotal roles in the immune response. We have used fluorescence in situ hybridization analysis to localize the Fc gamma RI gene to human chromosome 1. The human Fc gamma RI (CD64) gene has been assigned to human chromosome 1q21.2-q21.3 using R-banded human (pro)metaphase chromosomes.