Biomedical subjects
Publications and source records attributed to K Murata.
We isolated a plant homologue of Tcp-1 (t complex polypeptide 1) cDNA from Arabidopsis thaliana. It encodes a 545-amino acid (aa) protein, which has extensive aa and nucleotide sequence homology to the corresponding proteins of mouse, yeast, fruit fly and archaebacteria.
Mouse t haplotypes are variants of chromosome 17, consisting of four inversions. Despite the homozygous lethality and pleiotropic effect on embryonic development, sperm production, and recombination, they have widely spread in natural populations of the house mouse (10-40% in frequency) because of the meiotic drive advantage. We sequenced 14 Tcp-1 (t-complex polypeptide 1) genes from four t haplotypes, nine wild mice, and a rat as a reference. From a comparison of intron sequences of 610 base pairs, we dated the origin of t haplotypes to 2.9 +/- 0.7 million years ago, which predates the splitting of Mus musculus subspecies (approximately 1 million years ago). However, the Tcp-1 intron sequences of t haplotypes from different M. musculus subspecies from various parts of the world show no divergence, indicating the recent introgression (no earlier than 0.8 million years ago) of a single ancestral type. Nucleotide changes in coding regions are also consistent with this conclusion. Hence, polymorphisms among t haplotypes including lethality factors have accumulated during this short time period independently in each M. musculus subspecies.
Regional aortic distensibility was measured noninvasively using cine MR imaging to determine whether it correlates with aging or risk of coronary artery disease (CAD). Twenty-two patients with CAD confirmed by angiography and 33 without CAD underwent cine MR imaging. Thirty-two sequential images were obtained in one cardiac cycle. The cross sectional area of the descending thoracic aorta was measured on both diastolic (A) and systolic (A') images. Aortic distensibility (A.D.) was calculated from the following equation: A.D. = (A'-A)/A/delta P. (delta P represents pulse pressure). Results of a simple regression analysis showed that decreased regional aortic distensibility was significantly correlated with the age of the patients (r = -0.762, p less than 0.005). In addition, the parameter was lower in patients with CAD than those without CAD (p less than 0.05). In conclusion, regional aortic distensibility derived from cine MR imaging is a useful parameter to evaluate not only aging but also pathological atherosclerosis of the aorta. In addition, this parameter might have some potential to evaluate the prediction of CAD in patients with normal serum cholesterol.
A recently developed portable capillary coagulation monitor device allows rapid determination of prothrombin time (PT) in sec. and in International Normalized Ratio (INR) from a drop of whole blood. Considering a possible application of this device for monitoring of warfarin therapy at bedside or at outpatient clinic, a comparative study was performed in patients receiving warfarin between the whole blood capillary PT(WBC-PT) and conventional laboratory tests such as plasma PT (LAB-PT) and Thrombotest (TTO). There was an excellent positive correlation (r = 0.95, n = 49) between LAB-PT(sec) and WBC-PT(sec). As the correlation coefficient between WBC-PT(sec) and the reciprocal of LAB-PT(%) was excellent (r = 0.95, n = 49), it is feasible to convert WBC-PT(sec) to LAB-PT(%) by the following formula; y = 313.48x +8.29 (x:reciprocal value of LAB-PT(%), y:WBC-PT). As the correlation between WBC-PT(sec) and TTO(sec) was also excellent (r = 0.85, n = 63), TTO(%) may be likewise estimated by the following formula; y = 66.49x + 11.36 (x:reciprocal value of TTO(%), y:WBC-PT). From these observations it is concluded that the determination of WBC-PT is simple and accurate and that the monitoring of warfarin therapy is easily performed by the present method.
An inhibitor of activated factor XI (FXIa) in human platelets was recently identified as an amyloid beta-protein precursor (APP). We purified an FXIa inhibitor (XIaI) from the supernatant of activated human platelets, and assessed its inhibitor activity toward FXIa amidolytic activity. Approximately 90 micrograms of XIaI that cross-reacted with anti-APP antibody was obtained from two hundred units of platelet suspension by employing a six-step column chromatography procedure. The molecular weight of the purified XIaI was 94,000. The Ki value of XIaI to factor XIa was 526 +/- 120 pM, and the inhibition was enhanced by the addition of ZnCl2. The amino-terminal sequence of XIaI was L-E-V-P-T-D-G-N-A-, which is identical to that for the leucine (N18) to alanine (N26) sequence of APP751 and the amino-terminal sequence of protease nexin-2.
Bone mineral density (BMD) in the lumbar vertebrae (L2-L4) was assessed by dual energy X-ray absorptiometry (DEXA: QDR-1000), and the values obtained were compared with the frequency of vertebral fracture as assessed by spinal X-ray photographs. Patients with spondylosis or scoliosis, which affect BMD values, were excluded from the study. An essentially linear correlation was observed between the frequency of vertebral fracture and lumbar BMD values: no vertebral fractures were observed in those whose BMD more than 0.8 g/cm2, whereas the frequency of fracture was 100% in patients whose BMD was less than 0.45 g/cm2. Thus, measurement of lumbar vertebrae by DEXA would be very useful in predicting vertebral fractures.
Cases of adult T-cell leukemia/lymphoma (ATLL) display several peculiar clinical features, including skin rash, hypercalcemia, and an increase in the absolute neutrophil count. The patients rarely have pronounced eosinophilia. In this study, the eosinophilia observed in lymphoproliferative disorders of 62 patients with ATLL, 27 with T-cell lymphoma (TL), and 19 with B-cell lymphoma (BL) was investigated. The incidence of eosinophilia (greater than or equal to 570/microliters) was higher in patients with ATLL than in patients with TL or BL. Thirteen patients with ATLL (21.0%), 3 with TL (11.1%), and 2 with BL (10.5%) had eosinophilia. Of these patients, three with ATLL and one with TL who had a pathologic diagnosis of immunoblastic lymphadenopathy (IBL) showed pronounced eosinophilia up to 10,934/microliters. Because the number of eosinophils in the peripheral blood of these patients correlated both with the number of ATLL cells and the degree of lymphadenopathy and because this fluctuated with chemotherapy, it seems likely that the secretion of some lymphokines by the lymphoma cells is responsible for the eosinophilia.
By measuring auditory event-related potential (P300 and N100) and peripheral nerve conduction velocities, the subclinical effects of lead, zinc, and copper on the central and peripheral nervous system were examined in 22 male gun metal foundry workers exposed to these metals. Their blood lead (BPb) concentrations ranged from 12 to 59 micrograms/dl (median 30). Control subjects were 14 healthy workers, employed at the same factory, who had never been occupationally exposed to these metals. In the gun metal foundry workers, the latencies of P300 and N100 were significantly prolonged; the latency of P300 was significantly correlated with BPb concentrations and other indicators of lead absorption. Similarly, the maximal motor and sensory conduction velocities in the radial and median nerves were significantly slowed, and were significantly correlated with indicators of lead absorption. The data suggest that lead exposure at low levels affects cognitive and central auditory nervous system function together with peripheral nerve conduction.
Lobenzarit (CCA) is a newly developed immunomodulating drug that has been demonstrated to enhance suppressor T-cell number and function. In this study we investigated the effect of CCA on murine myocarditis induced by the encephalomyocarditis (EMC) virus. Mice were first inoculated with the EMC virus. CCA (100 mg/kg) was administered daily for 14 days, starting on the day the mice were inoculated. The concentrations of Lyt2+ (suppressor/cytotoxic T) cells in the peripheral blood and heart were examined by laser flow cytometry and in situ staining. The concentration of Lyt2+ cells increased significantly in the peripheral blood and heart of CCA-treated mice when compared with untreated mice (blood: 23.0 +/- 2.6% vs. 18.8 +/- 2.8%, p less than 0.05; heart: 30.1 +/- 4.6% vs. 15.8 +/- 4.3%, p less than 0.05, respectively). Surprisingly, however, the severity of myocardial inflammation in CCA-treated mice was significantly greater than in untreated mice (area of inflammation: 33.1 +/- 10.5% vs. 18.8 +/- 19.5%, respectively, p less than 0.05). Thus, these findings suggest that CCA may aggravate EMC-induced acute myocarditis by enhancing the number of Lyt2+ cells.
A large Japanese family with hypertrophic cardiomyopathy (HCM) was examined (n = 61). Ten of 14 affected family members who showed HCM on the basis of electrocardiography and two-dimensional echocardiography were subjected to human leukocyte antigen (HL-A)-A,B,C typing by the lymphocyte cytotoxicity test and D, DR typing by restriction fragment length polymorphism (RFLP). As control, the HLA genotype of 14 non-affected family members was analyzed. HLA typing of the affected subjects with HCM revealed a very close association (67%) of HLA-DR (4w8) among A,B,C,D and DR. However, the LOD scores of HLA-DR4 and -DR w8 were 0.693 (theta = 0.35) and 0.642 (theta = 0.30) respectively. These data suggest that HLA-loci, analyzed on the basis of RFLP, may not be related with familial HCM with or without obstruction.
To evaluate the possibly confounding effects of age, gender, heart rate, tobacco and alcohol ingestion on the coefficient of variation of the electrocardiographic R-R interval (CVRR), ECGs in the supine posture were obtained in 68 healthy men and 33 healthy women. The C-CVRSA and C-CVMWSA (two component CVs reflecting respiratory sinus arrhythmia and Mayer wave related sinus arrhythmia, respectively) were computed in each subject from component spectral powers using autoregressive spectral and component analyses. Results of multiple regression analysis indicated that age was inversely related to CVRR, C-CVRSA and C-CVMWSA in both sexes. Heart rate was positively related to C-CVMWSA in males. However, no significant difference in the CVRR, C-CVRSA or C-CVMWSA was found between males and females. The C-CVMWSA was not correlated with the C-CVRSA in either males or females. These data indicate that the CVRR, C-CVRSA and C-CVMWSA are affected by age and partly by heart rate; gender, moderate smoking or drinking habits might not strongly influence autonomic nervous system function. On the other hand, the C-CVRSA in the supine posture appears to be independent of the C-CVMWSA. The positive relationship observed between the C-CVMWSA and heart rate suggests that the C-CVMWSA may be associated with sympathetic activity.
The effects of urbanisation, low income and rejuvenation of the population on life expectancy at birth and at 20, 40 and 65 years of age for males and females in Japan were examined twice, in 1980 and 1985. For males, urbanisation was the major factor determining life expectancy at birth and at age 20 years, and low income was the key determinant of decreased life expectancy except at 65 years of age. For females high income was the factor significantly decreasing life expectancy at 65 years of age in 1980, and rejuvenation of the population inversely influenced life expectancy except at birth in 1985. Life expectancy for all age groups in 1985 was significantly longer than in 1980 for both males and females.
The expression of blood group-related antigens, A, B, H type 2, Lewis type 1 (Lewis(a) [Le(a)] and Lewis(b) [Le(b)]), Lewis type 2 (Lewis(x) [Le(x)] and Lewis(y) [Le(y)]), sialylated Le(a) (CA19-9), and sialylated Le(x) (CSLEX1), was analyzed sequentially with immunohistochemical methods in early gastric cancer, intestinal metaplasia, and uninvolved gastric mucosa obtained from 35 surgical specimens of patients who underwent gastrectomy. The high incidence of the inappropriate expression of Lewis type 1 antigens and the deletion of H and Lewis type 2 antigens was observed similarly in patients with cancer and intestinal metaplasia. The acquisition of CA19-9 and CSLEX1 and the deletion of B antigen frequently were found in intestinal-type cancer and all types of intestinal metaplasia. The simultaneous deletion of A antigen was detected only in the combination of intestinal-type cancer and incomplete-type intestinal metaplasia. Thus the present study shows that similar changes of tissue antigenicities exist in early gastric cancer and intestinal metaplasia.
The vasoconstrictive peptide endothelin-1 (ET-1) has been reported to exert a very important positive inotropic effect in vitro. To assess the effect of ET-1 on myocardial contractility in vivo, we compared the effect of intracoronary infusion of 10(-8) M ET-1 (constant coronary blood flow) to that of 10(-8) M dobutamine in 8 swine. ET infusion did not produce changes in segmental shortening (control vs. drug, mean +/- SD): 33.8 +/- 14.3 vs. 30.8 +/- 12.1%, shortening velocity: 10.3 +/- 4.3 vs. 10.7 +/- 4.5 mm/s, or maximum +dP/dt: 1,691 +/- 701 vs. 1,772 +/- 773 mm Hg/s, whereas dobutamine infusion induced an important increase in these measurements; segmental shortening: 36.9 +/- 14 vs. 48.4 +/- 18.8%, shortening velocity: 10.1 +/- 2.6 vs. 14.7 +/- 4.5 mm/s, and maximum +dP/dt: 2,041 +/- 567 vs. 2,389 +/- 765 mm Hg/s (all p less than 0.05). Mean myocardial blood flow assessed by microspheres was unchanged by ET-1 despite a marked increase in coronary artery pressure (88.6 +/- 12.9 vs. 157 +/- 8.8 mm Hg, p less than 0.001). Regional infusion of ET-1 at a dose provoking extensive coronary vasoconstriction does not induce any change in regional or global myocardial function in swine.
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important causative microorganisms for nosocomial infections. Recently, the incidence of isolation of MRSA has been increasing every year in Japan and is, notably, much more frequently found in inpatients than in outpatients. Therefore, we have done epidemiological studies of MRSA isolated from medical staff, inpatients, and the hospital environment in one ward of our hospital. Thereafter, we examined the antibiotic susceptibility (ABPC, DMPPC, CET, CMZ, IPM, GM, MINO, OFLX, EM, CLDM, VCM), phage typing, and coagulase typing of these MRSA. MRSA were isolated more frequently from anterior nares of inpatients than from doctors and nurses. MRSA were isolated more frequently from the environment near carriers of MRSA. Coagulase type II and phage type N.T. (not typable) were the dominant types of MRSA in our hospital (69% and 61%). MRSA strains were resistant to most antibiotics with a few exceptions (VCM, IPM, CMZ, CET). The high isolation frequency of MRSA in our hospital seems to suggest that inpatients who are carrying MRSA spread MRSA throughout the hospital environment and that the anterior nares of inpatients are the major MRSA harbor.
The Treponema pallidum hemagglutination assay (TPHA) is a widely used method for screening syphilis. We report our experience with six elderly (age 72.4 +/- 8.3 years) patients with syphilis, whose TPHA was negative. Their cardiolipin (RPR) and absorbed fluorescence treponemal tests (FTA-ABS) were positive. TPHA-negative patients with syphilis were compared with TPHA-positive syphilitics by immunological analysis. We found that both the numbers and the percentage of CD4 cells in TPHA-negative syphilitics were significantly lower than those in TPHA-positive syphilitics (722 +/- 142 vs. 1,064 +/- 141/mm3, P less than 0.01: 35.1 +/- 6.9 vs. 48.4 +/- 6.4%, P less than 0.01) and that the ratio of CD4 to CD8 was also lower in TPHA-negative syphilitics compared with TPHA-positive syphilitics (1.08 +/- 0.46 vs. 2.24 +/- 1.07, P less than 0.05). These data suggest that the TPHA is insufficient for excluding elderly syphilitics because of immunological impairment seen in aged patients.
The effects of a mitotic arrestant, IKP-104, which has an antitumor activity, on the in vitro polymerization and depolymerization of rat brain microtubules were investigated. IKP-104 inhibited microtubule polymerization at concentrations greater than 0.71 x 10(-6) M, and its IC50 value was determined to be 1.31 x 10(-6) M by probit analysis. Fifty-two percent of pre-polymerized microtubules depolymerized at 1.31 x 10(-6) M IKP-104. Electron micrographs of microtubules taken immediately after treatment with 1 x 10(-3) M IKP-104 revealed a fraying of microtubule ends into elongated coil-like filaments, which were composed of 2 or 3 protofilaments. When microtubule protein treated with 1 x 10(-3) M IKP-104 was cleaved by trypsin, fragments of 41, 36, 34, 23, 21, 19 and 16 kilodaltons (kDa) derived from alpha-tubulin were produced. In particular, the 19, 23, and 34 kDa fragments were characteristically observed in the trypsin cleavage of microtubules tested with IKP-104, and these fragments were not observed with untreated microtubules. The effects of IKP-104 on microtubule protein mentioned above were mostly similar to those of vinblastine (VLB) and we suggest that IKP-104 bound to the site or sites near "VLB-binding site or sites" of alpha-tubulin subunit, resulting in induction of conformational changes.
The antitumor effect of PSK, a Coriolus preparation, was analyzed with the double grafted tumor system in which BALB/c mice received intradermal inoculations of syngeneic Meth-A fibrosarcoma in the right (primary tumor, 10(6) cells) and left (distant tumor, 2 x 10(5) cells) flanks. Intratumoral administration of PSK significantly inhibited the growth of not only the right but also the left tumor. PSK also inhibited the growth of a methylcholanthrene-induced fibrosarcoma BAMC-1, and a methylurethane-induced adenocarcinoma Colon 26 in the double grafted tumor system of syngeneic BALB/c mice. However, when the left distant tumor was different from the right Meth-A tumor, the intratumoral administration of PSK in the right tumor was unable to inhibit the growth of the left BAMC-1 or RL male-1 tumor. The PSK-induced immunity, therefore, is tumor-specific and T lymphocytes may play an important role in antitumor memory function. The enhancement of concomitant immunity by PSK treatment was completely impaired by previous intravenous administration of an alkylating agent, cyclophosphamide (CY). The enhancement of sinecomitant immunity by PSK treatment was also impaired by previous CY intravenous administration. The antitumor effect of PSK was suppressed by previous intravenous administration of another alkylating agent, ACNU. It is possible that alkylating agents suppress the function of effector T cells and granulocytes which are very important for the antitumor immune cascade reaction due to PSK treatment. On the other hand, the antitumor effect of PSK was enhanced by previous intravenous administration of an anti-metabolite, 5-fluorouracil.