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Biomedical subjects

K Komatsu

Publications and source records attributed to K Komatsu.

At least 163 records · Page 9Linked to original sources

Minimally invasive axillary-coronary artery bypass for acute occlusion of the coronary artery.

We performed minimally invasive axillary-coronary bypass using a reversed saphenous vein graft to treat a patient with acute occlusion of the left anterior descending artery after failed percutaneous transluminal coronary angioplasty (PTCA). For patients with acute myocardial ischemia, this procedure is useful to reduce the ischemic time and is less invasive. We believe this procedure may be an alternative intervention for selected patients with acute myocardial infarction or unstable angina after PTCA. However, a large series with sufficient follow-up and late angiography is required to evaluate the long-term patency and effectiveness of this approach.

Anastomosis, Surgical↗

The phosphatidylinositol 3-kinase inhibitor wortmannin sensitizes quiescent but not proliferating MG-63 human osteosarcoma cells to radiation.

Recent genetic and biochemical studies indicate that DNA-dependent protein kinase (DNA-PK) plays an important role in DNA double-strand break (dsb) repair and V(D)J recombination. Since the catalytic subunit of DNA-PK (DNA-PKcs) has high sequence homology with phosphatidylinositol 3-kinase (PI 3-kinase), we examined the effect of wortmannin, a specific inhibitor of PI 3-kinase, on the survival of human tumor cells after X-irradiation. The present study demonstrates that wortmannin at 20 microM is an effective radiosensitizer of quiescent (Q), but not proliferating (P) cells. In addition, the rejoining of DNA dsb is significantly inhibited in Q, but not in P cells. Finally, we found that Q cell extracts have approximately five-fold less DNA-PK activity than those of P cells. After a 2 h exposure to wortmannin, the DNA-PK activity of Q cell extracts was considerably lower than that of P cells. This can explain why wortmannin sensitizes Q, but not P cells to radiation.

Androstadienes↗

Radiation induction of p53 in cells from Nijmegen breakage syndrome is defective but not similar to ataxia-telangiectasia.

p53-mediated signal transduction after exposure to ionizing radiation was examined in cells from patients with Nijmegen breakage syndrome (NBS), an autosomal recessive disease characterized by microcephaly, immunodeficiency, predisposition to malignancy, and a high sensitivity to ionizing radiation. NBS cells accumulated p53 protein in a dose-dependent fashion, with a peak level 2 hrs after irradiation with 5 Gy. However, the maximal level of p53 protein in NBS cells was constantly lower than in normal cells. Moreover, this attenuation of p53 induction was confirmed by decreased levels of p21WAF1 protein, which is transcriptionally regulated by p53 protein. This defective induction of p53 protein in NBS is similar to that in ataxia-telangiectasia (AT), although the induced levels of p53 protein in NBS appeared to be the intermediate between normal cells and AT cells. This moderate p53 induction in NBS cells is consistent with the relatively mild radiation sensitivity and the abnormal cell cycle regulation post-irradiation, as present in NBS. Furthermore, all NBS cell lines used here exhibited time courses of p53 induction similar to normal cells, which is in contrast with p53 induction in AT cells, where the maximum induction shows a delay of approximately 2 hrs compared with normal cells. These evidences suggest a different function of each gene product in an upstream p53 response to radiation-induced DNA damage.

Ataxia Telangiectasia↗

Comparison of biomechanical properties of the incisor periodontal ligament among different species.

BACKGROUND: The aim of this study was to obtain a more precise understanding of the mechanical properties of the periodontal ligament in continuously erupting incisors by comparing the shear stress-strain relations among teeth from four closely related species. METHODS: Four species of experimental animals (mice, hamsters, rats, and rabbits) were used. Transverse sections of the left mandibular incisors were cut from the incisal, middle, and basal regions of each incisor. The tooth was pushed out of the alveolar bone in an extrusive direction at 5 mm/min using a materials testing machine. The maximum shear stress, maximum shear strain, tangent modulus, and failure strain energy density were estimated from the resulting stress-strain curve. Polarized light microscopic observations of collagen fibers were also made. RESULTS: All the biomechanical measures tended to decrease from the incisal toward the basal regions in all species. There were large species differences, especially in the incisal region, with the greatest maximum shear stress and failure strain energy density in hamsters. The greatest tangent modulus and the smallest maximum shear strain were observed in mice. The birefringent fiber architectures of the periodontal ligaments in the four species appeared to be similarly organized; the incisal periodontal ligament appeared to have more organized and thicker collagen fibres than did the middle and basal ligaments in the four species. CONCLUSIONS: These results suggest that the regional differences in the biomechanical properties of the periodontal ligament depend upon the developmental stages of the periodontal collagen fibers that may be related to the general arrangement, diameters, and densities of the collagen fiber bundles and the fiber insertions into the alveolar bone and cementum. The species differences in the biomechanical properties may be due to differences in the width of the periodontal ligament and the waviness as well as the strength and stiffness of the periodontal collagen fibers.

Animals↗

ATM mutations in patients with ataxia telangiectasia screened by a hierarchical strategy.

ATM has been identified as a gene that is responsible for ataxia telangiectasia (AT), a pleiotropic disorder of autosomal recessive inheritance. While many mutations of this gene in AT patients of various ethnicities have been reported, data on Japanese patients are scarce. In this report, we present the results of a thorough survey of ATM mutations in 14 unrelated AT patients, with an emphasis on Japanese subjects. We used a hierarchical strategy in which we extensively analyzed the entire coding region of the cDNA. In the first stage, point mutations were sought by PCR-SSCP in short patches. In the second and third stages, the products of medium- and long-patch PCR, each covering the entire region, were examined by agarose gel electrophoresis to search for length changes. We found a total of 15 mutations (including 12 new) and 4 polymorphisms. Abnormal splicing of ATM was frequent among Japanese, and no hotspot was obvious, suggesting no strong founder effects in this ethnic group. Eleven patients carried either one homozygous or two compound heterozygous mutations, one patient carried only one detectable heterozygous mutation, and no mutation was found in two patients. Overall, mutations were found in at least 75% of the different ATM alleles examined. Possible reasons for the inability to detect mutations in some patients are discussed.

Ataxia Telangiectasia↗

Long-term results of porcine bioprostheses in the tricuspid position.

From January 1976 to September 1994, 26 patients underwent a tricuspid valve replacement (TVR) with porcine bioprostheses (Hancock II in 19 patients, Carpentier-Edwards in 3, Hancock standard in 2, Medtronic-Intact in 1, and Liotta in 1). The mean age of these patients was 38.4 years (range, 9 to 70 years). The mean follow-up period was 6.7 years (range, 1.8 to 16.5 years). There was a complete follow-up in 100%. There were two hospital deaths and three late deaths. The actuarial survival rate at 16 years was 78.7%+/-8.6%. Five patients developed structural deterioration. Four of these 5 patients underwent re-TVR. The actuarial freedom rate from structural deterioration at 10 years was 47.1%+/-19.1%. There were no instances of thromboembolism and prosthetic valve endocarditis. Our experience indicated the major problem of the porcine bioprostheses in the tricuspid position thus to be valve durability: however, the long-term actuarial survival rate was satisfactory, including no operative morality with re-TVR due to tricuspid prosthetic structural deterioration. We therefore conclude that the choice of a porcine bioprosthesis in the tricuspid position should be considered not only for patients with isolated tricuspid valve disease, but also for the patients who have not previously received mechanical valves in the mitral or the aortic valve position.

Adolescent↗

Is atrial fibrillation resulting from rheumatic mitral valve disease a proper indication for the maze procedure?

BACKGROUND: There are a few patients without detectable atrial contraction despite restoration of atrial rhythm after the maze procedure for atrial fibrillation (AF) associated with mitral valve disease. METHODS: From January 1995 to March 1997, 29 consecutive patients with AF associated with mitral valve disease underwent our modified maze procedure combined with mitral or other valve operations. The causes of mitral valve disease were rheumatic mitral stenosis (n = 22) and nonrheumatic mitral regurgitation (n = 7). The 17 patients with postoperative atrial rhythm were divided into group I with rheumatic mitral stenosis (n = 10), and group II with mitral regurgitation of nonrheumatic origins (n = 7). RESULTS: Seventeen patients regained atrial rhythm, 2 patients had junctional rhythm, and another 10 remained in AF. Between the group of patients with restoration of atrial rhythm and that of patients remaining in AF, significant differences were found in the percentage with rheumatic disease, history of AF, and maximum f-wave voltage. The postoperative peak velocity of the atrial filling wave to peak velocity of early filling wave ratio for the left atrium measured using Doppler echocardiography was 0.25 in group I, which was significantly lower than that (0.42) in group II. CONCLUSIONS: Reconsideration of the indications for the maze procedure for AF associated with rheumatic mitral stenosis may thus be reasonable, particularly for cases in which replacement using a prosthetic valve is necessary, but we believe that patients with nonrheumatic mitral valve disease, especially those able to undergo reconstructive operations, are the best candidates for the maze procedure.

Adult↗

Effects of MK-801 on bladder overactivity in rats with cerebral infarction.

PURPOSE: Our objective was to evaluate the underlying mechanisms of neurogenic voiding dysfunction following cerebral infarction. MATERIALS AND METHODS: The left middle cerebral artery (MCA) was occluded using 4-0 monofilament nylon thread in male S-D rats. Cystometric examination was performed in unanesthetized and urethane-anesthetized rats through a catheter chronically implanted in the dome of the bladder. RESULTS: Bladder capacity of unanesthetized or urethane anesthetized rats was significantly reduced just after occlusion of the left MCA; 2 weeks after the occlusion, the capacity was less than half that in sham-operated rats. Intravenous administration of N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 to the unanesthetized sham-operated rats led to a marked dose-dependent decrease in bladder capacity. Its administration to unanesthetized rats with cerebral infarction resulted in a slight decrease in bladder capacity. In the urethane-anesthetized state, the bladder capacity of the rats with cerebral infarction was significantly increased by MK-801, 0.1 mg./kg., without inhibiting the contraction pressure or increasing the amount of residual urine. A high dose (1 mg./kg.) of MK-801 was required to increase the bladder capacity of sham-operated rats. This led to an inhibition of contraction pressure and an increase in residual urine. CONCLUSION: Results in urethane anesthetized rats indicate that NMDA glutamatergic transmission is important in the overactivity of the bladder following a cerebral infarction. This model is useful in studying the neurogenic voiding dysfunction observed in patients with cerebrovascular disease.

Anesthesia↗

Change in bladder contractility associated with bladder overactivity in rats with cerebral infarction.

PURPOSE: To evaluate the contractile properties of overactive bladder from rats in the chronic stage of experimental cerebral infarction. MATERIALS AND METHODS: Cystometry was performed in conscious male S-D rats after inducing occlusion of the left middle cerebral artery. Bladder muscle strips were evaluated for force development in response to field stimulation, acetylcholine and KCl. By measuring the contractile response to field stimulation after adding atropine and alpha,beta-methylene-ATP, contributions of cholinergic and purinergic transmission were determined. RESULTS: Bladder capacity of cerebral-infarcted rats was <50% of the capacity of sham-operated rats and significantly less than that of sham-operated rats even 4 months after surgery. There was no significant difference in bladder weight between sham-operated rats and cerebral-infarcted rats. No differences in the contractile response of detrusor strips to field stimulation and acetylcholine, or in the relative contribution of cholinergic and purinergic transmission to the contractile response, were observed over time or between strips from sham-operated rats and cerebral-infarcted rats. KCl induced significantly less contraction in strips from 4 month infarcted rats than in strips from 4 month sham-operated rats, 2 week infarcted rats and 2 month infarcted rats. CONCLUSIONS: This animal model will be useful for chronic studies on the mechanism of detrusor hyperactivity (DH).

Animals↗

Purification and characterization of cannabichromenic acid synthase from Cannabis sativa.

Cannabichromenic acid synthase was purified to apparent homogeneity by sequential column chromatography including DEAE-cellulose, phenyl-Sepharose CL-4B, and hydroxylapatite. The enzyme catalysed the oxidocyclization of cannabigerolic acid and cannabinerolic acid to cannabichromenic acid. The K(m) values for both substrates were in the same order of magnitude although the Vmax value for the former was higher than that for the latter. These results suggested that cannabichromenic acid is predominantly formed from cannabigerolic acid rather than cannabinerolic acid. The enzyme required neither molecular oxygen nor hydrogen peroxide, indicating that the cannabichromenic acid synthase reaction proceeds through direct dehydrogenation without hydroxylation.

Cannabis↗

Positional cloning of the gene for Nijmegen breakage syndrome.

Nijmegen breakage syndrome (NBS), also known as ataxia-telangiectasia (AT) variant, is an autosomal recessive disorder characterized by microcephaly, growth retardation, severe combined immunodeficiency and a high incidence of lymphoid cancers. Cells from NBS patients display chromosome instability, hypersensitivity to ionizing radiation and abnormal cell-cycle regulation after irradiation, all of which are characteristics shared with AT. Recently, the NBS locus was mapped at 8q21 by two independent approaches, complementation studies and linkage analysis. Here, we report the positional cloning of the NBS gene, NBS1, from an 800-kb candidate region. The gene comprises 50 kb and encodes a protein of 754 amino acids. The amino-terminal region of the protein shows weak homology to the yeast XRS2, MEK1, CDS1 and SPK1 proteins. The gene is expressed at high levels in the testes, suggesting that it might be involved in meiotic recombination. We detected the same 5-bp deletion in 13 individuals, and conclude that it is likely to be a founder mutation.

Amino Acid Sequence↗

Congenital ectopic nail with bone deformity.

This report describes two cases of congenital ectopic nail with bone deformity. Histologically, the squamous epithelium of the nail matrix lacked a definite granular layer. Resected nail tissue was connected with the periosteum of the tip of the ungual phalanx, which suggested that the contact of the ectopic nail matrix with the periosteum could impede intramembranous ossification and deform the bone shape.

Child↗

Electromyographic activity of the jaw-closing muscles before and after unilateral coronoidectomy performed on a patient with coronoid hyperplasia: a case study.

There have been few reports analyzing the activity of the jaw-closing muscles after coronoidectomy performed on a patient with coronoid hyperplasia. This paper presents a case study using electromyograms (EMGs) to evaluate the effects of unilateral coronoidectomy on the activity of masseter and temporal muscles. The patient was a 25-year-old male whose maximal range of jaw opening was 24 mm. After coronoidectomy of the left region, the range improved to 43 mm. EMGs were recorded in the center of the masseter muscles and the anterior part of the temporal muscles during gum chewing. Preoperatively, no abnormal EMG activity was observed. Eight months after surgery, increase in the ratio of the bilateral temporal muscle activity and a decrease in the ratio of the right masseter muscle activity were observed, and the proportion of activity of jaw closing muscles was out of the normal range. Eighteen months after surgery, there was slight return to the preoperative EMG activity. It was concluded that unilateral coronoidectomy could result in EMG changes of masseter and temporal muscles with a gradual return.

Adult↗

Developmental malformations and intrauterine deaths in gamma-ray-irradiated scid mouse embryos.

PURPOSE: To examine the induction by radiation of developmental malformations and intrauterine deaths in severe combined immunodeficiency (scid) mice. MATERIALS AND METHODS: The scid embryos, as well as those of C.B-17 control mice, were irradiated with graded doses of 60Co gamma-rays on gestation day 8. RESULTS: Intrauterine deaths in scid mice increased with radiation dose, and their frequency was substantially higher than in C.B-17 mice. The LD50 for intrauterine death in scid mice was 0.58 Gy and 1.25 Gy in C.B-17 mice. In addition, after irradiation scid mice showed several types of developmental malformations, including meningoencephalocele, spina bifida, eye defects, tail defects and oedema. Malformation incidences were higher in scid than in C.B-17 mice: 33.3% in scid mice irradiated with 0.75 Gy and 13.0% in C.B-17 mice irradiated with 1.0 Gy. However, when malformation incidences were plotted against intrauterine deaths, all the data, irrespective of the type of mouse, essentially fell along a single straight line. CONCLUSIONS: These results suggest that some mechanism common to both scid and normal mice induces developmental malformations. This mechanism involves cell killing. Residual DNA damage, such as double-strand breaks, could be associated with radiation-induced teratogenesis.

Abnormalities, Radiation-Induced↗

Fine localization of the Nijmegen breakage syndrome gene to 8q21: evidence for a common founder haplotype.

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by microcephaly, a birdlike face, growth retardation, immunodeficiency, lack of secondary sex characteristics in females, and increased incidence of lymphoid cancers. NBS cells display a phenotype similar to that of cells from ataxia-telangiectasia patients, including chromosomal instability, radiation sensitivity, and aberrant cell-cycle-checkpoint control following exposure to ionizing radiation. A recent study reported genetic linkage of NBS to human chromosome 8q21, with strong linkage disequilibrium detected at marker D8S1811 in eastern European NBS families. We collected a geographically diverse group of NBS families and tested them for linkage, using an expanded panel of markers at 8q21. In this article, we report linkage of NBS to 8q21 in 6/7 of these families, with a maximum LOD score of 3.58. Significant linkage disequilibrium was detected for 8/13 markers tested in the 8q21 region, including D8S1811. In order to further localize the gene for NBS, we generated a radiation-hybrid map of markers at 8q21 and constructed haplotypes based on this map. Examination of disease haplotypes segregating in 11 NBS pedigrees revealed recombination events that place the NBS gene between D8S1757 and D8S270. A common founder haplotype was present on 15/18 disease chromosomes from 9/11 NBS families. Inferred (ancestral) recombination events involving this common haplotype suggest that NBS can be localized further, to an interval flanked by markers D8S273 and D8S88.

Chromosome Breakage↗

Coccidioidomycosis in Arizona: increase in incidence from 1990 to 1995.

The number of cases of coccidioidomycosis (incidence) reported to the Arizona Department of Health Services increased from 255 (7.0 per 100,000 population) in 1990 to 623 (14.9 per 100,000 population) in 1995 (P < .001). Four counties in the south central region of the state, which contained 80% of the state's population, had the largest increase and accounted for 95% of all cases in 1995. Cases in persons aged 65 years or older and men were reported more frequently (for both, P < .001). During 1995, 890 patients were discharged from Arizona hospitals with a diagnosis of coccidioidomycosis. Rates of hospitalization were greater among persons aged 55 years or older, men, and African-American (for all three, P < .01). Of the hospitalized patients, 48 died, and 12 (25%) of these patients had a concurrent diagnosis of human immunodeficiency virus infection. These data demonstrate that coccidioidomycosis is a growing health problem in Arizona.

Adult↗