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Biomedical subjects

S Takeuchi

Publications and source records attributed to S Takeuchi.

At least 217 records · Page 12Linked to original sources

Strand specificity and absence of hot spots for p53 mutations in ultraviolet B-induced skin tumors of XPA-deficient mice.

We examined the spectrum of p53 mutations found in 40 UV-induced skin tumors of xeroderma pigmentosum group A gene (XPA)-deficient mice. p53 mutations were detected in 48% of the tumors. Nearly all of the mutations were induced at dipyrimidine sites. Ninety-three % of the mutations were G.C-->A.T transitions at dipyrimidine sites, including tandem transitions (CC-->TT), which are the hallmark of the UVB-induced mutation. Seventy-two % of the mutations at dipyrimidine sites could be ascribed to damage on the transcribed strand. In addition, no evident mutational hot spots were detected. This is in contrast to the UVB-induced skin tumors of normal mice, in which 92% of p53 mutations occurred as a result of DNA damage on the nontranscribed strand, and clear hot spots were observed. Thus, XPA-deficient mice showed significant mutation features that might be characteristic of the absence of nucleotide excision repair and may provide a good animal model for the analysis of the high incidence of skin cancer in xeroderma pigmentosum group A patients.

Animals↗

Mechanism of short-term memory and repetition in conduction aphasia and related cognitive disorders: a neuropsychological, audiological and neuroimaging study.

To evaluate the role of the sub-cortical white matter and cortical areas of the supramarginal gyrus in short-term memory impairment (shortened digit or letter span) and repetition difficulty, four patients with conduction aphasia and impaired short-term memory and two patients with only short-term memory impairment were given digit span, letter span, speech audiometry and dichotic listening tests. The results showed that in most of the patients letter span was inferior to digit span and that bilateral ear suppression in the dichotic listening test was observed in two patients with a lesion in the inferior part of the supramarginal gyrus, suggesting that what was affected was phonological information and that the supramarginal gyrus was the storage site. The overlapped lesion of conduction aphasia patients with short-term memory impairment was the periventricular white matter at the upper to middle part of the trigone, while patients with only short-term memory impairment had a lesion in the inferior supramarginal gyrus in common. Thus, damage to the periventricular white matter at the trigone may yield the phonemic paraphasia characteristic of conduction aphasia, while damage to the inferior part of the supramarginal gyrus may result in the impairment of short-term memory. We believe that as a part of the mechanisms of short-term memory and repetition, phonological information is processed in the primary auditory cortex and goes through the periventricular white matter to the inferior part of the supramarginal gyrus and is temporarily stored there.

Aged↗

Production of toxic shock syndrome toxin by Staphylococcus aureus isolated from mastitic cow's milk and farm bulk milk.

The production of toxic shock syndrome toxin (TSST) by Staphylococcus aureus isolated from mastitic cow's milk and farm bulk milk was examined by a reverse passive latex agglutination method (RPLA). TSST was detected in 25 (58.1%) of 43 isolates from clinical mastitic cow's milk, in 79 (76.7%) of 103 isolates from subclinical mastitic cow's milk, and in 95 (75.4%) of 126 isolates from farm bulk milk, respectively. When the quantity of TSST in the isolates was determined by RPLA, the titers ranged from 5 to 2560. TSST with RPLA titers of 640 to 2,560 was produced by 83 (30.5%) of 272 isolates tested. Almost all of the isolates showing RPLA titers of 640 and over produced enterotoxin C, whereas isolates showing titers of 5 to 320 produced enterotoxin C or both enterotoxin A and C. SDS-polyacrylamide gel electrophoresis and isoelectric focusing with immunoblotting showed that the TSST from bovine isolates had same molecular size (22 kDa) and isoelectric point (7.2) as TSST-1 from human isolates. These findings are consistent with previous reports.

Animals↗

Melanocortin receptor genes in the chicken--tissue distributions.

Two receptor genes belonging to the melanocortin receptor (MC-R) family were isolated in the chicken, the CMC4 and CMC5, each of which is a chicken homologue of the mammalian MC4-R and MC5-R, respectively. The CMC4 encodes a 331 amino acid protein, sharing 86. 4-88.1% identity with mammalian analogs, and the CMC5 encodes a 325 amino acid protein, which is 72.3-79.1% identical to mammalian counterparts. Both genes contain no intron in their coding regions and exist in the chicken genome as single copy genes. Reverse transcription-PCR analysis revealed that the CMC4 mRNA is expressed in a wide variety of peripheral tissues, including the adrenal, gonads, spleen, and adipose tissues, as well as in the brain, where mammalian counterparts are exclusively expressed in the brain, indicating that the regulation of MC4-R gene expression differs between mammals and chickens. The CMC5 mRNA, on the other hand, is expressed in the liver, gonads, adrenal, kidney, brain, and adipose tissues as well as in the uropygial gland. These findings raise the possibility that melanocortins affect a variety of functions both in the brain and in the peripheral tissues of the chicken.

Amino Acid Sequence↗

[The surgical treatment for acute aortic dissection--a retrospective study from the statistics of affiliated hospitals of a medical school].

A retrospective study was conducted for the surgical treatment on acute aortic dissection among the cardiovascular services of 5 affiliated hospital of medical school. The total of 74 cases were operated for the last 5 years period from Jan., 1991 to Dec., 1995, in which 64 cases were classified as Type A and 10 for Type B. The average age for Type A was 58.4 years old and 10% of patients were consisted of Marfan syndrome. The most frequent complications associated with dissection was aortic regurgitation (37.5%), followed by cardiac tamponade (23.4%). The surgeries were undertaken in less than 24 hours from the onset of symptom in 45.3% of patients. The localization of initial tear as was proved by intraoperative finding was at ascending aorta in 64.0%, whereas it was found at aortic arch in 21.8% of patients. The most frequent application of operative procedure was simultaneous graft replacement of ascending aorta and aortic arch (68.7%) with the use of profound hypothermia and antegrade selective cerebral perfusion (85.4%). The overall mortality rate was 25.0%, however when compared as ascending only vs ascending + arch replacement, the later group demonstrated higher mortality rate (16.6% vs 28.9%). The majority of surgical indication for Type B was hemorrhage from the dissection and 20.0% of mortality was recorded in this group of patients.

Acute Disease↗

Dye-coupling of melanocytes with endothelial cells and pericytes in the cochlea of gerbils.

Intercellular connections via gap junctions in the stria vascularis, which constitutes the lateral wall of the cochlear duct, were investigated by the Lucifer yellow microinjection method with the aid of a confocal laser microscope. The dye injected into an intermediate cell (melanocyte) diffused into capillary endothelial cells and pericytes as well as other intermediate cells, basal cells, and fibrocytes in the spiral ligament; whereas the dye injected into a marginal cell (epithelial cell) was confined to the injected cell. The observation of dye-coupling between intermediate cells and endothelial cells and pericytes makes likely the possibility that these cells work together to play a role in the specific function of the stria vascularis (i.e., production of the positive endocochlear potential and the endolymph) and adds endothelial cells and pericytes to the current "two-cell model" of the stria vascularis.

Animals↗

Complications following reparative surgery for aortic coarctation or interrupted aortic arch.

Repair of aortic coarctation or interrupted aortic arch continues to be associated with major long-term morbidity. Thus, we conducted a review of 87 consecutive patients who underwent aortic arch repairs, focusing particular attention on the complications that developed. A two-stage strategy was employed if cardiac lesions were associated. The median age at surgery was 1.5 months with a range of 12 h to 56 years. The aortic arch was repaired using end-to-end anastomosis, subclavian flap aortoplasty, subclavian arterial turning-down aortoplasty, patch aortoplasty, tube graft interposition, or other methods. There were 10 patients who died soon after repair, and all of whom had complex cardiac anomalies. Of the remaining 77 patients, 8 developed recurrent stenosis. These 8 patients were all similar in age, being under 3 months old, and weighing 4 kg or less. A multivariable analysis of the infants identified interrupted aortic arch as an independent risk factor for the development of this complication with an odds ratio of 6.45. Complications following prosthesis-free techniques were similar in prevalence and timing. All reinterventions were mortality-free, but catheter dilation and patch aortoplasty were not always successful. Three extraanatomic bypasses were successfully performed, and one adult who had undergone a previous graft and pseudoaneurysm operation was successfully treated with an extraanatomic bypass. These findings led us to conclude that the initial repair should be performed without a prosthesis, and that reintervention for stenosis should combine catheter dilation and extraanatomic bypass.

Adolescent↗

Haemodynamic evaluation of cerebral gliomas using XeCT.

The purpose of this study was to characterize regional blood flow (BF) in untreated cerebral gliomas (CG) using stable Xe-enhanced computed tomography (XeCT). XeCT of 38 patients with untreated CG were analyzed and compared with CT and magnetic resonance images (MRI) and histopathological findings. Individual averaged BF values for tumour in 29 high grade gliomas (HGGs) and 9 low grade gliomas (LGGs) were intermediate between averaged BF values for cortex and white matter in the non-tumour bearing hemisphere. All averaged BF values for cyst and central necrosis were very low. In 27 HGGs, BF in tumour was relatively high in ring-enhancement lesions on CT and MRI, but was low even in viable tumour centers showing no contrast enhancement. In the other 2 HGGs, BF was low in tumour center and relatively high in tumour periphery regardless of homogeneous enhancement. In 5 HGGs, averaged BF value of the cortex outside surrounding oedema was higher than that of cortex in the non-tumour bearing hemisphere. In LGGs, BF distribution in tumour was homogeneously low in 3 small-sized and heterogeneous in 6 large-sized lesions including moderately high and low BF regions. These differences in BF pattern between HGGs and LGGs on XeCT might be helpful in considering to some extent the histopathology of untreated cerebral glioma pre-operatively.

Adolescent↗

Possible direct effect of gonadotropin releasing hormone on human endometrium and decidua.

Decidualization of endometrial tissues, which is essential for implantation and the continuation of pregnancy, is induced by pituitary hormones that are regulated by gonadotropin releasing hormone (GnRH). Our objective was to determine the role of a direct action of GnRH on endometrial tissues by comparing the characteristics of receptors for GnRH in human endometrial and decidual tissues. Competitive binding studies were performed with the protease-resistant GnRH analogues, buserelin and [125I] buserelin. The effects of buserelin on phosphoinositol turnover were determined by the measurement of inositol 1,4,5-triphosphate(IP3). The values for the dissociation constant (Kd) and number of binding sites (Bmax) per unit protein versus buserelin for endometrial tissues did not differ from the values for decidual tissues. However, the Bmax per unit DNA was significantly higher in endometrial tissues. Also, buserelin induced a significant increase in IP3 in decidual tissue. These results indicate that GnRH may be a potential modulator of the function in human endometrium and decidua. The signal transduction mechanism for GnRH action appeared to involve the accelerated turnover of phosphoinositol.

Binding, Competitive↗

Postnatal vascular development in the lateral wall of the cochlear duct of gerbils: quantitative analysis by electron microscopy and confocal laser microscopy.

The development of the capillary network in the stria vascularis and in the underlying spiral ligament of gerbils was systematically and quantitatively investigated by conventional electron microscopy and confocal laser microscopy in association with vascular labeling with fluorescent gelatin. The developmental changes of capillaries in the lateral wall were observed as the following series of events. (i) At 0 days after birth (DAB) capillaries already existed in the spiral ligament as a network. (ii) At 3-9 DAB the capillary network developed into two layers starting from the scala vestibuli side to the scala tympani side; one layer was located in the stria and the other in the spiral ligament. (iii) At 9 DAB capillaries in the stria became separated from the spiral ligament, and the capillary network consisting of a two-layered structure was complete. (iv) Total capillary length and capillary density in the lateral wall increased until 9 DAB and leveled off thereafter, but changes in the relative position of capillaries in the stria toward the luminal surface of marginal cells continued until 31 DAB. On the basis of the above observations, we propose two possible mechanisms underlying the vascular development in the lateral wall: (i) the formation of new vasculature (angiogenesis), and (ii) changes in the position of cellular components relative to capillaries in association with the differentiation and maturation of marginal cells and intermediate cells.

Animals↗

Increase in the peripheral lymphocyte populations expressing CD54 (ICAM-1) after hyperthermic isolated limb perfusion in patients with malignant melanoma: an analysis of four cases.

The lymphocytes isolated from perfused or non-perfused circulations before, during, and after hyperthermic isolated limb perfusion (HILP) in the four patients with malignant melanoma were analysed for the expression of CD54 (ICAM-1), CD58 (LFA-3), CD4, CD8, HLA class I and class II in order to investigate the mechanism(s) of the activation of such immunocompetent cells as natural killer (NK)-cells or T-lymphocytes by HILP. It was thus found that the lymphocyte populations expressing CD54 increased significantly 1 day after HILP in the four patients examined. The lymphocyte populations expressing CD58 apparently increased. It was also found that the NK-cell and T-lymphocyte activities increased during or after HILP in the present four cases as observed previously in the other melanoma patients. These results indicate that our HILP system may augment the immunological activities through the mechanisms of the induction of CD54 or CD58 expression in the peripheral lymphocytes of the melanoma patients who receive HILP.

Adult↗

Correction of total anomalous pulmonary venous connection of the cardiac type.

Surgical treatment of the cardiac type of total anomalous pulmonary venous connection requires special techniques. The treatment and outcome in 17 consecutive patients who had undergone primary repairs of the cardiac type between 1965 and 1996 were reviewed. The median age was 3 months and median weight 4.2 kg. The connection was the coronary sinus in ten patients, and the right atrium in six. Interatrial communication was routinely augmented. The right atrial cavity was partitioned using a patch to direct the anomalous pulmonary veins into the left atrium through the atrial septal defect in the first 13 patients. In the last four patients, the free wall flap of the right atrium was developed as a neoseptum. There were three early postoperative deaths during the early period of conventional repair. Two patients developed residual or recurrent diffuse obstruction in the individual lobar veins; reoperation to relieve the obstruction was attempted but unsuccessful. One sudden death occurred in a patient with occasional heart block. Ten survivors have been asymptomatic during follow-up, but two incomplete heart blocks and one atrial flutter were noted among patients who underwent conventional repair. The right atrial wall flap technique was not associated with any mortality or morbidity, such as arrhythmia and recurrent pulmonary vein stenosis during 12 to 63 months of postoperative obstruction. In conclusions, a flap technique using the right atrial wall appears to be a promising method to decrease the incidence of supraventricular arrhythmias and pulmonary vein drainage obstruction following repair of the cardiac type.

Cardiac Surgical Procedures↗

Analysis of the Smad2 gene in hematological malignancies.

A total of 34 leukemia and lymphoma samples (17 clinical samples and 17 cell lines) were analyzed for mutations of the Smad2 gene by reverse transcriptase-polymerase chain reaction single strand conformation polymorphism (RT-PCR-SSCP) analysis. Nine of the 34 samples had 18q chromosomal abnormalities. No shifted bands were detected in any of the hematological malignancies. Our results suggest that resistance to cell growth inhibitory effects of TGF-beta in hematological malignancies is not due to alterations of the Smad2 gene.

Adolescent↗

The ATM gene and susceptibility to childhood T-cell acute lymphoblastic leukaemia.

Ataxia-telangiectasia (A-T) is a multisystem recessive disease characterized by cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency and increased risk of cancer. The ATM gene, responsible for A-T, was recently cloned at human chromosome band 11q22-23, a region of frequent alterations in childhood acute lymphoblastic leukaemia (ALL). Children with A-T frequently develop T-ALL. We investigated 18 T-ALL samples for ATM mutations and loss of heterozygosity (LOH) at the ATM locus. No mutations of ATM were found within the coding region in the 18 T-ALL samples, and LOH at the ATM locus was detected in three. The ATM gene appears to be an infrequently altered tumour suppressor gene in childhood T-ALL.

Ataxia Telangiectasia Mutated Proteins↗

Arsenic trioxide inhibits growth of human T-cell leukaemia virus type I infected T-cell lines more effectively than retinoic acids.

Adult T-cell leukaemia (ATL) is difficult to cure using conventional therapies. Recently the therapeutic possibility of retinoic acids (RA) has been reported. In this study, suppression of in vitro growth of human T-cell leukaemia virus type I (HTLV-I) infected T-cell lines and fresh ATL cells by arsenic trioxide (As2O3) were evaluated by comparison with a series of RA derivatives. Proliferation of four HTLV-I-infected T-cell lines was significantly reduced within 72 h by 1.0 micromol/l As2O3. Growth of two out of four HTLV-I-infected T-cell lines was also inhibited by 1.0 micromol/l RA, but to a lesser extent than by As2O3. The mechanism of this growth inhibition was due to the induction of apoptosis. Apoptosis was also induced in fresh ATL cells from patients by AS2O3, but far less by RA. As described in patients with acute promyelocytic leukaemia, 1.0 micromol/l of As2O3 can be safely achieved in the serum of patients; however, it is difficult to maintain this concentration of RA. In conclusion, As2O3 has therapeutic potential for the treatment of ATL and may be far more clinically beneficial than RA.

Antineoplastic Agents↗