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Biomedical subjects

Y Adachi

Publications and source records attributed to Y Adachi.

At least 721 records · Page 40Linked to original sources

Gene expression for calpain isozymes in human hematopoietic system cells.

Calpain (EC 3.4.22.17; Ca2(+)-dependent cysteine endopeptidase) is known to exist in two forms of isozyme. Calpain I requires low (or microM)-Ca2+ for activation and calpain II requires high (or mM)-Ca2+. Both isozymes consist of one heavy (approx.80 kDa) and one light (approx. 30 kDa) subunit each. The heavy subunits of isozymes I and II are different genetic products, while the light subunits are identical. Antibodies respectively specific for the heavy subunits of pig calpains I and II were raised in rabbits, and the affinity-purified IgG proteins were used for Western blot analysis. When 23 human hematopoietic system cells were examined for the degree of their expression of the genes for calpains I and II, all of them were found to contain calpain I of detectable amounts in their cytosolic fluid. By contrast, only nine cell-line cells were positive in calpain II, and they were, without exception, the lineage which had been infected with HTLV-I, the retrovirus responsible for human adult T-cell leukemia. The enhanced production of calpain II in HTLV-I infected T-cells was also confirmed by running chromatographic analyses on the homogenates of these cells, and comparing them with those of uninfected T-cells. When YT-C3 cell, which is an uninfected, natural killer-like cell, was transfected with HTLV-I gene, the resulting transformed stable cells, YT-4 and YT-5.1, were found to produce increased amounts of calpain II concomitant with that of interleukin (IL)-2 receptor protein. These results suggest that the gene expression for calpain isozymes may vary during the course of differentiation of T-lymphocytes. The mechanism of regulation of calpain isozyme genes and the biological significance of the variation in expression during differentiation still remain unanswered.

Animals↗

Equilibrium dialysis studies on aqueous taurocholate-lecithin solutions: further validation of the method.

Since the 1980 publication by Mazer, Benedek and Carey on the concept of the simple micelle-mixed micelle coexistence phenomenon in the bile salt-lecithin systems, it became apparent that a reliable method was needed for measuring the coexisting species concentrations. We recently published a method based on membrane dialysis equilibrium, and the purpose of this report is to review and to validate this previous work. In the present studies, two dialysis membranes with molecular weight cut-off of 8,000 and 12,000 to 14,000 Da, respectively, and two sets of solution volume conditions were investigated with the taurocholate-lecithin system. Coexistence data were obtained over a wide range of lecithin concentrations and the results were found to be in good agreement with those from the previous studies. The bile salt/lecithin molar ratios for the mixed micelles were also deduced from the data. The principal conclusion of this study is that although there is a moderate amount of variability (10% to 15%), the method is both satisfactory and useful in studying bile salt-lecithin equilibria and dynamics.

Bile Acids and Salts↗

Persistence of mucosal gastric carcinomas for 8 and 6 years in two patients.

A small gastric carcinoma was detected in a man, but he refused surgery. Eight years later, he was readmitted for a check-up, and a partial gastrectomy was performed. Pathologic examination revealed a well-differentiated adenocarcinoma restricted within the mucosa. In another man, an irregularly shaped, grossly depressed lesion indicating a malignancy was present at the gastric angle, and 6 years later he agreed to a partial gastrectomy. The lesion proved to be a well-differentiated adenocarcinoma confined to the mucosa. Retrospective examination of the original biopsy specimen revealed a small area of adenocarcinoma, presumably overlooked at the initial examination. Thus, some gastric carcinomas of the well-differentiated type can grow at an extremely slow rate, without extensive spread or invasion. Findings in these cases contribute to knowledge of the biological behavior of gastric carcinomas.

Adenocarcinoma↗

[Nationwide intradermal test with chironomid midge extract in asthmatic children in Japan].

Chironomidea (Insecta) is recently considered one of the most common inhalant antigen in Japan. Intradermal tests with Chironomus plumosus (CP) extract were undertaken on seven hundred and eighteen asthmatic children aged from 6 to 15 years in 10 areas (11 medical institutions) in Japan. The number of cases who showed positive intradermal tests with CP extract was 200 (27.9%) and the positive rate increased in proportion to their age (p less than 0.005). In each of the 11 medical institutions the positive rates ranged from 12.6% in Akita to 45.5% in Okinawa. There were no significant correlations between the results of the intradermal test with CP and those of RAST, prick test and intradermal test with mite, HD and silk, whereas correlation was noted in the prick test with silk (p less than 0.01). The CP positive asthmatics had significantly more attacks than the CP negative ones in the summer (p less than 0.01). The positive rate of asthmatics living near paddy or farm fields was significantly higher than that of those in urban residential areas (31.3% vs 23.8%, p less than 0.05). Chironomid midge is one of the most common and important allergen in Japan.

Adolescent↗

[Indication for surgery in a patient with tuberculoma accompanied by chronic myeloid leukemia].

Patients with chronic myeloid leukemia (CML) tend to suffer from non-reactive form of tuberculosis (TB) and often dissemination and death are the consequence when the blast crisis occurs. In those patients the eradication of pulmonary TB is essential to prolong their life. In a 58-year-old man with a tuberculoma and CML, right upper lobectomy was performed and was discharged 2 weeks later uneventfully. He succumbed to blast crisis 59 months after the onset of CML with no autopsy finding of recurrence nor dissemination of TB. The lobectomy in this patient was effective in preventing dissemination of TB. Controversy exists as to the indication for surgery but this case illustrates the effectiveness of surgery preventing the dissemination of TB in patients accompanying CML.

Humans↗

[A case report of corrected transposition of the great arteries without any associated defects in a 36-year-old man and the review of adult cases reported in Japan].

We report a case in a 36-year-old man of corrected transposion of the great arteries (CTGA) without any associated defects. We also review clinical characteristics and later complications of adult CTGA cases reported in Japan. The patients was referred to our hospital for further examination of the abnormal ECG found during regular medical check-up. His ECG showed left axis deviation, first degree AV block, abnormal Q waves in the left precordial leads, and disappearance of septal q waves in the left precordial leads. His exercise capacity was found to be more than 12 METS by treadmill exercise testing. His roentgenogram revealed an egg-shaped ventricle with normal CTR (45%). The following findings were obtained by two-dimensional echocardiogram and heart catheterization: 1) the functional left ventricle had the characteristics of the anatomical right ventricle, 2) The positions of the left and right atrioventricular valves were reversed, 3) Other cardiac anomalies such as VSD, pulmonary stenosis, tricuspid regurgitation (TR) were not proved. Therefore, he was diagnosed as having CTGA without any cardiac defects (SLL type). At present, with ages more than 15 years, 36 cases of CTGA without cardiac anomalies have been reported in Japan including this case. But most cases had significant TR. This case was the 7th reported case without the accompaniment of TR. Among 36 cases, TR was found in 71%, complete AV block in 20%, and congestive heart failure was noted in 45%. Prognosis of CTGA without any defects is dependent on the appearance of TR, advanced AV block, and congestive heart failure. As these later fatal complications are observed very often, it is important to detect the patient of CTGA accurately.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Factors influencing the binding of calpain I to human erythrocyte inside-out vesicles.

The mechanism for binding of human erythrocyte calpain I to human erythrocyte inside-out vesicles was studied by immunoelectrophoretic blot analysis. Binding of calpain I to inside-out vesicles was observed both in the absence and presence of Ca2+. Moreover, in the absence of Ca2+, acidic proteins like casein, ovalbumin and calpastatin suppressed while basic proteins like arginase and lysozyme did not affect the binding of calpain I to inside-out vesicles. Here, we propose a model for the binding of calpain to the membrane.

Arginase↗

Measurement of bronchial hyperreactivity in infants and preschool children using a new method.

We report a new method for examination of bronchial reactivity by measuring transcutaneous oxygen pressure (tcPO2) during the inhalation of histamine in stepwise incremental concentrations. The correlation between changes in tcPO2 and those in PEFR or FEV1 was high (P less than .001). When the fall in PEFR or FEV1 was more than 20% compared with baseline, the fall in tcPO2 was more than 10%. We also measured the dose of radiolabeled aerosol (99mTc-DTPA) inhaled into the lung using a scintillation camera. When aerosol is inhaled during tidal breathing, there are adequate correlations between the dose of aerosol in the lung and both the age and height of the patients (P less than .001). When aerosol was inhaled during crying, little deposit within the lung was shown. When the inhalation challenge test was done during a sleeping period for children aged under 2 years, the loading dose of aerosol in the lung was sufficient. The geometrical means of respiratory threshold of histamine (RT-Hist) among 106 asthmatic and 11 control children, aged 2 to 6 years, were 1182 and 4414 micrograms/mL, respectively. The means of RT-Hist in 17 children with bronchial asthma, nine with atopic dermatitis, five with respiratory disease, and nine controls, aged under 2 years, were 1152, 964, 544, and 3402 micrograms/mL, respectively.

Administration, Inhalation↗

[Primary myelofibrosis with extramedullary haematopoiesis of the skin transformed into acute megakaryoblastic leukemia].

A 70-year-old man, who had been diagnosed as primary myelofibrosis in 1987 at Tokyo Women's Medical School, was admitted to our hospital because of left hip-joint pain in May 1988. Physical examinations revealed marked hepatosplenomegaly and multiple reddish papules on the skin. The peripheral blood showed marked leukoerythroblastosis and severe anemia with poikilocytosis. Bone marrow aspirations were dry tap. Needle biopsy of iliac crest showed a diffuse fibrosis. Biopsy of the papules showed an extramedullary haematopoiesis. He was treated with low dose Ara-C for seven days. Although hepatosplenomegaly and skin papules were reduced, he died of pneumonia a month later. At autopsy, leukemic cells massively infiltrated into the multiple organs, including bone marrow. The cells were identified with megakaryoblast, as those were positive for factor VIII related antigen. As far as we know, this is the third case of primary myelofibrosis transformed into acute megakaryoblastic leukemia.

Aged↗

[Postgastrectomy megaloblastic anemia--possible participation of anti-intrinsic factor antibody in its pathogenesis--report of a case].

A case of 78-year old man with megaloblastic anemia occurring 20 years after partial gastrectomy is reported. Since about 2 years earlier he had an episode of convulsion, and he had been on anti-convulsants (diphenylhydantion, phenobarbital) until admission. Physical examination revealed a pale lean man with polyneuropathy and mental impairment. Laboratory findings revealed WBC 3100/microliters, RBC 187 X 10(4)/microliters, HB 7.9 g/dl, MCV 124.4 microns3, MCH 42.7 micrograms, platelet counts 15.7 X 10(4)/microliters, serum vitamin B12 (VB12) 380 pg/ml, and serum folic acid 5.1 ng/ml. Serum autoantibodies to intrinsic factor (IF) and parietal cells were positive. Bone marrow examination revealed erythroid hyperplasia and megaloblastic changes. Schilling test revealed impaired absorption of VB12 with or without IF, but X-ray study of the small bowels was unremarkable. Treatment with intramuscular cyanocobalamin resulted in a rapid clinical improvement. A repeat Schilling test after 4 months of therapy showed a normal VB12 absorption in the presence of IF. These findings suggest that VB12 malabsorption of the 1st Schilling test was due to intestinal dysfunction caused by the VB12 deficiency state itself, and the improvement of VB12 absorption with IF after therapy suggests a pathogenesis similar to pernicious anemia in this patient.

Aged↗

Effect of UDP-glucuronic acid depletion by salicylamide on biliary bilirubin excretion in the rat.

To determine the effect of UDP-glucuronic acid (UDPGA) depletion on bilirubin metabolism, salicylamide (SAM, which is metabolized primarily through glucuronidation, was administered to rats at a dose of 2 mmol/kg, and biliary bilirubin excretion and the proportion of bilirubin glucuronides were determined. At 15 min after administration of SAM, the UDPGA level in the liver was markedly decreased. Although the total biliary excretion of bilirubin showed no change, the bilirubin diglucuronide level in the 0- to 30-min period after SAM administration was significantly lower (36.9 +/- 4.3%) than that of the untreated control group during the same period (47.5 +/- 1.7%; P less than .01). The biliary bilirubin monoglucuronide (BMG) level in the 0- to 30-min period was significantly increased, compared with the control group. The C8-BMG/C12-BMG ratio in the 0- to 30-min period was significantly higher than that of the control group. At 150 min after SAM administration, there was an increase in the UDPGA level in the liver accompanied by an increase in bilirubin diglucuronide and a decrease in BMG. These results indicate that changes in UDPGA in the liver due to SAM administration influence the bilirubin composition of the bile.

Animals↗

Preferential, cooperative binding of DNA topoisomerase II to scaffold-associated regions.

DNA elements termed scaffold-associated regions (SARs) are AT-rich stretches of several hundred base pairs which are known to bind specifically to nuclear or metaphase scaffolds and are proposed to specify the base of chromatin loops. SARs contain sequences homologous to the DNA topoisomerase II cleavage consensus and this enzyme is known to be the major structural component of the mitotic chromosome scaffold. We find that purified topoisomerase II preferentially binds and aggregates SAR-containing DNA. This interaction is highly cooperative and, with increasing concentrations of topoisomerase II, the protein titrates quantitatively first SAR-containing DNA and then non-SAR DNA. About one topoisomerase II dimer is bound per 200 bp of DNA. SARs exhibit a Circe effect; they promote in cis topoisomerase II-mediated double-strand cleavage in SAR-containing DNA fragments. The AT-rich SARs contain several oligo(dA).oligo(dT) tracts which determine their protein-binding specificity. Distamycin, which is known to interact highly selectively with runs of A.T base pairs, abolishes the specific interaction of SARs with topoisomerase II, and the homopolymer oligo(dA).oligo(dT) is, above a critical length of 240 bp, a highly specific artificial SAR. These results support the notion of an involvement of SARs and topoisomerase II in chromosome structure.

Base Composition↗

Small cell carcinoma of the esophagus.

Ten cases of small cell carcinoma of the esophagus were studied clinicopathologically and immunohistochemically. Seven of the ten were also examined by electron microscopy. Histologically, six were oat cell type, four the intermediate cell type, and multiple histologic sections revealed squamous and glandular differentiations in small or minute areas of seven and two tumors, respectively. In four of the six polypoid tumors, the epithelium covering the tumor showed a malignant conversion accompanied by a proliferation of small anaplastic cells. Another one showed a cribriform pattern in a small area of the tumor. Argyrophilic tumor cells were seen in six cases and tumor cells immunohistochemically positive for ACTH and calcitonin were seen in six, and three cases, respectively. Neurosecretory granules were evident in three of the seven cases examined by electron microscopy. These findings suggest that a small cell carcinoma of the esophagus differentiates toward a squamous, glandular, or neurosecretory lesion, thereby supporting the idea of a totipotential stem cell origin of this tumor. The prognosis of patients with this tumor was poor, in accord with the evidence of aggressive lymphatic and blood vessel permeation.

Adult↗

A community-based study of parental age at the birth of patients with dementia of the Alzheimer type.

The association of dementia of the Alzheimer type (DAT) with parental age at the birth of patients who develop DAT was investigated in a community-based study in Japan. Both maternal and paternal ages of patients who have developed DAT are significantly higher than those in controls and multi-infarct dementia. This study suggests that advanced age may become a cause of chromosome abnormality, and advanced parental age at subjects' birth may be a possible risk factor in DAT.

Adult↗

Histopathologic evaluation of survival time in patients with colorectal carcinoma.

A histopathologic study was done on tissues from 117 patients with colorectal carcinoma, and we compared data on 57 patients who died of a recurrence within 2 years (group I) with 60 others who survived for over 10 years (group II). All patients were surgically treated and followed for over 10 years. Particular attention was directed to the very advancing margin of the tumor, and we examined invading modes of sprouting tumor cells, reactive fibrosis, and inflammatory infiltration around the tumor, in addition to the other clinicopathologic features. In group II, extensive sprouting of individual tumor cells occurred less often, and intense reactive fibrosis and marked inflammatory infiltration around the tumor were more frequent than in group I in which conspicuous lymphatic and vascular permeations were often present. We propose that the invading mode of sprouting tumor cells and the presence or absence of reactive fibrosis and inflammatory infiltration at the advancing margin of the colorectal tumor are of prognostic value.

Carcinoma↗

The calpain-calpastatin system in hematopoietic cells.

Calpain I requires low Ca2+ for activation and calpain II requires high Ca2+. It was generally accepted that erythrocytes contain calpain I and calpastatin, but no calpain II. We have recently found, however, that nucleated chicken erythrocytes contain both calpains I and II in addition to calpastatin. The finding is significant in rectifying the previous view that the chicken has only one molecular species of calpain, whereas mammals have two. Another erroneous view which prevailed previously was that polymorphonuclear (PMN) cells contain only one calpain species. We could also recently demonstrate that pig PMN cells do contain both calpains I and II. The cloning of cDNAs for calpastatin enabled us to utilize them as the probes in studying the expression of calpastatin in various hematopoietic cell-line cells. We found that several T cells infected with human retrovirus HTLV-I markedly increased the production of calpastatin, which could be measured both by calpain-inhibition assay and by Western blot analysis, but the level of mRNA for calpastatin did not significantly change when compared with noninfected T cells. The increase in calpastatin protein always parallels with the expression of interleukin 2 receptor protein by the HTLV-I-infected T cells, although the biological implication of such phenomena is almost entirely unknown yet.

Animals↗

Expression of post-transcriptional regulatory gene of HTLV-I, rex, in Escherichia coli.

Human T-cell leukemia virus type-I (HTLV-I) has a post-transcriptional regulatory gene termed rex. We have designed the rex gene to express in E. coli. Synthesis of rex protein, p27rex, was examined by immunoblot analysis using anti-p27rex antibody. No difference in electrophoretic mobility in NaDadSO4-PAGE was observed between p27rex expressed in E. coli and in an HTLV-I-infected cell line, MT-2. Slower migration of p27rex, corresponding to a 27-kD protein, in NaDodSO4-PAGE when compared with the calculated molecular weight from the amino acid sequence (Mr = 20,367) is suggested to be caused not by post-translational modification, but by the intrinsic nature of the protein, which is rich in proline and arginine.

Escherichia coli↗