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Biomedical subjects

M Nasu

Publications and source records attributed to M Nasu.

At least 19 recordsLinked to original sources

Spatio-temporal pattern of frequency representation in the auditory cortex of guinea pigs.

The spatio-temporal pattern of sound-evoked neural activity in the guinea pig auditory cortex was studied by optical recording with the aid of voltage-sensitive dye. Changes in light intensity induced by sounds at various frequencies and pressure levels were recorded with a 12 x 12 array of photodiodes. The amplitudes of the responses were displayed as sequential two-dimensional images. Tonotopical organization was found in two subdivisions of the auditory cortex, the anterior field (field A) and the dorsocaudal field (field DC). The frequency gradients in fields A and DC had a mirror-image relationship. This agrees with results obtained by the microelectrode technique. However, the tonotopic response observed in our study was transient. The focal activity that began in field A propagated in two directions; dorsally along the iso-frequency bands in field A, and caudally toward field DC. This suggests that the sound information processing initiates at field A, and its outputs are transferred to field DC, which is probably a hierarchically higher center.

Acoustic Stimulation

Activation of human multidrug resistance-1 gene promoter in response to heat shock stress.

The multidrug resistance (MDR1) gene encodes a P-glycoprotein, which catalyzes the energy-dependent efflux of anticancer agents. Various environmental stresses including heat shock can induce the expression of endogenous MDR1 genes. In order to study the regulatory mechanisms of MDR1 gene expression, we have established human cancer KB cell lines which could stably integrate bacterial chloramphenicol acetyltransferase (CAT) gene driven by various lengths of the MDR1 promoter. Kst-6 has an integrated plasmid, pMDRCAT1, containing the human MDR1 promoter of -2 kilobases. The MDR1 gene promoter contains a typical heat shock element (HSE) motif located -152 bp to -178 bp from the initiation site. Heat shock at 45 degrees C for 90 min significantly induced CAT activity in Kst-6 cells. Northern blot analysis showed a 4-5 fold increase in CAT mRNA levels in Kst-6 cells. Deletion analysis of the MDR1 promoter demonstrated that the induction of CAT activity was observed in Kxh-14 cells containing a HSE-deleted MDR1 promoter construct, pMDRCAT7. However, further deletion analysis showed that heat shock could not induce CAT activity in Khp-1 cells containing -76 approximately +121 base sequence of the promoter, suggesting that a new heat shock responsible element was located at between -136 and -76. Gel shift assay showed that the heat shock factor (HSF) could bind to the HSE motif located at -152 bp to -178 bp in the MDR1 promoter. We also found that one distinct DNA-protein complex formed specifically within the MDR1 promoter region -99 to -66 was not significantly increased, but relatively more stabilized under mild denaturing condition in the nuclear extract of heat-shocked cells. In our present assay system, activation of the MDR1 promoter in response to heat shock appears to be mediated through both a new heat shock responsive element and MDR1 specific transcription factor.

ATP Binding Cassette Transporter, Subfamily B, Mem

Protein degradation by the phosphoinositide-specific phospholipase C-alpha family from rat liver endoplasmic reticulum.

A 60-kDa protein homologous to phosphoinositide-specific phospholipase C-alpha was purified to apparent homogeneity on sodium dodecyl sulfate-polyacrylamide gel electrophoresis from the rough endoplasmic reticulum of rat liver through three sequential chromatographies on DEAE Toyopearl 650, AF-heparin Toyopearl 650M, and TSK gel G3000SW. The purified protein was monomeric, with an M(r) of 60,000. Eight types of protein were further separated from the 60-kDa protein and named ER60A-ER60H according to the order of their elution from a TSK gel DEAE-5PW column. They were essentially identical in terms of immunochemical properties and the NH2-terminal amino acid sequence. The partial amino acid sequence of ER60F showed homology to that of phosphoinositide-specific phospholipase C-alpha. ER60A-ER60H showed no phosphoinositide-specific phospholipase C activity. However, ER60A-ER60H catalyzed cleavage of themselves and the endoplasmic reticulum proteins protein disulfide-isomerase and calreticulin. Proteolytic degradation was inhibited by p-chloromercuribenzoate. These results indicate that ER60A-ER60H comprise a group of endoplasmic reticulum resident proteins and show thiol group-related proteolytic activity.

Amino Acid Sequence

[A case of tracho-bronchial aspergillosis complicated with acute myeloblastic leukemia].

A 59-year-old male was admitted to our hospital in Jan. 1991 with complaints of general malaise and palpitation. Laboratory findings on admission showed anemia, thrombocytopenia and leukopenia consisted of 2.0% myeloblasts with Auerbodies. The bone marrow study showed granuloid hyperplasia with 45.5% myeloblasts. The diagnosis of acute myeloblastic leukemia (M1) was made. After BHAC-AMP therapy, he obtained complete remission. However, he complained of fever and cough, and his chest X ray film showed a focal infiltrative shadow in the right upper lung field. Antibiotics for bacteria and fungus were administered and the abnormal shadow improved in a week. However, as he had hemosputum, the bronchoscopic examination was performed, and multiple ulcers covered by yellow-white tissue were revealed on the wall of the trachea and bilateral main bronchi. Biopsy specimens obtained by transbronchial biopsy showed bronchial aspergillosis. Though intravenous infusion and inhalation of amphotericin B were effective for aspergillosis, he had a relapse of the leukemia and died in autumn, 1991.

Aspergillosis

[Cytomegalovirus pneumonia treated with ganciclovir and intravenous CMV-hyperimmune globulin: case report].

A 60-year-old male with adult T-cell leukemia (ATL) complained of fever, cough and dyspnea, after anti-leukemic chemotherapy. Chest X-ray film showed a diffuse interstitial shadow, and cytomegalic inclusions and cytomegalovirus (CMV) antigen were detected in the bronchoalveolar lavage specimen and sputum. The diagnosis of CMV pneumonia was made, then ganciclovir and intravenous CMV-hyperimmune globin was administered. Although CMV pneumonia was improved with the treatment, the patient died of ATL. There was no cytomegalic inclusions in the lung but in the adrenal at autopsy. The combination therapy of ganciclovir and intravenous CMV-hyperimmune globulin is considered to be effective for CMV pneumonia.

Cytomegalovirus

[A case of penicillin-resistant pneumococcal pneumonia and penicillin-binding proteins of the clinical isolates].

We experienced a case of a 68-year-old female with beta-lactam antibiotics including penicillin G (PCG) resistant pneumococcal pneumonia, leading to death during the treatment with ceftizoxime (CZX). We reported the clinical course and the mechanism of resistance of isolated bacteria. The present case is the first in Japan. Minimum inhibitory concentration (MIC) against Streptococcus pneumoniae 88031 isolated from the present case was 1.56 micrograms/ml in PCG and 6.25 micrograms/ml in CZX, showing PCG resistance. The isolate was no beta-lactamase production and serotype 23. The drug susceptibility in 34 strains of S. pneumoniae which were isolated as causative organism of respiratory infection in our department in 1988 was studied. PCG high resistant strain (PCG MIC greater than 1.56 micrograms/ml) was only observed in the isolated strain in the present case and PCG low sensitive strains (PCG MIC = 0.1-1.0 micrograms/ml) were observed in 3 strains (8.8%). The CZX resistance was observed only in the present case. The detection of penicillin-binding protein (PBP) and binding affinity of beta-lactam antibiotics were studied using PCG sensitive strain, S. pneumoniae type I (preserved strain PCG MIC = 0.05 micrograms/ml, CZX MIC = 0.1 micrograms/ml, CMX MIC = 0.025 micrograms/ml) and PCG resistant strain, S. pneumoniae 88031. The result obtained showed that PBP1a, detected in sensitive strain type I, was not detected in resistant strain 88031 and PBP1b was increased. The binding of 14C-PCG of PCG resistant strain to PBP1b showed lower affinity for CZX and CMX than PCG sensitive strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Examination of antithyroid effects of smoking products in cultured thyroid follicles: only thiocyanate is a potent antithyroid agent.

We studied the antithyroid action of cigarette smoking products (nicotine, cotinine, and thiocyanate) in the physiological culture system of porcine thyroid follicles. Iodide uptake, iodine organification, de novo thyroid hormone formation, and iodide efflux were measured in the presence of 0-200 mumol/l nicotine, cotinine, or potassium thiocyanate. Nicotine and cotinine did not inhibit iodide transport or thyroid hormone formation. Thiocyanate concentrations equivalent to serum levels of smokers showed three independent antithyroid actions: (i) inhibition of iodide transport, (ii) inhibition of iodine organification, and (iii) increased iodide efflux. Inhibition of iodide transport by thiocyanate was competitive with iodide and independent of TSH concentration. Thiocyanate did not inhibit TSH mediated cAMP production or Na+K+ ATPase activity, a sodium pump for iodide transport. When 50 mumol/l thiocyanate was added 2 h after incubation with iodide or when 1 mumol/l thiocyanate was added from the beginning of incubation, iodine organification was inhibited without changing iodide transport. De novo thyroid hormone formation was clearly inhibited by 50 mumol/l thiocyanate. Thiocyanate increased iodide efflux although the degrees of iodide efflux by 10 mumol/l and 100 mumol/l thiocyanate did not differ significantly. In summary, thiocyanate, a product of smoking, has three independent antithyroid activities. The data of iodide transport kinetics suggest that thiocyanate can be an antithyroid agent particularly in iodine deficiency.

Animals

Immunological studies on opportunistic infection and the development of adult T-cell leukemia.

Three patients with opportunistic infection preceding adult T-cell leukemia (ATL) are presented: a 66-year-old woman with cryptococcosis and Pneumocystis carinii pneumonia, a 46-year-old man with Pneumocystis carinii pneumonia, and a 55-year-old woman with cryptococcosis. Although, at the first examination, the first two had smoldering type ATL and the third case was an HTLV-I carrier, all three developed overt ATL 14-16 months after the onset of opportunistic infection. It is considered that there is immune suppression already present in HTLV-I carriers and in patients with smoldering ATL, and opportunistic infection is predictive of the development of ATL.

Aged

Increase in peripheral natural killer cell activity in patients with autoimmune thyroid disease.

Changes in the activity and number of natural killer (NK) cells in peripheral blood in patients with autoimmune thyroid disease were examined. NK activity was measured in a 4-hr 51Cr-release assay and the number of NK cells was analyzed with FITC-conjugated monoclonal antibodies by use of an automated flow cytometer. NK activity in patients with untreated Graves' disease (n = 25, 39.7 +/- 13.5%, P less than 0.05) and Hashimoto's thyroiditis (n = 18, 41.0 +/- 14.2%, P less than 0.05) was high compared to the activity in non-pregnant controls (n = 61, 32.6 +/- 15.0%). NK activity in patients with postpartum Graves' thyrotoxicosis (n = 11, 48.6 +/- 18.9%) was markedly increased compared to the activity in non-pregnant controls (P less than 0.01) and in postpartum controls (n = 29, 33.8 +/- 15.2%, P less than 0.05), although the mean ages of each group did not differ significantly. Moreover, NK activities in the thyrotoxic state were significantly higher than those in the euthyroid state in the same patients with postpartum Graves' thyrotoxicosis or with postpartum destructive thyrotoxicosis. The number of CD16 positive cells increased in patients with postpartum Graves' thyrotoxicosis. However the number of CD16 and CD57 positive cells were normal in all other groups of patients. These results indicate that an increase of NK activity is associated with exacerbation of autoimmune thyroid disease both in Hashimoto's thyroiditis and in Graves' disease and suggest that NK cells might have an important role for the control of disease activity in autoimmune thyroid disease.

Adult

[Changes of differential leukocyte counts during pregnancy and in the postpartum period].

We examined differential leukocyte counts in peripheral blood from 177 pregnant and postpartum women with an automated leukocyte differential system, and compared them with those of 52 nonpregnant and non-postpartum women. The proportions and numbers of neutrophils and monocytes increased throughout pregnancy, returned to the non-pregnant levels within one month after delivery, and decreased transiently at 4 or 7 to 10 months postpartum. The proportions and numbers of lymphocytes and eosinophils decreased throughout pregnancy, and increased transiently at 4 to 10 months postpartum and one month postpartum, respectively. The proportion and number of basophils decreased during pregnancy and one month postpartum, and those of large unstained cells (LUC) decreased in the third trimester of pregnancy, and both returned to the non-pregnant levels at 4 months postpartum and within one month postpartum, respectively. These data indicate that differential leukocyte counts change dynamically during pregnancy and after delivery until 1 year postpartum.

Adult

[A case of idiopathic interstitial pneumonia with cytomegalovirus infection].

A 67-year-old female was admitted to our hospital because of fever, dry cough, and exertional dyspnea. The findings of chest X-ray, transbronchial lung biopsy, and bronchoalveolar lavage were compatible with the diagnosis of idiopathic interstitial pneumonia. Prednisolone was administered and she felt better for a while. However, she developed severe dyspnea, and marked diffuse infiltrative shadows were observed on chest X-ray after 3 months of steroid therapy. In spite of pulse therapy with methylprednisolone, she died of severe respiratory failure. Complement fixation test and IgG antibody enzyme immunoassay for cytomegalovirus were positive, but there was no change the titers between admission and death. IgM antibody was negative. The lung findings at autopsy compatible with usual interstitial pneumonia and diffuse alveolar damage, moreover, cytomegalovirus infection was observed. We consider that recurrent cytomegalovirus pneumonia had been present due to secondary immunodeficiency caused by administration of steroid hormones.

Aged

[A case of foreign body granuloma due to aspiration of a twig of Cryptomeria].

A 65-year-old man was admitted to Oita Medical School Hospital with complaints of hemoptysis and left anterior chest pain. Chest X-ray film showed a nodular shadow, about 1 cm in diameter, in the left S8 area. A specimen obtained by transbronchial biopsy showed no malignant findings. However, left lower lobectomy was performed because of the possibility of malignancy. The resected specimen contained a twig of cryptomeria within dark-red lung tissue. Histologically, the foreign body granuloma was surrounding a vegetable fiber. We had no information of an episode of pruning a cryptomeria and aspiration of a twig before the operation. Cryptomeria is an extremely rare bronchopulmonary foreign body, and the present case suggests that bronchopulmonary foreign body granuloma is an important disease in the differential diagnosis of pulmonary nodules.

Aged

Biodegradation of aniline and abundance of potential degraders in river waters.

Total dissolved organic carbon (TOC), number of colony forming units (CFU), and total direct count (TDC) were compared to the biodegradation of aniline and the number of potential degraders in water samples from head waters to down stream of the Ina River and several other sites of rivers traversing Osaka city. The results indicate that aniline degrading populations of these various microbial communities exhibit different activities probably depending on the extent of adaptation to pollutants to which the microbes are exposed. The number of aniline degraders found in river water samples was in agreement with other parameters which were used to demonstrate the degree of pollution in river water even though higher biodegradability was evident in waters which show comparatively low TOC and CFU. These results suggest that biodegradation of aniline and enumeration of its potential degraders may serve as valuable indicators for the assessment of pollution in river waters.

Aniline Compounds

Hydrogen peroxide inhibits iodide uptake and iodine organification in cultured porcine thyroid follicles.

We investigated the effect of hydrogen peroxide on the process of thyroid hormone formation in a physiologic culture system of porcine thyroid follicles that we recently established. Porcine thyroid follicles cultured in medium containing 1 mU/mL TSH were exposed to 0 to 500 microM hydrogen peroxide in the presence of 0.1 microCi carrier-free Na125 and sodium iodide for 2 h. Iodide uptake and iodine organification were measured in this incubation system. The kinetics of iodide uptake were used to explain the action of hydrogen peroxide. In addition, cAMP content and Na+,K(+)-ATPase activity (an enzyme necessary for iodide uptake) were measured to investigate the mechanism of hydrogen peroxide action. Hydrogen peroxide at concentrations of 100, 200, and 500 microM inhibited iodide uptake in a dose-dependent manner. Iodide organification was inhibited only when the concentration of hydrogen peroxide was greater than 200 microM. The kinetics of iodide uptake indicated that hydrogen peroxide was a noncompetitive inhibitor with iodide. Inhibition of iodide uptake and iodine organification by hydrogen peroxide were not mediated by alteration of cAMP content of Na+,K(+)-ATPase activity, since exposure to even 500 microM hydrogen peroxide did not change these parameters in the follicle when compared with those of control samples. Our results suggest that the iodide transport system in the thyroid follicle is inhibited at 200 microM hydrogen peroxide or greater.

Analysis of Variance

Hemostatic alterations caused by ventricular assist devices for postcardiotomy heart failure.

The hemostatic alterations in two adult patients who were supported by left ventricular assist devices (LVADs) because of postcardiotomy heart failure were evaluated. In both patients, fibrinopeptide A and thrombin-antithrombin III complex increased markedly during the first several days, and thereafter decreased moderately but remained above normal over the entire procedure. Furthermore, fibrinopeptide B beta 15-42 and alpha 2 plasmin inhibitor-plasmin complex were also markedly increased over the entire course of LVAD treatment. These data show that the LVAD system strongly activates both the coagulation and the fibrinolytic system, even when thromboembolic or bleeding complications are not clinically evident. Furthermore, the decrease in physiological coagulation inhibitors, especially protein C, indicates that these factors are activated and consumed during LVAD treatment. Because protein C is important in regulating the coagulation cascade during LVAD treatment, exhaustion of this system might result in thromboembolic complications during LVAD treatment.

Aged

[A case of smoldering adult T-cell leukemia complicated by various pulmonary infections].

A 46-year-old man was admitted to Oita Medical College Hospital on October 16, 1987, because of cough and sputum. Chest X-ray and chest CT films showed diffuse reticulonodular shadow. The specimens obtained by transbronchial lung biopsy revealed cysts of pneumocystis carinii. Abnormal lymphocytes with lobulated nuclei were found 2-7% of peripheral leucocytes. The anti HTLV-I antibody was positive. According to these data, we diagnosed the patient as smoldering adult T cell leukemia with pneumocystis carinii pneumonia. The abnormal shadow on chest X-ray disappeared after SMX-TMP and pentamidine treatment. After about 1 year, he was again admitted for high fever. Chest X-ray showed infiltration with cavity in right upper lobe. Streptococcus pneumoniae was isolated from the sputum. The infiltration shadow on chest X-ray disappeared after antibiotics treatment. However, multiple nodular shadow appeared on the chest X-ray and ATL cell infiltration was found in the specimens of transbronchial lung biopsy. ATL cells in peripheral blood also increased and serum LDH and Calcium levels were markedly high. According to these data, we diagnosed the patient as having a ATL crisis. Although chemotherapy for ATL was started, the ATL, cell infiltration shadow on the chest X-ray enlarged, and bilateral diffuse patchy shadows was appeared on the chest X-ray. He died of respiratory failure on April 26, 1989. Cytomegalovirus pneumonia and ATL cell infiltration were revealed by necropsy.

Anemia, Refractory, with Excess of Blasts

[A clinical study on liver dysfunction in patients with acute measles infection].

Liver dysfunction in patients with measles infection is reported commonly in European and American literatures, but those in Japan are relatively rare. We observed the abnormal elevation of serum transaminase in 17 of 18 juvenile patients with measles from December 1989 to February 1990, however severe complications such as pneumonia or meningitis were not observed. A diagnosis of measles was made by typical clinical symptoms and the elevation of IgM antibody against measles (EIA method). Ninety four percent of the patients showed the elevation of serum transaminase, (GOT 118.6 +/- 96.2 IU/l, GPT 161.5 +/- 167.6 IU/l), and all patients recovered completely in 30.5 +/- 12.8 days after the onset. The abnormal evaluation of serum LDH was seen in 94% of the patients, (mean value was 872.2 +/- 216.2 IU/l). LDH4 mainly elevated in most cases, however, LDH5 elevated only in 4 cases. The intensity of liver dysfunction did not correlate to the severity of measles in the present cases. It is considered to be characteristic to the patients with measles that the serum level of LDH is markedly high as compared with that of transaminase.

Adolescent