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Biomedical subjects

T Miwa

Publications and source records attributed to T Miwa.

At least 217 records · Page 12Linked to original sources

[Study on adrenergic acid secretion using isolated parietal cells of guinea-pigs].

In order to investigate the effect of adrenergic nerve system on acid secretion at the cell-levels, acid secretion of isolated parietal cells stimulated by various adrenergic agonists was observed by measuring the accumulation of 14C-aminopyrine (A.P.). Both isoproterenol, beta receptor agonist, and salbutamol, beta-2 receptor selective agonist, increased A.P. accumulation, whereas dobutamine, beta-1 receptor selective agonist, showed no effect. And beta-2 receptor on parietal cells was detected by binding assay. These data may suggest that parietal cells have beta-2 receptors through which acid secretion will occur.

Adrenergic beta-Agonists↗

[Effect of long-term administration of antisecretary drugs on rat gastric histamine synthesis and acid secretion--compare with omeprazole and cimetidine].

To investigate the effect of 6 weeks administration of proton pump inhibitor (omeprazole) and H2-receptor antagonist (cimetidine) on gastric histamine synthesis and acid secretion, we studied experimentally in the rat stomach. Then gastric mucosal histamine concentration, histidine decarboxylase (HDC) activity and serum gastrin concentration, and HDC positive cell number were examined in time-course. The 6 weeks administration of omeprazole caused more increase of HDC positive cells than cimetidine. After cessation of administration with omeprazole, high plasma gastrin level immediately reduced. However the increase of gastric mucosal HDC activity and histamine concentration were prolonged, compared with cimetidine. These findings suggest to affect differently between omeprazole and cimetidine on gastric acid secretion after cessation of long-term treatment.

Animals↗

[A report of four cases of intrathoracic meningocele].

Intrathoracic meningocele is regarded as an uncommon pathological entity frequently associated with von Recklinghausen's disease. In this paper, four cases of intrathoracic meningocele, treated between 1966 and 1986, are presented. There were three males and one female, all between the ages of 40 and 50. These were referred to our clinic for further evaluation of an asymptomatic lesion which had been seen on a routine chest roentgenogram. There was definite evidence of von Recklinghausen's disease in three cases: two males and one female. All four cases had no pain, dyspnea or neurological disorder. Chest and vertebral tomograms revealed masses in the posterior mediastinum and enlarged vertebral canals at the location of the lesion which varied from T-3 to T-11; three on the left side and one on the right side. None of them revealed scoliosis or kyphosis of the spine. In three cases, myelography was performed and showed an egg-shaped mass dorsolaterally. In two cases, metrizamide computed tomographic myelography was carried out and demonstrated deformity of the vertebral bone and passage of the contrast material through the enlarged vertebral canal into the paravertebral mass. Furthermore, magnetic resonance imaging was performed in two cases, and showed a homogeneous low signal intensity paravertebral mass communicating with the spinal canal on T1-weighted image. In two cases, the meningoceles were ligated or wrapped surgically. Postoperatively one presented a paraparesis and severe meningitis, and died; the other had an uneventful postoperative course. Two patients were followed conservatively without developing any symptoms or signs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[In vitro susceptibilities of Mycobacterium avium and Mycobacterium intracellulare to new macrolides, new quinolones, and antituberculous drugs on Dubos agar medium].

Mycobacterium avium and M. intracellulare were isolated from the sputum of patients infected with atypical mycobacteria using 1% Ogawa medium and identified by the DNA probe test. Then the MICs of various kinds of drugs against these mycobacterial species were determined on Dubos agar medium, and the drug susceptibilities were also determined on 1% Ogawa medium in parallel. The drugs tested were new macrolides, such as clarithromycin (CAM) and roxithromycin (RXM), new quinolones, such as ofloxacin (OFLX) and ciprofloxacin (CPFX), and antituberculous drugs, such as isoniazid (INH), rifampicin (PFP), streptomycin (SM), and ethambutol (EB). The MICs of the drugs tested, especially those of CAM, OFLX, and RFP, when determined on Dubos agar medium, were generally lower against M. intracellulare than against M. avium. The susceptibilities of the mycobacterial isolates tested to RFP and SM determined on Dubos agar medium were markedly different from those determined on 1% Ogawa medium. Such discrepancies may be accounted for by absorption of these drugs to the egg medium and instability of RFP in the egg medium. Overall, our results indicate that the new macrolides and new quinolones are effective against atypical mycobacteria.

4-Quinolones↗

[Time-related changes in the cerebral blood flow in subarachnoid hemorrhage due to ruptured cerebral aneurysm].

Cerebral blood flow (CBF) was determined by the 123I-IMP SPECT reference sample method in 39 patients with subarachnoid hemorrhage (SAH) due to ruptured cerebral aneurysm. They were examined according to the time lapse after onset, severity, CT findings, and prognosis. These 39 patients were admitted to our medical center within 36 hours after the onset, and SAH and ruptured aneurysm were diagnosed by CT scan and angiography, respectively. Patients with intraventricular hemorrhage, intracerebral hematoma, and other severe complications were excluded. The stage of SAH was divided into three, by designating the day of onset as day 0: day 0-4 as the acute stage, day 5-20 as the subacute stage, and day 21 and after that as the chronic stage. Acute stage surgery was conducted within 48 hours after the onset on principle. Hyperdynamic therapy and cisternal drainage were conducted in severe case of SAH. The prognosis was evaluated with Glasgow outcome scale (GOS). The average CBF was 33.39, 29.44, and 33.15 in the acute, subacute, and chronic stages, respectively. These are values lower than the reference sample value, 43.39 (ml/100 g/min). Only a small number of cases, however, revealed vasospasm by angiography conducted in the acute stage. There was a correlation between the CT severity in the acute stage and the decrease in CBF. In the group with low density area (LDA) on CT due to delayed cerebral ischemia in the subacute stage, the average CBF was 28.28 and 23.95 in the acute and subacute stages, respectively. These values were significantly lower than 35.97 and 32.45, respectively, in the group without LDA.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

[Erythroleukemia in pregnancy with successful outcome of delivery].

A 37-year-old woman was admitted to our hospital because of anemia in the 33rd week of pregnancy. On admission, the hemoglobin was 7.6 g/dl, platelets 508,000/microliters and WBC 8,300/microliters with 4% blast cells. Bone marrow aspirate demonstrated 50% erythroblasts of nucleated cells, which had prominent megaloid and polynucleic changes, and 20% myeloblast cells. We diagnosed her as having erythroleukemia. Receiving packed-red-cell transfusions, she had a cesarean section, and gave birth to a female infant (BW 2,175 g) in the 34th week of pregnancy. At the same time, she had a total hysterectomy with left adnexectomy. The postoperative course was favorable. She had a combination chemotherapy of BHAC-DMP, resulting in a partial remission. After the second induction chemotherapy with subcutaneous use of G-CSF and BHAC-DMP, complete remission was obtained, which lasted for almost 17 months. The child is growing well without any hematological disorder.

Adult↗

Application of an ovomucoid-conjugated polymer column for the enantiospecific determination of chlorprenaline concentrations in plasma.

An ovomucoid-conjugated polymer column was prepared for the liquid chromatographic resolution of racemic compounds. The column showed strong retention of acidic solutes, a characteristic attributed to the structure of the stationary phase support gel. Although the efficiency of the column was lower than that of an ovomucoid-conjugated silica gel column, enantiospecific chlorprenaline determination in plasma was achieved with solute amounts from 1.0 ng to 0.1 microgram.

Chromatography, High Pressure Liquid↗

Transcriptional regulatory elements in the 5' upstream and first intron regions of the human smooth muscle (aortic type) alpha-actin-encoding gene.

We have determined the nucleotide (nt) sequence of 5.5 kb including the 5' flanking, first untranslated exon and first intron regions of the human smooth muscle (SM) (aortic type) alpha-actin-(Sm alpha A)- encoding gene. The promoter region and a part of the first intron show remarkably high sequence conservation with equivalent regions of the chicken gene, and contain multiple transcriptional regulatory elements. From transient chloramphenicol acetyltransferase gene (cat) expression assays in SM cells, a DNA fragment from nt -123 to +49 containing two CArG boxes showed strong positive promoter activity, whereas a far upstream region from nt -253 to -124 showed a negative effect. The conserved region in the first intron also contains the CArG box and showed an enhancer activity. Therefore, the human SM alpha A gene is controlled under positive and negative mechanisms.

Actins↗

Experimental haemarthrosis in rhesus monkeys: morphometric, biochemical and metabolic analyses.

The effects of a single episode of massive haemarthrosis in rhesus monkeys were studied. Autologous whole blood was injected into a femorotibial joint of 16 anaesthetized monkeys, equally divided into four groups and killed 7 days, 2, 3 and 6 months post-injection (PI). Synovial membrane and femoral articular cartilage were analysed morphometrically and articular cartilage was further analysed biochemically and metabolically. At 7 days PI, morphometric evaluation revealed a significant increase (P less than 0.05) in synovial membrane cellularity and synovial intimal thickness of injected joints versus control joints. This change was no longer evident 2 months PI. There was also an overall (n = 16) significant increase (P less than 0.05) in femoral articular cartilage cellularity in injected joints. The average chondrocyte lacuna area of injected joints was not statistically different from the control joints. Biochemical analyses of femoral articular cartilage revealed a significant decrease in hexosamine concentration (P less than 0.05) of injected joints. There was no significant difference between the injected and control joints in hydroxyproline or total protein concentration. Metabolic analyses revealed a significant increase (P less than 0.05) in cartilage collagenous protein production by injected joints compared with control joints. There were no significant differences in cartilage or secreted total protein production between injected and control joints. There were also no significant differences in cartilage or secreted proteoglycan production between joints. Morphometric evaluation of articular tissues following massive haemarthrosis has quantified a temporary hyperplastic reaction. A significant decrease in cartilage hexosamine concentration in haemarthrotic joints suggests this is a crucial biochemical event in the pathogenesis of blood-induced cartilage destruction.

Animals↗

Novel pyrrolo[2,3-d]pyrimidine antifolates: synthesis and antitumor activities.

New antifolates, characterized by a 6-5 fused ring system, a pyrrolo[2,3-d]pyrimidine ring, and a trimethylene bridge at position 5 (12a,b and 13a,b) were designed and efficiently synthesized. The synthetic method included (1) construction of the key intermediary acyclic skeleton, 5-[4-(tert-butoxycarbonyl)phenyl]- 2-(dicyanomethyl)pentanoates (6a,b), (2) cyclization with guanidine, followed by reduction to the pyrrolo[2,3-d]pyrimidine derivatives (8a,b and 9a,b), and (3) subsequent glutamate coupling and saponification. These antifolates were more growth-inhibitory by about 1 order of magnitude than methotrexate (MTX) against KB human epidermoid carcinoma cells and A549 human nonsmall cell lung carcinoma cells in in vitro culture. Growth inhibitory IC50 values for N-[4-[3-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5- yl)propyl]benzoyl]-L-glutamic acid (12a) against KB and A549 were 0.27 and 4.5 ng/mL, while those for MTX were 5.0 and 35 ng/mL, respectively. Other members of this class of antifolates, 12b and 13a,b, showed good activities nearly equal to that of 12a.

Antineoplastic Agents↗

Structure, chromosome location, and expression of the human smooth muscle (enteric type) gamma-actin gene: evolution of six human actin genes.

Recombinant phages that carry the human smooth muscle (enteric type) gamma-actin gene were isolated from human genomic DNA libraries. The amino acid sequence deduced from the nucleotide sequence matches those of cDNAs but differs from the protein sequence previously reported at one amino acid position, codon 359. The gene containing one 5' untranslated exon and eight coding exons extends for 27 kb on human chromosome 2. The intron between codons 84 and 85 (site 3) is unique to the two smooth muscle actin genes. In the 5' flanking region, there are several CArG boxes and E boxes, which are regulatory elements in some muscle-specific genes. Hybridization with the 3' untranslated region, which is specific for the human smooth muscle gamma-actin gene, suggests the single gene in the human genome and specific expressions in enteric and aortic tissues. From characterized molecular structures of the six human actin isoform genes, we propose a hypothesis of evolutionary pathway of the actin gene family. A presumed ancestral actin gene had introns at least sites 1, 2, and 4 through 8. Cytoplasmic actin genes may have directly evolved from it through loss of introns at sites 5 and 6. However, through duplication of the ancestral actin gene with substitutions of many amino acids, a prototype of muscle actin genes had been created. Subsequently, striated muscle actin and smooth muscle actin genes may have evolved from this prototype by loss of an intron at site 4 and acquisition of a new intron at site 3, respectively.

Actins↗

Comparative studies on the anticonvulsant activity of lipophilic derivatives of gamma-aminobutyric acid and 2-pyrrolidinone in mice.

Anticonvulsant activity, degradation into gamma-aminobutyric acid (GABA), and concentration in brain of 1-dodecanoyl-2-pyrrolidinone (I), a lipophilic derivative of a lactam of GABA, were compared with those of N-dodecanoyl GABA (II) and 1-dodecyl-2-pyrrolidinone (III) to get information about their pharmacological mechanisms. Compounds I and II degraded into GABA in mouse liver homogenate, gradually into GABA in brain homogenate and more slowly in plasma. Compound III had no degradation in the biological media. The derivatives administered intraperitoneally had dose-dependent anticonvulsant activity on picrotoxin-induced seizure in mice. Their anticonvulsant activities were changed by the time intervals between pretreatment of derivatives and administration of picrotoxin. Compounds II and III showed anticonvulsant activity on pentylenetetrazole-induced seizure and a prolonged sleeping time induced by sodium pentobarbital in mice. However, these three derivatives never significantly increased the GABA level in mouse brain after intraperitoneal administration compared to the endogenous GABA level. They were detected as intact derivatives in the brain. In the previous report, we demonstrated the anticonvulsant activity of sodium dodecanoate. These results suggested that the dodecyl chain of derivatives may be important for their anticonvulsant activities and I does not act as GABA via prodrug.

Animals↗

[Mouse fetal brain specific protein "GP68" is expressed in human tumor cells].

It is well known that some fetal antigens are expressed in malignant tumor cells. Likewise, brain tumors, especially histologically malignant cases, may have any antigenic relationships with fetal brain. So, we investigated the relationship by immunohistochemical technique, utilizing a polyclonal antibody to mouse fetal stage-specific polypeptide "GP68". We prepared GP68 from homogenate of head part of embryos at the 14th day of gestation mice by RCA-1 agarose column chromatography. And immunized it to Japanese white rabbits and the titer was measured by enzyme-linked immunosorbent assay. We analyzed operatively resected brain tumors and autopsy brain tissues. Frozen tissues were fixed in cold acetone and immunostained with anti-GP68 serum according to biotin-streptavidin peroxidase method. Remained tissues were homogenized in Laemmli's sample buffer and electrophoresed. The proteins were transferred to nitrocellulose membrane and immunostained with anti-GP68. Normal brain tissues were not positively stained, except for capillary endothelium which showed a weak staining. On the other hand, brain tumors of neuroectodermal origin were positively stained in varying degrees, and other tumors were negative. It is especially noteworthy that, in astrocytoma cases, there exists a definite correlation between the intensity of stain and the degree of histological malignancy. Immunoblot studies demonstrated a very weak band at 68 KD in normal brain and meningioma. In contrast, very strong band at the same position was seen in malignant astrocytomas. These results suggested that in brain tumors, especially those of neuroectodermal origin, GP68 antigen is expressed and the degree of expression is related to their histological malignancy. So this fetal antigen may be useful for evaluation of biological malignancy of gliomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Glioblastoma of the cerebellum: report of an autopsy case associated with intratumoral hemorrhage and CSF seedings].

An autopsy case of glioblastoma of the cerebellum associated with an intracerebellar hemorrhage and showing CSF seedings is reported. A 26 year-old male was admitted to our hospital with a 10-day history of headache, nausea and vertigo. On admission, disturbance of consciousness (10-20 by JCS), irregular respiration and central fixation of both eyes suggesting increased intracranial pressure and early stage of central herniation were recognized clinically. The cerebellar signs of dysmetria and nystagmus were also observed. CT scan and angiography revealed an avascular large mass in the right cerebellar hemisphere, obstructive hydrocephalus and upward transtentorial herniation. On MRI study, the mass was demonstrated to be a subacute hematoma with a small tumor in its margin. Total removal of the tumor and aspiration of the hematoma were performed. Histological examination revealed a highly cellular and pleomorphic astrocytic tumor with scattered small necrosis and glomeruloid capillary endothelial proliferation, typical of glioblastoma multiforme. During postoperative radiochemotherapy (focal irradiation to the posterior fossa), the tumor showed rapid regrowth and a second look operation was performed. He was readmitted 3 weeks after radiochemotherapy with complaints of severe headache, nausea and lumbago. He then suddenly became dyspnea, tetraplegic and bradycardic. Neuroradiological investigation revealed multiple masses in the suprasellar region, medulla oblongata and the cervical spinal cord, but no recurrence in the cerebellum. Malignant cells were noted on CSF cytology. During chemotherapy for CSF tumor dissemination, his condition deteriorated rapidly and he died 7 months after the onset of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗