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Biomedical subjects

T Hashimoto

Publications and source records attributed to T Hashimoto.

At least 145 records · Page 8Linked to original sources
PubMed1992

Human pulmonary hypoplasia. Statistical, morphological, morphometric, and biochemical study.

Human pulmonary hypoplasia was studied statistically and pathologically in a large series of autopsy cases. Multiple logistic regression analysis indicated five independent risk factors from 10 statistically significant factors for pulmonary hypoplasia: (1) hydrops fetalis; (2) renal anomalies; (3) hernia, including diaphragmatic hernia and omphalocele; (4) skeletal anomalies; and (5) abnormalities of amniotic fluid, such as oligohydramnios and polyhydramnios. The characteristics of pulmonary hypoplasia for each factor were defined by morphological, morphometric, and biochemical methods. All bronchiolar branching, acinar complexity, and acinar maturation were retarded in hypoplastic lungs with hydrops fetalis, renal anomalies, affected side of diaphragmatic hernia, omphalocele, and skeletal anomalies. Only acinar complexity and maturation were impaired in the lung with oligohydramnios due to prolonged rupture of membranes. The pathogenesis of pulmonary hypoplasias should be considered differently with each associated anomaly and time of impairment. While impairment in early gestational stage before 16 weeks' gestation results in both reduced bronchiolar branching and retarded acinar development, that, at late stage, influences only acinar development.

Amino Acids↗
PubMed1992

[Intramuscular degeneration process in Duchenne muscular dystrophy--investigation by longitudinal MR imaging of the skeletal muscles].

Intramuscular degeneration process of Duchenne dystrophy skeletal muscles was investigated by longitudinal skeletal muscle imaging with high-field-strength NMR-CT of 1.5 Tesla. Thigh muscles in 10 cases ranging in age from 4 to 19 years were examined by T1-weighed longitudinal images (TR = 215-505 ms, TE = 19-20 ms). Following results were obtained: (1) Skeletal muscle degeneration was depicted as high signal intensity area reflecting its high fat contents. (2) These high signal intensity areas had a longitudinally streaky appearance in parallel direction with myofibers. (3) These findings were more prominent toward myotendon junction than muscle bellies. (4) Skeletal muscle degeneration progressed rapidly between 7 to 10 years of age, and reached a plateau after that.

Adult↗
PubMed1992

[A case of a small thymoma associated with myasthenia gravis in which the tumor was reduced by corticosteroid therapy].

The case in this study was a 34-year-old male with a small thymoma associated with myasthenia gravis. The patient had been treated with corticosteroids for 10 months against myasthenia gravis. During the course of the treatment a chest CT revealed that the tumor had reduced. Thereafter the extended thymectomy was performed. A close examination of the excised thymus revealed the presence of a flat cystic tumor measuring 1.5 x 0.8 x 0.5 cm at the site corresponding to the CT image. This tumor was histologically ascertained to be a thymoma. The thymoma is sensitive to corticosteroids, which can effectively reduce it. As conclusion, it is necessary to check thoroughly on the presence of thymoma prior to the initiation of corticosteroid therapy to treat myasthenia gravis.

Adult↗
PubMed1992

Clinical features of Japanese family with autosomal dominant retinitis pigmentosa caused by point mutation in codon 347 of rhodopsin gene.

Four members in a Japanese family had autosomal dominant retinitis pigmentosa caused by a single point mutation in codon 347 of the rhodopsin gene. The youngest, an 11-year-old girl, had an abnormal electroretinographic response, although her fundus appeared normal. The other affected family members noticed night blindness in the second decade. Their fundi showed diffuse pigmentation with concentric visual field loss, and there was no recordable electroretinographic response. Cataract developed in the fourth decade in the older patients. Good visual acuity was retained however, even in the fifth decade, after cataract extraction. These clinical features were similar to those of American patients (European family origin) with the same mutation of the rhodopsin gene reported previously.

Adult↗
PubMed1992

[Deep white matter hyperintensity in the occipital lobe on T2-weighted MRI in children. II. Classification based on the signal intensity].

Twenty-seven children, who had deep white matter hyperintensity in the occipital lobe (DWMH) on T2-weighted MRI, were classified into two groups, mild and severe, based on the signal intensity. The frequency of mild DWMH, which was iso-or hyperintense relative to the gray matter but hypointense relative to cerebrospinal fluid (CSF), decreased with aging; mild DWMH might result from a delayed myelination in the central nervous system. However, the frequency of severe DWMH, which was iso-or hyperintense relative to CSF, was not related to aging and was significantly high in severely retarded children. Therefore, severe DWMH might be a new indicator of mental retardation in children.

Adolescent↗
PubMed1991

Amino-terminal presequence of the precursor of peroxisomal 3-ketoacyl-CoA thiolase is a cleavable signal peptide for peroxisomal targeting.

To examine the function of the amino-terminal presequence of rat peroxisomal 3-ketoacyl-CoA thiolase precursor, fusion proteins of various amino-terminal regions of the precursor with non-peroxisomal enzymes were expressed in cultured mammalian cells. On immunofluorescence microscopy, all constructs carrying the presequence part exhibited punctate patterns of distribution, identical with that of catalase, a peroxisomal marker. Proteins lacking all or a part of the prepiece were found in the cytosol. These results indicate that the presequence of the thiolase has sufficient information for peroxisomal targeting.

Acetyl-CoA C-Acyltransferase↗
PubMed1991

Structure and expression of the human mitochondrial acetoacetyl-CoA thiolase-encoding gene.

To examine 3-ketothiolase deficiency at the gene level, we analyzed the structure of the human mitochondrial acetoacetyl-CoA thiolase (MAT; EC 2.3.1.9)-encoding gene (MAT). From the genomic library of a normal subject in lambda EMBL3, we isolated seven overlapping clones covering the entire length of MAT and the structural organization was determined. The gene spans approx. 27 kb and contains twelve exons interrupted by eleven introns. The 5'-flanking region of the gene lacks a conventional TATA box, but is G + C-rich and contains two CAAT boxes. Included are a putative binding site for the transcription factor, Sp1, and sequences resembling the binding sites of several other transcription factors, all features characteristic of housekeeping genes. A CAT assay revealed that a 101-bp DNA fragment immediately upstream from the cap site has promoter activity, and suggested that a DNA fragment from bp -888 to -102 probably contains a negative regulatory element(s).

Acetyl-CoA C-Acetyltransferase↗
PubMed1991

Protective effect of WEB 1881 FU on AF64A (ethylcholine aziridinium ion)-induced impairment of hippocampal cholinergic neurons and learning acquisition.

The effect of continuous administration of 4-aminomethyl-1-benzylpyrrolidin-2-one-hemifumarate (WEB 1881 FU) on cerebral cholinergic neurons was studied using rats treated with ethylcholine aziridinium ion (AF64A), a neurotoxic choline analog. AF64A (2.0 nmol, administered i.c.v.) caused a significant decrease in the hippocampal acetylcholine (ACh) content. This decrease in hippocampal ACh content was accompanied by a reduction of choline acetyltransferase (CAT) activity. Under these experimental conditions, the latency of the passive avoidance response of rats, determined with a step-through method, was strongly decreased as compared with that of sham-operated rats. Although treatment with WEB 1881 FU (50 mg/kg per day, administered orally for 7 days) from immediately after the administration of AF64A did not affect the AF64A-induced decrease of ACh in the hippocampus, 100 mg/kg per day of WEB 1881 FU (orally for 7 days) significantly suppressed the AF64A-induced declines in hippocampal ACh content and CAT activity. The AF64A-induced reduction in latency of the passive avoidance response was also significantly antagonized by the treatment with 100 mg/kg per day of WEB 1881 FU (administered orally for 7 days) from immediately after the administration of AF64A. Continuous administration of WEB 1881 FU (100 mg/kg per day, orally for 7 days) from 7 days after the treatment with AF64A also had a significant inhibitory effect on the AF64A-induced decrease in ACh content in the hippocampus. These results suggest that WEB 1881 FU may have protective actions on the destruction of hippocampal cholingergic neurons as well as memory impairment induced by AF64A administration.

Acetylcholine↗
PubMed1991

A tentative tumor-node-metastasis classification of thymoma.

To establish a tumor-node-metastasis (TNM) classification of thymoma, 207 thymoma patients seen at the First Department of Surgery, Osaka University, and the Second Department of Surgery, Nagoya City University, were evaluated. Lymphogenous and hematogenous metastases of thymoma were infrequent, but their frequency increased with the duration of the course. Lymphogenous metastasis was observed in few cases, but it was considered to progress from anterior mediastinal lymph nodes to intrathoracic and then to extrathoracic lymph nodes. No particular characteristics were observed in hematogenous metastasis. On the basis of these observations, a TNM classification of thymoma was established and applied it to 207 thymoma cases, but it had little advantage over conventional clinical staging. High percentages of thymic carcinomas and thymic carcinoids were in Stage IVB, and the TNM classification of these tumors was considered to be more useful.

Adult↗
PubMed1991

Effect of thyrotropin-releasing hormone on the neurologic impairment in rats with spinal cord injury: treatment starting 24 h and 7 days after injury.

The effect of treatment with thyrotropin-releasing hormone (TRH) or naloxone on the neurologic impairment after spinal cord injury was studied in rats with the severest neurologic impairment (complete paraplegia, no withdrawal response upon tail pinching, and urinary incontinence) 24 h and 7 days after injury. Subcutaneous treatment with TRH (2.5, 10 and 40 mg/kg per day) once daily for 7 consecutive days starting 24 h or 7 days after injury improved the neurologic function in the rats with cord injury in a dose-related manner, with a minimum effective dose of less than 2.5 mg/kg per day in both cases. However, subcutaneous treatment with naloxone (40 mg/kg per day) once daily for 7 consecutive days starting 24 h after injury did not exert any beneficial effects on neurologic function. These results indicate that TRH but not naloxone treatment starting 24 h and as late as 7 days after injury is effective in rats with the severest neurologic impairment following spinal cord injury. Thus, it is suggested that the duration of the effectiveness of late treatment with TRH on the neurologic impairment in rats with spinal cord injury is more than 1 week, while the duration with naloxone is less than 24 h.

Animals↗
PubMed1991

Magnetic resonance imaging of neurohypophyseal germinomas.

The authors reviewed magnetic resonance (MR) images in seven cases of germinoma in the hypothalamoneurohypophyseal axis (HNA). The intrasellar portions were clearly identified in six germinomas. Two small germinomas of these six were located only in the neurohypophysis. The major parts of the four large germinomas were located below the optic chiasm, and the large intrasellar portions were demonstrated. The remaining one small germinoma was localized from the pituitary stalk to the third ventricular floor. These findings strongly suggest that the primary site of germinomas in the HNA is the neurohypophysis. In the four large germinomas, the tumor shape was similar to that of pituitary adenoma. The authors believe that age (limited to first three decades), symptoms (diabetes insipidus), MR findings (absence of normal hyperintense signal of the posterior pituitary on T1-weighted (T1WI) images, and homogeneous hypointensity to the pons on T1WI images/isointensity on T2-weighted images are important in differential diagnosis.

Adolescent↗
PubMed1991

Evidence for a structural mutation (347Ala to Thr) in a German family with 3-ketothiolase deficiency.

The molecular basis of 3-ketothiolase deficiency (3KTD) was examined in a 3KTD family. Immunochemical analyses showed that mitochondrial acetoacetyl-CoA thiolase (T2) biosynthesized in the patient's fibroblasts (GK06) was unstable and that the parents and brother were obligatory carriers of 3KTD. When sequencing the PCR-amplified patient's T2 cDNA, we noted a G to A replacement which caused 347Ala to Thr substitution of the mature T2 subunit. Transfection analysis revealed that this substitution resulted in an instability of the T2 protein. Analyses of the T2 cDNA and gene of the family indicated that the patient was a compound heterozygote; the allele that derived from the mother had a point mutation (347Ala to Thr) and the other allele from the father has a mutation which would abolish the T2 gene expression. This report is apparently the first definition of a mutant allele for 3KTD, at the gene level.

Acetyl-CoA C-Acyltransferase↗
PubMed1991

Developmental immunohistochemistry of catalase in the human brain.

The immunohistochemical studies on a peroxisomal enzyme, catalase, were done on brains from human fetuses to adults. The catalase-positive neurons appeared in the basal ganglia, thalamus and cerebellum at 27-28 weeks of gestation, and in the frontal cortex at 35 weeks. They then increased in number with gestational age. The extent of immunopositive staining increased with enlargement of perikaryonal size. However, the extent gradually decreased with postnatal age. On the other hand, catalase-positive glia appeared in the deep white matter at 31-32 weeks of gestation, their appearance shifting from the deep to the superficial white matter with increasing age. These results suggest that peroxisomes are closely related to neuronal growth and myelinogenesis in the human brain during development.

Adolescent↗
PubMed1991

Decreased histamine H1 receptors in the frontal cortex of brains from patients with chronic schizophrenia.

Involvement of histamine H1 receptor in the brains of schizophrenic patients was investigated using 3H-mepyramine as a ligand. The specific 3H-mepyramine binding in the frontal cortex was saturable with the dissociation constant (Kd) of about 0.6 nM and the maximum number of binding sites (Bmax) of 64 fmol/mg protein. Specific H1 antagonists, mepyramine (Ki = 1.4 nM), promethazine (Ki = 1.4 nM), diphenylpyraline (Ki = 4.1 nM), triprolidine (Ki = 5.3 nM), diphenylhydramine (Ki = 35 nM), but not the specific H2 antagonist, cimetidine (Ki greater than 10(5) nM), strongly inhibited the 3H-mepyramine binding. Regional distribution of the specific 3H-mepyramine binding was in the order of: frontal cortex greater than hippocampus greater than cerebellum greater than hypothalamus greater than thalamus, putamen, and pallidum. The specific 3H-mepyramine binding in schizophrenic brains was reduced by 56% in the frontal cortex. Representative Scatchard analyses of the specific 3H-mepyramine binding revealed changes resulting from a decrease in receptor density but not in receptor affinity. Down-regulation of the histamine H1 receptor in the frontal cortex may be involved in the pathophysiology of schizophrenia.

Adult↗
PubMed1991

Modification of gelsolin with 4-fluoro-7-nitrobenz-2-oxa-1,3-diazole.

Pig plasma gelsolin was modified with the fluorescent reagent 4-fluoro-7-nitrobenz-2-oxa-1,3-diazole (NBD-F) for lysyl residues. The relationship between the gelsolin activity and the degree of NBD labeling suggested that a single lysyl residue, which reacted five times slower than the other reactive lysyl residues, was essential for the activity. Taking advantage of the slow reactivity of the essential residue, active NBD-gelsolin was prepared. Limited cleavage of NBD-gelsolin by chymotrypsin indicated that the fluorescent reagents were randomly incorporated into all fragments observed. When NBD-gelsolin formed a gelsolin/actin (1:2) complex in the presence of micromolar Ca2+, the fluorescence spectra of NBD-gelsolin were red-shifted by 5 nm and the intensity decreased by 30%. However, on binding to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), the fluorescence spectra were blue-shifted by 5 nm with a concomitant increase in intensity by 20%. The addition of PtdIns(4,5)P2 to the NBD-gelsolin actin (1:2) complex restored the fluorescence spectra to that obtained in the presence of PtdIns(4,5)P2 alone. These results indicated that NBD-gelsolin, selectively labeled on lysyl residues not essential for activity, can be a useful probe to monitor the binding of PtdIns(4,5)P2 and actin.

4-Chloro-7-nitrobenzofurazan↗
PubMed1991

The retinoblastoma gene functions as a growth and tumor suppressor in human bladder carcinoma cells.

The product of the human retinoblastoma gene (RB) is a nuclear phosphoprotein that is thought to function as a tumor suppressor. Mutations of RB frequently occur in human bladder carcinoma. To investigate the significance of the functional loss of this gene in bladder cancer, an RB expression plasmid (pBARB) under control of the human beta-actin promoter was transfected into the bladder carcinoma cell line HTB9, which lacks RB expression. Marker-selected transfectants that expressed RB protein were identified by immunoblotting and immunohistochemical staining. In selected clones, stable RB expression has persisted over 1 yr under standard culture conditions with 10% serum. However, RB expression caused major alterations of HTB9 growth properties both in vitro and in vivo. RB+ transfectants lacked the ability to form colonies in semi-solid medium, and their growth rate was significantly decreased in 3% serum. In addition, the tumorigenicity of these transfectants was markedly decreased. Tumors that formed in nude mice were much smaller and had a longer latency period but were indistinguishable microscopically from those produced by parental cells. Slower growing tumors were RB+, as measured by nuclear staining of their RB protein and by a normal RB protein pattern on immunoblots. These findings support the concept that the RB gene acts as both a growth and tumor suppressor in bladder cancer cells.

Actins↗