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Biomedical subjects

A Honda

Publications and source records attributed to A Honda.

At least 109 records · Page 6Linked to original sources
PubMed1997

Synthesis of [3 alpha-3H]7-dehydrocholesterol via stable tritiated 4-phenyl-1,2,4-triazoline-3,5-dione derivative.

Synthesis of [3 alpha-3H]7-dehydrocholesterol is described via protection of the 5,7-diene system in 7-dehydrocholesterol as the Diels-Alder adduct with 4-phenyl-1,2,4-triazoline-3,5-dione followed by oxidation of the hydroxyl group to give the 3-oxo adduct. Reduction of the keto adduct with [3H]sodium borohydride produced the adduct of [3 alpha-3H]7-dehydrocholesterol from which the radiolabeled sterol was obtained via treatment with lithium aluminum hydride. The advantage of the method is that highly labeled [3 alpha-3H]7-dehydrocholesterol can be prepared. Further, unlike 7-dehydrocholesterol, its adduct with 4-phenyl-1,2,4-triazoline-3,5-dione is stable and can be stored. This allows the preparation of small batches of [3 alpha-3H]7-dehydrocholesterol for immediate use in biological experiments, and losses due to decomposition of excess radiolabeled 7-dehydrocholesterol are minimized.

Aluminum Compounds↗
PubMed1997

Sodium phenobarbital-enhanced mutation frequency in the liver DNA of lacZ transgenic mice treated with diethylnitrosamine.

To investigate how a carcinogenic promoter acts on cells mutated by an initiator, we used as a model, lacZ transgenic mouse and a positive selection system. Preliminary data for the mutational events in liver DNA of the mice was generated using diethylnitrosamine (DEN) and sodium phenobarbital (S-PB) as initiator and promoter, respectively. In our first experiment, male MutaMice received a single i.p. injection of saline or 100 mg/kg DEN and were fed a normal diet for 7 days and 500 p.p.m. S-PB in the diet for 21 days. Liver DNA was harvested after a 1 night fast on days 7 and 28 post-DEN treatment. In our second experiment, male mice received a single i.p. injection of phosphate buffered saline or 50 mg/kg DEN and were fed a normal diet for 7 days, a diet with S-PB for 14 days and then a normal diet for 7 days. Liver DNA was harvested after a 1 night fast on days 7, 21 and 28 post-DEN treatment. The S-PB diet enhanced absolute and relative liver weights in all groups. The single intraperitoneal dose of 50 or 100 mg/kg DEN induced high mutation frequencies (MF) in liver, lacZ genes on days 7, 21 and 28. There were no remarkable differences of the MF among any sampling days for animals receiving DEN and a normal diet. S-PB feeding at 500 p.p.m. for 21 days failed to affect the MF in groups given saline or 100 mg/kg DEN. On the other hand, when 50 mg/kg DEN was given, S-PB feeding at 500 p.p.m. for 14 days elevated the MF in liver DNA on days 21 and 28 to approximately 1.8 and 4.0 times the MF, respectively, of the mice fed the normal diet. Consequently, S-PB might preferentially promote certain initiated cells participating in a balance between cell death and proliferation.

Animals↗
PubMed1997

[Primary pulmonary lymphoma diagnosed from monoclonality of lymphocytes in a transbronchial biopsy specimen].

A 57-year-old man was found on a routine chest X-ray examination to have three infiltrative shadows: two in the right lung field and one in the left. Examination of a transbronchial biopsy specimen revealed infiltration of many small lymphocytes under the bronchial mucosa. In situ hybridization showed that they were monoclonal, and primary pulmonary lymphoma was diagnosed. The patient also had liver cirrhosis, diabetes mellitus, and hypertension. He was treated with a combination of pirarubein, cyclo-phosphamide, vindesine, prednisolone, and etoposide, but the tumors did not shrink. Therefore, as of the time of this writing he was being given only etoposide.

Biopsy↗
PubMed1997

[An operative case of bilateral peripheral pulmonary arterial aneurysms].

An operative case of bilateral peripheral pulmonary arterial aneurysms is described. Nine cases of bilateral peripheral pulmonary arterial aneurysms reported in Japan are reviewed. The patient was a 26-year-old woman complaining of massive hemoptysis. Her chest X-ray showed coin lesions in the bilateral hilus region. After admission, body CT and pulmonary arteriography revealed saccular dilatation of the bilateral peripheral pulmonary artery. We diagnosed as bilateral peripheral pulmonary arterial aneurysms. Bronchoscopic examination revealed bleeding from the left lower lobe bronchus. She underwent left lower lobectomy. Histological examination of the resected specimen demonstrated a marked destruction of the wall of the aneurysm. This patient died of recurrence of hemoptysis from bilateral lung on the 42nd postoperative day.

Adult↗
PubMed1997

[Pleural B cell lymphoma presenting as paraplegia].

A 54-year-old man felt pain on the right side of his chest. Two months later, paraplegia developed. A chest CT scan revealed a pleural effusion and a mass lesion along the right parietal pleura. The lesion extended directly into the adjacent part of the spinal canal and compressed the spinal cord. Cytologic examination of the pleural effusion revealed atypical lymphoid cells, and examination of a transcutaneous biopsy specimen showed monotonous atypical B lymphocytes. The diagnosis was pleural malignant lymphoma. Chemotherapy induced a partial remission, but 14 months after the first examination he died of central nervous system involvement. Pleural lymphoma can directly compress the spinal cord and cause paraplegia. Early diagnosis and therapy greatly affect the outcome in patients with spinal cord compression.

Humans↗
PubMed1997

The molecular anatomy of influenza virus RNA polymerase.

The genome of influenza virus is composed of eight RNA segments of negative polarity. The RNA-dependent RNA polymerase is associated with each viral RNA (vRNA) segment and in virus-infected cells, involved in both transcription, i.e. vRNA-directed synthesis of viral mRNA, and two step reactions of vRNA replication, i.e. vRNA-dependent synthesis of complementary RNA (cRNA) and cRNA-dependent synthesis of vRNA. The RNA polymerase is composed of three viral proteins, PB1, PB2 and PA. PB1 is the core subunit for not only the RNA synthesis but also the assembly of PB2 and PA into this multifunctional enzyme complex. PB1 alone is able to catalyze vRNA-dependent RNA synthesis, but PB2 is required for capped RNA-dependent transcription, both together forming the transcriptase. The third P protein, PA, and an as yet unidentified host factor(s) are involved in the conversion of RNA polymerase from transcriptase to replicase. The functional map is being made for both PB1 and PB2 proteins.

Animals↗
PubMed1997

[Morphological reversion of tumor cells by histone deacetylase inhibitors and radicicol].

Trichostatins and trapoxins, structurally unrelated microbial metabolites, are specific inhibitors of histone deacetylases. Radicicol inhibits Src family protein-tyrosine kinases. Recently, these agents were found to induce morphological reversion and enhanced expression of gelsolin, an actin regulatory protein, in a variety of transformed cells. Microinjection of an anti-gelsolin antibody that neutralizes the gelsolin function caused inhibition of the morphological change, suggesting that gelsolin expression is associated with the suppression of transformation.

Animals↗
PubMed1997

[Transcription and replication of influenza virus genome].

The genome of influenza virus is composed of eight RNA segments of negative polarity. The RNA-dependent RNA polymerase is associated with each viral RNA (vRNA) segment and after infection, involved in both transcription (vRNA-directed synthesis of viral mRNA) and vRNA replication (vRNA-dependent synthesis of complementary RNA(cRNA) and cRNA-dependent synthesis of vRNA). The RNA polymerase is composed of three viral proteins, PB1, PB2 and PA. PB1 is the core subunit for not only the RNA synthesis but also the assembly of PB2 and PA into this multifunctional enzyme complex. PB1 alone is able to catalyze vRNA-dependent RNA synthesis, but PB2 is required for capped RNA-dependent transcription, both together forming the transcriptase. The third P protein, PA, and an as yet unidentified host factor(s) are involved for the conversion of RNA polymerase from transcriptase to replicase. The functional map including both subunit-subunit contact sites and catalytic sites for capped RNA endonuclease and RNA polymerization is being made for both PB1 and PB2 proteins.

Genome, Viral↗
PubMed1997

[A case of successful treatment with ganciclovir for cytomegalovirus pneumonia after pulmonary lobectomy].

The premortem diagnosis of cytomegalovirus (CMV) pneumonia is usually difficult, and mortality of it is high. A case of successful treatment with ganciclovir for cytomegalovirus pneumonia after pulmonary lobectomy is reported. The patient was a 76-year-old man. Under diagnosis as lung cancer, the right lower lobectomy was performed. After operation, pneumonia occurred on the nonoperated side and in a few days reticular shadows rapidly spread to the whole lung. Although pulse steroid therapy was performed, the interstitial pneumonitis improved only a little. Then intranuclear inclusion body-bearing giant cells were found in sputum obtained by bronchoscopy. So we diagnosed the interstitial pneumonitis as CMV pneumonia and ganciclovir was administrated. CMV pneumonia had improved for two weeks and the patient has no recurrence. When interstitial pneumonitis develop in patients after operation or steroid therapy, the differential diagnosis should include the possibility of CMV pneumonia.

Aged↗
PubMed1996

Physiological dose of estrogen regulates extrathymic T cells in female mice.

Bilateral ovariectomy was performed in female C57BL/6 mice to investigate whether extrathymic T cells in the liver are regulated by physiological doses of estrogen or progesterone. Extrathymic T cells were identified using a two-color immunofluorescence test for CD3 and interleukin-2 receptor beta-chain (IL-2R beta) antigens. The T cells were identified as intermediate CD3+ cells with a high expression of IL-2R beta. It was further demonstrated that the proportion and number of intermediate CD3+ cells decreased in response to ovariectomy, an effect that was countered by estrogen administration. These results suggest that the activation of extrathymic T cells may be regulated by physiological levels of estrogen.

Animals↗
PubMed1996

Suppression of translation frameshift by upstream termination codon.

Retroviruses employ translation frameshift for gene expression. Translation frameshift takes place at the slippery heptanucleotide sequence on mRNA. A downstream stem-loop structure (and a pseudoknot formed by the stem-loop) enhances the level of ribosomal frameshifting. Here, we describe that an upstream termination codon suppresses the ribosomal frameshifting, leading to reduction in the expression of downstream genes.

Amino Acid Sequence↗
PubMed1996

The changes of the stromal elastotic framework in the growth of peripheral lung adenocarcinomas.

BACKGROUND: Most peripheral lung adenocarcinomas form a characteristic central fibrosis; however, the mechanism of formation has not yet been clarified. METHODS: The stromal elastosis of 176 patients with peripheral lung adenocarcinomas was studied histologically, morphometrically, radiographically, and clinicopathologically. RESULTS: The tumors were classified into two types, according to the histomorphological pattern of the stromal elastosis: (1) a preserved framework composed of a uniformly thick stroma (Type 1; 20 patients) and (2) a disrupted framework in the central fibrosis in which many air spaces were collagenized or collapsed (Type 2; 156 patients). Around the central fibrosis in the Type 2 tumors, replacement growth took the form of a thin-walled, elastic framework. Image analysis disclosed that the elastotic framework had an increased elastic fiber volume (approximately three- to nine-fold, compared with the normal alveolar wall), especially in Type 1 tumors, related to the contraction of the pre-existing alveolar wall. In Type 2 replacement growth, the amount of elastic fibers was slightly increased, which suggested mild reaction of the pre-existing alveolar wall. Radiographically, Type 1 tumors were characterized by a gradual increase of the density without enlargement, while the Type 2 tumors often enlarged within a short period. Recurrence was seen in 54% of the patients with Type 2 tumors, but in none of those with Type 1 tumors. CONCLUSIONS: In the early development of peripheral adenocarcinoma, there is preservation of the elastotic framework (Type 1) of the stroma due to contraction and thickening of the alveolar walls. As the tumors grow, the elastotic framework is disrupted (Type 2), indicating stromal invasion. Based on the clinicopathologic findings and the outcome, Type 1 tumors may be in situ peripheral lung adenocarcinomas.

Adenocarcinoma↗
PubMed1996

Regulation of the last two enzymatic reactions in cholesterol biosynthesis in rats: effects of BM 15.766, cholesterol, cholic acid, lovastatin, and their combinations.

The Smith-Lemli-Opitz syndrome is a common inherited birth disorder caused by markedly reduced 7-dehydrocholesterol delta 7-reductase activity, the final enzyme in the cholesterol biosynthetic pathway. BM 15.766 (4-[2-[1-(4-chlorocinnamyl)piperazin-4-yl]ethyl]-benzoic acid) inhibits 7-dehydrocholesterol delta 7-reductase activity, reduces plasma cholesterol levels, and increases 7-dehydrocholesterol levels to reproduce the biochemical abnormalities of the syndrome in rats. Cholesterol, cholic acid, and lovastatin, alone or in combinations, were fed to rats given BM 15.766, and hepatic activities of the last two enzymes in the cholesterol biosynthetic pathway, lathosterol 5-dehydrogenase and 7-dehydrocholesterol delta 7-reductase, were measured. After feeding BM 15.766, hepatic 7-dehydrocholesterol delta 7-reductase activity decreased by 77% while lathosterol 5-dehydrogenase activity tended to increase, so that the ratio of 5-dehydrogenase to delta 7-reductase activities increased from 0.33 to 2.8. In BM 15.766-fed rats, treatment with cholesterol suppressed both 5-dehydrogenase and delta 7-reductase activities by 76% and 66%, respectively, and decreased the 5-dehydrogenase: delta 7-reductase activities ratio from 2.8 to 2.2. In contrast, treatment with cholic acid and BM 15.766 further inhibited delta 7-reductase activity by 67% without changing significantly the 5-dehydrogenase activity that had increased the ratio to 5.5. Combining BM 15.766 with lovastatin increased 5-dehydrogenase activity fivefold but did not change delta 7-reductase activity, raising the ratio to 14.3. In BM 15.766-treated rats, the first and last two enzymatic reactions in the cholesterol biosynthetic pathway catalyzed by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, lathosterol 5-dehydrogenase, and 7-dehydrocholesterol delta 7-reductase are down-regulated by cholesterol. Thus, only cholesterol and not cholic acid or lovastatin could reduce elevated plasma 7-dehydrocholesterol levels induced by BM 15.766.

Animals↗
PubMed1996

Abnormal cholesterol biosynthesis in sitosterolaemia and the Smith-Lemli-Opitz syndrome.

We investigated the enzyme defects in two inherited disorders of cholesterol biosynthesis: sitosterolaemia and the Smith-Lemli-Opitz syndrome. In sitosterolaemic homozygotes, plasma plant sterols (sitosterol and campesterol) concentrations are elevated because of enhanced intestinal absorption and diminished removal. Underlying these changes is very low cholesterol biosynthesis to provide extra sterol for cell growth. Extremely reduced activities of HMG-CoA reductase, the rate-controlling enzyme for cholesterol biosynthesis, caused by deficient HMG-CoA reductase mRNA is responsible and is the suspected inherited abnormality. The Smith-Lemli-Opitz syndrome is caused by a block in the last reaction in the cholesterol biosynthetic pathway, the conversion of 7-dehydrocholesterol to cholesterol, which is catalysed by 7-dehydrocholesterol delta 7-reductase. As a result, low plasma and tissue cholesterol with high 7-dehydrocholesterol levels are found in homozygotes, who show characteristic phenotypes of mental retardation, facial dysmorphism, and organ and limb congenital anomalies. Similar biochemical findings are produced in rats fed BM 15,766, an inhibitor of 7-dehydrocholesterol delta 7-reductase. Interestingly, feeding cholesterol can suppress abnormal cholesterol biosynthesis and improve symptoms in homozygotes and rats fed BM 15,766.

Animals↗
PubMed1996

Effect of YM 9429, a potent teratogen, on cholesterol biosynthesis in cultured cells and rat liver microsomes.

YM 9429 (cis-1-[4-(p-menthan-8-yloxy)phenyl]piperidine) is a hypolipidemic agent with a potent and specific teratogenicity, inducing cleft palate and skeletal variations in rats. Since cleft palate is generally observed in the Smith-Lemli-Opitz syndrome, a common syndrome of multiple congenital anomalies caused by reduced activity of 7-dehydrocholesterol delta 7-reductase (3 beta-hydroxysteroid delta 7-reductase), the final enzyme in the cholesterol biosynthetic pathway, YM 9429 was suspected of being an inhibitor of this enzyme. To prove this hypothesis, YM 9429 was added to cultured human skin fibroblasts and to cultured Morris hepatoma cells and incubated with [5-3H]mevalonolactone. After 24 h, radiolabeled 7-dehydrocholesterol accumulated in the cells, whereas the formation of radiolabeled cholesterol was markedly reduced. The results indicate that YM 9429 inhibits the conversion of 7-dehydrocholesterol to cholesterol catalyzed by the microsomal enzyme 7-dehydrocholesterol delta 7-reductase. In rat liver microsomes, the mode of inhibition was found to be noncompetitive, with a Ki of 40 microM. These results suggest that YM 9429 induced developmental abnormalities in rats by the same mechanism as the Smith-Lemli-Opitz syndrome. This compound might be useful for studying the pathogenesis of anomalies in animal models of the Smith-Lemli-Opitz syndrome.

Animals↗
PubMed1996

Abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz syndrome.

The Smith-Lemli-Opitz syndrome is caused by an inherited defect in 7-dehydrocholesterol-delta7-reductase, the enzyme that catalyzes the last reaction in cholesterol biosynthesis, the conversion of 7-dehydrocholesterol to cholesterol. As a result, deficient cholesterol is produced and the precursor 7-dehydrocholesterol and derivatives (8-dehydrocholesterol and 19-nor-5,7,9(10)-cholestatrien-3 beta-ol) accumulate. Tissues (especially brain) deprived of cholesterol, or because of the deposited sterol precursors and derivatives, develop abnormally and function poorly. Replacement with dietary cholesterol may help correct the biochemical defects and improve symptoms.

Adolescent↗
PubMed1996

Measurement of 3 beta-hydroxysteroid delta 7-reductase activity in cultured skin fibroblasts utilizing ergosterol as a substrate: a new method for the diagnosis of the Smith-Lemli-Opitz syndrome.

A new sensitive and specific method for the evaluation of 3 beta-hydroxysteroid delta 7-reductase activity, the defective enzyme in the Smith-Lemli-Opitz (SLO) syndrome, is described. The assay is based on the use of gas chromatography-mass spectrometry with selected-ion monitoring to measure the mass of brassicasterol (ergosta-5,22-dien-3 beta-ol) produced by the incubation of ergosterol (ergosta-5,7,22-trien-3 beta-ol) with cultured human skin fibroblasts. Although the conversion of ergosterol to brassicasterol was slower than the transformation of [3H]7-dehydrocholesterol to [3H] cholesterol, cells from control subjects produced brassicasterol efficiently. In contrast, cells form SLO patients produced very little brassicasterol (P < 0.0001, patients vs. parents or vs. controls). These results indicate that the reduction of ergosterol can be used as an assay for 3 beta-hydroxysteroid delta 7-reductase in human skin fibroblasts, which avoids the many problems caused by the instability and lack of availability of radiolabeled 7-dehydrocholesterol. The present method made it possible to diagnose the SLO syndrome with high sensitivity and reliability using a commercially available compound.

Cholestadienols↗