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Biomedical subjects

S Sakoda

Publications and source records attributed to S Sakoda.

At least 109 records · Page 6Linked to original sources

[Cardiac sarcoidosis with multinucleated giant cells detected in endomyocardial biopsy specimens: report of 3 cases].

This is a report of 3 cases of cardiac sarcoidosis. None of the 3 patients had other overt systemic involvement. Multinucleated giant cells and non-caseating epithelial cell granulomas with small lymphocytic infiltrations were detected in the endomyocardial biopsy specimen. Some focal left ventricular wall motion abnormalities were detected by echocardiography and angiography in all 3 patients. Paroxysmal ventricular tachycardia and multifocal ventricular premature complexes were observed by Holter 24-hour electrocardiography in all 3 patients. Two of the 3 patients did not receive corticosteroids, but remaining patient is on a regimen of corticosteroid.

Adult↗

Extraadrenal expression of steroid 21-hydroxylase and 11 beta-hydroxylase by a benign testicular Leydig cell tumor.

We present an unusual case with bilateral testicular Leydig cell tumors displaying extraadrenal expression of steroid 21-hydroxylase and 11 beta-hydroxylase. Histological examination of a 38-yr-old man infertile due to azoospermia showed him to have bilateral testicular Leydig cell tumors. The in vitro steroidogenic potential of the tumors and their adjacent testicular tissue was evaluated using organ culture. Tumor tissue was found to secrete deoxycorticosterone (DOC), corticosterone (B) and cortisol, which are not produced in normal adult testis, into the medium, while testicular tissue adjacent to the tumors secreted a small amount of DOC and B. Northern blot analysis with cytochrome P-450C21 complementary DNA (cDNA) and P-45011 beta cDNA as probes revealed that the tumor contained a considerable amount of mRNA for P-450C21 and P-45011 beta, while the MRNAs were not detected in the testicular tissues adjacent to the tumors. It is suggested that the high local levels of estrogen and/or progesterone within the Leydig cell tumors and their adjacent testicular tissues induced extraadrenal expression of steroid 21-hydroxylase and 11 beta-hydroxylase by the tumors and their adjacent testicular tissues.

Adult↗

Evidence for the presence of androgen receptors in human Leydig cells.

Localization of androgen receptors (ARs) in the human testis Leydig cells was examined with an AR assay and Northern blot analysis. Leydig cells, highly purified on a Percoll gradient, were used for the experiments. AR concentration in the total cell extract containing both the cytosol and nuclear fractions in Leydig cells was measured using [3H]methyltrienolone. ARs in Leydig cells showed a high affinity for [3H]methyltrienolone and the Kd and Bmax of the receptors were 1.24 nM and 11.7 fmol/mg protein, respectively. Northern blot analysis, using a 32P-labeled full-length human AR complementary DNA (cDNA) detected a 9.5-kb hybridizing band in the total RNA extracted from Leydig cells. These data can be interpreted as evidence of the existence of ARs in human Leydig cells.

Blotting, Northern↗

Effect of long-term L-threo-3,4-dihydroxyphenylserine administration on alpha 2-adrenergic receptors in platelet membranes in neurologic disorders.

The effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), an unnatural norepinephrine precursor, on alpha 2-adrenergic receptors in platelet membranes were investigated in a patient with familial amyloidotic polyneuropathy, two patients with multiple system atrophy, and two patients with Parkinson's disease. Each patient was treated for at least six months. While L-threo-DOPS alone, or in combination with decarboxylase inhibitor benserazide hydrochloride, produced sustained increase in plasma norepinephrine and clinical improvement, it did not induce a change in the number of alpha 2-adrenergic receptors in platelet membranes.

Aged↗

A novel antineuronal antibody in serum and CSF of a patient with motor neuron disease.

A patient with motor neuron disease and tonic pupil who had an antinuclear antibody (Ab) in the serum and oligoclonal pattern in IgG in the CSF is described. Sera and CSF from this patient and controls (37 sera and 30 CSF) were screened for an antineuronal Ab using immunoblotting. Only the serum and CSF from this patient contained an Ab to a 70-kD protein in the human spinal cord but not in the human muscle or cerebellar cortex. This patient's serum immunohistochemically stained human and Japanese monkey anterior horn cells but not Japanese monkey dorsal root ganglion.

Animals↗

[Combined preoperative treatment with bilateral intra-arterial chemotherapy (CBDCA + PEP) and radiotherapy of oral cancer on the midline].

Intra-arterial chemotherapy from bilateral superficial temporal arteries and radiotherapy were carried out preoperatively on two patients with oral cancer on the midline. Total doses of preoperative chemo- and radio-therapies were 160 mg/m2 of carboplatin, 50 mg of peplomycin and 20 Gy of 60Co-irradiation, respectively. Therapeutic effect of preoperative chemo- and radio-therapies was evaluated on the resected materials from histological point of view. In case 1, the effect was judged as Grade II A in Oboshi's classification, which indicated a mild destruction of architecture of tumor tissue and a few viable tumor cells, but an extreme reduction of the primary lesion was observed on clinical appearance. In case 2, the therapeutic effect was regarded as Grade II B, which indicated a severe destruction of architecture of tumor tissue and few viable tumor cells. Concerning toxicity, mucositis and slight thrombocytopenia (96,000/mm3) in case 1, and mucositis and leukopenia (2,300/mm3) in case 2 appeared. However, they soon recovered after termination of the preoperative therapies. From the above results, it was considered that a combination of bilateral intra-arterial chemotherapy and radiotherapy was quite effective as a preoperative treatment for oral cancers on the midline at the same doses of anti-neoplastic agents and irradiation as for the other unilateral oral cancers.

Aged↗

[Evaluation of hepatic venous flow patterns using a pulsed Doppler technique].

Evaluation of hepatic venous flow patterns was attempted by pulsed Doppler echocardiography. Subjects were 80 patients including those with dilated cardiomyopathy, old myocardial infarction, angina pectoris, pulmonary hypertension, constrictive pericarditis, tricuspid regurgitation (TR), lone atrial fibrillation, and post-cardiac surgery. Eleven normal subjects served as controls. The mean age was 53.0 +/- 12.4 years. Most of the TR patients had atrial fibrillation. Patients with aortic regurgitation and significant mitral regurgitation were excluded. Afterload stress by angiotensin II infusion was performed in 51 subjects, mainly for those with ischemic heart disease, cardiomyopathy and the normal controls. Hepatic venous flow patterns included double-peaked flow signals toward the right atrium, and the relationship between systolic (S) and diastolic flow velocities (D) was expressed as the velocity ratio [S/(S+D)]. A reversed flow during atrial systole was expressed as an "A wave" and that between the S and D waves, as an "O wave". Systolic flow velocity was less than diastolic flow velocity in cases with atrial fibrillation and the post-surgical cases. The velocity ratio was greater than 0.5 in nearly all patients with normal sinus rhythm, and less than 0.5 in cases with atrial fibrillation and the post-surgical cases. In the former, systolic flow velocity was less than diastolic flow velocity after defibrillation, in spite of restoration of normal sinus rhythm. These findings indicate that systolic flow velocity was influenced by atrial relaxation; diastolic flow velocity, by ventricular diastolic function. The A wave was increased in cases with pulmonary hypertension and A wave velocity in the hepatic vein correlated with systolic pulmonary artery pressure. In cases with tricuspid regurgitation, reversed flows were detected during ventricular systole both in normal sinus rhythm and in atrial fibrillation. After infusions of angiotensin II the velocity ratio increased in cases with dilated cardiomyopathy and in normal controls (p less than 0.01). The hepatic venous flow pattern after infusion in the former was characterized by dominant systolic and diminished diastolic flow velocities with a consequent increase in the velocity ratio toward 1.0, while a change in the ratio was less marked in normal controls. In conclusion, analysis of the hepatic venous flow pattern by pulsed Doppler echocardiography is very useful for evaluating cardiac function. A marked increase in the velocity ratio after angiotensin II infusion suggests decreased cardiac function.

Adult↗

Structure of the gene encoding the muscle-specific subunit of human phosphoglycerate mutase.

We report the isolation and analysis of genomic clones containing the entire gene encoding the muscle-specific subunit of human phosphoglycerate mutase. The gene spans 2.83 kilobase pairs and has a three-exon/two-intron structure that is similar to the organization of the human 2,3-bisphosphoglycerate mutase gene (Joulin, V., Garel, M.-C., LeBoulch, P., Valentin, C., Rosa, R., Rosa, J., and Cohen-Solal, M. (1988) J. Biol. Chem. 263, 15785-15790), in that the second introns of both genes are localized precisely at the same position. A canonical TATA box and an inverted CCAAT box are present immediately upstream of this gene. Comparison with other muscle-specific enzyme genes reveals a conserved 9-base pair element (GGGGCTGGG) in the 5'-flanking region that may be associated with the expression of genes encoding muscle-specific enzymes.

Amino Acid Sequence↗

[Left ventricular thrombi detected by Ga-67-DFO-DAS-fibrinogen imaging and two-dimensional echocardiography].

The capability of diagnosing left ventricular thrombi was compared by scintigraphy using Ga-67-DFO-DAS-fibrinogen (Ga: gallium, DFO: deferoxamine, DAS: dialdehyde starch) and two-dimensional echocardiography. 1. Ga-67-DFO-DAS-fibrinogen scintigraphy and two-dimensional echocardiography were performed in 17 consecutive patients following myocardial infarction. In 11 of the 17 patients, left ventricular thrombi were visualized by Ga-67-DFO-DAS-fibrinogen scintigraphy, but only five of the 11 patients were found to have thrombi by two-dimensional echocardiography. 2. In eight patients with inferior or posterior myocardial infarction, no left ventricular thrombi were detected by two-dimensional echocardiography, while in six of the eight patients, ventricular thrombi were visualized by Ga-67-DFO-DAS-fibrinogen scintigraphy. 3. Among the patients receiving adequate anticoagulants from the episode, only three patients had thrombi. In contrast, the remaining eight patients with thrombi were either receiving no anticoagulants, or were receiving inadequate anticoagulant therapy. Ga-67-DFO-DAS-fibrinogen scintigraphy is a very simple and useful method for detecting thrombi in the left ventricle after myocardial infarction. It is more sensitive for detecting thrombi in the ventricle than was two-dimensional echocardiography. With this method, we can demonstrate the preventive effect of anticoagulants for left ventricular thrombus formation following myocardial infarction.

Adult↗

Isolation of a cDNA encoding the B isozyme of human phosphoglycerate mutase (PGAM) and characterization of the PGAM gene family.

We previously reported the isolation of a full-length cDNA specifying the muscle-specific isozyme of human phosphoglycerate mutase (PGAM-M). We now report the isolation of a full-length cDNA specifying the non-muscle-specific, or brain (B), isozyme of human PGAM (PGAM-B). The PGAM-B cDNA encodes a deduced protein 254 amino acids long, 79% identical to PGAM-M, and contains a 913-nucleotide 3'-untranslated region, as compared to the unusually short 37-nucleotide 3'-untranslated region of PGAM-M. Northern analysis demonstrates the non-muscle-specific nature of PGAM-B transcription, while genomic Southern analysis implies the presence of a large PGAM family in the human genome. Most of the PGAM-hybridizing sequences in both the human and mouse genomes seem to be related to the B-isozyme gene; many members of the PGAM-B gene family in humans are apparently processed genes. These results agree with the evolutionary analysis, which indicates that the PGAM-B gene is the progenitor of the PGAM-M gene.

Amino Acid Sequence↗

Sequence of cDNAs encoding subunit Vb of human and bovine cytochrome c oxidase.

We have isolated a full-length human fetal muscle cDNA clone specifying the nuclear-encoded subunit Vb of the human mitochondrial respiratory chain enzyme, cytochrome c oxidase (COX; EC 1.9.3.1), and a partial-length brain cDNA clone specifying the analogous bovine subunit. The two cDNAs are 85% identical at the nucleotide level. Similar to other proteins imported into mitochondria, the deduced human COX Vb protein contains a presequence, 31 amino acids long, rich in basic residues. We find no evidence for tissue-specific transcripts for subunit Vb of human COX, as Northern analysis of total RNA from human muscle, liver, and brain showed a single, identically sized transcript in each cell type, while partial-length cDNA clones isolated from human muscle and endothelial cell cDNA libraries were identical in sequence to the fetal muscle cDNA.

Amino Acid Sequence↗

Clinicopharmacological studies of a newly synthesized cardiotonic agent (TA-064) in patients with congestive heart failure.

In animal experiments, a new inotropic agent, (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenetyl)amino] ethanol, designated TA-064 was found to possess a more positive inotropic than chronotropic action. Its effectiveness and lack of significant toxicity make it beneficial for clinical use as a cardiotonic in human heart failure. The effects of TA-064 were investigated in patients with various types of heart disease (n = 29). Cardiac output increased, left ventricular end-systolic dimension decreased, and left ventricular fractional shortening increased for 15 minutes after a single intravenous dose (1 mg). The plasma level of TA-064 at the cessation of infusion was 61.1 +/- 49.6 ng/ml and thereafter declined biexponentially. After a single oral dose (10 mg), TA-064 appeared in the plasma at 30 minutes and reached its peak levels of 13.7 +/- 5.6 ng/ml at 60 minutes. Seven hours later, the plasma level was 5.9 +/- 3.1 ng/ml which was considered to be within the effective range according to the results after intravenous administration. In conclusion, minimal effective plasma levels of TA-064 are obtained by oral administration of 10 mg three times a day.

Administration, Oral↗

Myocarditis with multinucleated giant cells detected in biopsy specimens.

A 42-year-old woman was transferred to our hospital for evaluation of bradycardia with a complete atrioventricular block. Her pulse was 41 regular beats/min with blood pressure 166/92 mmHg. There were no skin lesions, edema, or lymphadenopathy. The white blood cell count was 6300/mm3. The serum glutamic oxaloacetic transaminase was 21 IU and creatine phosphokinase was 34 IU. C-reactive protein was negative. The level of serum angiotensin converting enzyme was slightly increased at 25.8 IU/l/37.0 degrees C (normal range: 7-24.0). Chest radiography showed congestive heart failure with a cardiothoracic ratio of 54%. There was no bilateral lymphadenopathy or fibrous changes during her clinical course. The coronary arteries were completely normal angiographically. Left ventriculograms revealed slight hypokinesis and dilatation (end-diastolic volume index of 112 ml/m2, ejection fraction of 53%). Left ventricular end-diastolic pressure was slightly abnormal at 16 mmHg. Two right and two left ventricular endomyocardial biopsies were performed. Right ventricular biopsy demonstrated edematous tissue and a slight mononuclear cell infiltration with little fibrosis. Left ventricular specimens showed an extensive area of fibrosis, with large, multinucleated giant cells with an asteroid body and chronic inflammation without epithelioid cells. The less affected areas of another specimen showed mild interstitial fibrosis and degenerative myocytes with vacuolation, and some multinucleated myocytes without an asteroid body were present. This case was diagnosed as cardiac sarcoidosis rather than idiopathic giant cell myocarditis. The patient has been implanted with a permanent pacemaker.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The aortic alpha 1-adrenergic receptor in familial amyloidotic polyneuropathy.

To assess the pathophysiology of the sympathetic nervous system in familial amyloidotic polyneuropathy (FAP), we used 3H-bunazosin to identify and characterize the alpha 1-adrenergic receptor in human aortic membranes. The binding of 3H-bunazosin was rapid, readily reversible, stereospecific, and saturable. The Scatchard analysis described a single class of binding sites with a dissociation constant (KD) of 0.370 +/- 0.035 nM and a maximal binding capacity (Bmax) of 11.8 +/- 1.30 fmol/mg protein in control patients. Competition analysis demonstrated the alpha 1-adrenergic specificity of the 3H-bunazosin binding sites in human aortic membranes. The KD and Bmax of 3H-bunazosin binding in four FAP patients was 0.274 +/- 0.052 nM and 7.79 +/- 0.15 fmol/mg protein, respectively; these values did not differ significantly from those in 14 control patients. An increase in Bmax or affinity of alpha 1-adrenergic receptors may not be the cause for denervation supersensitivity in FAP.

Adrenergic alpha-Antagonists↗

Isolation of a cDNA encoding the muscle-specific subunit of human phosphoglycerate mutase.

We have isolated a full-length cDNA specifying the muscle-specific subunit of human phosphoglycerate mutase (PGAM-M). The cDNA encodes a deduced protein 253 amino acids in length and contains an unusually short (37 nucleotides) 3'-untranslated region. The deduced human PGAM-M protein is clearly related to yeast PGAM and to human diphosphoglycerate mutase. Genomic Southern analysis using the PGAM-M cDNA as a probe implies the presence of a large PGAM gene family in the human genome, while Northern analysis demonstrates tissue-specific transcription of this isoenzyme gene.

Amino Acid Sequence↗