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Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 1,009 records · Page 56Linked to original sources
PubMed1993

Contribution of endogenous endothelin-1 to the progression of cardiopulmonary alterations in rats with monocrotaline-induced pulmonary hypertension.

Endothelin-1 (ET-1) is known to have potent contractile and proliferative effects on vascular smooth muscle cells and is known to induce myocardial cell hypertrophy. We studied the pathophysiological role of endogenous ET-1 in rats with monocrotaline-induced pulmonary hypertension. Four-week-old rats were given a single subcutaneous injection of 60 mg/kg monocrotaline (MCT rats) or saline (control rats) and were killed after 6, 10, 14, 18, and 25 days. In the MCT rats, right ventricular systolic pressure progressively increased and right ventricular hypertrophy developed in a parallel fashion. The venous plasma ET-1 concentration also progressively increased, and this increase preceded the development of pulmonary hypertension. The isolated pulmonary artery exhibited a significantly weaker response to ET-1 in the MCT rats on day 25 but not on days 6 and 14. In the MCT rats, the expression of prepro ET-1 mRNA as measured by Northern blot analysis significantly increased in the heart on days 18 and 25, whereas it gradually decreased in the lungs. The peptide level of ET-1 in the lungs also significantly decreased in the pulmonary hypertensive stage. The expression of prepro ET-1 mRNA had increased by day 6 only in the kidneys. Continuous infusion of BQ-123, a selective ETA receptor antagonist, by an osmotic minipump (14.3 mg per day per rat for 18 days) significantly inhibited the progression of both pulmonary hypertension (right ventricular systolic pressure, 77.8 +/- 4.2 [mean +/- SEM] mm Hg [n = 10] versus 52.3 +/- 2.4 mm Hg [n = 7]; P < .01) and right ventricular hypertrophy (right ventricle/[left ventricle +/- septum], 0.56 +/- 0.03 [n = 10] versus 0.41 +/- 0.02 [n = 7]; P < .01). Histological examination revealed that BQ-123 also effectively prevented pulmonary arterial medial thickening. The inhibition of right ventricular hypertrophy by BQ-123 may be partly ascribed to the blockade of excessive stimulation of the heart by ET-1, in addition to the prevention of pulmonary hypertension. The present findings suggest that endogenous ET-1 contributes to the progression of cardiopulmonary alterations in rats with MCT-induced pulmonary hypertension.

Animals↗
PubMed1993

Bone marrow-derived osteoclast-like cells from a patient with craniometaphyseal dysplasia lack expression of osteoclast-reactive vacuolar proton pump.

Craniometaphyseal dysplasia (CMD) is a rare craniotubular bone dysplasia transmitted in autosomal dominant or recessive form. This disease is characterized by cranial bone hyperostosis and deformity of the metaphyses of the long bones. Using osteoclast-like cells formed from patient bone marrow cells, we investigated the pathophysiology of CMD in a 3-yr-old patient. Untreated bone marrow cells from the patient differentiated into osteoclast-like cells in vitro. These cells were shown to have vitronectin beta-receptors using a specific monoclonal antibody, i.e., 23C6 (CD51), which reacts with osteoclasts in human bone biopsy samples. However, the number of these osteoclast-like cells formed from the patient's bone marrow was only 40% of the normal controls. 1,25-dihydroxyvitamin-D3, bovine 1-34 parathyroid hormone, recombinant human interleukin-1 beta, recombinant human interleukin-6, or recombinant human macrophage colony-stimulating factor significantly increased, while salmon calcitonin significantly inhibited, the number of osteoclast-like cells. However, these cells could not resorb sperm whale dentin slices and lacked the osteoclast-reactive vacuolar proton pump as evidenced by a monoclonal antibody (E11). Western blot analysis using a monoclonal antibody to pp60c-src (327) revealed that protooncogene c-src expression by the platelets of the CMD patient was comparable to the normal control. These data suggest that: (a) the hyperostosis and the metaphyseal long bone deformity in the present CMD patient might be explained by osteoclast dysfunction due to impaired expression of the osteoclast-reactive vacuolar proton pump; and (b) a protooncogene c-src was not associated with the pathogenesis of the present CMD patient.

Blood Platelets↗
PubMed1993

Experimental manufacture of a catheter for the measurement of blood flow rate.

The authors manufactured an experimental catheter to obtain blood flow rate, measuring not only the flow velocity but also the vessel diameter. This catheter consists of 3F Doppler and 7F external sheath catheters, and four thin wires 3 cm in length are attached to the catheters at both tips at a 90 degrees pitch. After the insertion of the catheter into the vessel, vessel diameter is calculated from the maximal width of the wires, which are expanded to a spindle shape inside the vessel; the maximal width is corrected with calibration metal markers also attached at the proximal site of the external sheath catheter. The flow velocity of the blood is calculated with the FFT (Fast Fourier Transform) analyzer. In experimental circuits as well as in the canine aorta, wires were adequately expanded, and the catheter was placed at the center of the tube or the aorta. The blood flow rate, which was calculated as a product of flow velocity and vessel diameter, was well correlated to that from the electromagnetic flowmeter, not only in the experimental circuits, but also in the canine aorta.

Animals↗
PubMed1993

A rapid method for measuring serum amyloid A protein by latex agglutination nephelometric immunoassay.

Serum amyloid A protein (SAA) is a sensitive acute phase reactant. We developed a method for the rapid measurement of human SAA in serum by kinetic nephelometry of anti-SAA antibody-coated latex agglutination. Measurement takes less than 6 min using an automated analyser. Standardization of the assay employs SAA-enriched high density lipoprotein as the primary standard. The values determined by our new method and by conventional enzyme-immunoassay showed good agreement (r = 0.988). The normal range was 0.17-10.0 mg/L [mean(SD)]. This rapid method should prove useful in clinical laboratories.

Antibodies, Monoclonal↗
PubMed1993

Two types of pole cells are present in the Drosophila embryo, one with and one without splicing activity for the third P-element intron.

In Drosophila, it has been postulated that the third intron of the P-element is spliced only in germ-line cells. To test whether this postulate is applicable to pole cells, the progenitor cells of germ line, we carried out a histochemical assay to detect the splicing activity in embryos. The splicing activity was detected in pole cells and primordial germ cells. The activity increased to reach a maximum at 5-6 hours AEL (after egg laying), then decreased to an undetectable level by 8-9 hours AEL. The splicing activity showed a small second peak at 12-15 hours AEL. It was rather unexpected that not all pole cells were capable of splicing the third intron. Almost all pole cells that had the splicing activity at 5-6 hours AEL penetrated the embryonic gonads and differentiated into primordial germ cells. Our findings suggest that pole cells are selected to penetrate the gonads while they are migrating from the proctodeal cavity to the gonads. Furthermore, these results suggest that the machinery to splice the P-element is active in some pole cells, and that this activity is used for processing transcripts of genes that play important roles in the differentiation of pole cells into primordial germ cells.

Animals↗
PubMed1993

Sustained changes in acetylcholine and amino acid contents of brain regions following microsphere embolism in rats.

The present study was undertaken to explore changes in neurotransmitters and neuromodulators of brain regions impaired by microsphere embolism-induced, sustained ischemia. Nine hundred microspheres (48 microns) were injected into the right internal carotid artery of rats, and the time course of changes in the triphenyltetrazolium chloride (TTC)-stained areas of their brain slices and acetylcholine and amino acid contents in the cerebral cortex, striatum and hippocampus of both hemispheres were determined. The TTC-unstained area, a measure of infarction, was developed in the right hemisphere by the 3rd day after the embolism, which was similar to that on the 28th day. A marked decline in acetylcholine content of these three regions of the right hemisphere was detected throughout the experiment (28 days). The glutamate, aspartate, GABA, and taurine levels were markedly decreased following microsphere-embolism. Most of these decreases were significantly attenuated during the first 5 days following the embolism, and they then partially recovered with time after the operation. Minor metabolic changes were observed in the left hemisphere. The results suggest that microsphere-embolism induces cerebral infarction and/or sustained damage to acetylcholine and neurotransmitter amino acid synthesis and/or catabolism of the brain regions. This model may provide information concerning the pathophysiological alterations in long-term cerebral ischemia and infarction.

Acetylcholine↗
PubMed1993

Experimental pneumonia of pigs infected with Aujeszky's disease virus and Actinobacillus pleuropneumoniae.

Experimental infections were induced out to examine whether Aujeszky's disease virus (ADV) infection in pigs results in a severe pneumonia by Actinobacillus pleuropneumoniae. Intranasal inoculation of ADV (10(6.9) median tissue culture infective dose/head) in 4-month-old primary specific-pathogen-free pigs was followed by the inoculation of A. pleuropneumoniae type 1 (10(3.1) or 10(5.1) colony-forming-units/head). The pigs inoculated with ADV alone developed clinical signs of Aujeszky's disease but not pneumonia, and those inoculated with A. pleuropneumoniae (10(3.1) CFU/head) alone did not develop clinical symptoms and lung lesions. Whereas all the pigs inoculated dually with ADV and A. pleuropneumoniae (10(3.1) CFU/head) showed severe or very severe clinical symptoms and moderate or severe pneumonia and one of them died. The pigs inoculated with A. pleuropneumoniae (10(5.1) CFU/head) alone had severe clinical symptoms and one of the 2 pigs died acutely. Furthermore, all of the 3 pigs inoculated with ADV and A. pleuropneumoniae (10(5.1) CFU/head) showed clinical symptoms and moderate or severe pneumonic lesions and one pig died of disease. It was concluded that the clinical symptoms of A. pleuropneumoniae became severer by concomitant infection with ADV.

Actinobacillus pleuropneumoniae↗
PubMed1993

Distinct responses of interleukin-6 and other laboratory parameters to treatment in a patient with Wegener's granulomatosis.

We describe a patient with Wegener's granulomatosis in whom the serum levels of interleukin-6 (IL-6) and other laboratory parameters were monitored. The IL-6 and CRP levels, which were extremely high before treatment, declined rapidly with corticosteroid and cyclophosphamide. IgG, leukocyte count and platelet count declined more gradually. Thus, determination of the serum IL-6 level might be useful in diagnosing and monitoring Wegener's granulomatosis.

Biomarkers↗
PubMed1993

A double staining technique using 5-bromo,4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) and immunoperoxidase in whole Drosophila embryos.

We have developed a double staining method using 5-bromo,4-chloro-3-indolyl-beta-D-galactopyranoside X-gal and immunoperoxidase for whole Drosophila embryos. The dechorionated embryos are fixed in heptane saturated with 4% formaldehyde, then in heptane and 50% methanol. Fixed embryos are devitellinized with a tungsten needle and processed for immunoperoxidase staining immediately prior to peroxidase color development. The embryos are stained with X-gal, then peroxidase staining is resumed. This procedure enables us to observe cells stained with both X-gal and a specific antibody in whole embryos.

Animals↗
PubMed1993

Influences of some low molecular compounds on enzymatic activity and isoelectric point of aspartate aminotransferase from rat liver.

The substances responsible for regulating cytosolic aspartate aminotransferase (AspATc) activity in the cytosolic fraction of rat liver were examined. AspATc was removed from the cytosolic fraction by passing the fraction through an affinity column to which anti-AspATc antiserum was conjugated. The unbound fraction from the column was found to decrease the activity of the purified AspATc. A fraction containing compounds of less than MW 1,000 was obtained by filtering the cytosolic fraction through a YM 2 membrane. This YM 2 filtrate decreased the activity of the purified enzyme; however, the enzymic activity was protected partially by the addition of 2-oxoglutarate or pyridoxal phosphate (PLP). The YM 2 filtrate also decreased the isoelectric points (pIs) of the purified enzyme. Influences of glucose and fructose on AspATc were examined, and fructose was found to decrease the enzymic activity and the pIs. Fructose was more effective on apoenzyme than holoenzyme, suggesting that fructose may bind to the Lys258 residue of AspATc which is the binding site of PLP. The effects of various amino acids including substrates on the enzymic activity were also examined. Some amino acids were found to decrease the enzymic activity to various extents, though the pIs were unaltered. These results suggest that under physiological conditions, AspATc activity is modified by various low molecular substances in various ways.

Amino Acids↗
PubMed1993

[Primary non-Hodgkin lymphoma of the prostate: a case report].

A 24-year-old man presented with gross hematuria and pain on micturition. Cystoscopically the prostatic urethra appeared to be pale, edematous and partly elevated mucosa, from which multiple biopsy specimens were taken by TUR-P. A pathological diagnosis of malignant lymphoma (diffuse and large-cell type, according to the LSG classification: B-cell origin according to immunohistochemistry) was established. The results of the physical examination and imaging studies were compatible with the diagnosis of primary lymphoma of the prostate. The patient underwent a combination chemotherapy consisting of vincristine, cyclophosphamide, adriamycin and prednisolone. After completion of 6 courses of chemotherapy over 7 months, another TUR biopsy of the prostate confirmed complete remission. Now, 1 year after completion of chemotherapy, he remains free of the disease. To our knowledge, this is the 21st clinical case of lymphoma of the prostate ever reported in the Japanese literature.

Adult↗
PubMed1993

[Expression of fibronectin receptor and vitronectin receptor in diseased human kidneys].

Expression of fibronectin and vitronectin receptors was studied in normal human kidney tissues and renal tissue biopsies from patients with several types of glomerulonephritis. Immunofluorescent staining of the normal kidneys showed that fibronectin receptor was present along the glomerular capillary walls, and that vitronectin receptor was present in the vessel walls, but was almost absent from the glomerulus. In kidney tissues biopsied from patients with various renal diseases, expression of fibronectin and vitronectin receptors was correlated with increase in the mesangial expansion. Expression of these receptors was decreased in the sclerosed area and hyalinized glomeruli compared with normal tissues. Fibronectin and vitronectin receptors were occasionally colocalized in the glomeruli with fibronectin and vitronectin, respectively. In situ hybridization showed that fibronectin receptor mRNA and vitronectin receptor mRNA were expressed in the diseased glomeruli. These findings indicate that expression of fibronectin and vitronectin receptors was altered in human glomerulonephritis, and that integrin expression may be important in cell-matrix interaction in the diseased glomeruli.

Glomerulonephritis↗
PubMed1993

Phosphorylation of Src mutants at Tyr 527 in fibroblasts does not correlate with in vitro phosphorylation by CSK.

In normal fibroblasts, the product of the cellular src gene, p60c-src or Src, is repressed by phosphorylation at its C-terminal tyrosine residue, Tyr 527. Mutations in Src that prevent phosphorylation cause enzymatic activation and malignant transformation. The tyrosine kinases that phosphorylate Src at Tyr 527 in vivo have not been identified, but a tyrosine kinase known as CSK is an excellent candidate. CSK has the unusual ability to phosphorylate Src in vitro only at Tyr 527. To examine whether CSK has the appropriate sequence specificy to explain the phosphorylation of Src at Tyr 527 in fibroblasts, we have made use of a set of C-terminal substitution mutants of Src. These mutants were previously characterized for their levels of Tyr 527 phosphorylation when expressed in Rat2 fibroblasts. The ability of CSK to phosphorylate selected mutants has now been tested, using both in vitro phosphorylation assays and co-expression of CSK with the Src mutants in a heterologous organism, Saccharomyces cerevisiae. We also tested whether the mutant Src molecules could autophosphorylate at Try 527, by examining the phosphorylation state of catalytically active forms expressed in the absence of CSK in yeast cells. The results show that CSK has strict sequence specificity for the normal Src sequence, although it can also phosphorylate the Lck sequence. The other mutant Src molecules tested were not phophorylated by CSK, even though some of these mutants are highly phosphorylated at Tyr 527 in Rat 2 cells. All the mutants that are phosphorylated at Tyr 527 in Rat2 cells are also able to autophosphorylate at Tyr 527. The results suggest that CSK, autophosphorylation, and phosphorylation by kinases other than CSK, may all contribution to repressing Src catalytic activity in fibroblasts.

Amino Acid Sequence↗
PubMed1993

[Two case reports of refractory heart failure treated by continuous ambulatory peritoneal dialysis].

In this report, we present 2 cases of severe congestive heart failure and mild renal insufficiency in patients who underwent continuous ambulatory peritoneal dialysis (CAPD) after stabilization using the extracorporeal ultrafiltration method (ECUM). Long-term good control of congestive heart failure was achieved following the institution of CAPD. Case 1, a 58-year-old woman with rheumatic arthritis and diabetes mellitus had anteroseptal myocardial infarction at the age of 52. And case 2, a 68-year-old man, who underwent coronary artery bypass surgery at the age of 66 and had extensive anterior infarction after the operation. They were admitted to the hospital with dyspnea due to congestive heart failure. In both cases, systolic cardiac function was severely impaired and mild renal insufficiency was present at the time of hospitalization. After admission, symptomatic relief was not obtained by conventional therapies and symptoms of congestive heart failure worsened until the patients suffered from severe respiratory distress even at rest. ECUM was then instituted to remove excess fluid and clinical improvement was achieved. After the initiation of ECUM, responsiveness to diuretics was not restored, and the procedure was necessary every day or every other day for the prevention of symptoms due to fluid overload. About 20 days after the initiation of ECUM, CAPD was begun for the long-term control of congestive heart failure and renal failure, and for the purpose of hospital discharge. Good control of heart failure was achieved after the initiation of CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

[A case of bronchogenic squamous cell carcinoma associated with Swyer-James syndrome].

Swyer-James syndrome is considered to be a relatively uncommon disease entity presenting with unilateral hyperlucent lung due to hypoplasia of a pulmonary artery and bronchiectasis of the affected lung. Association of bronchogenic carcinoma with Swyer-James syndrome has not apparently been reported in any previous literature, except for one Japanese case. In the present paper, we describe a 48-year-old male individual, who developed poorly differentiated squamous cell carcinoma of the right upper lobe bronchus after he had been diagnosed to have Swyer-James syndrome with unilateral hyperradiancy of the left lung. It is suggested that the bronchial epithelium of the unaffected lung in Swyer-James syndrome is likely to be more exposed to extrinsic carcinogens than that of the affected, underventilated lung, hence resulting in a higher risk of developing bronchogenic carcinoma.

Carcinoma, Squamous Cell↗
PubMed1993

Evaluation of various mechanical heart values in the mitral and aortic positions.

To evaluate the function of various types of mechanical heart valves (Björk-Shiley = BS, Medtronic Hall = MH, St. Jude Medical = SJM, Duromedics = DM), hemodynamic studies were performed in 236 patients with valve replacement in addition to the evaluation of the clinical results. In 144 patients with mitral valve replacement including patients with double valve replacement, the degree of the postoperative improvements of clinical symptoms and hemodynamics were similar in patients with BS, DM and MH valves. There was a tendency for the effective orifice area calculated from pressure-half time obtained by continuous-wave Doppler (CWD) echocardiography to be larger in MH or DM valves than in BS valve of the same size on the average. In 115 patients with aortic valve replacement including patients with double valve replacement, there was no significant difference in the degree of postoperative reduction of the left ventricular hypertrophy among the patients with BS, MH and SJM valves. The mean value of the pressure gradient (PG) across the valve at rest obtained by CWD was less than 20 mmHg in each type of valve without significant difference among the valves. PG well correlated with cardiac output (CO) in each type and size of valve, and the rate of increase in PG with the increase in CO was smaller in the larger-sized valve of the same type and also smaller in MH valve than in BS valve of the same size. The frequency of valve-related complications was extremely low in each type of valve except for a higher incidence of occult hemolysis in SJM and DM valves. Overall, there were no significant differences in the clinical results among the patients with valvular prostheses examined. However, MH valve had advantages in hemodynamics and a lower incidence of hemolysis.

Adolescent↗