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Biomedical subjects

K Sudo

Publications and source records attributed to K Sudo.

At least 181 records · Page 10Linked to original sources
PubMed1991

Effects of TAP-144-SR, a sustained-release formulation of a potent GnRH agonist, on experimental endometriosis in the rat.

A new, simple experimental endometriosis model was established by auto-transplanting endometrial tissue fragments beneath kidney capsules in female rats. The transplanted endometrial tissue grew well, forming a fluid-filled cyst, which reached maximal size 2 to 3 weeks after transplantation. The growth and maintenance of the transplants was dependent on the ovary: ovariectomy induced regression of well grown transplants. The therapeutic effects of TAP-144-SR (biodegradable microcapsules of copoly (DL-lactic/glycolic acid) copolymer containing a potent GnRH agonist, TAP-144 (D-Leu6-[des-Gly10-NH2]-GnRH ethylamide, leuprolide acetate) were studied with this rat endometriosis model. A single sc injection of TAP-144-SR (corresponding to 1, 10 or 100 micrograms/kg/day of TAP-144), suppressed the growth of the transplanted endometrial tissues and uterine weight in a dose-dependent manner. At 100 micrograms/kg/day, the suppressive effect was more marked in rats given TAP-144-SR than in those given TAP-144 solution. The extent of suppression was comparable to that caused by ovariectomy. Serum and pituitary concentrations of LH and FSH were also reduced more markedly by the administration of TAP-144-SR than by TAP-144 solution. From these results, the present endometriosis model was found to be useful for the evaluation of compounds with potential therapeutic activity. The sustained-release formulation of TAP-144 seems to be beneficial over its solution in terms of both convenience and efficiency for therapy of patients with endometriosis.

Animals↗
PubMed1991

TAN-931, a novel nonsteroidal aromatase inhibitor produced by Penicillium funiculosum No. 8974. I. Taxonomy, fermentation, isolation,characterization and biological activities.

A novel nonsteroidal aromatase inhibitor, TAN-931, was isolated from the culture filtrate of a soil isolate fungus, No. 8974. The strain was identified as Penicillium funiculosum No. 8974. TAN-931 inhibited human placental and rat ovarian aromatase activity, and the IC50 value was 17.2 and 162 microM, respectively. The inhibition of human placental aromatase was uncompetitive with respect to androstenedione conversion with a Ki value of 40 microM. When TAN-931 was subcutaneously administered at doses of 25, 50 and 100 mg/kg (once/day, x4) to 20-day-old female Sprague-Dawley rats treated with gonadotropin, the plasma estradiol-17 beta level and the weight of ovaries and uterus were markedly reduced in a dose-dependent manner. The in vivo inhibitory activity of TAN-931 was more potent than that of 4-hydroxyandrostenedione. Consecutive administration of TAN-931 (100 mg/kg, sc, twice/day, x 7) to 9-week-old male Sprague-Dawley rats did not induce any adrenal hypertrophy even though administration of aminoglutethimide caused 2-fold enlargement of the adrenal under the same conditions. Specific binding of TAN-931 to the estrogen receptor from a human breast cancer cell line, MCF-7, was not detected.

Adrenal Glands↗
PubMed1991

[A case report of surgical treatment of acute aortic dissection (DeBakey III B) in association with thoracic aortic aneurysm].

This is a case report of 63-year-old man suffering from DeBakey III B acute dissection in association with thoracic aortic aneurysm. He had been following up for hypertension and thoracic aortic aneurysm. He was brought to the hospital by city ambulance complaining of sudden onset of severe back pain. Emergency operation was carried out. It revealed aneurysm of 90 mm in diameter located just distal to the aortic arch and an intimal tear or entry of the dissection located distal to the left subclavian artery. A low porosity Dacron graft was interposed between the distal aortic arch and middle portion of the thoracic descending aorta using inclusion technique. Systemic circulation was bypassing external iliac vein to artery using pump-oxygenator during aortic clamping. His postoperative course was uneventful. In review of the literature, association of the atherosclerotic aneurysm and acute dissection occurred approximately 5% in the cases of aortic dissection with increasing risk of aneurysmal rupture.

Acute Disease↗
PubMed1991

[Myoglobinuria due to enzyme abnormalities in glycolytic pathway--especially lactate dehydrogenase M subunit deficiency].

Glycolysis is an important energy productive system. Enzyme abnormalities the in glycolytic pathway, which cause myoglobinuria, are deficiencies of phosphofructokinase, phosphoglycerate kinase, phosphoglycerate mutase, and lactate dehydrogenase (LDH). Common symptoms of these enzyme abnormalities are muscle cramp, muscle pain, and rhabdomyolysis after strenuous exercise. Acute renal failure owing to myoglobinuria is the most noteworthy symptom. In daily life, symptoms are rarely observed and prognosis is usually good. Correct and fast diagnosis of such latent symptomatic disorders is important to prevent a turn for the worse of these symptoms. LDH M subunit deficiency was first discovered by urinary discoloration and a discrepancy of laboratory data. Since then, only four cases have been reported in the Japanese population. The response to ischemic forearm work is characteristic (an increase of venous lactate concentration after ischemic work is not observed and a marked increase of venous pyruvate is found). The increase of pyruvate concentration is specific in LDH-M subunit deficiency, and is not observed in other abnormalities of the glycolytic pathway. Glycolysis was markedly retarded in the patient's muscle in the glyceraldehyde 3-phosphate dehydrogenase (GA3PD) step, possibly due to the impaired reoxidation of NADH produced by GA3PD activity. Then, the excess NADH is reoxidized by alpha-glycerophosphate dehydrogenase and triose phosphates are drained to alpha-glycerophosphate and glycerol. Therefore ATP production is significantly impaired and muscle tissue is damaged. A genetical study revealed a deletion of 20 base-pairs in exon 6 in LDH-M subunit deficiency. This mutation results in a frame-shift translation and premature termination.

Adolescent↗
PubMed1991

[Surgical repair of postinfarction cardiac rupture in three cases].

Operative managements and results of postinfarction left ventricular (LV) rupture in 2 patients and right atrial (RA) rupture in one patient are reviewed. Two patients showed both subacute onset of LV rupture in association with cardiac tamponade. The site of infarction was inferior wall in one and anterior wall in the other. Both patients underwent infarctectomy with closure of the defect using a Dacron felt patch. Endocardial site of the Dacron patches were covered with own pericardium to avoid bleeding from the patch and postoperative complication of endocardial clot formation. The case with extended inferior wall infarction was succumbed to cardiac failure and acute renal failure at the twelfth postoperative day. The other case was uneventful postoperatively and shows excellent long-term result. Left ventriculography and coronary angiographic studies were carried out 3 months after the surgery. It demonstrated 43% of LVEF. Multiple stenotic lesions were also noted in left coronary artery. The third patient was rupture of the RA in association with cardiac tamponade. Direct suture closure of the rupture was carried out under extracorporeal circulatory support. Patient tolerated the procedure well. Postoperatively, he suffered from exacerbation of renal insufficiency necessitating hemodialysis for a month. He discharged from hospital and now in the good condition. Postoperative RI study and coronary angiography demonstrated no compatible finding of right atrial infarction. However, pathological specimen revealed definite diagnosis of the infarction at the RA appendage.

Aged↗
PubMed1991

[A case report of emergency surgical repair of traumatic transection of thoracic descending aorta].

The injury to the thoracic aorta caused by blunt chest trauma is often fatal. This case is 22-year-old male suffering from transection of the thoracic descending aorta caused by traffic accident. He was transported to our emergency room by an ambulance 15 minutes after the accident. Hundred fifty minutes after arrival to the hospital, we were rush to bring him to the operation theater suspecting serious injury of the thoracic organs in association with left hemothorax. The left standard thoracotomy disclosed the injury of the thoracic descending aorta. Simple cross clamp was applied to the thoracic descending aorta distal to the left subclavian artery for 20 minutes. Completely transected aorta was reapproximated using monofilament 3-0 polypropylene sutures with running manner. He tolerated the procedure well without any complication. His postoperative course was uneventful. He was followed up at the orthopedic department for associated hip fracture thereafter.

Accidents, Traffic↗
PubMed1991

[Supravalvular aortic stenosis syndrome with advanced mitral regurgitation requiring extended aortoplasty and mitral valve replacement: a case report].

This is a case report of a 28-year-old male, suffering from supravalvular aortic stenosis (systolic pressure gradient 60 mmHg) and severe mitral regurgitation associated with elfin face and mental retardation. Severely prolapsed mitral valve with elongated chordae tendineae was replaced with Björk-Shiley mitral valve prosthesis. Simultaneously, extended aortoplasty was carried out using Doty's method. His postoperative course was uneventful. Catheterization study, carried on one month after surgery, revealed complete disappearance of supravalvular aortic stenosis and mitral regurgitation. In review of the literature, as far as we know, report of successful combined correction for supravalvular aortic stenosis and mitral regurgitation is extremely rare.

Adult↗
PubMed1990

Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth.

Neovascularization is critical for the growth of tumours and is a dominant feature in a variety of angiogenic diseases such as diabetic retinopathy, haemangiomas, arthritis and psoriasis. Recognition of the potential therapeutic benefit of controlling unabated capillary growth has led to a search for safe and effective angiogenesis inhibitors. We report here the synthesis of a family of novel inhibitors that are analogues of fumagillin, a naturally secreted antibiotic of Aspergillus fumigatus fresenius. We first isolated this fungus from a contaminated culture of capillary endothelial cells. Purified fumagillin inhibited endothelial cell proliferation in vitro and tumour-induced angiogenesis in vivo; it also inhibited tumour growth in mice, but prolonged administration was limited because it caused severe weight loss. Synthesis of fumagillin analogues yielded potent angiogenesis inhibitors ('angioinhibins') which suppress the growth of a wide variety of tumours with relatively few side-effects.

Animals↗
PubMed1990

Cloned origin of DNA replication in c-myc gene can function and be transmitted in transgenic mice in an episomal state.

The c-myc protein has recently been shown to interact with a region possessing putative origin of DNA replication and enhancer activities located 2 kb upstream of the c-myc gene itself. Transgenic mice were obtained by injecting constructs containing this region, termed pmyc(H-P), into fertilized mouse eggs. The transgenic elements were capable of efficient replication in all mouse tissues examined and were maintained in an episomal state even in highly differentiated cells. Moreover, pmyc(H-P) was transmittable to the progeny throughout several generations, which suggests that the fragment derived from the region upstream of the c-myc gene possesses sequences necessary for partition, stability and DNA replication of the plasmid in the cells. In addition, we have shown that the plasmid might be captured only by eggs, not by sperm.

Animals↗
PubMed1990

Human lactate dehydrogenase-B processed pseudogene: nucleotide sequence analysis and assignment to the X-chromosome.

Two human genomic clones containing the lactate dehydrogenase-B processed pseudogene were isolated from two patients deficient in lactate dehydrogenase-B isozyme. The sequences of 3,287 nucleotides, including the pseudogenes and its flanking regions, from both clones were found to be identical except for three differences in the pseudogenes. The sequences of 1,286 nucleotides from these two pseudogenes exhibited 93% homology with the cDNA sequence of the lactate dehydrogenase-B functional gene, and the pseudogene contained 75/76 base substitutions, 11/12 single-base deletions, and 5 single-base insertions. This pseudogene was mapped to the x-chromosome by dot-blot analysis using a probe for the pseudogene or its 5' flanking sequence.

Base Sequence↗
PubMed1990

Isolation of fatty acid amide as an angiogenic principle from bovine mesentery.

Erucamide (13-docosenamide) was found to be the major bovine mesentery angiogenic lipid as assessed by chorioallantoic membrane (CAM) assay. Two micrograms of this lipid caused angiogenesis in the assay. Angiogenic activity of this naturally occurring lipid was also found by rat corneal micropocket and mouse dorsal air-sac assays. Specificity of the chemical structure which elicited activity was low, however. The mechanism of angiogenic activity is unknown and this lipid does not promote proliferation of endothelial cells or induce inflammatory effects.

Angiogenesis Inducing Agents↗
PubMed1990

A missense mutation found in human lactate dehydrogenase-B (H) variant gene.

A human lactate dehydrogenase-B mutant gene was isolated from a genomic DNA library constructed from a patient with unstable LDH-B (heart) subunit. The nucleotide sequences of seven protein-coding exons were determined and a single nucleotide substitution of G by A at Arg codon CGC in exon 4 was found. This mutation results in an amino-acid replacement of a conserved arginine by histidine at the residue "173," which is involved in an anion-binding site at the P-axis of LDH subunits.

Adult↗
PubMed1990

Molecular characterization of genetic mutation in human lactate dehydrogenase-A (M) deficiency.

Human lactate dehydrogenase-A mutant gene was isolated from the genomic DNA library of a patient deficient in LDH-A (Muscle) subunit. The nucleotide sequences of seven protein-coding exons were determined and a deletion of 20 base-pairs in exon 6 was found. This mutation results in a frame-shift translation and premature termination. The predicted incomplete LDH-A (M) subunit containing only 259 instead of 331 amino acids appears to be degraded rapidly, since no protein was detected immunologically (Maekawa et al., Am J Hum Genet 39:232-238, 1986). In addition, three synonymous (silent) substitutions, A to C, T to C, and G to A, were observed at codons 115, 160 and 172, respectively, in this LDH-A mutant gene.

Amino Acid Sequence↗
PubMed1990

Quantitation of C4 nephritic factor by an enzyme-linked immunosorbent assay.

We have developed an enzyme-linked immunosorbent assay (ELISA) for the quantitation of C4 nephritic factor (C4NeF). Incubation of the C4NeF-positive serum from patient M.I. with normal human serum (NHS) in the presence of human aggregated IgG (AHG) resulted in the formation of stable C4-C2 complex. No complex was formed in EDTA or under the condition free of AHG. The reaction mixture was filtered through an ACA 22 column, from which the C4-C2 complex was eluted at the first protein peak. When IgG purified from M.I. serum was incubated with NHS and AHG, C4-C2 complex also increased in proportion to dose of the purified M.I. IgG. These results show that C4NeF in M.I. serum stabilizes C4b2a convertase of the classical complement pathway, and is quantified by the ELISA. C4NeF activity was measured, using the ELISA method, in patients with various glomerular diseases, and found elevated in three of 24 patients with membranoproliferative glomerulonephritis (MPGN) type I and slightly but distinctly positive in seven of 24. No C4NeF was detected in two C3 nephritic factor-positive patients with MPGN type II and six with active systemic lupus erythematosus. The new method was more simple and quantitative than C4b2a stabilization assay for C4NeF.

Animals↗
PubMed1990

Effects of danazol, gonadotropin-releasing hormone agonist, and a combination of danazol and gonadotropin-releasing hormone agonist on experimental endometriosis.

Effects of danazol, gonadotropin-releasing hormone agonist (leuprolide), and danazol-leuprolide combination on experimental endometriosis were evaluated in female rats. A complete resorption of the fluid and a marked decrease in the volume of endometrium autotransplanted under the renal capsule were found after castration (1.4 +/- 0.1 mm3 in castrated, n = 14, vs 26.7 +/- 5.6 mm3 in intact control, n = 16). Histologic examination indicated atrophy and regression of the endometrial explant. These atrophic changes of endometrial explant were also induced by danazol, leuprolide, and the combination treatment. However, the volume of explants after combination therapy with danazol and leuprolide (1.8 +/- 1.0 mm3, n = 17) was significantly less than that after therapy with danazol (11.6 +/- 2.8 mm3, n = 20) or leuprolide alone (5.9 +/- 1.4 mm3, n = 24). The combination therapy (16/17) was also shown to be superior to danazol (9/20) or leuprolide alone (14/24) to induce the regression of fluid in experimental endometriosis. As expected, administration of leuprolide decreased the serum estradiol level, but use of danazol did not. These findings suggest that a combination therapy of danazol and gonadotropin-releasing hormone agonist, which show different modes of action, may be a potential modality in treatment of patients with advanced endometriosis.

Analysis of Variance↗
PubMed1990

Age-dependent changes in monkey lenticular gangliosides.

The content, composition, and distribution of gangliosides were examined in the lenses of normal rhesus monkeys aged 6-16 years. Gangliosides were isolated by organic solvent extraction. DEAE-Sephadex ion-exchange column chromatography, and thin-layer chromatography (TLC). Ganglioside contents determined by the thiobarbituric acid method increased in the lens with aging. TLC analysis of gangliosides showed a much more complex pattern with aging, and the predominant gangliosides were tentatively identified as GM3, GM1, and GD1a. Individual lenticular gangliosides were identified by TLC-immunostaining procedures using anti-GM1 and anti-asialoGM1 antisera.

Aging↗
PubMed1990

Identification and mapping of mba regions of the Salmonella choleraesuis virulence plasmid pKDSC50 responsible for mouse bacteremia.

A restriction cleavage map was constructed for pKDSC50, the 50 kb virulence plasmid of Salmonella choleraesuis. Using Tn1 transposon-insertion mutagenesis, we obtained 19 mutant strains of S. choleraesuis with a diminished ability to cause bacteremia in the mouse. pKDSC50::Tn1 DNA of the mutant strains was extracted and introduced into a pKDSC50-cured S. choleraesuis strain. Nine of the 19 transformants showed the diminished ability to cause mouse bacteremia. Tn1-insertion of the nine mutant strains was clustered within a 6.2 kb segment of pKDSC50, demonstrating that this region was necessary for conferring ability to cause mouse bacteremia (Mba) on the host organism. Two regions, mba-1 and mba-2, were identified within the 6.2 kb fragment. In E. coli minicells, the cloned fragments containing the mba region expressed at least three proteins with apparent molecular weights of 29,000, 32,000 and 32,000.

Animals↗