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Biomedical subjects

K Sudo

Publications and source records attributed to K Sudo.

At least 199 records · Page 11Linked to original sources

Endocrinological studies on TAP-144-SR, a sustained-release formulation of a potent GnRH agonist (D-Leu6-[des-Gly10-NH2]-GnRH ethylamide), in male rats.

The paradoxical effects of TAP-144-SR, a biodegradable sustained-release formulation of a potent GnRH agonist (TAP-144, leuprolide acetate) were evaluated in male rats by comparing its potency with that of TAP-144 solution. A single sc injection of TAP-144-SR (equivalent to 0.1 mg/kg/day as TAP-144), prepared by encapsulating the agonist in microcapsules of copoly (DL-lactic/glycolic acid), suppressed serum levels of androgens, and the levels remained suppressed for 4 weeks. The potency of the paradoxical effects of TAP-144-SR was evaluated 4 weeks after treatment by comparing it with that of TAP-144 solution administered daily for 4 weeks. Both daily injections of TAP-144 solution and a single injection of TAP-144-SR (equivalent to 0.02, 0.2 or 2 mg/kg/day as TAP-144) decreased the weight of the testes, prostates and seminal vesicles in a dose-dependent manner in a 4-week assay in male rats. TAP-144-SR was more effective than TAP-144 solution in reducing these organ weights. Serum and pituitary concentrations of LH and FSH and serum testosterone levels were also lower in TAP-144-SR-treated than in TAP-144 solution-treated rats. These results indicate that the paradoxical effects were more extensive upon TAP-144-SR treatment, suggesting that maintaining constant serum TAP-144 levels results in more extensive desensitization of the pituitary and testes. These results also suggest advantages of TAP-144-SR over TAP-144 solution in both efficacy and convenience as an anti-prostatic tumor agent.

Androgens↗

Histological studies on the therapeutic effect of sustained-release microspheres of a potent LHRH agonist (leuprorelin acetate) in an experimental endometriosis model in rats.

The therapeutic effect of sustained-release microspheres of a potent LHRH agonist (leuprorelin acetate) on experimental endometriosis in female rats was examined histologically. Endometriosis was produced in rats by autotransplantation of endometrial tissue obtained from the left uterine horn into the renal subcapsular space. In the nontreated rats, the transplants were well established and had formed large cysts containing fluid. The walls of the cysts were composed of epithelium and stroma resembling that of normal endometrium. In the rats which received the microspheres of leuprorelin acetate, growth of the transplant was markedly suppressed as evidenced by the reduced size of the cystic cavity and the flattened and pyknotic epithelium. Also, the uterine and ovarian weight decreased significantly. In the ovariectomized rats, growth of the transplant was also markedly suppressed, and the uterine weight decreased. The present results clearly indicate that a single injection of the sustained-release microspheres of leuprorelin acetate markedly suppresses growth of the transplant and produces uterine and ovarian atrophy in the rats.

Animals↗

Biotransformation of a new pyrrolidinone cognition-enhancing agent: isolation and identification of metabolites in human urine.

1. The metabolites of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide (DMPPA; MH-1), in the urine of human volunteers have been investigated. 2. Ten metabolites together with the unchanged drug (MH-1) were isolated by h.p.l.c. and identified by n.m.r. and mass spectrometry as: three metabolites hydroxylated in the pyrrolidine ring of MH-1 (MH-2, MH-3 and MH-4), three metabolites hydroxylated in the dimethylphenyl ring of MH-1 (MH-6, MH-7 and MH-8), N-[(2,6-dimethylphenylcarbamoyl)methyl]-4-hydroxybutyrylamide++ + (MH-5), N-[(2,6-dimethylphenyl-carbamoyl)methyl]succinamic acid (MH-9), the 3-O-sulphate of MH-6 (MH-10) and the 3-O-sulphate of N-(2,6-dimethyl-3-hydroxyphenyl)-2-(5-hydroxy-2-oxo-1-pyrrolidinyl)aceta mide (MH-11). 3. DMPPA was extensively metabolized. The principal metabolic transformations were hydroxylation of the pyrrolidine ring at the C5 carbon followed by oxidative C-N cleavage, and hydroxylation of the phenyl ring followed by sulphate conjugation.

Biotransformation↗

Increase in lens gangliosides due to aging and cataract progression in human senile cataract.

Gangliosides were isolated from human senile cataractous lenses by solvent extraction, DEAE-Sephadex column chromatography, and thin-layer chromatography. The content and composition of gangliosides were examined in individual lens tissues. Three predominant gangliosides, GM3, GM1, and GD1a, were tentatively identified in comparison with authentic brain gangliosides, and several unidentified gangliosides were also recognized. The increase in ganglioside content per mg of protein content in cataractous lenses was found to be influenced by two physiologic parameters: aging and cataract progression. The mature cataractous lenses showed a higher ganglioside level on a protein basis than the immature lenses compared with the same age group. On the basis of statistical analysis, an age-dependent increase in ganglioside concentration was recognized in both mature and immature lens groups. The relative increase in slow-moving polysialogangliosides on thin-layer chromatography seemed to be caused by the maturation of cataract. The sugar composition of one of the polysialogangliosides was found to be glucose, galactose, and sialic acid in the molar ratio of 2:1:4; this suggests the presence of a unique ganglioside species in human cataractous lens.

Adult↗

[Clinical and neuroradiological features of syringomyelia associated with Chiari malformation].

The clinical presentation and radiological features were analyzed in 30 cases of syringomyelia associated with Chiari malformation. None of the patients had spinal dysraphism. The age on admission ranged from 6 to 59 years with a mean of 27 years. Syringomyelia was diagnosed by CT myelography and or MRI from 1982 to 1988. The initial symptoms were skeletal abnormality (43%) such as scoliosis (12 cases) or pes cavus (one case), unilateral pain or numbness (40%) and unilateral motor weakness (17%). Frequently seen signs on admission were sensory deficit (100%), scoliosis (57%), muscle weakness (57%), muscle atrophy (37%) and lower cranial nerve palsy (40%). The neurological findings were asymmetrical in all patients. The characteristic neurological findings in the cases presenting under 20 years of age were unilateral sensory and motor deficits (61%) with decreased or absent deep tendon reflex on the same side. The localization of the syrinx in axial section varied according to the level even in the same case. In 15 cases with unilateral sensory disturbance or unilateral sensory and motor deficit, the syrinx was located in the region corresponding to the posterolateral portion on the same side as that of sensory disturbance in the cervical or thoracic level. On the other hand, in 15 cases with bilateral sensory and motor deficit, the syrinx was located in the central portion and extended into the posterolateral portion of the more affected side.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[A case of double bronchogenic cysts in the mediastinum].

A 42-year-old house wife had suffered from abnormal mass lesion in the right pulmonary hilum on her chest X-ray film. MRI showed another mediastinal mass between IVC and descending aorta with high T1 and T2 intensity. Thoracic CT done before MRI missed the latter lesion because only upper mediastinal scanning had been performed. At operation subcarinal and right paraesophageal cysts were successfully removed. Histological examination of the subcarinal cyst showed ciliated pseudostratified columnar epithelium lining, and its thin wall consisted of partly smooth muscle bundle, lymph node, calcification, inflammatory cell infiltration and hemorrhage. The paraesophageal cyst lined by a ciliated pseudostratified columnar epithelium, and the wall consisted of mostly fibrous connective tissue with partly smooth muscle bundle. Although the both cysts were diagnosed as bronchogenic origin, definitive bronchial glands and cartilage could not be recognized. The postoperative course was uneventful. This is the first case report of mediastinal double bronchogenic cysts appeared in the Japanese literature.

Bronchogenic Cyst↗

Adenocarcinoma and carcinoid developing spontaneously in the stomach of mutant strains of Mastomys natalensis.

Neoplastic and nonneoplastic lesions developing spontaneously in antral and fundic mucosae of stomachs of mutant chamois-coloured Z (130 animals) and Y (67 animals) strains of Mastomys aged 18 to 24 months were examined histologically and histochemically. The Z strain developed both antral lesions (hyperplasia 29.2%; dysplasia 23.8%; adenocarcinoma 17.7%) and fundic carcinoid(s) (72.3%). The antral lesions were limited to the lesser curvature near the pyloric ring. Macroscopically, adenocarcinomas resembled human gastric carcinomas of either Borrmann's type I or II. Histochemically, adenocarcinoma cells were characterised by marked reduction of total mucins produced and predominance of mucins with both periodic acid-Schiff and Alcian blue reactivities (neutral and sialated class II mucins). An infiltrating adenocarcinoma was successfully transplanted into nude mice, reaching the 7th generation of transplantations over 4 years, and retained histological features of the primary tumour. The ultrastructural appearance of growing transplanted tumours supported the reduced production of mucins by adenocarcinoma cells with scarcity of mucin granules and intracellular cysts. However, the Y strain never developed antral lesions like the wild strain, developing fundic carcinoid(s) only. Microscopically, these carcinoids contained argyrophilic nonargentaffin granules, and biochemically produced histamine consistently but no 5-hydroxytryptamine (5-HT, serotonin) like those of the wild strain. Since we found unexpectedly that a line of F2 but not F1 hybrids between wild and Z strains developed the same antral lesions as Z strain, a preliminary experiment was performed to confirm the development of antral lesions in F2 hybrids newly produced by brother-sister mating. Among 41 surviving F2 offspring, 4 (9.8%) developed hyperplasia, 2 (4.9%) dysplasia and none adenocarcinoma. The numbers (6) of animals observed with these lesions approximated to their expected numbers (7.3).

Adenocarcinoma↗

Histologic localization of terminal complement complexes in renal diseases. An immunohistochemical study.

Histologic localizations of terminal complement complexes (TCCs) were examined and compared with clinical findings in 154 patients with various renal diseases. Immunohistochemical demonstration of TCCs was carried out on ethanol-fixed paraffin-embedded renal biopsy specimens by indirect immunoperoxidase technique. In glomerular diseases that are thought to be immune-complex glomerulonephritis (IC-GN), such as IgA-nephropathy, membranous nephropathy, and systemic lupus erythematosus (SLE), TCCs were demonstrated in a pattern similar to that of immunoglobulins and C3, indicating that TCCs were induced by immune complexes. The intensity of TCC deposition was correlated with the morphologic destruction of glomeruli or serum creatinine levels in IgA-nephropathy, with urine protein in membranous nephropathy, and with serum C4 in SLE. TCC deposits without IC were also observed in tissue damages without disease specificity such as glomerular or vascular sclerosis and tubulointerstitial lesions. These findings suggested the existence of various roles of TCCs in renal injury, according to IC-mediated or non-IC-mediated mechanism acting in individual diseases.

Antibody Specificity↗

Calcium chloride inhibits stimulation of replicative DNA synthesis by sodium chloride in the pyloric mucosa of rat stomach.

Calcium chloride (CaCl2) inhibits stimulation of replicative DNA synthesis (RDS) induced in the pyloric mucosa of male Fischer 344 rats by sodium chloride (NaCl), which is a tumor promoter in the glandular stomach. Administration of 1 ml of 3.3 M NaCl by gastric intubation induced a maximal 15-fold increase in RDS in the pyloric mucosa by 17 h; this had returned to the control level by 48 h. Administration of 1 ml of 20-400 mM CaCl2 1 h before administration of NaCl resulted in a 60-100% inhibition of the increase in RDS within 4-48 h; the inhibition was dose-dependent. The 400 mM level of CaCl2 also decreased the histological damage to surface epithelial cells induced by NaCl. These results suggest that calcium ion acts as an anti-tumor promoter in stomach carcinogenesis.

Animals↗

Calcium metabolism, serum thyroid-stimulating hormone, prolactin, and growth hormone in spontaneously hypercholesterolemic rats.

We have shown previously that spontaneously hypercholesterolemic (SHC) rats exhibit abnormal bone metabolism with advanced bone resorption, which develops with age. In this study, we measured serum levels of growth hormone, thyroid-stimulating hormone, and prolactin in addition to several parameters of calcium metabolism and renal function in young (6-week) and old (24-week) SHC rats and compared these with age-matched Sprague-Dawley rats. In young SHC rats, urinary excretion of hydroxyproline and serum levels of calcium were significantly elevated and excretion of protein into urine and urea nitrogen in the serum were normal, suggesting that calcium metabolism was abnormal without kidney dysfunction at this age. Serum growth hormone and thyroid-stimulating hormone levels were markedly higher (20- to 30-fold and 4- to 5-fold, respectively) in young and old SHC rats, whereas serum prolactin levels were similar. A high level of serum thyroid-stimulating hormone was associated with elevated levels of thyroxine and triiodothyronine in young SHC rats, but not old ones. These results demonstrate that the rat exhibits abnormalities in endocrine function as well as calcium metabolism preceding the occurrence of renal dysfunction.

Animals↗

[Combination effect of UFT and gamma-irradiation against nude mice transplanted KB cells].

Combination effect of UFT and gamma-irradiation was examined using KB cell transplanted in nude mice. KB cell line is known as derived from human malignant tumor of the mouth floor. Although treatment with UFT or with gamma irradiation did not suppress the tumor growth, combination of these two treatments caused a marked suppression. Especially, when UFT was administered to the mice successively from the time of transplantation and the irradiation was applied after tumor growth, both suppression of the tumor growth and necrosis of the tumor tissue were observed.

Animals↗

[A family of pseudocholinesterase deficiency (silent type II)].

We report here a case of pseudocholinesterase (E.C. 3.1.1.8) deficiency, silent type II. The proband was a 29-year-old healthy man. His parents were cousins. A family study revealed that 9 out of 17 members of family investigated (paternal side 6, maternal side 3) concentrations. Serum cholinesterase activity were correlated well with serum albumin concentrations in both healthy people and patients with chronic liver diseases. The ratio of cholinesterase activity to albumin concentrations in serum was found more useful to detect heterozygous pseudocholinesterase deficiency than the serum cholinesterase activity alone. Both the dibucaine number and the fluoride number were within normal range in all family who showed low cholinesterase activity in serum. The amount of immunoreactive substance in serum against anticholinesterase antibody was normal in the proband as well as his family, while it was about twice of the value expected from their activity in those who had low ratio of serum cholinesterase activity to albumin concentrations. These results altogether suggested that the proband was a case of homozygous pseudocholinesterase deficiency, silent type II.

Adult↗

[A successful surgical treatment of acute dissecting aneurysm of the ascending aorta: repair of the proximal intimal tear necessitating bypass for the right coronary artery].

This is a case report of the successful surgical treatment of acute dissecting aneurysm of the ascending aorta. The patient was a 65-year-old female, who admitted to the hospital 3 hours after the onset of severe back pain. Enhanced CT of the chest and abdomen revealed acute dissection of the ascending aorta from its origin to the bilateral common iliac arteries. Thirteen hours initiation of the symptoms, operation was carried out using pump-oxygenator with hypothermia. Transverse incision of the ascending aorta revealed acute dissection in anterior aspect extending to two third of the circumference. The proximal small intimal tear was found 3 mm apart from the right coronary artery ostium. Upon closure of the tear resulting in obliteration of the right coronary artery, it required bypass procedure between the right coronary artery and the innominate artery using the saphenous vein graft. The aortic incision was directly closed using Dacron felt bolsters. Postoperative studies revealed disappearance of the proximal aortic dissection, patency of the bypass graft and existence of distal aortic dissection. Patient is in active life 6 months after operation.

Acute Disease↗

[Emergency aortic valve replacement in active infective endocarditis in a chronically hemodialyzed patient].

A 36-year-old housewife, who had been treated with hemodialysis for 15 years is reported. She had suffered from active infective endocarditis of the aortic valve caused by blood access infection for several weeks. She rapidly fell into severe cardiac failure. Five days after the onset of the cardiac failure she was transferred to our hospital. The aortic valve was replaced using #21 Björk-Shiley aortic valve prosthesis shortly after the arrival to the hospital. Postoperatively she was treated with vigorous antibiotics and was anticoagulated. Seven months after the surgery, patient is back to an active life with hemodialysis 3 times a week.

Adult↗

[Successful surgical treatment of infective endocarditis complicated with DIC and intracerebral hemorrhage].

This is a case report of a 61-year-old man, suffering from infective endocarditis of mitral valve in association with DIC and intracerebral hemorrhage. He was treated symptomatically and conservatively for 80 days after the onset of the DIC. His multiple cerebral hematomas gradually disappeared 2 months after conservative management. Then the diseased mitral valve was replaced with a Duromedics valve. He is doing well at present. In a review of the literature it appears that there is some room for surgical intervention in endocarditis despite the complication of coagulopathy. We feel that one of the most serious complications of infective endocarditis is DIC. Operative management of endocarditis with this complication is recommended to be followed by medical management.

Cerebral Hemorrhage↗