Biomedical subjects

M Koga

Publications and source records attributed to M Koga.

At least 19 recordsLinked to original sources

PubMed1992

(+-)-carbocyclic 5'-nor-2'-deoxyguanosine and related purine derivatives: synthesis and antiviral properties.

Beginning with 3-cyclopenten-1-ylamine hydrochloride, the 5'-nor derivatives of carbocyclic 2'-deoxyguanosine (2), 2'-deoxyadenosine (3), and 2,6-diaminopurine 2'-deoxyribofuranoside (4) have been prepared. These compounds were evaluated for antiviral potential versus herpes simplex virus, varicella-zoster virus, cytomegalovirus, vaccinia virus, vesicular stomatitis virus, and human immunodeficiency virus and found to lack activity. Also, compounds 2-4 were virtually nontoxic toward the host (human diploid fibroblast ESM and HEL) cells. These biological properties may be due to the inability of 2-4 to be phosphorylated to the requisite nucleotide level that is likely to be necessary for biological activity by correlation to carbocyclic 2'-deoxyguanosine (1), which possesses significant antiviral properties as a result of conversion to its 5'-triphosphate derivative.

2-Aminopurine↗

PubMed1992

Identification and quantitative analysis of urinary metabolites of dichloropropanols in rats.

Urinary metabolites of dichloropropanols in rats were analyzed by gas chromatography-mass spectrometry (GC/MS). Solutions of dichloropropanols consisting of 1, 3-dichloro-2-propanol (DC2P) and 2, 3-dichloro-1-propanol (DC1P) were diluted in a saline at the concentration of 100 mg/ml, and 0.1 ml of the solutions were subcutaneously injected into male Wistar rats weighing about 160g. The urine samples were collected over a period of 24 hours after the injections. DC2P and DC1P in the urine were extracted with ethylacetate and analyzed by a GC/MS. The derivatization procedure with 4-bromophenylboric acid after acetonitril extraction was applied for the analyses of diols in the urine. By the GC/MS analysis, 3-chloro-1, 2-propanediol (3CPD), 2-chloro-1, 3-propanediol (2CPD) and 1, 2-propanediol (PPD) were identified as the hydroxylated metabolites of dichlorpropanols. Based on the analytical results, the metabolic pathways of dichlorpropanols forming 3CPD and 2CPD, and then hydroxylating to PPD were elucidated.

Animals↗

PubMed1992

[Fulminant hepatitis after the inhalation of dichloropropanols].

A fatal case of acute fulminant hepatitis following exposure to dichloropropanols is reported. A 59-year-old male worker in a chemical plant developed general malaise, nausea and vomiting several hours after cleaning a tank that had contained dichloropropanols. He had no previous history of hepatic dysfunction. On admission, hepatomegaly was prominent. Because of highly elevated levels of GOT and GPT in the serum, reduced prothrombin time and a lowered consciousness level, a diagnosis of fulminant hepatitis was made. Significant decreases of leukocytes and platelets were also observed. Serum creatinine and BUN were slightly elevated. Although plasma exchanges were conducted on the third and fourth day, the liver functions continued to deteriorate. The patient died on the fifth day. Because dichloropropanols could be detected in the blood specimens obtained at the time of admission, we considered that fulminant hepatitis in this case was attributed to dichloropropanols exposure. To our knowledge, this is the first case of fulminant hepatitis after dichloropropanols-exposure.

Administration, Inhalation↗

PubMed1992

[Toxicity of dichloropropanols--changes in hematological findings and serum chemistry].

We investigated the toxicity of dichloropropanols (DCPs) in hematological findings and serum chemistry. The solutions of two isomers of DCPs, 1,3-dichloro-2-propanol (DC2P) and 2,3-dichloro-1-propanol (DC1P) were dissolved in saline at the concentration of 100 mg/ml, and 0.1 ml of each solution was subcutaneously injected into male Wistar rats weighing about 200 g. At 6 hours after the injections, in the DC2P group, the number of white blood cells and platelets showed a significant decrease. Transaminases, alkaline phosphatase and lactate dehydrogenase were greatly elevated. Blood urea nitrogen and creatinine also showed a significant increase. There were no changes in the measurements in the DC1P group. These results indicate that there is a prominent hepatotoxicity in DC2P, and that there is a considerable difference in the toxicity present in DC2P and DC1P. Furthermore, in the workplace where DCPs, especially DC2P, is used, the monitoring of the working environment and biological monitoring should be mandatory.

Alkaline Phosphatase↗

PubMed1992

Complete correction of the tetralogy of Fallot in adults using separated extracorporeal circulation to block intrathoracic collateral circulation and improve perfusion of the renal vasculature.

During the last 10 years, complete correction of the tetralogy of Fallot (TOF) has been performed on 28 adult patients using the "separated extracorporeal circulation" (separated ECC) technique developed by us. In addition to the usual ascending aortic and dual right arterial cannulations for ECC, the separated ECC also involved femoral arterial cannulation and the insertion of a catheter with two balloons via the other femoral artery. Flow via the ascending aorta and femoral artery were maintained separately during ECC. The urine output during separated ECC was significantly better than that during ordinary ECC (P < 0.01) and the operative field for intracardiac correction was clearer as a result of blocking the collateral circulation. Thus we believe separated ECC to be a superior method for total correction of TOF in adults, which may enhance the operative outcome.

Adult↗

PubMed1992

Active and inactive renin after exercise.

The effects of graded exercise on plasma concentrations of active and inactive renin were studied in seven healthy men. Exercise was performed on a cycle ergometer at four different exercise intensities (corresponding to 30%, 50%, 80% and 87% of VO2max) for 10 min each. Concentrations of active renin and total renin after activation by trypsin were measured by direct immunoradiometric assay. Non-trypsin-activated renin concentration (inactive) was obtained by subtraction. Active renin concentrations at 30%, 50%, 80% and 87% of VO2max were 1.2, 1.9, 3.1 and 4.6 times higher than the control concentration, respectively. Similar increases in plasma renin concentration, determined by conventional enzymatic assay, were observed at every stage. In contrast, changes in inactive renin concentration were not significant at any stage. Significant increases in noradrenaline concentration were found at every exercise stage, but adrenaline, aldosterone and lactate concentrations were significantly elevated only after exercise at 50%, 80% and 87% of VO2max. The similarity between the changes in concentration of active renin and noradrenaline would suggest that sympathetic nerve activity may have been responsible either for the release of active renin or for the conversion of inactive renin to its active form in the kidney.

Adult↗

PubMed1992

Farber bodies found in murine phagocytes after injection of ceramides and related sphingolipids.

Mice were injected subcutaneously with a single dose of sphingolipids. The sphingolipids tested were: ceramide with alpha-hydroxy fatty acids, ceramide with non-hydroxy fatty acids, glucocerebroside, sphingomyelin, and galactocerebroside. Lipids without sphingolipids served as a control. The mice were sacrificed 1, 2, 3, 4, 5 and 7 days after injection. Three mice were used for each experiment. The subcutaneous tissue at the injected area, the liver and the spleen were studied histologically. At 1-3 days after injection, numerous cytoplasmic inclusion bodies were observed in the macrophages and fibroblasts in the subcutaneous tissue, but not in the liver or the spleen. Ultrastructural studies of the inclusion bodies indicated that the sphingolipids taken up by the phagocytes retained their respective original shape during the 1-3 day stage. At days 4 and 5, the number of the inclusion bodies decreased, but they contained Farber bodies, i.e. curvilinear bodies 12 to 25 nm wide and up to 120 nm long. The mice with galactocerebroside were an exception, with parallel leaflets structures, but without the Farber bodies.

Animals↗

PubMed1992

Using microparticle labeling and counting for attomole-level detection in heterogeneous immunoassay.

A new heterogeneous "sandwich" immunoassay utilizing microparticles as labels to realize high sensitivity is described. In this method, antibody fixed on the microparticles reacts with antigen previously trapped on a microplate surface, which makes the antigen molecules visible and countable with an inverted optical microscope. The method is highly sensitive because the reacted single microparticle, therefore single antigen molecule, can be detected. The sensitivity depends both on the reaction efficiency of the immunoreaction and on nonspecific adsorption of the microparticles on the microplate surface. Therefore, the protocol for preparing microparticle having antibody on the surface and a microplate having capture antibody was investigated to realize high sensitivity. Carboxylated microparticles of 0.76 microns in diameter were conjugated with affinity-purified antibody using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. It was determined that 1 g microparticles had 880 micrograms antibody (approximately 1100 antibody molecules per 1 microparticle). The immunoreaction efficiency reached 18% at 1 x 10(-13) mol/liter antigen concentration. The lower detection limit was 3.1 x 10(-14) mol/liter (1.6 amol) using human alpha-fetoprotein as a model antigen.

Adsorption↗

PubMed1992

Comparison of hepatitis C virus markers in patients with NANB hepatitis.

10 different HCV-specific assays and RT-PCR of the 5' untranslated region of HCV RNA were used to analyze sixty-four patients with chronic NANB liver disease. Po, CP-9 and C22 antigens are located in the putative core; C33c in the putative NS3; C100-3 in the putative NS3/4; KCL in the putative NS4/5 and C825 is located in the putative NS5. GOR protein is not part of the HCV genome, but antibodies to it appear to be present in response to a hepatitis C infection. Positive rates were 91% for Po, 89% for CP-9, 94% for C22, 97% for C33c, 88% for C100-3 (Ortho, EIA), 86% for C100-3 (Abbott, EIA), 84% for C100-3 (Ohtsuka, RIA), 88% for KCL, 59% for C825, 58% for GOR, and 83% for RT-PCR. There were 8 cases which were negative by all anti-C100 tests. 7 of these cases were positive by other anti-HCV markers and/or PCR suggesting the need for improved blood screening assays. There is a variation in the relative reactivity for different markers with different samples. Of the tests employed, anti C33c shows the highest positivity rate.

Adult↗

PubMed1992

Effects of retinoic acid on estrogen- and thyroid hormone-induced growth in a newly established rat pituitary tumor cell line.

In order to elucidate the complex mechanism(s) of action of steroid hormones, thyroid hormone and retinoic acid in pituitary mammotrophs, a clonal cell line (G3) was isolated from the rat pituitary tumor MtT/F84. G3 cells were found to secrete prolactin constitutively and to contain receptors for estrogen, glucocorticoid, progesterone and thyroid hormone. Stimulation of G3 cells with thyroid hormone resulted in a modest but significant increase in estrogen and progesterone receptor levels, however, retinoic acid treatment had no effect. Simultaneous addition of thyroid hormone and estrogen showed an additive effect on progesterone receptor levels in G3 cells. Thyroid hormone as well as estrogen enhanced the growth of G3 cells. Interestingly, retinoic acid was also found to enhance their growth but its enhancement was less potent than thyroid hormone and estrogen. Low concentrations of estradiol and thyroid hormone showed additive effects, but G3 cells stimulated with high concentrations of thyroid hormone failed to elicit an additive effect with estrogen, suggesting the presence of a common pathway in the growth-stimulatory actions of these hormones. In addition, exposure of G3 cells to retinoic acid completely abolished the effects of estrogen or thyroid hormone in terms of cell growth. These results suggest that there are complex interactions in the signalling pathways for estrogen, thyroid hormone and retinoic acid action in G3 cells.

Animals↗

PubMed1992

Influence of workload on the antihypertensive effect of exercise.

1. The relation between workload and the antihypertensive effect of exercise therapy in hypertensive patients, and the mechanism of that effect, were investigated. 2. Twenty-six patients participated in the study and were randomly assigned to 10 weeks of either low or high workload exercise. In the low workload group, 16 mild hypertensive patients were treated with bicycle ergometer exercise at approximately 50% of their maximum oxygen consumption (VO2max) for 60 min three times a week for 10 weeks. In the high workload group, 10 mild hypertensive patients exercised on the same schedule, but at approximately 75% of VO2max. 3. After 10 weeks of exercise, the low workload group had significantly lower systolic (9 mmHg), mean (6 mmHg) and diastolic (6 mmHg) blood pressures. In the high workload group, decreases in systolic (3 mmHg), mean (4 mmHg) and diastolic (5 mmHg) blood pressure were not statistically significant. 4. In the low workload group, changes in haemodynamic and humoral variables were not significant, except for a reduction in plasma norepinephrine at week 7. Cardiac index and plasma norepinephrine tended to decrease. In the high workload group, plasma norepinephrine and the renin-angiotensin system were transiently stimulated after 4 weeks of exercise. Stroke volume significantly increased (+26.4%) after 10 weeks of high workload exercise. 5. Based on these results and better patient compliance with the exercise programme in the low workload group than in the high workload group, low workload exercise therapy was recommended to mild hypertensive patients.

Adult↗

PubMed1992

An autopsy case of Farber's lipogranulomatosis in a Japanese boy with gastrointestinal involvement.

A boy with Farber's lipogranulomatosis is reported. Excessive ceramide was revealed by thin-layer chromatography of the extracts from the liver. Acid ceramidase activity of the liver was 31.5% of control with exogenous substrate and 33.3% without exogenous substrate. The histological appearance showed granulomatous lesions, composed of spindle or oval-shaped storage cells and proliferation of the connective tissues, in the subcutaneous tissue of the lower lip, periarticular regions and the pericardium. Histochemically the storage cells were revealed to contain lipid and polysaccharide. The foreign body granuloma formed by the surgical suture in the liver was surrounded by a large number of foamy cells. In gastrointestinal mucosa widespread erosion, disappearance of glands and abundant collagen fibers were noted. On electron microscopy, the spindle or oval-shaped cells in the subcutis of the lip had intracytoplasmic inclusions containing granular or fibrillar materials and a smaller number of curvilinear structures, so called "Farber bodies". Our case was a typical clinical and histopathological presentation of Farber's lipogranulomatosis. However, ceramidase activity was higher than in previous descriptions, and severe gastrointestinal lesions and the appearance of a large number of foamy cells around the foreign body granuloma have not been described previously.

Acid Ceramidase↗

PubMed1992

A case of Farber disease.

We report a case of Farber disease (Farber lipogranulomatosis). The main features were a shrill voice, joint swelling, subcutaneous nodules and retarded psychomotor development. Cytological investigation revealed intracytoplasmic inclusion bodies characteristic of Farber disease. Lipid analysis of liver tissue indicated an accumulation of ceramide containing non-hydroxy fatty acids. It was found that the acid ceramidase activity in the liver was reduced to 31% of the control value. In this patient there was also persistent diarrhea, cholelithiasis, transient proteinuria and increased urinary total sialic acids. These features have not been noted in previously reported cases.

Acid Ceramidase↗

PubMed1992

Mild exercise decreases plasma endogenous digitalislike substance in hypertensive individuals.

Changes in a plasma endogenous digitalislike substance were investigated in relation to the antihypertensive mechanism of mild exercise. Fifteen women with mild essential hypertension and seven normotensive female volunteers were divided into exercised hypertensive (n = 10), nonexercised hypertensive (n = 5), and nonexercised normotensive (n = 7) groups. A 4-week general clinical observation period preceded the study period of 10 weeks. The exercised hypertensive individuals were treated with a lactate threshold exercise that corresponded to approximately 50% of the maximum oxygen consumption three times a week, whereas the nonexercised groups were observed at the outpatient clinic as control groups. In the exercised group, systolic blood pressure fell by 7 mm Hg (p = 0.05), diastolic by 6 mm Hg (p less than 0.01), and mean blood pressure by 7 mm Hg (p less than 0.01) after 10 weeks. The reduction in the plasma endogenous digitalislike substance was significant after 7 (-1.02 ng/ml, p less than 0.05) and 10 (-1.04 ng/ml, p less than 0.05) weeks in this group. It positively correlated with the reduction in diastolic (r = 0.70, p less than 0.05) or mean (r = 0.66, p less than 0.05) blood pressure and with changes in plasma norepinephrine (r = 0.76, p less than 0.05). The mean corpuscular volume of erythrocytes decreased (-1.7 fl, p less than 0.01) after 10 weeks of exercise, and the plasma volume index tended to decrease (-108 ml/m2, p = 0.28). In the control groups, significant changes in blood pressure and plasma endogenous digitalislike substance were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

PubMed1992

Identification and characterization of high molecular weight forms of basic fibroblast growth factor in human pituitary adenomas.

Basic fibroblast growth factor (bFGF) extracted from 23 human pituitary adenomas and 2 nontumorous anterior pituitary glands was examined by Western blot analysis to elucidate their molecular forms. Four bands that specifically interacted with anti-bFGF antibody were identified at the regions of 16K, 18K, 22K, and 24K mol wt. These immunodetectable bFGFs were bound to a heparin-Sepharose affinity column and eluted with 1-2 M NaCl. These partially purified tumor extracts could stimulate dose-dependently the growth of FGF-responsive cells. Some tumors contained bFGF with a mol wt of 24 K as a dominant form. In contrast, a major form of bFGF at the region of 18K was identified in the nontumorous anterior pituitary glands. We also addressed the possible presence of FGF receptor mRNA using Northern blot analysis. Many, but not all, human pituitary adenomas were found to contain detectable levels of FGF receptor mRNA with a size of 3.5 kilobases. The present results suggest that the role of bFGF in growth and hormone secretion in human pituitary adenomas should be examined using high mol wt forms of bFGF.

Adenoma↗

PubMed1992

Penetration in vitro of newly excysted juvenile flukes of Japanese Fasciola sp. through ligated intestines of rabbits, mice, rats and chickens.

Ligated intestines of rabbits, mice, rats and chickens were used to examine the penetration of newly excysted juvenile flukes of Japanese Fasciola sp. in vitro. In rabbit intestines, the penetration rate was relatively high in the rectum and duodenum. Penetration rates in the jejunum, ileum, cecum and colon were comparable to those in the rectum and duodenum, although it was lower in the appendix. In the case of mouse, juvenile flukes penetrated the duodenum, jejunum, cecum, and rectum at considerably high rates. In rat intestine, penetration by flukes was less in the duodenum and rectum, although flukes were detected in the jejunum. In chicken intestine, flukes barely penetrated the duodenum, jejunum and rectum. Consequently, newly excysted flukes of Fasciola sp. seem to penetrate any region of the intestine in rabbits and mice. In rats, the middle small intestine may be the site suitable for flukes to penetrate. In chickens, the difficulty in penetration of the intestinal wall may be one of the reasons why chickens are scarcely infected with Fasciola sp.

Animals↗

PubMed1992

Factors contributing to the resistance of chickens to infection with Japanese Fasciola sp.

Attempts were made to clarify the factors contributing to the resistance of chickens to infection with Japanese Fasciola sp. Infection was not successfully established in chickens by oral inoculation of metacercariae, nor by inoculation of excysted juvenile flukes into the body cavity or to the liver surface. Many metacercarial cysts were detected within two days in the feces of orally inoculated chickens. In the in vitro excystation test with chicken bile at 42 degrees C, metacercariae emerged successfully. These results indicate that the major resistant factors may not act during the migration from the mouth to the liver. Histopathological examination of the liver of experimental chickens could not prove the effect of a resistant factor. Excysted flukes were cultivated at 37-42 degrees C in RPMI1640 supplemented with calf serum, with the result that the survival rate of flukes fell with higher temperatures. When chicken serum was used instead of calf serum, flukes survived for a long period of time at 37 degrees C, while all died within four days at 42 degrees C. The higher body temperature of chickens than that of other mammalian hosts is considered to be the major factor contributing to the resistance of chickens to infection with Fasciola sp.

Animals↗

PubMed1992

Intracranial and intraspinal dissemination of an ACTH-secreting pituitary tumor.

A case of a 29-year-old man with an ACTH-producing pituitary tumor disseminated into the subarachnoid space is described. After total adrenalectomy for Cushing's disease at the age of 15, Nelson's syndrome developed. Transsphenoidal adenomectomy at 17 and 21 years of age, pituitary irradiation and medical therapies with sodium valproate, baclofen and bromocriptine failed to lower his plasma ACTH level. Multiple intracranial and intraspinal tumors associated with the symptoms of left hemiparesis developed. The removal of a tumor grown at the level of C1-3 was performed with successful palliation of his symptoms. Histologically, the tumor cells showed sinusoidal, papillary and diffuse patterns with a preponderance of the former over the latter two, although the papillary pattern predominated in the primary pituitary tumor. Immunohistochemical analysis demonstrated most cells to be positive for ACTH in the metastatic tumor as well as the primary adenoma. The clinical significance of his course is discussed with a review of 11 reported cases with metastatic ACTH-producing pituitary tumors.

Adrenocorticotropic Hormone↗