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Biomedical subjects

Y Homma

Publications and source records attributed to Y Homma.

At least 253 records · Page 14Linked to original sources
PubMed1989

[An autopsy case of senile dementia with numerous neocortical senile plaques and preserved subcortical nuclei].

An 80-year-old retired teacher developed impairment of memory and suffered from delusions of theft. Four years later, she became disoriented as to person, time and situation, restless, began mutter to herself, and displayed night delirium and insomnia. She was subsequently diagnosed as having senile dementia of the Alzheimer type (SDAT). She died of bronchopneumonia and multiple metastases from breast cancer at the age of 85 years. Family history was non-contributory. The brain weighed 1,020 g and showed diffuse atrophy. Histologically, there was moderate loss of neurons in the cerebral cortex, which was accentuated in the frontal and temporal lobes. In addition, numerous senile plaques were observed in the neocortex and hippocampus. Several senile plaques were also found in the amygdala, innominate substance, neostriatum, claustrum, thalamus, hypothalamus and tegmentum of the mesencephalon. Neurofibrillary tangles (NFTs) were mostly restricted to the hippocampus and parahippocampal gyrus, their number being compatible with the patient's age. No obvious neuronal loss was noted in the nucleus basalis of Meynert, neostriatum, substantia nigra or locus ceruleus, which are well known to be involved in Alzheimer's disease and SDAT. Recently, Terry et al proposed a new disease concept, "SDAT without neocortical NFTs". The histopathology of the cerebral cortex in our patient was very similar, if not identical, to those observed in their patients. However, the above authors did not mention any subcortical changes, leaving the detailed neuropathological picture unclear. Tentatively, we classified the present case as senile dementia with numerous neocortical senile plaques and preserved subcortical nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

[Extended surgery of renal cell carcinoma--its significance and limitation].

Extended surgery was divided into 4 types per below. (1) Extended local resection (1 case). Resection of descending colon and splenectomy were performed in a case with invading left renal cancer. The patient died of cancer in 9 months. Three other cases with locally invading renal cancer were inoperable because of multiple metastases or poor general condition. (2) Thrombectomy in vena cava inferior (6 cases). Successful thrombectomy was carried out in 5 of our 6 cases. All the cases died of metastases of cancer within 4 years. In the literature, long survival is reported after complete resection of thrombus. (3) Resection of distant metastases (11 cases). Palliative surgery was performed in 5 cases with symptomatic brain metastases. After radical resection of solitary metastases, 2 died of cancer, 2 are alive with cancer and the remaining 2 are alive with no evidence of disease (NED). (4) Surgery for contralateral kidney (4 cases). Partial nephrectomy or enucleation of tumor was undertaken in 3 cases (2 NED, 1 death). In the 4th case, as the tumor appeared to invade deeply in the renal parenchyma, ex vivo partial nephrectomy followed by autotransplantation was done (NED). The results indicate that the minimum requirement for radicality should be complete extirpation of the tumor mass and that the indication for radical extended surgery includes presumably resectable intracaval thrombus, solitary metastases and contralateral renal tumor.

Adult↗
PubMed1989

[Usefulness of an exercise pulmonary function test for differential diagnosis or treatment evaluation of restrictive pulmonary diseases].

To simplify its applications in patients in poor condition such as cases of idiopathic interstitial pneumonia (IIP), we chose a simple method of exercise test instead of the usual method. The method consisted of the single Master's two-step test and instant blood-gathering without keeping a needle in a vessel. By this method, PaO2 after exercise was estimated approximately 7 torr less than with the usual method, but tendencies of PaO2 changes were accurately observed. In a study on 8 patients with IIP, 20 collagen vascular disease cases with pulmonary changes (CVD), 11 hypersensitivity pneumonitis cases, and 5 sarcoidosis cases, the parameters such as delta PaO2 or delta AaDO2 differentiated the different physiological conditions of the 4 disease groups accurately. However, the exercise test was noted to be less sensitive in terms of differential diagnosis than the at-rest test after a multiple discriminant analysis in the 4 disease groups. For the estimate of patient prognosis delta AaDO2 was most useful in a study of IIP and CVD patients. We conclude that this simple exercise test is useful for the diagnosis or evaluating treatment of such restrictive pulmonary disease.

Aged↗
PubMed1989

Comparison in inhibitory effects of lipolysis products on cholesterol esterification.

The effects of lipolysis products (glycerol, free fatty acids and lysolecithin) on cholesterol esterification in LDL and HDL3 were studied. The effects of oleic acid, linoleic acid and EPA on cholesterol esterification in LDL and HDL3 were also compared. 14C-FC labeled lipoprotein, LCAT source (lipoprotein deficient plasma) and test substance were incubated at 37 degrees C, and cholesterol esterification rates were estimated. In LDL, glycerol and palmitic acid did not inhibit cholesterol esterification. The inhibition rates of cholesterol esterification by lysolecithin were same as those by linoleic acid in LDL and increased to 100% at 2.5 mM depending on the concentrations. The effects of oleic acid, linoleic acid, and EPA were compared. The inhibition rates of cholesterol esterification in LDL were highest by EPA, next by linoleic acid and lowest by oleic acid. In HDL3, glycerol did not inhibit cholesterol esterification. Palmitic acid inhibited cholesterol esterification in HDL3. The inhibition rates of cholesterol esterification by lysolecithin in HDL3 were always lower than those by linoleic acid. The inhibition rates by palmitic acid were almost same as those by lysolecithin in HDL3. The inhibition rates of cholesterol esterification by EPA were higher than those by linoleic acid in HDL3. The inhibition rates of cholesterol esterification by oleic acid were close to those by linoleic acid in HDL3. Polyunsaturated FA suppressed LCAT activities much stronger than saturated FA at physiological concentrations.

Apolipoproteins↗
PubMed1988

Enhancement of inositol phospholipid metabolism and activation of protein kinase C in ras-transformed rat fibroblasts.

The inositol phospholipid metabolism is one of the main pathways of signal transduction in cells. We measured the activities of its key enzymes in v-Ha-ras-transformed 208F rat fibroblasts. In the ras-transformed clones, incorporation of [32P]Pi into intermediates of the inositol phospholipid metabolism was stimulated. The activities of phosphatidylinositol and phosphatidylinositol-4-phosphate kinases in the transformed clones were about 35-50% more than in untransformed cells, indicating increased inositol phospholipid metabolism. However, the activity of diacylglycerol kinase in their membrane fraction was 25-35% less than that of untransformed cells, although the total diacylglycerol kinase activity did not change. The imbalance of these kinases could constitute one of the main reasons leading to the increased level of inositol phosphates and the accumulation of diacylglycerol to 2-2.2 times that in control 208F cells. Phosphatidylinositol-4,5-bisphosphate-phospholipase C activity did not change on the transformation when assayed under various conditions. The increased level of diacylglycerol caused intracellular translocation, activation, and down-regulation of protein kinase C changes which may be one of the essential events in transformation by the v-Ha-ras gene.

Animals↗
PubMed1988

Purification of two distinct types of phosphoinositide-specific phospholipase C from rat liver. Enzymological and structural studies.

Two kinds of phosphoinositide-specific phospholipase C (PLC) were purified from rat liver by acid precipitation and several steps of column chromatography. About 50% of the activity could be precipitated when the pH of the liver homogenate was lowered to pH 4.7. The redissolved precipitate yielded two peaks, PLC I and PLC II, in an Affi-gel Blue column, and each was further purified to homogeneity by three sequential h.p.l.c. steps, which were different for the two enzymes. The purified PLC I and PLC II had estimated Mr values of 140,000 and 71,000 respectively on SDS/polyacrylamide-gel electrophoresis. Both enzymes hydrolysed phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) in a Ca2+- and pH-dependent manner. PLC I was most active at 10 microM- and 0.1 mM-Ca2+ for hydrolysis of PI and PIP2 respectively, whereas PLC II showed the highest activity at 5 mM- and 10 microM-Ca2+ for that of PI and PIP2 respectively. The optimal pH of the two enzymes also differed with substrates or Ca2+ concentration, in the range pH 5.0-6.0. Hydrolysis of phosphoinositides by these enzymes was completely inhibited by Hg2+ and was affected by other bivalent cations. From data obtained by peptide mapping and partial amino acid sequencing, it was clarified that PLC I and PLC II had distinct structures. Moreover, partial amino acid sequences of three proteolytic fragments of PLC I completely coincided with those of PLC-148 [Stahl, Ferenz, Kelleher, Kriz & Knopf (1988) Nature (London) 332, 269-272].

Amino Acid Sequence↗
PubMed1988

Protein kinase C activities with different characteristics, including substrate specificity, from two human HL-60 leukemia cell variants.

To evaluate the role of protein kinase C in the cellular maturation processes induced by phorbol diesters, we examined the biochemical activity of protein kinase C from HL-205, a cell variant from the human promyelocytic HL-60 leukemia that is susceptible to differentiation induced by phorbol 12-myristate 13-acetate, and from HL-525, an HL-60 variant that is resistant to such an induction. The activities of protein kinase C from the two cell types differed in their requirements for the cofactors Ca2+ and lipids. These enzyme activities also differed in their abilities to phosphorylate protamine and a series of four oligopeptides. We suggest that the differences in vitro in the activities of protein kinase C between HL-205 and HL-525 cells, especially in their substrate specificity, are closely related to the different phosphorylation patterns induced in vivo by phorbol 12-myristate 13-acetate in these cells. We also suggest that these differences may be responsible for the different susceptibilities of the two cell types to maturation induced by phorbol diesters.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

Isolation and characterization of two different forms of inositol phospholipid-specific phospholipase C from rat brain.

Two different forms of inositol phospholipid-specific phospholipase C (PLC) have been purified 2810- and 4010-fold, respectively, from a crude extract of rat brain. The purification procedures consisted of chromatography of both enzymes on Affi-Gel blue and cellulose phosphate, followed by three sequential high performance liquid chromatography steps, which were different for the two enzymes. The resultant preparations each contained homogeneous enzyme with a Mr of 85,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. One of these enzymes (PLC-II) was found to hydrolyze phosphatidyl-inositol 4,5-bisphosphate (PIP2) at a rate of 15.3 mumol/min/mg of protein and also phosphatidylinositol 4-monophosphate and phosphatidylinositol (PI) at slower rates. For hydrolysis of PI, this enzyme was activated by an acidic pH and a high concentration of Ca2+ and showed a Vmax value of 19.2 mumol/min/mg of protein. The other enzyme (PLC-III) catalyzed hydrolysis of PIP2 preferentially at a Vmax rate of 12.9 mumol/min/mg of protein and catalyzed that of phosphatidylinositol 4-monophosphate slightly. The rate of PIP2 hydrolysis by this enzyme exceeded that of PI under all conditions tested. Neither of these enzymes had any activity on phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, or phosphatidic acid. These two enzymes showed not only biochemical but also structural differences. Western blotting showed that antibodies directed against PLC-II did not react with PLC-III. Furthermore, the two enzymes gave different peptide maps after digestion with alpha-chymotrypsin or Staphylococcus aureus V8 protease. These results suggest that these two forms of PLC belong to different families of PLC.

Animals↗
PubMed1988

Dose-dependent hypolipidemic effect of an inhibitor of HMG-CoA reductase, pravastatin (CS-514), in hypercholesterolemic subjects. A double blind test.

The hypolipidemic effect of a new HMG-CoA reductase inhibitor, pravastatin, was examined. The reductions of serum cholesterol and LDL-cholesterol were dose-dependent and significant differences were observed between placebo and 10 or 20 mg groups (P less than 0.01), and 10 and 20 mg (P less than 0.05) groups. The reduction rate of cholesterol after 8 weeks during medication was 16.1% in the 10 mg group, 20.5% in the 20 mg group compared to baseline serum cholesterol levels. LDL-cholesterol decreased by 23.9% in the 10 mg group, and 29.8% compared to baseline LDL-cholesterol in the 20 mg group. The lowering of total cholesterol was entirely attributed to a reduction in LDL-cholesterol.

Adult↗
PubMed1988

Importance of fatty acid substituents of chemically synthesized lipid A-subunit analogs in the expression of immunopharmacological activity.

The immunopharmacological activities of chemically synthesized lipid A-subunit analogs, 4-O-phosphono-D-glucosamine derivatives carrying different N- and 3-O-linked acyl groups, were investigated. None of the synthetic compounds tested exhibited any detectable pyrogenicity at a dose of 10 micrograms/kg. Weaker lethal toxicity in galactosamine-sensitized mice was detected at 1 microgram per mouse for all the synthetic compounds except GLA-58. Among (RS) stereoisomers of 4-O-phosphono-D-glucosamine derivatives carrying a 3-O-tetradecanoyl (C14) group with different N-linked acyloxyacyl groups, i.e., 3-dodecanoyloxytetradecanoyl [C14-O-(C12)], 3-tetradecanoyloxytetradecanoyl [C14-O-(C14)], and 3-hexadecanoyloxytetradecanoyl [C14-O-(C16)] groups (termed GLA-57, GLA-27, and GLA-58, respectively), GLA-27 exhibited significant colony-stimulating factor-inducing and tumor necrosis factor-inducing activities, mitogenicity, polyclonal B-cell activation activity, macrophage activation, and adjuvanticity. The activities of GLA-57, which had an N-linked C14-O-(C12) group, were equivalent to or somewhat weaker than those of GLA-27 with a C14-O-(C14) group. Significant immunopharmacological activities were not observed for GLA-58, carrying a C14-O-(C16) group bound to the amino group. GLA-59, carrying 3-O-linked 3-hydroxytetradecanoyl (C14OH) and N-linked C14-O-(C14) groups, showed much higher activities than GLA-27, GLA-60, a compound which possesses the same fatty acid substituents as GLA-59 but with reversed binding sites, showed the strongest B-cell activation and adjuvant activities among the synthetic compounds. Among stereoisomers of GLA-59 and GLA-60 composed of fatty acid substituents with the (RR) and (SS) configuration, compounds with the (RR) configuration elicited stronger activities than the (SS) stereoisomers. The importance of fatty acid substituents, including stereospecificity for the expression of immunopharmacological activities of 4-O-phosphono-D-glucosamine derivatives, was demonstrated.

Adjuvants, Immunologic↗
PubMed1988

Clinical evaluation of urethral tumors based on a simple classification system.

A simplified classification for primary urethral tumors is proposed. The T stage for tumors of male or female and of the upper or lower urethra has been combined into a single system. The system has been applied to 104 cases of urethral tumors. Although the cases were not necessarily very well qualified, a retrospective survival study demonstrated a general trend to a poorer prognosis in higher stages. Such a unified system might be useful for a simple classification of urethral tumors, a rare neoplasm with various clinical manifestations depending on sex or tumor site.

Adenocarcinoma↗
PubMed1988

Effects of ketanserin tartrate on serum lipids in patients with essential hypertension.

Several antihypertensive agents such as thiazide diuretics and some beta-blockers have recently been shown to adversely affect lipid metabolism. Moreover, there is a growing suspicion that the adverse effect on plasma lipids might outweigh the favourable effect of lowering blood pressure. The effect of ketanserin tartrate (20 to 60 mg daily), a new antihypertensive drug, on blood lipids was evaluated in a 12-week non-comparative clinical trial in 34 patients with mild or moderate hypertension. Ketanserin reduced systolic and diastolic blood pressure by 12.2 and 9.8%, respectively, without altering heart rates. Total cholesterol and low density lipoprotein (LDL)-cholesterol levels in the fasting plasma were observed to decrease significantly by 6.3 and 8.8% respectively, whereas mean triglyceride and high density lipoprotein (HDL)-cholesterol remained almost unchanged. These changes were consistent irrespective of their initial values. Significant decrease in apolipoprotein B and E was also observed. Apolipoprotein A-I, A-II, C-II and C-III were not altered significantly. It is speculated that ketanserin affects mainly LDL-cholesterol. Based on these findings, ketanserin is considered to have a potentially beneficial effect on coronary risk profile and should be given full consideration when drug therapy is selected for patients with mild to moderate hypertension.

Adult↗