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Biomedical subjects

A Kumagai

Publications and source records attributed to A Kumagai.

At least 19 recordsLinked to original sources
PubMed1992

Regulation of the cdc25 protein during the cell cycle in Xenopus extracts.

The cdc25 protein is a highly specific tyrosine phosphatase that triggers mitosis by dephosphorylating the cdc2 protein kinase. Using Xenopus extracts, we have found that the cdc25 protein is active at a low level throughout interphase. Near the onset of mitosis, the cdc25 protein undergoes a marked elevation in phosphatase activity that coincides with an extensive phosphorylation of the protein in its N-terminal region. In vitro dephosphorylation of this hyperphosphorylated form of cdc25 reduces its phosphatase activity back to the interphase level. Moreover, treatment of interphase Xenopus extracts with okadaic acid, a phosphatase inhibitor that accelerates the entry into mitosis, elicits both the premature hyperphosphorylation of cdc25 and the stimulation of its cdc2-specific tyrosine phosphatase activity. These experiments demonstrate the existence of a cdc25 regulatory system consisting of both a stimulatory kinase that phosphorylates a putative regulatory domain of the cdc25 protein and an inhibitory serine/threonine phosphatase that counteracts this kinase activity.

Amino Acid Sequence↗
PubMed1992

Clinical and basic aspects of an anorexiant, mazindol, as an antiobesity agent in Japan.

The Japanese Mazindol study group investigated the action of an anorexiant, mazindol, and found that it reduced food intake by directly suppressing neurons in the lateral hypothalamus, inhibited gastric acid secretion, increased motor activity, decreased glucose absorption, and inhibited insulin secretion. It thus appears that the main effect of mazindol is to decrease food intake through suppressing feeding centers in the hypothalamus. A multicenter open study of mazindol in Japan revealed that loss of body weight and relative body weight in 14 wk were 4.6 kg and 9.2%, respectively, with suppression of appetite in the majority of obese patients. A multicenter double-blind study demonstrated that mazindol was superior to the placebo in the treatment of simple obesity. We also suggest that mazindol is effective in the maintenance of reduced body weight after obesity therapy and in the treatment of obesity-related diseases such as diabetes, hypertension, or hyperlipidemia.

Animals↗
PubMed1991

The cdc25 protein contains an intrinsic phosphatase activity.

Genetic and biochemical studies have indicated that the cdc25 protein controls the entry into mitosis by triggering tyrosine dephosphorylation of the cdc2 protein kinase. We show that the isolated cdc25 protein can catalyze dephosphorylation of several model phosphatase substrates, including p-nitrophenyl phosphate and two distinct tyrosine-phosphorylated peptides. The cdc25-dependent cleavage reaction closely resembles dephosphorylation by known tyrosine phosphatases: the reaction requires a reducing agent, shows high sensitivity to sodium vanadate, and proceeds efficiently in the presence of metal chelators. Moreover, the phosphatase activity of the cdc25 protein is eliminated by treatment with N-ethylmaleimide or by alteration of a single conserved cysteine residue by site-directed mutagenesis. These observations indicate that the cdc25 protein can function as a tyrosine phosphatase in the absence of any other protein.

4-Nitrophenylphosphatase↗
PubMed1991

The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system.

As a prerequisite for the activation of MPF, the cdc2 protein kinase must undergo tyrosine dephosphorylation. Genetic studies have demonstrated that the cdc25 protein activates the cdc2 protein kinase once DNA replication has been completed. We have produced the cdc25 protein in bacteria and shown that it activates MPF in Xenopus extracts. In extracts that normally cannot enter mitosis owing to inhibition of DNA synthesis, the addition of active cdc25 protein efficiently elicits the mitotic state by inducing premature dephosphorylation of tyrosine on the cdc2 protein. The cdc25-dependent activation reaction can be reconstituted in a partially purified system lacking ATP. These biochemical experiments demonstrate that the cdc25 protein actively drives tyrosine dephosphorylation of the cdc2 protein and offer the prospect for characterizing the individual factors that regulate the activation of MPF during the progression from S phase to mitosis.

Animals↗
PubMed1991

Molecular genetic analysis of two G alpha protein subunits in Dictyostelium.

In Dictyostelium, chemotaxis to folate during growth and cAMP during aggregation is controlled via cell surface receptors. To study the role of two G alpha proteins (G alpha 1 and G alpha 2) in these responses, we examined the physiological and biochemical effects of null mutations caused by antisense mutagenesis and gene disruptions. Disruption of G alpha 2 results in an aggregation-deficient phenotype and a loss of cAMP receptor-mediated functions, including activation of adenylate cyclase, guanylate cyclase, and gene expression and in a loss of GTP-mediated decrease in receptor affinity for cAMP, but it has no effect on chemotaxis to folate or folate activation of guanylate cyclase. These phenotypes can be rescued by a vector expressing G alpha 2, suggesting G alpha 2 is coupled to a cAMP receptor but not to folate receptors. Loss of G alpha 1 expression resulted in no visible growth or developmental phenotype, including cAMP- and folate-stimulated responses, suggesting G alpha 1 function is either not essential under standard laboratory conditions or is encoded by multiple genes. Availability of null mutations provides suitable genetic backgrounds for expressing mutant G alpha protein subunits which can then be used to examine the physiological roles of G alpha 1 and G alpha 2. Construction of these gene disruptions was facilitated by using the auxotrophic marker THY1, which allowed for selection of single-copy insertions into the genome.

Blotting, Southern↗
PubMed1990

Plasma concentration of atrial natriuretic factor in idiopathic oedema.

Low level of plasma atrial natriuretic factor (ANF) under altered dietary sodium and its elevation during bigeminy were found in a 40-year-old woman with idiopathic oedema. The natriuretic effect of this peptide and the role of renin-angiotensin-aldosterone system in oedema formation in this disorder are discussed.

Adult↗
PubMed1990

[A report of renal cell carcinoma in a horseshoe kidney].

A case of renal cell carcinoma associated with horseshoe kidney is reported. The patient was a 67 years old man with the chief complaints of dull pain of right upper abdomen. Ultrasonography (US) revealed horseshoe kidney and abnormal mass sign at the right isthmus of the kidney. By the computed tomography (CT) and angiography, renal cell carcinoma associated with horseshoe kidney was diagnosed. Only 18 cases of this rare disease have been reported in Japan. The diagnostic procedures are discussed and the usefulness of selective arteriography of the isthmus is emphasized, as the presentation of vascular anatomy is of great value for diagnosis, surgical treatment and preoperative arterial embolization.

Aged↗
PubMed1989

Regulation and function of G alpha protein subunits in Dictyostelium.

We have examined the developmental regulation and function of two G alpha protein subunits, G alpha 1 and G alpha 2, from Dictyostelium. G alpha 1 is expressed in vegetative cells through aggregate stages while G alpha 2 is inducible by cAMP pulses and preferentially expressed in aggregation. Our results suggest that G alpha 2 encodes the G alpha protein subunit associated with the cAMP receptor and mediates all known receptor-activated intracellular signal transduction processes, including chemotaxis and gene regulation. G alpha 1 appears to function in both the cell cycle and development. Overexpression of G alpha 1 results in large, multinucleated cells that develop abnormally. The central role that these G alpha proteins play in signal transduction processes and in controlling Dictyostelium development is discussed.

Chromosome Deletion↗
PubMed1989

Multiple alpha subunits of guanine nucleotide-binding proteins in Dictyostelium.

Previous results have shown that chemotaxis and the expression of several classes of genes in Dictyostelium discoideum are regulated through a cell surface cAMP receptor interacting with guanine nucleotide-binding proteins (G proteins). We now describe cloning and sequencing of cDNAs encoding two G alpha protein subunits from Dictyostelium. The derived amino acid sequences show that they are 45% identical to each other and to G alpha protein subunits from mammals and yeast. Both cDNAs are complementary to multiple mRNAs that are differentially expressed during development. This evidence and analysis of mutants presented elsewhere suggest that they have distinct physiological functions.

Amino Acid Sequence↗
PubMed1989

Favorable effects of fish oil concentrate on risk factors for thrombosis in renal allograft recipients.

The incidence of thromboembolic complications in renal allograft recipients is very high. Since fish oil has antithrombotic properties, we administered 18 capsules of fish oil concentrate (1.5 g of eicosapentaenoic acid, EPA, and 0.7 g of docosahexaenoic acid) per day to 14 renal allograft recipients for 6 months. Another group of recipients served as controls. In the treated group the levels of EPA and docosahexaenoic acid in erythrocyte membrane lipids increased significantly after the fish oil treatment. Red blood cell filterability significantly increased in the treated group compared with the case of the control group. Epinephrine-induced platelet aggregation increased significantly in the control group, and this change was significantly different from that of the treated group (almost a null change). At the end of the study, the ratio of the main urinary metabolite of prostacyclin I2/3 to the metabolite of thromboxane A2/3 was significantly higher in the treated group than in the control group. In conclusion, we suggest that fish oil concentrate may favorably affect risk factors for thromboembolic complications in renal allograft recipients.

Adult↗
PubMed1987

The innervation of the external urethral sphincter; an ultrastructural study in male human subjects.

Innervation of the external urethral sphincter (EUS) was studied in male human subjects. In the region of EUS at the distal end of prostatic urethra, a large axon bundle surrounded by perineurium was evident in the intramural connective tissue gap. Because of the presence of dense core vesicles, the small nonmyelinated axon profiles in the bundle were considered to be adrenergic. After ramifications to smooth musculature, the axons were traced to the EUS. In the EUS, axon bundles containing many non-myelinated axons were recognized as a sole autonomic nerve among the striated muscle cells. A single or at most two or three axons were surrounded by a Schwann cell, and some possessed dense core vesicles which suggested an adrenergic function. These autonomic adrenergic nerve ends formed surface junctions with the striated muscle of EUS. The clinical relevance of these data are discussed.

Adrenergic Fibers↗
PubMed1987

Intake of different eicosapentaenoic acid-containing lipids and fatty acid pattern of plasma lipids in the rats.

The ethyl ester of eicosapentaenoic acid (EPA) is the only pure EPA-containing lipid available in bulk for oral administration. However, there is doubt as to whether EPA ethyl ester can efficiently increase the plasma levels of EPA in comparison with the ability of other kinds of EPA-containing lipids to do so. Therefore, two other kinds of EPA-containing lipids were prepared to study the efficiency of oral administration of those lipids for increasing the EPA content in plasma phospholipids and cholesteryl esters. EPA-containing lipids which were investigated were [A] 1,2,3-trieicosapentaenoyl-glycerol, [B] 2-eicosapentaenoyl-phosphatidylcholine and [C] ethyl ester of EPA. An adjusted amount of lipids [A], [B] and [C] was administered to rats through a gastric tube for 4 days (the first experiment) or for 10 days (the second experiment), and the fatty acid composition of plasma phospholipids and cholesteryl esters was determined. In the first experiment, there were no significant differences in the efficiency for increasing EPA levels in either phospholipids or cholesteryl esters among the lipids. In the second experiment, the EPA levels of both plasma phospholipids and cholesteryl esters of rats administered ethyl ester of EPA were significantly higher than those of rats administered 2-eicosapentaenoyl-phosphatidylcholine. The EPA levels of the rats administered 1,2,3-trieicosapentaenoyl-glycerol were between the levels of the two groups mentioned above, but the differences in the EPA levels were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Antiatherogenic action of eicosapentaenoic acid (EPA) in multiple oral doses.

The possible antiatherogenic action of eicosapentaenoic acid (EPA) was pharmacologically investigated using purified and ethylesterified fish oil containing 75% EPA (EPA-E) in multiple oral doses in rats and rabbits. EPA-E showed dose-dependent prevention of thrombus formation in a vascular shunt or sudden death caused by arachidonic acid injection in rats. EPA-E in daily doses ranging from 3 to 30 mg/kg slightly altered platelet aggregability and prostacyclin-like activity generated from arterial ring preparations of rats, but these alterations were not statistically significant. Further, EPA-E showed no effect on blood viscosity of rats. In cholesterol-fed rabbits, EPA-E in daily doses of 10 and 30 mg/kg moderately lowered the levels of plasma cholesterol, beta-lipoprotein, triglyceride and phospholipid, but these changes showed neither dose-dependency nor time-dependency. In this experiment, EPA-E moderately altered atherogenic plaque formation and platelet aggregability, but these alterations were not statistically significant. EPA-E showed no effect on prostacyclin-like activity generated from arterial ring preparations and blood viscosity of cholesterol-fed rabbits. It is, therefore, proposed that the antithrombotic action of EPA-E may be partially related to its effects on platelet aggregability and prostacyclin generation, but the major mechanism remains unclear.

Administration, Oral↗
PubMed1987

Infusion of fish oil emulsion: effects on platelet aggregation and fatty acid composition in phospholipids of plasma, platelets, and red blood cell membranes in rabbits.

An emulsion of fish oil was manufactured to contain 10 g of fish oil/100 mL. Of this, 3 g were eicosapentaenoic acid (EPA) and 1 g was docosahexaenoic acid (DHA). We administered 100 mL of the emulsion into six rabbits intravenously on days 1, 4, 7, 10, and 13. Blood samples were taken on days 0 and 16. The EPA content in phospholipids of plasma, platelets, and red blood cell (RBC) membranes increased 16, 4, and 5 times, respectively. The DHA content in phospholipids of plasma and RBC membranes increased two times whereas that in platelet phospholipids did not increase significantly. Platelet aggregation induced by collagen (10 micrograms/mL) and ADP (5 microM) was depressed significantly after infusion of the fish oil emulsion. In control experiments with soybean oil emulsion, there were almost no significant changes. Therefore, fish oil emulsion may be beneficial to patients who cannot take n-3 fatty acids orally but need them.

Animals↗