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Biomedical subjects

H Fukumi

Publications and source records attributed to H Fukumi.

At least 19 recordsLinked to original sources
PubMed1994

Developments in mucosal influenza virus vaccines.

Immunogenicity and efficacy of aerosol inactivated split influenza virus vaccines, which are threefold the strength of the vaccines for parenteral use, and cold-adapted reassortant live influenza virus vaccines were evaluated. Mucosal immune responses were evaluated by quantifying specific IgA antibody of the nasal swab solution, and systemic immune responses were evaluated by determining serum haemagglutination inhibition antibody levels. Efficacy of the aerosol inactivated vaccine was evaluated by a challenge test using live vaccine virus. It was concluded that mucosally administered inactivated influenza virus vaccine stimulated systemic and mucosal immune responses more strongly than live influenza virus vaccine and manifested a much stronger booster effect than live vaccine. Mucosal administration of inactivated influenza virus vaccine was effective in preventing infection by live vaccine virus.

Administration, Intranasal↗
PubMed1993

Piperidineacrylate derivatives as potential antiallergy agents.

A new series of piperidineacrylate derivatives was prepared and evaluated for antiallergic activity. Most of the compounds showed potent activities in the rat passive cutaneous anaphylaxis (PCA) assay. In particular, ethyl 1-[2-bis(4-fluorophenyl)methoxyethyl]-4-piperidineacrylate (1a) was more potent than oxatomide and terfenadine in this assay, and was selected for further study. Some pharmacological properties of 1a are presented.

Acrylates↗
PubMed1990

A new type of blood component collector: plasma separation using gravity without any electrical devices.

A new type of blood component collector (BCC) was developed to divide 450 ml of whole blood into plasma and a red cell concentrate using gravity without electrical devices. This BCC system is composed of one whole blood collection bag, two product collection bags and a plasma separator, which consists of a bundle of hydrophilized polyethylene hollow fibers (0.2 micron pore size). Without rinsing the plasma separator, the whole blood (458.1 +/- 13.5 ml, n = 22) was run through the separator using gravity without a pump. An average of 175.9 ml of plasma was collected within 11 min without hemolysis. In this completely cell-free plasma, the recovery of total protein, albumin, globulin, IgG and IgA was nearly 100%. Prothrombin time and activated partial thromboplastin time were in a normal range and the activity of coagulation factors did not change after the separation. In the red cell concentrate, the recovery of red cells, white cells and platelets was 94.7, 98.4 and 82.7%, respectively. Osmotic fragility of red cells, platelet morphology and functions did not change. These observations suggest that this new type of BCC is useful as a simple, fast and safe component collector.

Blood Platelets↗
PubMed1989

A novel heterocyclic compound. Synthesis and reactivities of an oxazolo[3,2-a]thieno[3,2-d]-pyrimidine derivative.

A practical preparation of 2,3-dihydro-5H-oxazolo[3,2-a]thieno[3,2-d]pyrimidin-5-one (2) from methyl 3-aminothiophene-2-carboxylate in two steps was developed. The addition reactions of various nucleophiles to 2 were investigated and oxazole-ring-opened compounds were produced (5, 6, 12, 13 and 14). Desulfurization reaction of 2 with Raney Ni gave an oxazolo[3,2-a]pyrimidine derivative (15). It was found that 2 showed potent anti-gastric secretion activity.

Animals↗
PubMed1989

Condensed thienopyrimidines. I. Synthesis and gastric antisecretory activity of 2,3-dihydro-5H-oxazolothienopyrimidin-5-one derivatives.

A practical preparation of various 2,3-dihydro-5H-oxazolo[3,2-a]thieno[3,2-d]-, [3,4-d]-, and [2,3-d]pyrimidin-5-one derivatives was developed starting from the corresponding aminothiopheneesters in two steps, and their chloro-substituted derivatives were prepared. These compounds were evaluated for gastric antisecretory activity in pylorus-ligated rats, compared to the anti-ulcer standard, cimetidine, and their structure-activity relationships are discussed.

Animals↗
PubMed1989

Condensed thienopyrimidines. II. Synthesis and gastric antisecretory activity of thiazole and polymethylene condensed thienopyrimidine derivatives.

Thiazolo[3,2-a]thieno[3,2-d]-, [3,4-d]- and [2,3-d]pyrimidin-5-one derivatives (6, 11 and 16), and polymethylene condensed thieno[3,2-d]-, [3,4-d]- and [2,3-d]pyrimidin-5-one derivatives (19-21), in which the oxygen atom of the oxazolidine moiety in 3 was replaced by a sulfur atom or methylene groups, were synthesized and evaluated for gastric antisecretory activity in pylorus-ligated rats. The structure-activity relationships of these compounds are discussed.

Animals↗
PubMed1987

Structure and physiological actions of rat atrial natriuretic factor.

Natriuretic substances were purified from rat atrium (atrial natriuretic factor, ANF) and were shown to be identical with the inhibitor of norepinephrine-induced contraction of smooth muscle. Four native forms were isolated and their amino acid sequences were determined. The presence of a high-molecular-weight prohormone was shown. Complementary DNA (cDNA) encoding for the precursor was cloned and used to deduce the amino acid sequence of the prohormone. Genomic DNA for ANF was cloned and two introns were found. Several ANF peptides were synthesized. Structure-function studies showed that the ring structure was essential for the activity. Antibodies produced against the synthetic 25-amino acid residue ANF were used to develop a radioimmunoassay. The presence of ANF in rat plasma demonstrated that ANF is a circulating hormone. ANF was also found in the hypothalamus of rats. The ANF in plasma was found to be a low-molecular form, whereas that in atria and hypothalamus consisted of both the high-molecular-weight precursor and low-molecular-weight active ANF. The presence of messenger RNA for ANF was determined using ANF cDNA as a probe and was considered as evidence for ANF synthesis in the brain, atrium, and ventricles. ANF was shown to be released from the brain. ANF administered intracerebroventricularly was shown to inhibit angiotensin II and thirst-induced dipsogenesis. In vitro and in vivo experiments showed ANF inhibits release of vasopressin from posterior pituitary and renin from the kidneys. The hypotensive effect of ANF was examined at various doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1986

Reinfection with influenza A (H2N2, H3N2, and H1N1) viruses in soldiers and students in Japan.

Reinfection with influenza A virus was studied by measuring hemagglutination-inhibiting antibody responses to infection in paired sera taken from groups of soldiers and students. Among 62 soldiers severely infected during the first wave of the A/Asian/57 (H2N2) pandemic in 1957, 17 were asymptomatically reinfected with the same virus within six months. In the 1962 epidemic the rate increased to 41%. Among reinfected soldiers studied, 68% had an asymptomatic infection; only 10% were severely symptomatic, and they were found to be infected with a virus closely related to A/Asian/57. For H3N2 epidemics, the rate of reinfection was 17% among students studied in 1970 who were reinfected with a virus closely related to the prototype A/Hong Kong/68 (H3N2). Reinfection with an extremely drifted variant of H3N2 was found to be 32% and 69% in two groups of students studied in 1972. Reinfection with a related virus was 32% in another group studied in 1983. Among the students studied who were reinfected with H3N2 viruses, the rates of asymptomatic infection were similar to those of symptomatic infection. The reinfection rates with a virus related to A/USSR/77 (H1N1) were 9.3% and 20% in two groups studied in 1980.

Adult↗
PubMed1986

Effects of new hypoglycemic agent 2-piperazinyl-4-methyl-amino-5-methylthieno [2,3-d]pyrimidine dihydrochloride hydrate.

The antidiabetic effects of 2-piperazinyl-4-methylamino-5-methylthieno [2,3-d]pyrimidine dihydrochloride hydrate (Compound-(I] were investigated in various animals and in various conditions. Compound-(I) is a new hypoglycemic agent structurally unrelated to sulfonylurea and biguanide. It produced dose dependent hypoglycemic effects (10-100 mg/kg) in rats and mice under fed, fasted and glucose tolerated states. However, it was ineffective in fasted guinea pigs even when given at 100 mg/kg. In normal fed rats and mice, hypoglycemic effects of Compound-(I) were estimated to be 3-19 times and 12-70 times more potent than tolbutamide and phenformin, respectively. Compound-(I) also produced hypoglycemic action in streptozocin diabetic rats and genetically diabetic KK mice. Especially, its hypoglycemic effect was observed at the dose as low as 3 mg/kg p.o. in KK mice. However, elevation of blood lactate was accompanied by lowering of blood glucose after oral administration of Compound-(I) in normal rats and mice and in streptozocin diabetic rats, while these effects were not observed in guinea pigs. In addition, plasma insulin significantly increased after administration of Compound-(I) in both normal and KK mice, while this increase in plasma insulin was not so prominent in fed rats. This elevation in plasma insulin might be produced by alpha 2-adrenergic antagonism at pancreatic B cell as Compound-(I) suppressed epinephrine induced hyperglycemia by elevating plasma insulin. In conclusion, Compound-(I) seems mainly to produce hypoglycemic action through extrapancreatic mechanism which increases blood lactate associated with anaerobic glycolysis or inhibition of gluconeogenesis. In addition, elevation of plasma insulin also might be responsible for hypoglycemic effects.

Adrenergic alpha-Antagonists↗
PubMed1985

Cross-subtype protection in humans during sequential, overlapping, and/or concurrent epidemics caused by H3N2 and H1N1 influenza viruses.

A total of 663 pupils at four schools were studied serologically and clinically during a period of large sequential and/or mixed epidemics of infection with two subtypes of influenza A virus, H3N2 and H1N1. Of 91 middle-school pupils infected with H3N2 virus shortly before and 82 pupils not previously infected with this subtype, 59% and 91% became infected with H1N1 virus, respectively; this difference was significant. Similar results were obtained at the two primary schools studied. At a high school where epidemics due to the H3N2 and H1N1 subtypes occurred concurrently, the rate of infection of individual pupils with both viruses (2%) was significantly lower than those at the other three schools (21%, 23%, and 31%, respectively), where an epidemic caused by the H3N2 subtype appeared first and was then partially overlapped and succeeded by an epidemic caused by the H1N1 subtype. These findings suggest the existence of cross-subtype protection in humans during sequential and/or concurrent epidemics caused by two viral subtypes.

Adolescent↗
PubMed1985

Biochemical studies of rat atrial natriuretic factor.

The natriuretic substances were purified from rat atrium (ANF, atrial natriuretic factor) and were shown to be identical with the inhibitor of norepinephrine-induced contraction of smooth muscle. Their four native forms were isolated. Amino acid sequence analyses showed they are peptides with 35, 31, 30 and 25 amino acid residues respectively and contain a ring structure consisting of 17 amino acid residues and a disulfide bridge. The presence of a high molecular weight prohormone was shown. cDNA coding for the precursor was cloned and used to deduce the amino acid sequence of the preprohormone. Genomic DNA for ANF was cloned and the presence of two introns were found. Several ANF peptides were synthesized. Structure-function studies showed that the ring structure is essential for the activity. Antibodies produced against the synthetic 25 amino acid residue ANF were used to develop radioimmunoassay. The presence of ANF in rat plasma was demonstrated as evidence that ANF is a circulating hormone. ANF was also found in the hypothalamus of rats. The quantitative determination of the synthetic ability of ANF has been determined by the application of ANF cDNA for the quantification of ANF messenger RNA. Immunohistochemical methods localized ANF in cardiac atriocytes, gonadotrophs in anterior pituitary and adrenal medulla (chromaffin cells). A strong immuno-reactivity was found in dark cells of the collecting ducts of the kidney. ANF increases cyclic GMP in target cells suggesting that cyclic GMP may be the intracellular mediator of ANF action.

Adrenal Cortex↗
PubMed1984

Rat atrial natriuretic factor: isolation, structure and biological activities of four major peptides.

Four peptides possessing both natriuretic activity and smooth muscle relaxant activity were isolated from rat atrium and their amino acid sequences determined. The four peptides designated ANF-I, ANF-II, ANF-III and ANF-IV containing 35, 31, 30 and 25 amino acid residues, respectively, were obtained in a molar ratio of 4:60:20:16. The predominant species ANF-II, which may represent the native form of ANF, has the following sequence: (H2N)-G-P-R-S-L-R-R-S-S-C-F-G-G-R-I-D-R-I-G-A-Q-S-G-L-G-C-N-S-F-R-Y-(COO H) in which Cys-10 and Cys-26 are disulfide linked. Cleavage of the aspartyl linkage at position 16 by staphylococcal protease caused complete inactivation, indicating that the ring conformation is essential. The dose-response relationships determined for the four peptides in relaxing norepinephrine-induced contraction of rabbit thoracic aorta showed half-maximum relaxation at concentrations ranging from 1.5 X 10(-9) to 2.5 X 10(-9) M. Comparable dose-response relationships were observed in relaxation of carbacol-induced contraction of chick rectum strips as tested with ANF-II and ANF-IV.

Amino Acid Sequence↗
PubMed1984

Synthesis of atrial natriuretic peptides and studies on structural factors in tissue specificity.

Two atrial natriuretic peptides, containing 25 amino acid residues, ANF IV, and 21 amino acid residues, ANF V, were synthesized by a solid phase method and oxidized with K3Fe(CN)6 to form a disulfide bridge. Synthetic ANF IV exhibited a natriuretic activity with an ED50 70 times higher than that of synthetic ANF V, whereas the longer peptide was only 2.5 times more potent in chick rectal smooth muscle relaxant activity. Both peptides inhibited norepinephrine-induced contraction of rabbit aorta. The shorter peptide, ANF V, was 300 times less efficient than the longer peptide, ANF IV. It is proposed that the carboxy-terminal of ANF IV seems to have a modulating effect on receptor affinity in kidney and vascular tissue.

Animals↗
PubMed1984

Rat atrial natriuretic factor: complete amino acid sequence and disulfide linkage essential for biological activity.

The complete amino acid sequence of an atrial natriuretic peptide from rat possessing both natriuretic and smooth muscle relaxant activity has been determined. The peptide has the structure (sequence in text) and a calculated molecular weight of 2,706. The ring structure formed by the disulfide linkage between the two half-cystine residues was found essential for both the natriuretic activity and smooth muscle relaxant activity. The purified peptide caused 50% relaxation of norepinephrine (5 X 10(-8)M) induced contraction of rabbit thoracic aorta at the concentration of 2 X 10(-9)M and complete relaxation at 6 X 10(-9)M.

Amino Acid Sequence↗
PubMed1984

Development of a pertussis component vaccine in Japan.

Antibodies against two physicochemically purified haemagglutinins (HAs) of Bordetella pertussis (filamentous HA and leucocytosis-promoting-factor HA) protect laboratory animals from pertussis. A vaccine containing these two HAs was prepared and tested in trials involving about 5000 children. Culture supernatant of Bordetella pertussis, phase I, was treated with ammonium sulphate, and a crude extract of the HAs was extracted from the precipitate by the use of concentrated sodium chloride. This crude extract was fractionated by sucrose density gradient centrifugation to obtain an HA preparation practically free of endotoxin. The HA preparation was treated with formalin to destroy its ability to induce leucocytosis and to cause histamine sensitisation. Aluminium hydroxide was added to the preparation as an adjuvant. The component vaccine is not only potent as judged by the mouse test but is also less than one-tenth as toxic as whole-cell vaccine as judged by leucocytosis promotion, histamine sensitisation, and endotoxicity tests. Field trials showed that component vaccine was as effective as and produced less side-effects than did conventional whole-cell vaccine. The vaccine has been used for mass immunisation in Japan since the autumn of 1981.

Antibodies, Bacterial↗