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Biomedical subjects

A Honda

Publications and source records attributed to A Honda.

At least 145 records · Page 8Linked to original sources
PubMed1994

Mapping of the genes encoding mouse thromboxane A2 receptor and prostaglandin E receptor subtypes EP2 and EP3.

Thromboxane A2 (TXA2) and prostaglandin E2 (PGE2) are two of the most representative eicosanoids that are formed from arachidonic acid. They produce a broad spectrum of biological effects mediated through specific cell surface receptors. We have mapped genetic loci for TXA2 receptor, Tbxa2r, and for PGE2 receptor subtypes EP2 and EP3, Ptgerep2 and Ptgerep3, respectively, using restriction fragment length variants in interspecific backcross mice. None of the three loci cosegregated with each other. Tbxa2r mapped to Chr 10, Ptgerep2 mapped to the distal end of Chr 3. Possible human loci for these receptors are predicted based on the homology between mouse and human chromosomes.

Animals↗
PubMed1994

Pharmacokinetics of doxorubicin and its active metabolite in patients with normal renal function and in patients on hemodialysis.

The comparative pharmacokinetics of doxorubicin (DOX) were investigated in five hemodialysis (HD) and eight non-hemodialysis (non-HD) patients who were infused with a 40- to 60-mg dose of DOX at a constant rate over 30 min. A significant difference was observed in the total body clearance (Cl tot) of DOX between HD and non-HD patients. The area under the curve (AUC) for both DOX and doxorubicinol (DOXol), an active metabolite, showed increases of approximately 1.5 and 3 times in HD patients as compared with non-HD patients. Although these differences were not statistically significant (P < 0.1), the mean residence time (MRT) of DOX and DOXol in HD patients showed a 2-fold increase in comparison with those in non-HD patients. Compartmental analysis indicated that the greater AUC values and longer MRT of DOX and DOXol in HD patients resulted from the lesser DOXol formation and disappearance of rate constants. As a consequence of the decrease in Cl tot for DOX and the marginal hemodialysis clearance of both DOX and DOXol, the present study suggests that the exposure to DOX and DOXol obtained in HD patients greater than achieved in non-HD patients. Careful attention should therefore be paid to HD patients receiving DOX.

Aged↗
PubMed1994

[Fulmonant group A streptococcal infection accompanied by massive pulmonary hemorrhage and subsequent asphyxia: a case report].

A case of fulminant group A streptococcal infection occurring in a 6-year-old Japanese child is reported. She was accompanied by massive pulmonary hemorrhage and subsequent asphyxia. She initially had pharyngalgia with fever. The cephalosporin antibiotic was given orally for 3 days. Three days after that recurrence of fever and pharyngalgia was noted. Twelve hours later tachypnea and a sudden onset of hemoptysis was noted. She manifested DOA (dead on arrival) and died in the emergency room. Autopsy revealed the presence of numerous cocci in the vessels and massive pulmonary hemorrhage. Streptococcus pyogenes was isolated from the blood. The serotype of this group A streptococcal organism was typed as M4, T4, which produces exotoxin type B and C, which was sensitive to the penicillins.

Asphyxia↗
PubMed1994

A family with optic atrophy and congenital hearing loss.

A 37-year-old woman had optic atrophy in both eyes and low-tone hearing disturbance of both ears noted after 34 years of age. Her visual acuity was 0.5 in the right eye and 0.6 in the left. The visual fields of both eyes showed slight progressive concentric narrowing. Hearing loss was gradually progressive. Her 13-year-old daughter also had optic atrophy in both eyes and low-tone hearing loss in both ears after 11 years of age. Her visual acuity was 0.8 in the right eye and 1.0 in the left. Her visual fields showed slight concentric narrowing. She had enlarged blind spots in both eyes. The mother and her daughter had deuteranomaly. Family history showed that the father, one brother and three sisters of the mother had congenital hearing loss. No other cause for the optic nerve atrophy and hearing disturbance could be found except heredity.

Adolescent↗
PubMed1994

Human papillomavirus type 60-associated plantar wart. Ridged wart.

BACKGROUND: We had recently cloned a new cutaneous human papillomavirus type 60 (HPV-60) from a plantar cyst with characteristic pathologic changes and identified it in additional cysts. However, it is not known whether or not HPV-60 infection causes the other cutaneous lesions. OBSERVATIONS: Six plantar warts were found in five patients. These warts were found either with concomitant plantar cysts (four patients) or without an accompanying cyst (one patient). All warts showed a similar clinical appearance, including a smooth and slightly elevated surface and the retained appearance of the dermal ridges. Their histopathologic features were identical to those found in the wall of the cysts reported previously, namely hyperkeratosis with vacuolated structure with or without nuclei in the horny layer and amorphous eosinophilic cytoplasmic inclusions in the cells with peripherally located nuclei in the granular and prickle cell layers. By Southern blot analysis, all warts were found to harbor HPV-60 DNA. In addition, immunohistochemistry and in situ hybridization analysis revealed the presence of viral capsid antigen and viral genome in these lesions, respectively. CONCLUSION: We conclude that HPV-60 infection on the plantar skin causes the warty lesion, designated as ridged wart, distinct from those infected with other cutaneous human papillomaviruses.

Adolescent↗
PubMed1993

Modification of 1 alpha,25-dihydroxyvitamin D3 metabolism by introduction of 26,26,26,27,27,27-hexafluoro atoms in human promyelocytic leukaemia (HL-60) cells: isolation and identification of a novel bioactive metabolite, 26,26,26,27,27,27-hexafluoro-1 alpha,23(S),25-trihydroxyvitamin D3.

To study whether the introduction of fluoro atoms into C-26 and C-27 positions on the 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] molecule could affect metabolism in human promyelocytic leukaemia (HL-60) cells, we compared the metabolism of 26,26,26,27,27,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 [26,27-F6-1 alpha,25(OH)2D3] and 1 alpha,25(OH)2D3 in HL-60 cells. 26,27-F6-1 alpha,25(OH)2D3 was mainly converted into a new bioactive metabolite, 26,26,26,27,27,27-hexafluoro-1 alpha,23(S),25- trihydroxyvitamin D3 [26,27-F6-1 alpha,23(S),25(OH)3D3], but not into 26,26,26,27,27,27-hexafluoro-1 alpha,24(R),25-trihydroxyvitamin D3 [26,27-F6-1 alpha,24(R),25(OH)3D3] in HL-60 cells. 26,27-F6-1 alpha,23(S),25(OH)3D3 was identified by combinations of h.p.l.c., u.v. spectroscopy and g.c.-mass spectrometry. Evidence is presented that 26,27-F6-1 alpha,25(OH)2D2 was metabolized to 26,27-F6-1 alpha,23(S),25(OH)3D3 by C-23 hydroxylation as a first step of the metabolism, and the 23-hydroxylated bioactive metabolite was accumulated in the cells, whereas 1 alpha,25(OH)2D3 was initially deactivated and metabolized to 1 alpha,24(R),25(OH)3D3 by C-24 hydroxylation through a side-chain oxidation pathway resulting in C23-C24 cleavage, yielding 24,25,26,27-tetranor-1 alpha,23(OH)2D3 in HL-60 cells. These results show that 26,27-F6-1 alpha,25(OH)2D3 and 1 alpha,25(OH)2D3 are metabolized by different metabolic pathways in HL-60 cells.

Calcitriol↗
PubMed1993

Third isoform of the prostaglandin-E-receptor EP3 subtype with different C-terminal tail coupling to both stimulation and inhibition of adenylate cyclase.

A functional cDNA clone for a third isoform of the mouse prostaglandin-E-receptor EP3 subtype, derived by alternative RNA splicing, named the EP3 gamma receptor, was obtained in addition to those for the two other isoforms, EP3 alpha and EP3 beta. The three isoforms are only different in the amino acid sequence of the putative cytoplasmic carboxy-terminal tail. When expressed, EP3 gamma shows identical ligand-binding properties to these of the other isoforms. The EP3-selective agonist, M&B 28767, increased the basal cAMP level and inhibited the forskolin-induced increase in the cAMP level in EP3 gamma, while it decreased both the basal and forskolin-elevated cAMP levels in EP3 alpha and EP3 beta. The M&B 28767-stimulated GTPase activity consisted of pertussis-toxin-sensitive and cholera-toxin-sensitive portions in the EP3 gamma-expressing cell membrane, suggested that EP3 gamma is coupled to both guanine nucleotide-binding inhibitory and stimulatory proteins. These results indicate that EP3 gamma is coupled to both stimulation and inhibition of adenylate cyclase, but that EP3 alpha and EP3 beta are exclusively coupled to inhibition of adenylate cyclase. Thus, alternative splicing produces a third isoform with a different carboxy-terminal tail, which differs from the other two isoforms in the specificity of coupling to a signal-transduction pathway.

Adenylyl Cyclase Inhibitors↗
PubMed1993

Cloning and expression of cDNA for a mouse EP1 subtype of prostaglandin E receptor.

A functional cDNA clone encoding a mouse EP1 subtype of prostaglandin (PG) E receptor was isolated from a mouse cDNA library by cross-hybridization with the mouse thromboxane A2 receptor cDNA. The clone isolated encodes a protein consisting of 405 amino acid residues with putative seven-transmembrane domains. [3H]PGE2 specifically bound to the membrane of Chinese hamster ovary cells expressing this clone. The binding to the membrane was displaced with unlabeled PGs in the order of PGE2 > iloprost (a prostacyclin analogue) > PGE1 > PGF2 alpha > U-46619 (a thromboxane A2 analogue) > PGD2. The binding was also inhibited by 17-phenyl trinor PGE2 (an EP1 agonist) and sulprostone (an EP1 and EP3 agonist) but not by 11-deoxy PGE1 (an EP2 and EP3 agonist) and butaprost (an EP2 agonist). PGE2 induced a rapid increase in intracellular Ca2+ concentration in Chinese hamster ovary cells expressing the receptor. These results suggest that this receptor belongs to EP1 subtype of PGE receptor. Northern blot analysis demonstrated that the mRNA of this receptor is expressed abundantly in kidney and in a lessor amount in lung.

Amino Acid Sequence↗
PubMed1993

Prostaglandin E2 stimulates cyclic AMP-mediated hyaluronan synthesis in rabbit pericardial mesothelial cells.

We studied the effects of prostaglandin E2 (PGE2) on hyaluronan synthesis in rabbit pericardial mesothelial cells, and the following results were obtained. (1) PGE2 (10-1000 ng/ml) stimulated hyaluronan synthesis and the level of hyaluronan synthase activity in a dose- and time-dependent manner, but PGF2 alpha did not. (2) Cyclic AMP (cAMP) levels in the cells peaked (about a 7-fold increase) at 5-10 min after adding PGE2 (1000 ng/ml). (3) Increased hyaluronan synthesis induced by PGE2 was significantly inhibited after pretreatment with either an adenylate cyclase inhibitor (2',5'-dideoxyadenosine) or a cAMP-dependent protein kinase inhibitor (PKI 5-24), but there was no inhibition with the protein kinase C inhibitor H-7. (4) When the intracellular cAMP level was raised by manipulating the levels of dibutyryl cyclic AMP or forskolin, hyaluronan synthesis and the level of hyaluronan synthase activity were also stimulated. These results suggest that PGE2 produced by cells stimulates hyaluronan synthesis in rabbit pericardial cells and that the stimulation mechanism involves the cAMP-mediated protein kinase signal transduction process.

Adenylyl Cyclase Inhibitors↗
PubMed1993

Cloning and expression of a cDNA for mouse prostaglandin E receptor EP2 subtype.

A functional cDNA clone encoding mouse EP2 subtype of prostaglandin (PG) E receptor was isolated from a mouse cDNA library by cross-hybridization with the mouse EP3 subtype PGE receptor cDNA. The mouse EP2 receptor consists of 513 amino acid residues with putative seven-transmembrane domains. In contrast to EP3 receptor, this receptor possesses long third intracellular loop and carboxyl-terminal tail. [3H] PGE2 specifically bound to the membrane of mammalian COS cells transfected with the cDNA. The binding to the membrane was displaced with unlabeled PG in the order of PGE2 = PGE1 >> iloprost > or = PGF2 alpha > or = PGD2. The binding was also inhibited by misoprostol, an EP2 and EP3 agonist, but not by sulprostone, an EP1 and EP3 agonist, and SC-19220, an EP1 antagonist. PGE2 markedly increased cAMP level in COS cells transfected with the cDNA. These results suggest that this receptor is EP2 subtype. Northern blot analysis demonstrated that the EP2 mRNA is widely expressed in various tissues, the abundant expression being observed in ileum, thymus, and mastocytoma P-815 cells.

Amino Acid Sequence↗
PubMed1993

Simultaneous determination of mevalonate and 7 alpha-hydroxycholesterol in human plasma by gas chromatography-mass spectrometry as indices of cholesterol and bile acid biosynthesis.

A very sensitive and specific method for the simultaneous determination of mevalonate and 7 alpha-hydroxycholesterol in human plasma is described. The assay is based on isotope dilution mass spectrometry: the extracts from plasma were treated with benzylamine followed by dimethylethylsilylimidazole, then the resulting dimethylethylsilyl ether derivatives of mevalonylbenzylamide and 7 alpha-hydroxycholesterol were determined by gas chromatography-mass spectrometry using high-resolution selected-ion monitoring. Simple regression analysis revealed significant correlations between the plasma level of mevalonate and the hepatic activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 1.1.1.34) (r = 0.83, P < 0.01) and between the plasma level of free 7 alpha-hydroxycholesterol and the hepatic activity of cholesterol 7 alpha-hydroxylase (EC 1.14.13.7) (r = 0.76, P < 0.05).

Adult↗
PubMed1993

Functional interaction of prostaglandin E receptor EP3 subtype with guanine nucleotide-binding proteins, showing low-affinity ligand binding.

The functional interaction of prostaglandin E (PGE) receptor EP3 subtype with GTP-binding proteins (G proteins) was characterized in the membranes prepared from mouse EP3 receptor cDNA-transfected Chinese hamster ovary cells. PGE2 inhibited forskolin-stimulated adenylate cyclase activity in CHO cells expressing EP3 receptor and this inhibition was abolished by pertussis toxin (PT) treatment. The PGE2 binding to the membranes was increased by GTP gamma S, and PT treatment also increased the binding activity to the same level as that increased by GTP gamma S, but the sensitivity of GTP gamma S was lost. Reconstitution with PT-sensitive G proteins into the ADP-ribosylated membranes reduced the PGE2 binding activity with the following preference: Gi1 = Gi2 > Gi3 > GO, but GTP gamma S completely blocked the reduction by G proteins. The G-protein-induced reduction of the binding was due to the increase in Kd without the change of Bmax, and due to suppression of association rate. [3H]PGE2-bound EP3 receptor solubilized from the ADP-ribosylated membranes in the presence or absence of GTP gamma S was eluted at the position of M(r) = approx. 60 kDa, similar to the relative molecular mass of EP3 receptor deduced from its amino acid sequence. In contrast, [3H]PGE2-bound receptor solubilized from Gi2-reconstituted membranes was eluted at the position of M(r) = approx. 130 kDa, corresponding to the M(r) of the complex of EP3 receptor and Gi2, but GTP gamma S shifted the position of its elution from M(r) = 130 to 60 kDa. Furthermore, addition of PGE2 stimulated the GDP release from G proteins reconstituted into the ADP-ribosylated membranes, and PGE2 inhibited forskolin-stimulated adenylate cyclase activity in G-protein-reconstituted membranes with a selectivity order of Gi1 = Gi2 > Gi3 > GO. These results indicate that EP3 receptor can functionally couple to PT-sensitive G proteins and unusually the complex form with G proteins has low affinity for the ligand but the form not associated with G proteins has high affinity.

Adenosine Diphosphate↗
PubMed1993

Two isoforms of the EP3 receptor with different carboxyl-terminal domains. Identical ligand binding properties and different coupling properties with Gi proteins.

Functional cDNA clones for two isoforms of the mouse prostaglandin E receptor EP3 subtype derived from alternative RNA splicing were obtained. The two isoforms are only different in the sequence of the putative cytoplasmic carboxyl-terminal tail and their hydrophobicity; one isoform, named EP3 alpha, has a hydrophilic tail, and the other, named EP3 beta, has a hydrophobic tail. When expressed, the two receptors displayed identical ligand binding properties but different responses to guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S). Without a change in the Bmax value, GTP gamma S increased Kd for prostaglandin E2 of EP3 beta and decreased that of EP3 alpha. These effects were abolished by the treatment of membranes with pertussis toxin and restored by the addition of Gi2. Although both isoforms exerted inhibition of forskolin-induced cAMP accumulation, three orders lower concentrations of agonists were required for EP3 alpha than EP3 beta for 50% inhibition of cAMP formation. A similar difference in agonist potency was observed also for agonist-induced stimulation of GTPase activity in membranes. Thus, the two receptors with different carboxyl-terminal tails show different coupling to the Gi protein, leading to the opposite responses to GTP in the ligand binding affinity and to different affinities of the agonist-occupied receptors to the G proteins.

Adenylyl Cyclases↗
PubMed1993

Nucleotide sequence of the cDNA encoding nucleoside diphosphate kinase II from spinach leaves.

The primary structure of nucleoside diphosphate (NDP) kinase II, one of the two isozymes found in spinach leaves, has been deduced from its cDNA sequence. NDP kinase II comprises 233 amino acid residues and has a molecular mass of 26,107 Da, which is larger than that of the purified NDP kinase II subunits (18 kDa) by about 8 kDa, suggesting that NDP kinase II might be post-translationally processed. Homology was found between the sequence of spinach NDP kinase II, and the sequences of spinach NDP kinase I, rat NDP kinases alpha and beta, Dictyostelium discoideum NDP kinase, the human Nm23-H1 and Nm23-H2 proteins and the awd protein of Drosophila melanogaster.

Amino Acid Sequence↗
PubMed1993

Antitumor effects of a novel monoclonal antibody with high binding affinity to ganglioside GD3.

Ganglioside GD3, which is one of the major gangliosides expressed on the cell surface human tumors of neuroectodermal origin, has been studied as a target molecule for passive immunotherapy. We established ten kinds of anti-GD3 monoclonal antibodies (mAb) of the mouse IgG3 subclass by immunization with purified GD3 and melanoma cells. One of the established mAb, KM641, showed major reactivity with GD3 and minor reactivity with GQ1b out of 11 common gangliosides in an enzyme-linked immunosorbent assay. Immunostaining of gangliosides, separated on thin-layer chromatography plates, using KM641 revealed that most of the melanoma cell lines contained immunoreactive GD3 and GD3-lactone at a high level, but only the adrenal gland and the urinary bladder out of 21 human normal tissues had immunoreactive GD3. In immunofluorescence, KM641 bound to a variety of living tumor cell lines especially melanoma cells, including some cell lines to which another anti-GD3 mAb R24, established previously, failed to bind. High-affinity binding of KM641 to a tumor cell line was quantified by Scatchard analysis (Kd = 1.9 x 10(-8) M). KM641 exerted tumor-killing activity in the presence of effector cells or complement against melanoma cells expressing GD3 at a high level. Not only natural killer cells but also polymorphonuclear cells were effective as the effector cells in antibody-dependent cellular cytotoxicity. Intravenous injection of KM641 markedly suppressed the tumor growth of a slightly positive cell line, C24.22 (7.2 x 10(5) binding sites/cell), as well as a very GD3-positive cell line, G361 (1.9 x 10(7) binding sites/cell), inoculated intradermally in nude mice. KM641, characterized by a high binding affinity for GD3, has the potential to be a useful agent for passive immunotherapy of human cancer.

Animals↗
PubMed1993

Hepatic cholesterol and bile acid synthesis in Japanese patients with cholesterol gallstones.

In Japan the composition of gallstones is changing rapidly from the once-predominant brown-pigment stones to cholesterol ones. The present work was undertaken to clarify the mechanism of cholesterol supersaturated bile production in Japanese patients with cholesterol gallstones. In 26 non-obese and normolipidemic patients (11 with cholesterol gallstones, 8 with black- or brown-pigment gallstones, 7 without gallstones) a liver biopsy and hepatic bile were surgically obtained under standardized conditions. The cholesterol saturation of hepatic bile was significantly higher in cholesterol gallstone patients than in gallstone-free controls (195 +/- 10 vs. 146 +/- 8%, respectively; P < 0.01). The microsomal activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for cholesterol synthesis, cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme for bile acid synthesis, and 7 alpha-hydroxy-4-cholesten-3-one 12 alpha-hydroxylase (12 alpha-hydroxylase), the rate-limiting enzyme for cholic acid synthesis, were assayed simultaneously in the same subjects. There were positive correlations between HMG-CoA reductase and cholesterol 7 alpha-hydroxylase activities (Rs = 0.62, P < 0.005), and between cholesterol 7 alpha-hydroxylase and 12 alpha-hydroxylase activities (Rs = 0.44, P < 0.05) in all subjects, irrespective of the existence of gallstones. The activities of the three rate-limiting enzymes did not differ significantly among the three groups (cholesterol stone, pigment stone and stone-free). In conclusion, the cholesterol supersaturation of hepatic bile in nonobese and normolipidemic Japanese patients with cholesterol gallstones does not result from an increased hepatic cholesterol synthesis or a decreased bile acid synthesis.

Bile Acids and Salts↗