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Biomedical subjects

T Ohkubo

Publications and source records attributed to T Ohkubo.

At least 289 records · Page 16Linked to original sources
PubMed1990

Synthesis of 2-hydroxyestriol monoglucuronides and monosulfates.

The ring A monoglucuronides and monosulfates of 2-hydroxyestriol were synthesized from 2-hydroxyestriol 16,17-diacetate by means of the Koenigs-Knorr reaction with methyl alpha-acetobromoglucuronate and sulfation with sulfur trioxide-pyridine complex, respectively. The conjugated positions of these compounds were definitely established by conversion to 2-hydroxyestriol monomethyl ethers by methylation, then enzymatic hydrolysis. The ring D monoglucuronides and monosulfates of 2-hydroxyestriol were also prepared from 2-hydroxyestriol 2,3-dibenzyl ether by glucuronidation and sulfation in a similar fashion followed by debenzylation, respectively. The positions of conjugation were established on the basis of their 1H-nuclear magnetic resonance spectral data.

Animals↗
PubMed1990

The differences in conformation between alpha-human atrial natriuretic polypeptide, alpha-hANP, and its derivative, Met(O)-alpha-hANP, in solution.

The differences in conformation between alpha-human atrial natriuretic polypeptide (alpha-hANP) and its inactive analog, Met(O)-alpha-hANP, have been analyzed by nuclear magnetic resonance spectroscopy. All proton resonances for both peptides were assigned by means of the sequential assignment procedure. The three-dimensional structure of alpha-hANP in solution had previously been determined by distance geometry calculation using distance constraints derived from nuclear Overhauser effects (NOEs). Here, the three-dimensional structure of Met(O)-alpha-hANP was determined. The conformational differences between these two molecules were as follows: three segments of alpha-hANP, Ser1-Cys7, Arg11-Ala17 and Gln18-Tyr28, have some ordered structures. In Met(O)-alpha-hANP the Gln18-Tyr28 region has a similar conformation, while the remaining two regions do not have the ordered structure found in alpha-hANP. It is suggested that the conserved conformation of the Gln18-Tyr28 region is required for binding to the ANP receptor and that the slight biological activity of Met(O)-alpha-hANP is due to loss of the ordered structures evoked in the Ser1-Cys7 and Arg11-Ala17 regions of alpha-hANP.

Amino Acid Sequence↗
PubMed1990

Impaired superoxide production in peripheral blood neutrophils of germ-free rats.

A method of separating neutrophils from the peripheral blood of rats with 95% purity is described. To determine the role of antigenic stimulation in neutrophil function, neutrophils from germ-free (GF) rats were compared with those of conventional (CV) rats. Neutrophil counts were lower in GF rats but the total number of monocytic cells was the same. To measure phagocytic killing, superoxide anion production was determined and found to be lower in GF neutrophils (2.1 +/- 0.5 nmol/min/10(6) cells) than in CV neutrophils (9.5 +/- 2.9 nmol/min/10(6) cells). Myeloperoxidase activity was found to be twofold higher in GF neutrophils. When a recombinant human granulocyte colony-stimulating factor (rhG-CSF) was intravenously injected, superoxide production did not change in either GF or CV neutrophils, but the myeloperoxidase activity of neutrophils in both types of rats decreased. rhG-CSF increased the number of neutrophils in both GF (10-fold) and CV rats (three- to fourfold).

Animals↗
PubMed1990

Systemic effects of carteolol, a beta-adrenoceptor antagonist in stroke-prone spontaneously hypertensive rats.

The preventive effects of carteolol, a beta-adrenoceptor antagonist, on secondary lesions were pathophysiologically examined in stroke-prone spontaneously hypertensive rats (SHRSP) from 8 to 30 weeks of age. Carteolol was added to the drinking water in doses of 0.005% (8 to 18 weeks of age) to 0.01% (19 to 30 weeks of age) (3.8 and 6.0 mg/kg/d, respectively). These animals gained significantly more weight than the untreated control SHRSP, and their heart rate reduced from 14 weeks of age. Suppression of blood pressure rise was not definite, however, histology revealed prevention of the development or aggravation of secondary hypertension-related lesions, such as myocardial fibrosis, proliferative arteriolitis, necrotic arteriolitis and renal glomerular lesions. A decrease in non-esterified fatty acids in the serum was evident. Thus, carteolol has cardiac as well as renal protective effects, in the SHRSP.

Adrenal Glands↗
PubMed1990

[Etoposide-induced deoxyribonucleic acid (DNA) damage and its effects on nucleotide pools in murine leukemia L1210 cells].

The effect of etoposide-induced deoxyribonucleic acid (DNA) damage and its effect on nucleotide pools were examined in murine leukemia L1210 cells. Etoposide (15 mg/kg) was administered intraperitoneally on the third day after peritoneal inoculation of 1 x 10(6) L1210 cells. The dosage of etoposide produced 175% of the increase of lifespan as described previously. Strand breaks in DNA occurred within 10 min after i.p. injection, but as the time interval between injection and removal of the cells from the mice was elongated to 1 and 3 h, the continuous repairing of DNA was observed. At 6 h after the injection, the maximum concentration of DNA was located in the vicinity of that of control. In our previous study, ara-C was most effective when given at 3 to 6 h after the administration of etoposide. The sensitivity to ara-C might increase during the repairing period from the etoposide-induced DNA damage. All four dNTPs increased progressively within 6 h up to 3-fold of control. The changes in rNTPs were similar, but the degree of the changes was smaller than that of dNTPs. These changes in dNTPs and rNTPs would be an important factor for the combination to determine the antitumor effect of etoposide and nucleoside analogues.

Animals↗
PubMed1990

[Participation of the sensory nerves in the inflammatory response induced by irritants].

Participation of the sensory neurons, especially substance P (SP)-containing neurons, in the inflammatory response induced by formalin (FOR), croton oil (CRO), mustard oil (MUS), carrageenin (CAR), dextran (DEX) and egg white (EGG) was studied in mice and rats. FOR-induced foot edema was significantly inhibited by denervation of the sciatic nerve of rats, but it was slightly facilitated by that of the saphenous nerve. CAR-induced edema was not influenced by denervation of both nerves. In mice pretreated with capsaicin of the sciatic nerve, the early phase of foot edema induced by FOR, CRO or MUS was significantly inhibited. Edema induced by CAR, DEX or EGG was not inhibited by the capsaicin treatment. Spantide (an SP antagonist) at 0.1 mg/kg showed the same result as the capsaicin treatment. FOR, CRO or MUS caused a marked plasma extravasation, which was inhibited by spantide. The weak plasma extravasation elicited by CAR, DEX or EGG was not inhibited by spantide. FOR, CRO or MUS caused an intense biphasic nociceptive response; and the early phase of the response was inhibited by spantide. CAR, DEX or EGG caused little or no nociception. These findings suggest that SP antidromically released from the primary sensory neurons may induce potent vascular responses such as vasodilatation and plasma extravasation in the early phase of inflammation induced by FOR, CRO and MUS, whereas inflammatory responses induced by CAR, DEX and EGG may progress through different processes.

Animals↗
PubMed1990

Roles of substance P and somatostatin on transmission of nociceptive information induced by formalin in spinal cord.

Nociceptive response induced by 0.5% Formalin in the hindpaw of mice had two peaks, 0-5 min (first phase) and 15-20 min (second phase). By using the distinct biphasic response, the nature of the transmitter systems activated by Formalin in the spinal cord was studied for the purpose of determining the difference of the role of substance P (SP) and somatostatin (SST). The injection of (D-Pro2, D-Trp7,9)SP, (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP and SP antiserum inhibited only the first phase response. The i.t. injection of -Aminoheptanoyl-Phe-D-Trp-Lys-(OBz)-Thr- (an SST antagonist), SST antiserum and cysteamine (an SST depletor) inhibited only the second phase. This result indicates that SP is involved in the transmission of the first phase, and SST is involved in the transmission of the second phase of the Formalin-induced nociceptive response. With regard to other nociceptive stimuli, two i.t. SP antagonists produced a significant analgesia in the hot plate and tail pinch tests but had no effect in the acetic acid writhing test. However, i.t. SST antagonist and cysteamine produced a significant analgesia in the writhing test but had no effect in the hot plate and tail pinch test. These results suggest that SP participates in the transient pain induced by such acute stimuli as hot plate, tail pinch and the first phase of Formalin response and that SST participates in the prolonged and inflammatory pain induced by stimuli such as acetic acid and the second phase response.

Animals↗
PubMed1990

Peripheral blood neutrophil function in germfree and conventional rats.

The superoxide anion production and the myeloperoxidase activity between polymorphonuclear cells (PMNs) from conventional and germfree rats were compared. Furthermore, the response to recombinant human granulocyte colony stimulating factor (G-CSF) between both groups of rats was also examined. Our present investigation showed that: (1) the basal superoxide anion production by PMNs in germfree rats (2.1 +/- 0.5 nmol/min/1 x 10(6) PMNs) is less than one fourth of that of conventional rats (9.5 +/- 2.9 nmol/min/1 x 10(6) PMNs). (2) the myeloperoxidase activity of PMNs from germfree rats (38.1 +/- 5.2 nmol/min/1 x 10(6) PMNs) is 1.7 times that of conventional rats (22.4 +/- 4.9 nmol/min/1 x 10(6) PMNs). (3) G-CSF administration increased the number of PMN, 12.4 times in the germfree rats compared with 3.9 times in the conventional rats. (4) the PMNs induced by G-CSF do not differ in the superoxide anion producing activity. However the myeloperoxidase activity decreased in the G-CSF induced PMNs of both groups of rats. From our data, the conventional rats could have a more effective killing activity than the germfree rats. Furthermore, germfree rats may be used as a powerful tool for assay of other biological substances relating to immune system and its regulation.

Animals↗
PubMed1990

[Malignant lymphoma diagnosed by the pericardial biopsy].

The biopsy findings of malignant lymphoma involving the pericardium in a 69-year-old male were reported. The initial presenting symptoms were heart failure followed by rapidly progressive complete heart block. Pacemaker was inserted. Chest roentgenogram showed a marked left pleural effusion. An echocardiogram demonstrated pericardial fluid. The diagnosis of lymphoma was suggested by gallium isotope study with markedly increased isotope uptake in heart, and was subsequently confirmed by pericardial biopsy. After chemotherapy the pleural effusion was decreased and the uptake of gallium disappeared. While the diagnosis of cardiac involved lymphoma was hard antemortem, experience in this case suggests that gallium isotope study and pericardial biopsy are helpful in establishing the correct diagnosis.

Aged↗
PubMed1990

[Histology and immunopathology of colonic carcinoma].

The correlation among lymphoid cell infiltration (LI), cell-mediated immunity and immunoglobulin-containing cells distribution in the colon cancer was studied in resected materials of 136 patients with colonic cancer. The results were as follows: 1) LI of the colon cancer tended to be found more commonly in patients with colonic cancer in clinical early stage than advanced stage. 2) The cumulative 5-year survival rate in patients with positive LI was longer than that in the patients with negative or normal LI. 3) In colonic cancer patients with the better prognosis, IgA-containing cells were distributed around the tumor tissues more abundantly than that in the poor ones. 4) These results suggest that the IgA system somewhat participates in cancer immunity.

Colonic Neoplasms↗
PubMed1989

Solution conformation of conotoxin GI determined by 1H nuclear magnetic resonance spectroscopy and distance geometry calculations.

Conformational analysis of conotoxin GI, one of the neurotoxic peptides produced by a marine snail, genus Conus, was performed by a combination of nuclear magnetic resonance spectroscopy (NMR) and distance geometry calculations. The resulting conformers on minimization of the target function were classified into two groups. The difference in the structures of the conformers is mainly due to the difference in the orientation of the side chain of the tyrosyl residue. The results show that the solution structure of conotoxin GI satisfies the conformational requirements for the biological activity of an antagonist toward nicotinic cholinergic receptors elucidated in a series of studies on alkaloids. The structure is discussed on the basis of the results of comparison of the atomic arrangements of the active sites of snake venom peptides and molecular models based on the results of secondary structure prediction.

Amino Acid Sequence↗
PubMed1989

Synergistic interaction between etoposide and 1-beta-D-arabinofuranosylcytosine.

The sequence-dependency of the antitumor effect of etoposide (VP-16) and 1-beta-D-arabinofuranosylcytosine (ara-C) and its mechanisms were investigated in L1210 ascites tumor. Treatment with VP-16 (15 mg/kg) and ara-C (25 mg/kg) was administered intraperitoneally on days 1, 4, and 7 after tumor inoculation. Three-hour pretreatment with VP-16 followed by ara-C produced 70% of cure rate, but only 20% of cure rate was obtained with the reverse sequence. Simultaneous administration led to the worst therapeutic result. To clarify this sequence-dependent interaction of the both drugs, the effect of VP-16 on incorporation of ara-C into DNA was investigated in vivo. On day 3 after intraperitoneal transplantation of 1 x 10(6) L1210 cells, 15 mg/kg of VP-16 and 1 microCi of (3H)ara-C was administered intraperitoneally with or without time interval. The effect of VP-16 on ara-C incorporation was also strikingly schedule-dependent and compatible with the schedule dependency of the antitumor effect. At 1 hr after injection of ara-C, simultaneous administration of 15 mg/kg of VP-16 reduced ara-C incorporation by 67% of ara-C injection alone. But in sharp contrast to simultaneous-administration, 3 hour preadministration of VP-16 increased ara-C incorporation up to 247%. From 1 to 6 hour after intraperitoneal administration of 15 mg/kg of VP-16, the sedimentation rate of L1210 DNA was increasing on alkaline sucrose gradients. This repairing period from VP-16 induced DNA damage might be the vulnerable time to ara-C through an increase in ara-C incorporation into DNA.

Animals↗
PubMed1989

"Aggressive" osteoblastoma of the maxilla.

A case of osteoblastoma in the maxilla of a 6-year-old boy is reported. The tumor was clinically characterized by locally aggressive behavior but histologically consisted of a relatively well-circumscribed mass of bone-producing epithelioid osteoblasts and occasional multinucleated osteoclasts characteristic of osteoblastoma. Radiographically the tumor appeared to penetrate the cortical plate. Because of the size of the lesion, its histologic features, and the clinical and radiographic impression of its being poorly confined, the diagnosis of "aggressive" osteoblastoma was rendered. The problem of differentiating between benign and aggressive forms of osteoblastoma is discussed.

Child↗
PubMed1989

Increased sensitivity to 1-beta-D-arabinofuranosylcytosine in P388 murine leukemic cells resistant to etoposide.

A variant P388 murine leukemic cell resistant to 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidine)-beta-D-gl ucopyranoside (etoposide) (VP-16-213) was cloned. The variant P388/VP-16 cell line was 159-fold resistant to VP-16. We found that this variant P388/VP-16 cell line showed collateral drug sensitivity to 1-beta-D-arabinofuranosylcytosine(Ara-C), determined by comparing the 50% inhibitory concentrations in 48-h growth inhibition assay. To clarify the mechanism of this increased sensitivity to Ara-C, we quantified the deoxyribonucleoside triphosphate pools and 1-beta-D-arabinofuranosylcytosine triphosphate(Ara-CTP) using high-performance liquid chromatography in the parent and drug-resistant sublines of P388 cells. The analysis of deoxyribonucleoside triphosphate pools revealed that the pyrimidine triphosphate pools were significantly decreased in the P388/VP-16 cell line and the Ara-CTP concentration of two variant cell lines were not significantly different. The Ara-CTP/dCTP ratio was significantly increased in P388/VP-16 cells. These data suggest that the inhibition of the dCTP de-novo pathway and the preservation of the dCTP salvage pathway in P388/VP-16 cells might correlate with the increased sensitivity to Ara-C.

Animals↗
PubMed1989

Influence of fecal anorexigenic substance (FS-T) on plasma amino acids in Wistar and Zucker obese (fa/fa) rats.

An anorexigenic substance (FS-T), found in feces, isolated and injected intraperitoneally, induced significant feeding suppression in Wistar rats and in genetically obese Zucker rats (fa/fa) and their lean littermates. The concentration of total plasma amino acids 2 h after FS-T injection (the time of maximum feeding suppression) was 71.0, 68.6 and 60.2% of that of controls for Wistar and Zucker obese and lean rats, respectively. By 48 h after injection of FS-T, food intake and the concentration of total plasma amino acids had returned to normal. Plasma tryptophan levels and the ratio of tryptophan to neutral amino acids were also monitored to elucidate the relation between FS-T and appetite. Two h after injection of FS-T, the ratio of tryptophan to neutral amino acids had increased in Wistar rats, while no change was detected in either obese or lean Zucker rats. However, no change was observed in plasma glucagon levels in Wistar rats, but a significant increase was found in both obese and lean Zucker rats at 2 h after FS-T injection.

Amino Acids↗