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Biomedical subjects

K Ohmori

Publications and source records attributed to K Ohmori.

At least 325 records · Page 18Linked to original sources

New bronchodilators. II. 3H-imidazo[4,5-c]quinolin-4(5H)-ones.

A series of novel 3-substituted imidazo[4,5-c]quinolin-4(5H)-ones (2a-w) was prepared by the reaction of imidazo[4,5-c]quinolin-4(5H)-ones (6) with several electrophiles under basic conditions. The bronchodilatory activity of these compounds was evaluated on the basis of their protective effects against antigen-induced contraction (the Schultz-Dale reaction) of guinea-pig trachea (in vitro) and antigen inhalation-induced bronchospasm in passively sensitized guinea-pigs (in vivo). Although correlations between in vitro and in vivo activities were not clear, short alkyl chains such as the methyl and ethyl groups at the 3-position were important for potent activity, especially in vivo. Substituents at the 5-position were more tolerant of the activity than those at the 3-position. 5-Ethyl-3-methyl-3H-imidazo[4,5-c]quinolin-4(5H)-one (21) exhibits the most potent bronchodilatory activity among our tested compounds and is at least 5-fold more active than theophylline in vivo.

Animals↗

Immune regulation by brain cells in the central nervous system: microglia but not astrocytes present myelin basic protein to encephalitogenic T cells under in vivo-mimicking conditions.

The antigen-presenting capability of various types of brain cell, such as primary mixed glial cells, astrocytes and microglia, was examined under conditions in which Ia antigen expression on the cultured cells mimicked that in the central nervous system (CNS) of rats with experimental autoimmune encephalomyelitis (EAE). In the CNS of rats with EAE, microglia but not astrocytes express Ia antigens. To produce such conditions, cultured brain cells were treated with various concentrations of interferon-gamma (IFN-gamma). It was revealed that in vivo-like conditions were produced when cultured brain cells were treated with less than 100 U/ml IFN-gamma. Under such conditions, microglia presented an antigen, myelin basic protein (MBP), to MBP-specific T-cell lines. Astrocytes, on the other hand, did not show antigen-presenting ability, but rather suppressed T-cell proliferation. Primary mixed glial cells, mainly comprising astrocytes and microglia, were also weak antigen-presenting cells (APC). These findings suggest that brain cells comprising various types of cell with regard to APC function do not up-regulate the proliferation of encephalitogenic T cells in vivo, although a particular type of brain cell, i.e. microglia, show antigen-presenting capability.

Animals↗

[Prevention of liver metastasis by intrasplenic injection of OK-432].

The effects of OK-432 on artificial liver metastasis of tumor-bearing mice were assessed using murine colon adenocarcinoma MCA-38 in C57 BL/6 mice. OK-432 injection into the spleen reduced the liver metastases. In gastro-intestinal cancer patients, the effects of OK-432 injection into the spleen were assessed with functional T cell subsets. The treatment resulted in an increase in the number of cytotoxic T cells, but a decrease in the suppressor T cells. The facts suggested that OK-432 injection into the spleen had an ability to prevent liver metastases.

Adenocarcinoma↗

[A study of urinary tegafur, 5-fluorouracil (5-FU) and uracil concentrations in the cases of gastric carcinoma for the confirmation of drug-taking compliance after UFT oral administration].

We have measured urinary tegafur (FT), 5-FU and uracil concentrations after UFT oral administration (300 mg daily for 7 days) to confirm drug-taking compliance in the 17 cases undergone gastrectomy. Urinary FT and 5-FU concentrations reached to the plateau 2 and 3 days after administration, respectively, and were maintained until the day after termination of administration. Subsequently, FT and 5-FU concentrations also decreased about 50% at 2 day, 20% at 3 day, 10% of the plateau values at 4 day after termination, respectively. The mean plateau value of urinary FT was 12.9 +/- 6.8 micrograms/dl, and that of urinary 5-FU was 0.67 +/- 0.50 microgram/dl. On the other hand, uracil concentration, was not different before and after administration because of the uracil being present endogenously. Therefore, it was suggested that measurement of urinary FT and 5-FU concentrations is useful for confirmation of UFT-taking compliance.

Administration, Oral↗

Exposure to ozone and erythrocyte osmotic resistance in the rat.

In order to learn the biological effect of photochemical oxidants on living bodies, we exposed newborn and adult rats, of both sexes, to ozone at a concentration of 0.25 ppm, which can be encountered in an urban environment, and then measured the osmotic resistance of their erythrocytes. The results of experiments using newborn rats indicated a positive increase in the osmotic resistance of erythrocytes in whole blood following ozone exposure for 4 weeks. An increase in the osmotic resistance of erythrocytes in the top part obtained by centrifugation was observed following ozone exposure for 12 weeks. This tendency was especially evident among male rats. On the other hand, no increase in the osmotic resistance of erythrocytes was recognized in the adult animals which had been exposed to the same concentration of ozone for 18 months.

Aging↗

Efficacy of a new quinolone, levofloxacin in patients with surgical infections.

The pharmacokinetics and clinical efficacy of levofloxacin (LVFX, DR-3355), an optically pure S(-)-enantiomer of ofloxacin, were studied in patients after surgery. In the pharmacokinetic study, 4 patients undergoing bile drainage were given 2 100-mg tablets by mouth. Peak levels of LVFX were from 2.22 to 4.02 micrograms/ml of plasma at 2-4 hours after the oral administration, and from 7.5 to 11.3 micrograms/ml of bile at 2-6 hours. Forty-three patients with surgical infections, including 16 skin and soft-tissue infections and 12 wound infections, were treated with LVFX. Twenty-eight (70%) of the 40 patients whose results could be evaluated had excellent or good results; 42 (93%) of the 45 causative organisms identified were eradicated. An episode of diarrhea with chills and fever occurred in a 38-year-old man. The results suggested that LVFX has satisfactory antimicrobial effects in surgical infections.

Adult↗

In situ demonstration of proliferating cells in the rat central nervous system during experimental autoimmune encephalomyelitis. Evidence suggesting that most infiltrating T cells do not proliferate in the target organ.

Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats and the bromodeoxyuridine (BrdU)-incorporating cells were demonstrated immunohistochemically in lesions in the central nervous system (CNS) to assess the extent of T cell proliferation during EAE. In active EAE, BrdU+ cells were most numerous on day 12 postimmunization, when both clinical signs and inflammation detected by histologic examination were most severe; they declined thereafter although a considerable number of inflammatory foci remained in some rats. In passive EAE, BrdU+ cells were most numerous 2 days before the full-blown EAE and then rapidly decreased in number. On day 6 post-transfer, the CNS showed the most severe histologic changes but virtually no inflammatory cells in the lesions were labeled with BrdU. Double immunofluorescence staining with T cell (OX52) and macrophage/microglia (OX42) markers showed that about half of the BrdU+ cells were labeled with OX52 at the peak of EAE. The proportion of BrdU+OX52+ T cells at later stages was about 20%. BrdU+OX42+ cells ranged between 50 and 80% throughout the course of the disease. Furthermore, serial pulsing experiments during passive EAE revealed that inflammatory cells that had been labeled with BrdU outside the CNS and found later in the CNS were 15 times more numerous than those labeled in situ in the CNS. Taken together, these findings indicate that the majority of T cells involved in EAE undergo DNA synthesis outside the CNS and then infiltrate into the CNS, and that T cells labeled in situ in the CNS are few, and decrease rapidly in number. Since interleukin-2-receptor-positive cells detected by mAb OX39 outnumbered BrdU+ T cells at these later stages, we postulate that an unresponsive state instead of T-cell proliferation was induced in the CNS.

Animals↗

Flow cytometric analysis of the nuclear DNA content of hepatoblastoma.

The nuclear DNA content of 15 hepatoblastoma cases was determined in paraffin-embedded tissues by flow cytometry. The DNA index (DI) was calculated, and the ploidy pattern of nuclear DNA was estimated. The correlation between the ploidy pattern and clinicopathologic findings was studied, and the prognostic significance of the ploidy pattern was investigated. An aneuploid pattern was seen in 50% of the lesions with histologic embryonal and anaplastic types. It was not seen in the fetal type. In the tumors with combined epithelial components, the fetal-type component had a diploid pattern in all five cases. The embryonal-type component was associated with aneuploidy in two of five cases. In aneuploid tumors, vascular invasion (tumor emboli in the vessels) was observed more frequently. The prognosis of the patients with an aneuploid tumor was significantly poorer. These results indicate that nuclear DNA ploidy pattern analysis might be useful in investigating the prognosis of hepatoblastoma.

Carcinoma, Hepatocellular↗

Tissue-specific and non-tissue-specific heavy-chain isoforms of myosin in the brain as revealed by monoclonal antibodies.

Four types of monoclonal antibody (BM-1, BM-2, BM-3 and BM-4) each having distinctive tissue specificity were obtained by immunizing mice with purified bovine cerebrum myosin. Both BM-1 and BM-2 reacted most efficiently with cerebrum myosin and less efficiently with myosins from other limited nonmuscle tissues, the tissue specificity of BM-1 being much narrower than that of BM-2. BM-3 reacted more efficiently with several other nonmuscle myosins than with cerebellar or cerebral myosin. BM-4 recognized various nonmuscle and smooth muscle myosins with a nearly equal efficiency. Cerebral myosin as well a cerebellar myosin contained two or more electrophoretic variants of the heavy chains. BM-1 and BM-3 as well as BM-2 and BM-3 were found to recognize selectively these distinct heavy-chain isoforms. The antigenic sites of the three tissue-specific antibodies (BM-1, BM-2 and BM-3) were all localized near the head/tail junction of the myosin molecules, while that of non-tissue-specific antibody BM-4 was near the center of the tail. These and additional results indicate that mammalian brain tissues as well as several other nonmuscle tissues contain multiple heavy-chain isoforms of myosin, the levels of which differed considerably from one tissue to another.

Animals↗

Trifluoperazine inhibits phosphoinositide hydrolysis as a histamine H1-receptor antagonist.

In human astrocytoma cells (1321N1), trifluoperazine potently inhibited histamine-induced phosphoinositide hydrolysis, while it slightly inhibited carbachol-induced phosphoinositide hydrolysis. Trifluoperazine as well as diphenhydramine inhibited [3H]mepyramine binding in astrocytoma cell membranes with Ki values of 0.052 microM and 0.005 microM, respectively. However, trifluoperazine only slightly inhibited [3H]quinuclidinyl benzilate binding with a Ki value of 3 microM. These results indicate that trifluoperazine specifically inhibits histamine-induced phosphoinositide hydrolysis as a histamine H1-receptor antagonist in human astrocytoma cells.

Astrocytoma↗

Adhesion of human cancer cells to vascular endothelium mediated by a carbohydrate antigen, sialyl Lewis A.

Recently the lectin-like domain on ELAM-1 (endothelial leukocyte adhesion molecule-1) was shown to recognize a carbohydrate antigen, sialyl Lewis x. In this paper we demonstrate, by a series of inhibition experiments utilizing specific monoclonal antibodies and pure glycolipid preparations, that the sialyl Lewis a antigen serves as a specific ligand for ELAM-1 as well as sialyl Lewis x and plays a significant role in the ELAM-1-mediated binding of human cancer cells to activated endothelial cells.

Antibodies, Monoclonal↗

Synthesis and biological properties of carba-analogs of heat-stable enterotoxin (ST) produced by enterotoxigenic Escherichia coli.

Analogs of a heat-stable enterotoxin (ST) that have a CH2-S linkage instead of an S-S linkage in the molecule were synthesized by conventional methods. The synthetic peptides showed toxicity, assayed as induction of fluid secretion in suckling mice, although their toxicities were hundredth that of native ST. This finding implies that ST is not recognized by its receptor protein through an exchange reaction between its disulfide linkages and thiol-groups of its receptor protein(s), but through hydrophobic or electrostatic interactions.

Amino Acid Sequence↗

Tissue distribution of 2-3 and 2-6 sialyl Lewis A antigens and significance of the ratio of two antigens for the differential diagnosis of malignant and benign disorders of the digestive tract.

The authors investigated the tissue distribution of two kinds of sialylated derivatives of Lewis A (Le(a)) antigen in patients with cancers of the digestive system using specific monoclonal antibodies, and evaluated the significance of determining the 2-3 and 2-6 sialylated Le(a) antigen levels for the diagnosis of cancer. In most specimens from patients with cancers of the pancreas, biliary tract, stomach, and colon, the 2-3 sialylated Le(a) antigen was strongly expressed in cancer cells. However, 2-6 sialylated Le(a) antigen was less frequently expressed in cancer cells. The former is therefore more specific to cancer than the latter. Also, the serum level of the 2-3 sialylated Le(a) antigen was significantly higher than that of the 2-6 counterpart in patients with cancers of pancreas, biliary tract, stomach, and colon. The resulting ratio of serum 2-3/2-6 sialylated Le(a) antigens was frequently high in patients with malignancy and was low in patients with benign disorders of these digestive organs. Therefore, the 2-3/2-6 sialylated Le(a) antigen ratio is a useful for the differential diagnosis of malignant disorders in these organs. However, liver disorders were found to be exceptional in that both antigens were mostly absent in hepatocellular carcinoma (HCC) cells in immunohistologic examination, as well as in nonmalignant parenchymal liver cells. Only the epithelial cells of the intrahepatic bile ducts expressed the 2-6 sialylated Le(a) antigen strongly, and expressed the 2-3 sialylated Le(a) antigen moderately. The levels of both antigens were sometimes high in patients with liver disorders, but the ratio always remained low in patients with HCC as well as benign liver disorders such as cirrhosis or chronic hepatitis. The sialylated Le(a) antigens, which sometimes accumulate in the sera of patients with HCC, were concluded to originate from the epithelial cells of the proliferating small bile ducts, and those serum antigens cannot be considered as evidence for the presence of liver cancer cells.

Antibodies, Monoclonal↗

Long term follow-up of diffuse idiopathic skeletal hyperostosis in the cervical spine. Analysis of progression of ossification.

In eleven patients with diffuse idiopathic skeletal hyperostosis who presented with extensive ossification in the cervical spine, progression or regression of ossification during the follow-up period were measured in extent and thickness radiographically. Intervertebral range of motion was also measured and the relation between changes of ossification and intervertebral mobility was analyzed. The range of motion at the segments at which ossification progressed was statistically quite different from those at which no progression was observed. It was found that ossification grew in thickness at mobile segments and no growth of ossification was present at immobile segments. Dysphagia caused by massive ossification was cured by surgical removal in two cases. Recurrent ossifications were detected in them some years after surgery, and one of them complained of dysphagia again. To prevent recurrent ossification and dysphagia, it was considered that immobilization of the concerned segment was necessary by bone grafting or preservation of the continuity of ossification.

Aged↗

A long surviving case of holoprosencephaly agnathia series.

The rare syndrome of the agnathia with microstomia, aglossia, synotia (the external ears approaching one another in the midline) and brain malformation (agnathia-holoprosencephaly) was reported by Pauli et al. (1983) as a developmental field defect. This syndrome has two subgroups. One is more severe with brain malformation (holoprosencephaly), and the other is less severe without brain malformation. This report presents a long surviving case of this syndrome without brain malformation.

Body Height↗

Relationship between sialographic findings of parotid glands and histopathologic finding of labial glands in Sjögren's syndrome. Relation to clinical and immunologic findings.

We investigated a relationship between sialographic findings of parotid glands and histopathologic changes of labial glands, in relation to Sjögren's syndrome. We examined 107 patients, suspected to have Sjögren's syndrome because of dry mouth and dry eyes, in whom no other autoimmune diseases were diagnosed. Parotid sialography identified 37 patients with punctate, globular, cavitary, or destructive sialectasia (S-positive group). These sialographic findings were not seen in the other 70 patients (S-negative group). Among these patients, 54 demonstrated periductal lymphocytic infiltration in the labial glands (H-positive group), whereas the other 53 patients did not demonstrate this histologic finding (H-negative group). Significant differences in stimulated parotid salivary flow rate and incidence of keratoconjunctivitis sicca were observed between patients in the S-positive and the S-negative groups. Differences in the salivary flow rate and the incidence of keratoconjunctivitis sicca were also seen between patients in the H-positive and the H-negative groups, although the differences were not statistically significant. The rate of incidence of serum rheumatoid factor, anti-SS-A, and anti-SS-B antibodies were significantly higher in the S-positive and the H-positive groups than in their negative counterparts.

Antibodies, Antinuclear↗

Restoration of the anterior neck surface in the burned patient by free groin flap.

In treating extensive burn contractures of the anterior neck, we obtained good results using free flaps. Ninety-nine patients with neck contractures were treated with free flaps. The ages of the patients range from 2 to 64 years. We used 84 free groin flaps, 10 free latissimus dorsi musculocutaneous flaps, 2 free deltopectoral flaps, 2 free scapular flaps, and 1 free anterolateral thigh flap. In all patients, contractures were sufficiently released and no recurrences followed after a mean follow-up of 8.7 years. After defatting procedures, natural profiles and good appearances were restored, especially in patients in whom groin flaps were used.

Adolescent↗