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Biomedical subjects

K Kubo

Publications and source records attributed to K Kubo.

At least 505 records · Page 28Linked to original sources

Multiple growths of primary calvarial meningiomas.

The authors present the case of a 68-year-old woman with multiple growths of primary calvarial meningiomas. Histological examination revealed one tumor arising in the left parietal bone that showed some malignant aspects, including hypercellularity, cellular pleomorphism, necrotic foci, and some mitoses; the tumor partially had a meningotheliomatous pattern. Two other tumors in the right parietal bone were meningotheliomatous meningiomas without any malignant features. With a review of the literature, the pathogenesis of the multiplicity is discussed.

Aged↗

Loss of heterozygosity on chromosome 1p in thyroid adenoma and medullary carcinoma, but not in papillary carcinoma.

We analyzed 53 loci on 21 chromosomes other than chromosome 4 to detect possible loss of heterozygosity in 31 thyroid tumors using polymorphic DNA markers that detect allelic deletions at specific chromosomal loci. Loss of heterozygosity on chromosomes 1, 7 and 12 was detected in one follicular thyroid adenoma, and on chromosome 1 in two medullary thyroid carcinomas. However, no loss of heterozygosity was detected at any of the loci examined in papillary thyroid carcinomas. These results suggest that chromosomal loss detected in thyroid adenoma is one of the signals for risk of premalignant transformation, and that inactivation of unknown genes on chromosome 1p contributes to tumorigenesis of medullary thyroid carcinoma. Some genetic changes other than chromosomal losses may participate in the tumorigenesis of papillary thyroid carcinoma.

Adenoma↗

Allele loss on chromosome 11 in a pituitary tumor from a patient with multiple endocrine neoplasia type 1.

We have examined the allele loss of chromosome 11 in a pituitary tumor from a patient with familial multiple endocrine neoplasia type 1 (MEN 1). The extensive loss of chromosome 11, including loci of D11S149, HRAS1 and F2, was detected by the loss of heterozygosity. All of the lost alleles of these loci were transmitted from the unaffected father and not from an affected mother. This is the first evidence of allele loss of chromosome 11 in a pituitary tumor of MEN 1 and supports the idea that similar allelic deletion of MEN1 locus on chromosome 11 is the common genetic basis for tumorigenesis in the pituitary, endocrine pancreas, and parathyroid gland in MEN 1.

Adult↗

Alpha-fetoprotein-producing papillary adenocarcinoma originating from a uterine body. A case report.

A rare case of alpha-fetoprotein (AFP)-producing papillary adenocarcinoma originating from the uterine body of a 55-year-old Japanese woman is reported. The histologic appearance of the tumor was reminiscent of a serous papillary carcinoma of the ovary, in clear contrast to that of common endometrial adenocarcinomas. No features of embryonal carcinoma or yolk sac tumor were evident. Immunohistochemical examination demonstrated the production of AFP by the tumor cells. To our knowledge there are six reported cases of AFP-producing malignant tumors of the uterine body in the literature, four of them being yolk sac tumor, one mixed mesodermal tumor, and one endometrial adenocarcinoma. This is therefore the first case of an AFP-producing papillary adenocarcinoma that developed in the uterine body. This report should contribute to a better understanding of the histogenesis of AFP-producing tumors in this organ.

Adenocarcinoma, Papillary↗

Effect of protonation on the isomerization properties of n-butylamine Schiff base of isomeric retinal as revealed by direct HPLC analyses: selection of isomerization pathways by retinal proteins.

Alumina adsorption chromatography and ion-pair reversed-phase chromatography were developed to analyze the isomers of unprotonated and protonated n-butylamine Schiff base of retinal (RSB and PRSB), respectively. Photoisomerization starting from the all-trans, 11-cis and 13-cis isomers was traced for RSB in n-hexane, acetonitrile, methanol and 1-butanol, and for PRSB in methanol, acetonitrile and 1-butanol. The quantum yields of photoisomerization for the all-trans, 9-cis, 11-cis and 13-cis isomers were determined for RSB and PRSB in the above solvents except 1-butanol. On the other hand, photoisomerization of isomeric retinal bound (through Schiff base linkage) to bovine serum albumin (RBSA) in aqueous solution (pH 3, 7 and 12) as well as thermal isomerization of RSB (in n-hexane), PRSB (in methanol) and RBSA (in aqueous solution, pH 7) were traced starting from the all-trans, 11-cis, and 13-cis isomers. Protonation of RSB drastically changes the pathway of photoisomerization and increases the quantum yields of isomeric RSB. The solvent polarity increases the quantum yields of RSB differently depending on the configuration. Protonation enhances thermal isomerization also. The results of the above model systems are compared with those of retinal proteins to rationalize their selection of the particular isomerization pathways.

Butylamines↗

Lansoprazole, a novel benzimidazole proton pump inhibitor, and its related compounds have selective activity against Helicobacter pylori.

The activities of various types of antiulcer agents against Helicobacter pylori (formerly called Campylobacter pylori) strains were determined by an agar dilution method. Among the compounds tested, two benzimidazole proton pump inhibitors, lansoprazole (AG-1749) and omeprazole, were found to have significant activities against this organism. The activity of lansoprazole was comparable to that of bismuth citrate, with MICs ranging from 3.13 to 12.5 micrograms/ml, and fourfold more potent than that of omeprazole. A major metabolite and two acid-converted rearrangement products of lansoprazole also exhibited good activities comparable or superior to that of the parent compound. Exposure to lansoprazole of H. pylori growing in a liquid medium led to an extensive loss of viability without a reduction in culture turbidity and produced an aberrant bacterial morphology characterized by the irregular constriction of cells and the collapse of cell surface structures. The antibacterial activity of lansoprazole and its related compounds was selective against H. pylori; common aerobic and anaerobic bacteria and Campylobacter jejuni were not inhibited by 100 micrograms/ml.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Effects of KF-14363 on liver fibrosis in rats with chronic liver injury induced by carbon tetrachloride.

The present study examined the effects of (1-[(2-thiazolin-2-yl)amino]-acetyl-4-(1,3-dithiol-2-ylidene)-2,3, 4,5- tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363) on liver fibrosis in rats with chronic liver injury induced by carbon tetrachloride (CCl4). Liver injury in male rats was induced by repeated administration of CCl4 at 0.5 ml/kg twice a week. The progression of liver fibrosis was checked in the 4th, 6th, 8th and 10th weeks using the relative amount of hepatic 4-hydroxy proline (4-hyp) to total proteine as an index of hepatic collagen. The relative amount of hepatic 4-hyp in these rats exceeded significantly that in rats not administered CCl4 by the 4th week. This progressed in proportion to the duration of CCl4 administration. In groups concurrently administered KF-14363 at 30 and 100 mg/kg/d from the 5th or 8th week of the CCl4 administration, the relative amount of hepatic 4-hyp was found to be lower in the 10th week than at the start of the KF-14363 administration. The inhibition of liver fibrosis was also observed histopathologically. The concurrently co-administration with CCl4 or KF-14363 at 30 and 100 mg/kg for 2 or 5 weeks inhibited the increases in serum transaminases and alkaline phosphatase induced by CCl4. The results show that KF-14363 inhibits liver fibrosis in a dose dependent fashion in rats with progressive liver injury.

Alkaline Phosphatase↗

Studies on cardiotonic agents. VI. Synthesis of novel 4,5-dihydro-3(2H)-pyridazinone derivatives carrying some benzoheterocycles at the 6-position.

Several benzothiazolyl, imidazobenzothiazolyl, benzothienyl, benzothienopyrimidinyl and quinazolinyl 4,5-dihydro-3(2H)-pyridazinones were synthesized and examined for cardiotonic activity in anesthetized dogs after i.v. administration. Among them, 4-methylamino-7-(2,3,4,5-tetrahydro-5-methyl-3-oxo-6- pyridazinyl)quinazoline (36) showed potent and long-lasting inotropic activity (relative potency = 2.11, milrinone = 1). The activity of 36 was more potent than indolidan (2) (relative potency = 1.53) which is one of the most potent inotropic agents to date.

Animals↗

Studies on cardiotonic agents. V. Synthesis of 1-(6,7-dimethoxy-4-quinazolinyl)piperidine derivatives carrying various 5-membered heterocyclic rings at the 4-position.

A series of 1-(6,7-dimethoxy-4-quinazolinyl)piperidines carrying various 5-membered heterocycles at the 4-position was synthesized and examined for cardiotonic activity in anesthesized dogs. The (4-oxo-2-thioxo-3-imidazolindinyl)amino derivatives showed the most potent inotropic activity. Marked loss of activity was observed in the 2,4-dihydro-3-thioxo-3H-1,2,4-triazolyl, the 2,4-dihydro-3-oxo-3H-pyrazolyl and the (2,3-dihydro-2-thioxo-3H-1,3,4-thiadiazol-5-yl)amino derivatives. The synthesis and structure-activity relationships are discussed.

Animals↗

Studies on cardiotonic agents. VII. Potent cardiotonic agent KF15232 with myofibrillar Ca2+ sensitizing effect.

A series of novel 4,5-dihydro-5-methyl-6-(2 or 4-substituted 7-quinazolinyl)-3(2H)-pyridazinones was synthesized and examined for cardiotonic activity in anesthetized dogs. The 4-substituted aminoquinazolines generally showed potent and long-lasting inotropic activity. Fall in the activity was observed on the introduction of substituent at the 2-position of the quinazoline ring. The 3-substituted 4 (3H)-quinazolinimines generally exhibited weak activity. Ca2+ sensitizing effect of the 4-substituted amino derivatives was also examined in chemically skinned fiber from papillary muscle of guinea pig. The alkylamino derivatives exhibited small sensitizing effect, while the benzylamino derivatives exhibited large effect. Among them, KF15232 (Ix) was found to have the most potent cardiotonic and Ca2+ sensitizing activities.

Animals↗

Hepatoprotective effects of 1-[(2-thiazolin-2-yl)-amino]acetyl-4-(1,3-dithiol-2-ylidene)-2,3,4,5- tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363) in various experimental liver injuries.

Hepatoprotective effects of KF-14363 were investigated in the following experimental models. KF-14363 inhibited the increase in serum glutamate pyruvate transaminase (GPT) dose-dependently, and a significant inhibition was noted at a dose of 30 mg/kg or more. KF-14363 significantly inhibited the D-galactosamine (D-gal)-induced increase in serum transaminase by oral administration at 250 mg/kg x 1 and 250 mg/kg x 2 doses. The D-gal-induced decrease in total protein levels was inhibited at doses of 100 mg/kg x 2 and 250 mg/kg x 2. KF-14363 (100 mg/kg or more) significantly inhibited the increase in liver triglyceride levels induced by DL-ethionine (250 mg/kg x 3). KF-14363 (300 mg/kg) significantly inhibited the D-gal plus lipopolysaccharide-induced increase in GPT. At 100 mg/kg or less, however, an inhibiting tendency was noted, which was not significant as the values varied widely. KF-14363 (100 mg/kg) significantly inhibited Propionibacterium acnes plus lipopolysaccharide-induced mortality at 7 and 8 hr, and it showed an inhibitory tendency at 24 hr. These results demonstrate that KF-14363 is a compound that has a protective effect against the damage induced in various experimental liver injury models with different mechanisms.

Alanine Transaminase↗

Effects of 1-[(2-thiazolin-2-yl)amino]acetyl-4-(1,3-dithiol-2-ylidene)- 2,3,4,5-tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363) on active oxygen production.

The effects of KF-14363 on active oxygen production and membrane stabilization were studied. KF-14363 did not affect hypotonic hemolysis (10% and 70%) and did not inhibit lipid peroxide production induced by t-butyl hydroperoxide at concentrations of less than 100 microM. KF-14363 significantly inhibited active oxygen production in peritoneal exudate cells (PEEC) stimulated with arachidonic acid, A23187 and carbon tetrachloride (CCl4) at concentrations over 10 microM, 100 microM and 1 microM, respectively. It tended to inhibit formyl-methionyl-leucyl-phenylalanine-stimulated production of active oxygen in PEEC at concentrations over 10 microM, but there was no significant difference owing to large dispersion. Superoxide dismutase (SOD, 10(4) U/ml) significantly inhibited CCl4-stimulated production of active oxygen in PEEC. KF-14363 inhibited the radical production from CCl4 in the presence of a 9000 x g supernatant fraction of the rat liver which was administered with enzyme induction compounds (S9 mix). SOD (10(4) U/ml) was not effective in this system. In conclusion, KF-14363 inhibited active oxygen production in PEEC induced by various stimulants and also the radical formation from CCl4 in the presence of S9 mix solution.

Animals↗

Exercise-induced phospholipid degradation in the equine skeletal muscle and erythrocytes.

To understand the pathogenesis of equine exercise-induced myopathies and hemolysis, changes of phospholipid peroxidation products in the equine middle gluteal muscle and erythrocytes following the high-speed treadmill exercise were studied. In the skeletal muscle, the peroxidized phosphatidylethanolamine (PE) were increased at 24 hours after the exercise. The malondialdehydes (MDAs) were also increased as the protein-bound MDAs following exercise. In the erythrocytes, the peroxidized PE were significantly decreased at 24 hours after the exercise. The protein-bound MDAs were significantly increased at 5 min after the exercise and returned to the base values at 24 hours after the exercise. These findings indicate that the PE is more susceptible to in vivo oxidative effects than the other phospholipid classes, and the accumulation of the protein-bound MDAs is considered to play some cytotoxic roles in the equine skeletal muscle and erythrocytes following exercise.

Animals↗

HLA typing using IL-2 activated T lymphocytes: usefulness in pediatric candidates for allogeneic bone marrow transplantation.

Following a preliminary study in healthy blood donors, we have performed serological HLA-A, B, C, DR and DQ typing using recombinant IL-2 activated T lymphocytes (IL-2.aTLs) in pediatric candidates for allogeneic bone marrow transplantation. In such patients, it is often difficult to obtain the quantity of lymphocytes required for HLA typing, particularly for class II typing using B lymphocytes, considering the timing of sampling and the volume of blood to be collected. Peripheral blood mononuclear cells (PBMCs) were activated and expanded with IL-2 until a sufficient number of IL-2.aTLs of good viability were available for the typing. In the first 10 cases, analyses of surface markers (CD2, CD20, CD25, CD36, HLA-DR and HLA-DQ, CD2/HLA-DR: two color) of IL-2.aTLs were done using flow cytometry at the time of HLA typing and indicated that IL-2.aTLs expressed HLA-DR and DQ antigens sufficient for evaluation. A small number (less than 10(6] of fresh or cryopreserved PBMCs, even those containing leukemic blast cells, were sufficient to induce and expand IL-2.aTLs for HLA typing. To date we have been able to successfully HLA-A, B, C, DR and DQ type 20/20 pediatric candidates. The HLA antigens identified on the patients' IL-2.aTLs were confirmed by a family study.

Adolescent↗

[Effect of natural panting frequency and cheek support on the plethysmographic determination of thoracic gas volume in patients with chronic obstructive pulmonary disease].

The authors studied the effects of natural panting frequency (NF) and the cheek support on the plethysmographic measurement of thoracic gas volume (TGV) in 8 normal subjects (non-smokers) and 46 patients with chronic obstructive pulmonary disease (COPD). The patients were divided into 2 groups according to the degree of airway obstruction (group I; specific airway conductance (SGaw) greater than 0.1 (n = 18), group II; SGaw less than 0.1 (n = 28)). TGV was measured with a pressure-type body plethysmograph (BP). NF was 2.00 +/- 0.43 Hz (mean +/- SD) in control subjects, 1.92 +/- 0.78 Hz in group I, and 1.39 +/- 0.59 Hz in group II, respectively, indicating lower NF in the patients with severe airway obstruction. In control subjects and group I, the differences between TGV at NF and at 0.5-1.0 Hz (TGVNF-TGV1.0) were -0.01 +/- 0.07L, and -0.06 +/- 0.16L, respectively, and cheek support did not alter the difference. On the other hand, in group II, the difference was slightly larger than other groups in spite of the lower NF, and this overestimation was abolished by cheek support (0.13 +/- 0.25L-----0.06 +/- 0.27L, p less than 0.05). These results suggest that, in patients with severe airway obstruction, TGVNF may be overestimated even if NF is relatively low. This overestimation may be mainly due to the extrathoracic airway compliance including the cheek.

Adult↗

[Operative management of the calcified patent ductus arteriosus in the elderly].

Two cases of the calcified PDA were experienced in subjects aged more than 50 years. A 63-year-old woman was successfully operated upon. A Fogarty's balloon catheter was wedged into the PDA through the ductus after a pulmonary arteriotomy under cardiopulmonary (CP) bypass. A 57-year-old woman was safely operated. PDA was repaired under partial CP bypass with Bio-pump. Postoperative courses of these cases were uneventful. Brief review of surgical treatment for PDA was given.

Calcinosis↗