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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 1,099 records · Page 61Linked to original sources

A new monoclonal antibody to human subcapsular thymic epithelial cells.

A monoclonal antibody, termed K-20, was generated against an anaplastic thymic carcinoma cell line, Ty-82. Subcapsular thymic epithelial cells of the thymus and blood vessels in various organs were shown to react with the K-20 monoclonal antibody by immunohistochemical staining. Immunofluorescent study revealed that various haematopoietic fresh cells and cell lines did not show any significant reactivity with K-20, except for one Epstein-Barr-virus-carrying lymphoma cell line (SP-50B). Western immunoblotting and affinity purification procedure revealed that K-20 was directed to a protein with a molecular weight of 28 kDa. K-20 is unique in its restrictive reactivity with human subcapsular thymic epithelial cells.

Antibodies, Monoclonal↗

Possible role of adrenergic mechanism in starvation-induced reduction in circulating thyroxine and triiodothyronine in rats.

To elucidate the possible role of adrenergic mechanism in thyroid hormone metabolism during starvation, serum thyrotropin (TSH), thyroxine (T4), and 3,5,3'-triiodothyronine (T3) levels and conversion of T4 to T3 in perfused liver were investigated in fasting (60 h) and fed rats. Propranolol (0.5 mg/kg), yohimbine (0.3 mg/kg) or phentolamine (5.0 mg/kg) was subcutaneously injected to the rat every 12 h. Serum levels of TSH, T4, and T3 were significantly lower in fasting rats than in fed rats. Although propranolol, yohimbine, and phentolamine administration did not significantly alter circulating TSH, T4 and T3 levels in fed rats, phentolamine partly inhibited the starvation-induced reduction in circulating TSH, T4, and T3. Thyroxine uptake and T3 production in perfused liver were significantly lower in fasting rats than in fed rats. Phentolamine treatment did not alter the T4 uptake and T3 production in perfused liver of fasting rats. These results suggest that alpha-adrenergic mechanism may have some role in starvation-induced reduction in circulating T4 and T3, and that phentolamine partly inhibited this phenomenon probably through the inhibitory effect on reduction in circulating TSH during starvation.

Animals↗

Schistosoma mansoni: higher free proline levels in the livers of infected mice.

The concentration of L-hydroxyproline in the liver of ICR female mice increased rapidly during the 8th to 11th weeks of Schistosoma mansoni infection. Free L-proline concentration began to increase about the 7th week and reached its maximum at the 8th to 9th weeks of the infection, when the granulomatous response to the schistosome eggs in the liver was most prominent, as indicated by the increase in liver wet weight and its deoxyribonucleic acid concentration. A significant increment in the total activity of ornithine-delta-transaminase (EC 2.6.1.13) and the decrease in the specific activity of proline oxidase (EC 1.4.3.2) became detectable in the liver homogenate of infected mice on the 8th week. However, changes in these enzymatic activities were not parallel to that of the hepatic free L-proline content. Intraperitoneal administration of S. mansoni egg granulomas or 15,000g x 30 min supernatant fluid of their extracts into uninfected, normal mice significantly increased the hepatic free L-proline content without any appreciable effect on the enzymatic activities of proline oxidase and ornithine-delta-transaminase. These findings suggest that S. mansoni egg granulomas contain a factor(s) which may be responsible for the elevation of free L-proline content in the fibrotic liver caused by experimental schistosomiasis mansoni.

Animals↗

Uptake of beta-hydroxybutyrate in perfused hindquarter of starved and diabetic rats.

To elucidate the peripheral ketone body uptake and the role of insulin in regulating peripheral ketone body utilization in starvation and diabetes mellitus, uptake of beta-hydroxybutyrate (BOHB) was investigated in the perfused hindquarter of starved (72 hour) or streptozotocin-induced (65 mg/kg, intraperitoneally) diabetic rats. Blood concentration of BOHB was significantly higher in diabetic (1,380 +/- 250 mumol/L) and starved (1,229 +/- 245 mumol/L) rats than in controls (104 +/- 8 mumol/L). The hindquarter was perfused with synthetic medium at a flow rate of 0.5 mL/g muscle weight/min. BOHB was added to the medium at a concentration of 0.1, 0.5, 2, or 10 mmol/L, and insulin was added at a concentration of 20, 100, or 500 microU/mL. In the hindquarter perfused with 0.1, 0.5, 2, or 10 mmol/L BOHB, fractional uptake of BOHB in the absence or presence of insulin was significantly lower in diabetic and starved rats than in controls. The addition of 100 or 500 microU/mL insulin significantly increased BOHB uptake in the perfused hindquarter of control rats; however, insulin addition did not significantly increase BOHB uptake in the perfused hindquarter of starved and diabetic rats. These results suggest that BOHB uptake is markedly reduced in the perfused hindquarter of starved and diabetic rats, and that physiological dose of insulin stimulates BOHB uptake in control rats, but not in starved and diabetic rats.

3-Hydroxybutyric Acid↗

Prostaglandin E2 selectively affects purinergic transmission in guinea pig vas deferens.

The effect of prostaglandin E2 (PGE2) on the contractile response of the guinea pig vas deferens was examined. Postganglionic hypogastric nerve stimulation for 7 sec at 20 Hz induced a biphasic contractile response, consisting of fast phasic and delayed tonic components. Prostaglandin E2 delayed the onset and increased the maximum contractile responses. Stimulation in the presence of prazosin induced only a fast phasic contraction. Treatment with PGE2, in the presence of prazosin, delayed the onset of this response and increased its maximum. The delayed contraction, observed on stimulation in the presence of alpha,beta-methylene adenosine triphosphate (ATP), was enhanced moderately and concentration-dependently by PGE2. Short-term stimulation with 5 pulses induced a small fast phasic contraction. This contraction, which could be desensitized by alpha,beta-methylene ATP, was inhibited by PGE2 but not by prazosin. Prostaglandin E2 significantly enhanced the transient phasic contraction, induced by addition of exogenous ATP to the organ bath and had a similar but somewhat smaller effect on the tonic contraction induced by the addition of exogenous norepinephrine (NE). These findings suggest that PGE2 selectively delayed neurotransmission, mediated by ATP and enhanced contractions of the smooth muscle of guinea pig vas deferens, elicited by ATP or NE.

Adenosine Triphosphate↗

Fine-needle aspiration cytology of xanthogranulomatous pyelonephritis.

Fine-needle aspiration cytology of xanthogranulomatous pyelonephritis in a fifty-seven-year-old Japanese woman is reported. Foamy cells and cells showing a gland-like pattern originating from degenerative renal tubules were found in the aspirated smears. Multinucleated giant cells and cells with pale yellowish cytoplasm were seen in the imprint smears at operation. These findings were diagnostic for xanthogranulomatous pyelonephritis. The cytologic diagnostic differences among xanthogranulomatous pyelonephritis, well-differentiated renal cell carcinoma, and renal oncocytoma are also described.

Biopsy, Needle↗

Application of ATP measurement to evaluation of the growth of parasitic protozoa in vitro with a special reference to Pneumocystis carinii.

1. There was a significant correlation between the increase in the number of Entamoeba histolytica, Trichomonas vaginalis, Giardia lamblia and Leishmania donovani in culture, and their ATP contents determined by luciferase reaction. 2. The similar correlation was also demonstrated between the decreased number of E. histolytica in the presence of an anti-amebic quassinoid and the nucleotide content in vitro. 3. In the case of Pneumocystis carinii, the numbers of the organism remained relatively constant in culture for at least 7 days without growth; however, the ATP content dropped rapidly in 1 to 3 days except in RPMI 1640. 4. The possibility that ATP determination of P. carinii is complicated by the host cell nucleotide seemed to be excluded, since the concentration of this nucleotide in normal lung was almost negligible. These observations suggest that the present procedure is useful for evaluating the growth and viability of these organisms in vitro.

Adenosine Triphosphate↗

Calcium metabolism in acidotic patients induced by carbonic anhydrase inhibitors: responses to citrate.

Calcium metabolism and its response to citrate were examined in 51 patients with glaucoma receiving carbonic anhydrase inhibitors (acetazolamide or methazolamide). Metabolic acidosis, hypocitraturia and increased incidence of nephrolithiasis were induced by both drugs. However, the acidosis was milder with methazolamide administration. Normocalciuria was observed in 29 patients and was shown to be a result of low filtered calcium. Renal hypercalciuria in 16 patients was associated with elevated parathyroid hormone but nephrogenic cyclic adenosine monophosphate remained within normal limits. Citrate in the form of potassium citrate (4.3 mmol.) and sodium citrate (4.0 mmol.) did not correct the metabolic acidosis or hypocitraturia but consistently decreased fasting and 24-hour urinary calcium excretion in patients with renal hypercalciuria. This event did not occur in patients with normocalciuria or absorptive hypercalciuria. These results suggest that a small amount of citrate could reverse renal hypercalciuria without correcting the metabolic acidosis.

Acetazolamide↗

Compressive behavior of human bone-cement composites.

Current surgical practice in the implantation of cemented total joint arthroplasties generally creates a zone of variable thickness in which polymethylmethacrylate (PMMA) is intermixed with trabecular bone. The authors' objectives in these experiments were to characterize the compressive mechanical properties of this bone-cement composite material. They found that the mechanical properties of bone-cement composite specimens, fabricated under in vitro conditions that would promote nearly complete cement filling, are closer to the properties of trabecular bone than to those of cement. For both low-viscosity cement (LVC) and PMMA specimens, with the cement introduced by either hand-packing or pressurized injection at periods of 2 and 7 minutes, the compressive strengths ranged from 29 MPa to 50 MPa and the compressive moduli from 539 MPa to 1,210 MPa. Cement volume fractions achieved using different filling methods ranged from 76% to 87%. In contrast to previous studies of bone-cement composites using high-density bovine bone, neither mechanical properties nor filling parameters correlated significantly with bone porosity measured prior to filling. The authors expect that the mechanical properties of bone-cement regions created at surgery under less than these ideal in vitro filling conditions will only approach their values as an upper limit. Thus, bone-cement composites created in situ at surgery will also exhibit mechanical properties well below previously assumed values.

Aged↗

The diagnostic significance of lactate dehydrogenase isoenzymes in urinary cytology.

Lactate dehydrogenase (LDH) isoenzyme distribution was examined in 106 urine samples being tested cytologically for evidence of bladder cancer; the samples were selected to have less than 20 leucocytes and erythrocytes per high power field and the LDH pattern determined by electrophoresis. The Papanicolaou stained-smears showed 68 negative, 17 suspicious and 21 positive. The LDH M-fraction of the urinary supernatant in cytologically positive cases was significantly greater than in negative cases, although the latter included a few false negative samples. Some of the false negatives gave positive results for the LDH M-fraction; these results suggest that the determination of LDH isoenzymes in the urine is useful in diagnosing urinary tract cancers, including early stage, and for follow-up of patients with bladder cancers after surgical resection.

Carcinoma, Transitional Cell↗

Modifying effects of anticancer drugs adriamycin, actinomycin D, and cisplatin on N-2-fluorenylacetamide-induced hepatocarcinogenesis in male ACI/N rats.

The effects of some well-known anticancer agents, adriamycin (ADR), actinomycin D (ACT), and cisplatin (CIS), on hepatocarcinogenesis induced by N-2-fluorenylacetamide (FAA) were examined in male ACI/N rats. Animals were divided into 15 groups and treated as follows: group 1, 0.02% FAA diet (13 wk); group 2, FAA diet and 0.05% phenobarbital (PB) diet (16 wk); group 3, FAA diet and ADR (3 ip injections of 1.00 mg/kg body weight/wk); group 4, FAA, ADR, and PB; group 5, FAA and ACT (3 ip injections of 0.02 mg/kg body weight/wk); group 6, FAA, ACT, and PB; group 7, FAA and CIS (3 ip injections of 1.00 mg/kg body weight/wk); group 8, FAA, CIS, and PB; group 9, ADR; group 10, ADR and PB; group 11, ACT; group 12, ACT and PB; group 13, CIS; group 14, CIS and PB; group 15, nontreatment. At the end of the experiment (30 wk), the incidence of preneoplastic and neoplastic hepatocellular lesions was evaluated. All three tested compounds, especially CIS, inhibited the development of preneoplastic and neoplastic liver lesions, indicating CIS could be valuable as a therapeutic agent for hepatocellular malignancies.

2-Acetylaminofluorene↗

Ascorbic acid and adriamycin toxicity.

Adriamycin (ADR) is effective against a wide range of human neoplasms. However, its clinical use is compromised by serious cardiac toxicity, possibly through induction of peroxidation in cardiac lipids. Ascorbic acid, a potent antioxidant, was examined for effect in reducing ADR toxicity in mice and guinea pigs. Ascorbic acid had no effect on the antitumor activity of ADR in mice inoculated with leukemia L1210 or Ehrlich ascites carcinoma, but it significantly prolonged the life of animals treated with ADR. ADR elevated lipid peroxide levels in mouse heart, and ascorbic acid prevented the elevation. The significant prevention of ADR-induced cardiomyopathy in guinea pigs by ascorbic acid was proved by electron microscopy. Ascorbic acid and the derivatives may delay general toxicity of ADR and also prevent the cardiac toxicity. The results also suggest the clinical efficacy of the combined treatment of ADR and ascorbic acid or the derivatives.

Animals↗

Secretin as a potential mediator of antiulcer actions of mucosal protective agents.

Recently, we have reported that several nonacid agents including phenylpentol, methanol extract of licorice root (FM 100), plaunotol, and teprenon stimulate release of endogenous secretin in humans, dogs, and rats. The latter three are antiulcer agents developed in Japan that have a protective effect on the gastric mucosa. We have clearly shown that plaunotol inhibits postprandial gastrin release and gastric acid secretion that parallel the increase in plasma secretin concentration. It has also been recently demonstrated that the secretin-induced inhibition of gastric acid secretion in rats is completely blocked by indomethacin, a potent inhibitor of prostaglandin synthesis. It appears that the inhibitory action of secretin on gastric acid secretion is mediated mainly by endogenous prostaglandins. Because the three antiulcer agents FM 100, plaunotol, and teprenon have been shown to increase the content of endogenous prostaglandins in the gastric mucosa, endogenous secretin released by these agents may play a significant role in their mucosal protective action. It is concluded that the antiulcer effect of these drugs could in part be attributable to their unique ability to release endogenous secretin, and that secretin is a potential mediator of the antiulcer actions of mucosal protective agents.

Animals↗

Somatostatin analog, SMS 201-995, inhibits pancreatic exocrine secretion and release of secretin and cholecystokinin in rats.

We studied the effect of a synthetic octapeptide somatostatin analog, SMS 201-995 (sandostatin), on pancreatic exocrine secretion and on plasma secretin and cholecystokinin (CCK) levels in vivo in anesthetized rats. The exocrine pancreas was stimulated by either intravenous infusion of both secretin (0.06 CU/kg/h) and cholecystokinin octapeptide (CCK-8) (0.03 micrograms/kg/h) or intraduodenal infusion of oleic acid (pH 6.5) in a dose of 0.25 mmol/h. Intravenous administration of SMS 201-995 in three different doses of 100, 200, and 400 ng/kg/h resulted in dose-related inhibition of pancreatic secretion in terms of volume, bicarbonate, and amylase stimulated by exogenous secretin and CCK. Intraduodenal oleic acid stimulated pancreatic secretion, including volume, bicarbonate, and amylase, and this was accompanied by a significant elevation in the plasma concentrations of secretin and CCK. Intravenous administration of SMS 201-995 in the three different doses described above caused dose-dependent suppression of the increase in pancreatic exocrine secretion as well as the plasma concentration of secretin and CCK induced by intraduodenal infusion of oleic acid. It is concluded that SMS 201-995 inhibits pancreatic exocrine secretion and the release of endogenous hormones, such as secretin and CCK, in rats.

Amylases↗

Fecal isoamylase activity in patients with pancreatic diseases.

Fecal isoamylase activity was studied in 93 consecutive patients (26 in the recovery stage of acute pancreatitis, 24 with chronic pancreatitis, 13 with pancreatic cancer, and 30 with other gastrointestinal diseases) and compared with fecal chymotrypsin activity and the results of the secretin test. Seventy-six healthy subjects were studied as controls. Both pancreatic (p)-type and salivary (s)-type isoamylase activities in stool were determined by inhibitor assay as well as cellulose acetate electrophoresis. The mean fecal amylase activity in healthy subjects was 757 +/- 88 IU/g (p-type isoamylase: 77 +/- 2%, s-type isoamylase: 23 +/- 2%). There was a good correlation between fecal p-type isoamylase and chymotrypsin activities (r = 0.625, p less than 0.001). Fecal p-type isoamylase activity in patients with chronic pancreatitis and pancreatic cancer was significantly lower than in healthy subjects (p less than 0.001). Patients with moderate and severe exocrine pancreatic insufficiency as determined by the secretin test had significantly lower fecal p-type isoamylase activity. Daily fat intake did not affect fecal amylase or isoamylase activities. Fecal s-type isoamylase activity in patients with hypoacidity was significantly higher than in patients with hyperacidity, but no difference in fecal p-type isoamylase activity was observed. It is concluded that analysis of fecal isoamylase activity is useful in the assessment of pancreatic function.

Acute Disease↗

Potentiating effect of CCK and secretin on rat exocrine pancreas and its cholinergic dependence.

We investigated whether physiological doses of cholecystokinin (CCK) potentiate the stimulating effect of a physiological dose of secretin on exocrine pancreatic secretion, and the effect of atropine on this potentiating action in rats. Pure pancreatic juice was collected from anesthetized rats prepared by pancreatic duct and bile duct cannulation. Intravenous infusion of CCK-8 in three different doses, 0.03, 0.06, and 0.12 micrograms/kg/h, significantly increased pancreatic juice volume and amylase output, dose-dependently. Simultaneous infusion of CCK-8 in graded doses with secretin in a dose of 0.03 CU/kg/h, produced a dose-related increase in pancreatic secretory response significantly greater than the response to CCK-8 alone (p less than 0.05) and greater than the sum of the response to secretin alone and CCK-8 alone. The incremental pancreatic secretion, including juice volume and amylase output, in response to intravenous infusion of CCK-8 with secretin, was significantly suppressed by intravenous administration of atropine in a dose of 100 micrograms/kg/h (p less than 0.01). Thus, it is concluded that CCK-8 and secretin in physiological doses potentiate each other's stimulatory action on exocrine pancreatic secretion and this potentiating action appears to be cholinergic-dependent.

Amylases↗

Deoxyspergualin in lethal murine graft-versus-host disease.

The beneficial effect of deoxyspergualin (DSG, NKT-01) on lethal graft-versus-host disease in mice has been studied in a major histoincompatible donor-recipient combination. Suppression of the effector mechanisms responsible for the lethal outcome in this GVHD model is also noted. This study reveals: (1) DSG has a marked potential for treatment of lethal GVHD; (2) DSG and methotrexate in combination yield longer survival times than DSG or MTX alone; (3) long-term survivors, following DSG treatment, become stable chimeras as evidenced by cell-surface analysis of spleen cells; and (4) high activity of H-2-reactive cytotoxic T lymphocytes is detected in spleens of the mice with lethal GVHD, whereas natural killer activity is only slightly increased. DSG inhibits CTL activity not only in the induction stage but also in the advanced stage of the disease. These findings indicate that DSG might be beneficial in clinical bone marrow transplantation either alone or in combination with MTX.

Animals↗

Cytostatic effect of deoxyspergualin on a murine leukemia cell line L1210.

The mode of antiproliferative action of deoxyspergualin (NKT-01) was examined. The growth-inhibitory effect on a murine leukemia cell line L1210 following treatment with NKT-01 was time-dependent, and there was little or no effect on the syntheses of DNA and RNA. Thus, the inhibitory activity of NKT-01 was not attributable to the inhibition of DNA and RNA syntheses. The influence of NKT-01 on cell cycle progression was studied by flow cytometric analysis. Bromodeoxyuridine/DNA distribution patterns in cells that were treated for 72 h, showed that the growth inhibition is due to the delay of cell cycle progression but not to cytotoxicity. This finding was also supported by evidence that the treated cells were re-proliferative in fresh medium. In addition, a majority of drug-treated cells was prevented from traversing from the G0/G1 phase to the S phase by 144 h or longer exposure to NKT-01. The results suggest that NKT-01 is cytostatic, preventing G0/G1-S progression.

Animals↗