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Biomedical subjects

M Takimoto

Publications and source records attributed to M Takimoto.

At least 109 records · Page 6Linked to original sources

Recognition by a natural cytotoxic antibody of lactoneotetraglycosyl ceramide as an antigenic molecule in a syngeneic rat fibrosarcoma.

Conventionally bred rats possess in their sera an NA which has a cytotoxic effect on a tumor cell line (KMT-17) derived from a fibrosarcoma induced by 3-methylcholanthrene and which can be absorbed by normal rat tissues. We have succeeded in purifying a glycosphingolipid as an antigen reactive to NA. GSLs isolated from the tumor cells were separated into neutral and acidic fractions. The former fraction was judged to be antigenic as detected by its capacity to absorb NA. The antigenic fraction was further separated into 7 fractions (Frs. A to G) by silicic acid chromatography. The antigenic activity was detected in only Frs.D and E, although Fr.D was a more potent antigen than Fr.E. Chemical and immunochemical analyses showed that both fractions are composed of lactoneotetraglycosyl ceramide (paragloboside), Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)Glc(beta 1-1)ceramide, and that the more active GSL, Fr.D, contains larger amounts of long fatty-acid chains. Inhibition studies using disaccharides and monosaccharides indicated that a N-acetyllactosamine moiety, Gal(beta 1-4)GlcNAc, of the GSL is a specific site of NA. These results suggest that paragloboside is an NA antigen and that a sugar chain portion of this GSL is required for defining specificity while the ceramide portion plays a role in potentiating the antigenicity of this GSL antigen for NA.

Amino Sugars↗

[Effectiveness of cefotaxime in pediatric infectious diseases].

Cefotaxime (CTX) was administered to 117 pediatric patients. Although 26 of these patients were excluded from the clinical evaluation of the study because other antimicrobial agents were given concomitantly with CTX or because no infectious diseases were proved, these cases were evaluated for adverse effects of the drug. The remaining 91 cases were evaluated for clinical effect; pneumonia in 56 cases, septicemia in 5, suspected septicemia in 5, meningitis (aseptic cases included) in 3, urinary tract infection in 5 and other diseases in 17. No pathogenic organisms were identified in any of the pneumonia cases, even either by bacterial culture or other laboratory test methods. Pathogens of septicemia were E. coli in 3 cases, K. pneumoniae in 1 and E. agglomerans in 1. Those of urinary tract infections were E. coli in 3 cases, a mixed infection of S. aureus and an unidentified species of Gram-negative rods in 1, and unknown in 1. Clinical effectiveness rates of CTX were 78.6% in pneumonia and 100% in septicemia, suspected septicemia and urinary tract infections. One patient with purulent meningitis caused by H. influenzae was also treated with CTX successfully. Adverse reactions and abnormal laboratory findings were observed in 12 cases (12/117 = 10.3%); rash in 2 cases, vomiting in 1, abdominal pain in 1, diarrhea in 5, granulocytopenia and thrombocytopenia in 1, eosinophilia in 3 and elevation of liver enzymes (GOT and LDH) in 1.

Bacterial Infections↗

[Study on a tumor associated antigen on a rat fibrosarcoma cell line--chemical structure of an antigen reactive to a rat natural antibody].

Conventionally bred rats possess a natural antibody (NA) in their sera, which is cytotoxic in its effect on a KMT-17 tumor cell line derived from a fibrosarcoma induced by 3-methylcholanthrene and can be absorbed by normal rat tissues. We have succeeded in isolating and purifying an antigen reactive to NA from the tumor cells as a glycosphingolipid (GSL). GSLs from the tumor cells were separated into neutral and acidic fractions. The former fraction was judged to be antigenic as detected by its capacity to absorb NA. The antigenic fraction was further separated into 7 fractions, Fr.A to Fr.G, by silicic acid chromatography. The antigenic activity was detected in only Frs.D and E, although Fr.D was a more potent antigen than Fr.E. Chemical and immunochemical analyses showed that both the fractions are lactoneotetraosylceramide (paragloboside), Gal (beta 1-4) GlcNAc (beta 1-3) Gal (beta 1-4) Glc (beta 1-1) ceramide, and that the more active GSL, Fr.D, contains larger amounts of long fatty acid chains. Inhibition studies using disaccharides and monosaccharides indicated that a N-acetyllactosamine moiety, Gal (beta 1-4) GlcNAc, is a specific site of the GSL antigen to NA. These results suggest that a sugar chain portion of this GSL is required for defining specificity and that the ceramide portion plays a role in potentiating the antigenicity of this GSL antigen.

Animals↗

Crystal structure of 3-(adenin-9-yl)propionhistamide hydrochloride monohydrate and the role of protonation in protein-nucleic acid interactions.

The three-dimensional structure of 3-(adenin-9-yl)propionhistamide hydrochloride, as a model of interactions between the protonated imidazolyl group and adenine moiety, has been determined by X-ray crystallography. The crystal data are a = 10.314 (1), b = 7.854 (1), c = 20.780 (1) A, beta = 92.765 (4), Z = 4, Dm = 1.32 g X cm-3, space group P2(1)/n. The imidazolium group interacts with adenine moiety by stacking. A comparison with the related neutral derivatives leads to a hypothesis that adenine stacks with the protonated, but not with the neutral, imidazolyl group. Such a characteristic behaviour of the imidazolyl group depending on protonation was shown by ultraviolet and NMR spectroscopy, and by polarographic experiments in solution. We note that a role of the essential histidine in RNAase reaction is a switch between capture and ejection of the substrate, which depends upon proton uptake and its release, respectively.

Adenine↗

[Clinical and pharmacokinetic evaluation of ceftazidime in children].

Forty-two pediatric patients were treated with ceftazidime ( CAZ ) in the doses ranging from 45.6 to 120 mg/kg/day for 2 to 10 days, and the clinical efficacy and side effects were evaluated. Among the 37 children with bacterial infections including pneumonia, bronchitis, tonsillitis, croup, cervical lymphadenitis, abdominal abscess and urinary tract infections, the results were excellent in 22, good in 12, fair in 2, and poor in 1 patient with pneumonia. Out of the 42 patients, 5 cases showed eosinophilia, but no clinical sign such as rash, fever or diarrhea, attributable to CAZ was observed during the study. The serum concentrations of CAZ in 4 patients ranged from 60.8 to 71.0 micrograms/ml (mean 66.1 micrograms/ml) at 30 minutes and from 0.5 to 1.2 micrograms/ml (mean 0.8 micrograms/ml) at 8 hours after 20 mg/kg intravenous bolus injection of the antibiotic. The mean serum half-life was 1.42 hours (85 minutes). Patients with impairment of renal function were excluded from this study.

Age Factors↗

[Adjuvant BCG immunotherapy for breast cancer (T1N0M0, T2N0M0)].

The present study was performed to evaluate the effect of BCG immunotherapy for breast cancer (T1n0M0, T2n0M0) in nonrandomized series. During a 5-year follow-up study, patients in the BCG-treated group suffered neither recurrence nor death, while the historical control group had 6 cases of recurrence and 5 cases of disease death. As seen in our series, we concluded that breast cancer patients should be advised to accept adjuvant BCG immunotherapy after mastectomy.

Adjuvants, Immunologic↗

[Pharmacokinetic and clinical studies of latamoxef (moxalactam) in neonates and premature infants].

Studies were carried out on the in vivo kinetics and clinical efficacy of latamoxef (LMOX) in neonates and premature infants. The results are summarized below. Serum concentration and T1/2 following intravenous injection of LMOX to neonates LMOX was intravenously administered to neonates as one shot doses of 10 mg/kg and 20 mg/kg. The serum concentration of LMOX showed a dose-response to the 10 and 20 mg/kg doses in each of the 0--3 day-old group, 4--7 day-old group and 8--28 day-old group. The T 1/2 values were as follows; for the 10 mg/kg dose, 5.17 hours in the 0--3 day-old group, 3.28 hours in the 4--7 day-old group and 2.79 hours in the 8--28 day-old group; for the 20 mg/kg dose, 5.58 hours in the 0--3 day-old group, 3.46 hours in the 4--7 day-old group and 3.14 hours in the 8--28 day-old group. Thus, it is seen that the half-life of both dosages decreased as the infants became older. Serum concentration and T 1/2 following intravenous injection of LMOX to premature infants Similar to the case of neonates described above, the concentration of LMOX in the serum of the premature infants showed a dose-response to the 10 mg/kg and 20 mg/kg dosages. The T 1/2 values for the 0--3, 4--7 day-old and 8--28 day-old groups were 7.54, 3.93 hours and 6.25 hours, respectively, for the 10 mg/kg dose, and 10.8, 4.05 hours and 3.23 hours, respectively, for the 20 mg/kg dose. Again, it is seen that the half-life of both dosages decreased as the age of the prematurely-born infants increased. Serum concentration and T1/2 following 1-hour intravenous drip infusion of LMOX to neonates LMOX was administered to neonates in doses of 10 mg/kg and 20 mg/kg, by i.v. drip infusion over a 1-hour period. With both dosages, the peak serum concentration of LMOX occurred at the time of completion of the infusion. The T1/2 values for the 0--3, 4--7 day-old and 8--28 day-old groups were 5.41, 3.68 hours and 1.92 hours, respectively, for the 10 mg/kg dose, and 5.31, 2.67 hours and 4.86 hours, respectively, for the 20 mg/kg dose. Urinary excretion of LMOX in neonates and premature infants. The percentage of the administered LMOX dose contained in the urine excreted during the 6-hour period following intravenous administration of LMOX to neonates and premature infants was determined.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗

A role of elementary interactions between nucleic-acid base and amino-acid side chains in specificity of ribonuclease.

Several X-ray structures of model crystals that contain hydroxyl group and nucleic-acid bases suggest that hydroxyl group interacts preferentially with pyrimidines than with purines through hydrogen bonds. This explains a role of Thr 45 and Ser 123 at the B1 site of RNAase A. The stacking energies of nucleic-acid bases with the protonated imidazolyl group are estimated to be in the order of C greater than A greater than G greater than U from 1H-NMR spectra and CNDO/2 calculations. Such interactions, in addition to hydrogen bondings, would stabilize the binding of substrates at the B2 site.

Amino Acids↗

Myocardial protection during cardiac ischemia by coronary perfusion with cold lactated Ringer's solution plus mannitol.

This experimental and clinical study evaluates the degree of myocardial protection afforded by coronary perfusion with cold lactated Ringer's solution plus mannitol. In the experimental study, diluted blood at 30 degrees C (Control G.), lactated Ringer's solution at 4 degrees C (G. A), 1,000 ml lactated Ringer's solution plus 200 ml of 20% mannitol at 4 degrees C (G. B), and 1,000 ml lactated Ringer's solution plus 500 ml of 20% mannitol at 4 degrees C (G. C) were used for coronary perfusion. The myocardial-protecting effect of each perfusate was evaluated by examining serum isoenzymes (CPK-MB, LDH1+2), left ventricular function (Vmax, LVEDP, CO), and the ultrastructure of myocardium. there were no significant differences in myocardial changes between the control group, G. A and G. B. Left ventricular enddiastolic pressure increased significantly in G. A and a significant increase in CPK-MB was seen in G. C. Mitochondrial scores for each group were 98 (Control G.), 86 (G. A), 93 (G. B), and 51 (G. C). Minimal myocardial change was seen in G. B. In the clinical study aortic root perfusion with cold lactated Ringer' s solution (400 m Osm) under aortic cross clamping (27-144 min) was employed in 25 patients. They all survived and CPK-MB returned to preoperative values within 49 hours after operation. In 6 cases, the ultrastructure of left ventricular papillary muscle was examined. It was confirmed that no significant mitochondrial changes developed during aortic cross-clamping.

Animals↗

Effects of hypertonic mannitol on renal function in open heart surgery.

An extracorporeal bypass was performed in mongrel dogs for 2 hours with or without hypertonic mannitol infusions. In animals given mannitol, the plasma osmolality was elevated maximally to 344 +/- 7.1 mOsm/L and the urine volume was maintained well during bypass. A hypertonic mannitol solution was effective in maintaining the CPAH during and after bypass, but was not effective in minimizing the reduction in Ccr. When the mean arterial pressure during bypass was kept at 60 mmHg, the carbon filling rates in glomeruli showed the favorable effects of mannitol upon renal function, but no effects were observed at a mean arterial pressure of 80 mmHg. In 11 patients who had undergone a bypass lasting more than 2 hrs with mannitol infusions, the plasma osmolality reflected the serum mannitol level and reached 320 +/- 11.0 mOsm/L at 150 min of bypass. The mean urine volume was 5.0 +/- 3.3 ml/min/M2 during the bypass, which was about 7 times as great as before the bypass. The Ccr increased during the first 30 min of the bypass, but it fell to about one half of the initial value after 90 min of the bypass. It was concluded that a hypertonic mannitol solution is effective in maintaining the RPF and urine volume during and after the bypass and that it also preserved the glomerular perfusion even at a low arterial pressure.

Acute Kidney Injury↗

Comparative pharmacological evaluation of oral benzathine penicillin G and phenoxymethyl penicillin potassium in children.

Serum penicillin concentrations and urine excretion rates of oral benzathine penicillin G and phenoxymethyl penicillin potassium were evaluated in children. Mean peak serum concentration of 0.134 microgram/ml of benzathine penicillin G and 1.018 microgram/ml of phenoxymethyl penicillin potassium were measured at 125 and 35 min. The mean half-life times were 1.36 and 0.74 hr, and for area under the curve, the values were 0.34 and 1.68 microgram . hr/ml for benzathine penicillin G and phenoxymethyl penicillin potassium groups, respectively. Phenoxymethyl penicillin potassium had more reliable pharmacokinetic properties and would be the preferred forms of oral penicillin. However, all patients receiving penicillin G had penicillinemia, which was enough to inhibit most strains of Streptococcus pyogenes for a longer period than phenoxymethyl penicillin potassium. Palatability of phenoxymethyl penicillin is less than for benzathine penicillin G; the latter may be used for children in whom compliance may be a problem.

Biological Availability↗

[Clinical effect of latamoxef on newborn and premature infants].

Eleven infants ranging 2 days to 3 months of age were studied for clinical evaluation. Ten of them were diagnosed as sepsis or suspected to be septic. Another one contracted umbilical infection. In 7 of 10 cases, causative bacteria were detected by blood culture, that is S. epidermidis in 3 cases, E. cloacae in 2 cases, K. pneumoniae in 1 case and A. calcoaceticus in another. Those infants were treated by parenteral LMOX. Dosage was 30 to 75 mg/kg per day. Clinical results were excellent in 6 cases (3 cases of S. epidermidis, 2 of E. cloacae and 1 of K. pneumoniae) and good in another case (A. calcoaceticus). The other 3 infants clinically diagnosed as sepsis but not proven by blood culture were also treated successfully. The result of the umbilical infection in 1 case was good. Another group of 5 infants ranging 4 to 22 days of age were also treated by LMOX because of suspected bacterial infections. With these infants pharmacokinetic study was done. Peak serum levels after 1 hour drip infusion of 20 mg/kg ranged from 43 to 53 micrograms/ml. Average of half-lives was 2.7 hours. Estimation of distribution volume resulted in 350 to 523 ml/kg body weight.

Bacterial Infections↗