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Biomedical subjects

M Kondo

Publications and source records attributed to M Kondo.

At least 1,081 records · Page 60Linked to original sources

Toxicological significance of hepatic responses to furylfuramide(AF-2) in the rat.

In male rats fed furylfuramide [2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide, AF-2] at a dietary level of 0.1%, a marked increase in the liver weight was observed with a concomitant reduction of microsomal mixed function oxidase activity. To clarify the significance of these hepatic responses to furylfuramide, a series of biochemical parameters that reflect hepatotoxicity was measured. The most significant elevations were seen in hepatic glycogen and glucose 6-phosphate dehydrogenase levels over 29-day feeding interval. A marked decrease was observed in mixed-function oxidases and glucose 6-phosphatase activities. Moderate decreases were seen in several other parameters, especially in the early phase of feeding. Measurement of serum parameters showed significant elevation in cholesterol and a transient increase in serum glutamic pyruvic transaminase. A comparative study demonstrated small differences between furylfuramide and carbon tetrachloride in their effects on hepatic parameters. The furylfuramide-induced changes appear to be reversible within 14 days after withdrawal of furylfuramide from the diet. Reduction of mixed-function oxidase activity by furylfuramide might be caused partly by the elevation of heme degrading enzyme. The results indicate a dysfunction of drug-metabolizing activity and acute and slight toxication of the liver by furylfuramide.

Administration, Oral↗

Local control of squamous cell carcinoma of the mobile tongue: an experience of different modalities.

From 1966 through 1983, 163 patients with squamous cell carcinoma of the mobile tongue were treated. Fifty-two patients were staged as T1N0, 77 as T2N0, 14 as T2N+, 8 as T3N0, 7 as T3N+, and 5 as T4. The follow-ups were complete. Treatment modalities varied considerably during that period, because of increasing difficulty to use radioactive sources by regulations. All T3N+ and T4 patients died shortly after treatment. Five year absolute survivals for the T1N0, T2N0, T2N+, and T3N0 patients were 87%, 60%, 27% and 63%, respectively. Local recurrence free survivals at 5 years for the T1N0, T2N0, T2N+, and T3N0 patients were 72, 48, 58, and 88%, respectively. Local recurrence free survivals seemed to be better with Ra-226 needling +/- external irradiation (EXT) than other modalities. Because many patients with local recurrence were salvaged, ultimate local-disease-free survivals should also be considered. They were 96 and 70% at 5 years for the T1N0 patients treated with Ra-226 +/- EXT, and with surgery +/- EXT, respectively; the corresponding figures for the T2N0 patients were 83 and 64%. For these reasons, Ra-226 needling may be preferable to other modalities as initial treatment. Although cervical failures did not develop after 2 years of treatment, late local recurrences were rather common, even after 5 years. Long-term follow-up is mandatory for the management of the patients, and analyzing and comparing the results.

Adult↗

Improved survival of patients with nasopharyngeal squamous cell carcinoma.

One hundred and one patients with nasopharyngeal squamous cell carcinoma (NPC) were treated with irradiation. The UICC TNM staging system (1978) was used: 6 patients were T1N0, 10 T2N0, 5 T3N0, 13 T4N0, 11 T1N+, 18 T2N+, 19 T3N+ and 19 T4N+. Since 1978, 34 patients were examined with computed tomography (CT) at first presentation. Fourteen (41%) of the 34 tumors were upstaged based on the CT findings alone. The technique of radiation therapy was markedly changed around 1978. The fields to the primary site and neck were enlarged. Two-year relapse-free survival was significantly better for the post-CT era than pre-CT era. This was mainly because of improved local-recurrence-free survival, and cervical-relapse-free survival. Improved local-recurrence-free survival, however, was appreciated in only T3 + T4 patients; there was no difference in T1 + T2 patients. It is suggested that merely enlarging radiation fields or increasing radiation doses could not be curative for some subpopulations. In order to increase local control rates further, we have started to use intracavitary irradiation with an after-loading technique as a boost. Preliminary results are encouraging.

Adolescent↗

Maxillary squamous cell carcinomas staged by computed tomography.

In 72 patients with maxillary squamous cell carcinoma, computed tomography (CT) alone was used for T-staging according to the AJC classification. Five, 31, and 36 tumors were diagnosed as T2, T3, T4, respectively. In N0 patients with a minimum follow-up of 2 years, local control rates for T2, T3, and T4 tumors were 33% (1/3), 64% (16/25) and 38% (9/24), respectively. Addition of maxillectomy to treatment seemed to have improved the local prognoses in T3 and T4 tumors. High radiation doses of 60 Gy or more seemed to be beneficial for patients with T3 tumors and without maxillectomy. CT will be of great help in classifying tumors objectively. But more importantly, it will reveal resectability and dictate treatment of choice by delineating the tumor extent precisely.

Carcinoma, Squamous Cell↗

Bactericidal and bacteriolytic activities of carumonam and its effect on bacterial morphology.

The in-vitro bactericidal and bacteriolytic activities and the effect on bacterial morphology of carumonam, a new N-sulfonated monocyclic beta-lactam antibiotic, against aerobic Gram-negative bacilli were compared with those of aztreonam. Both antibiotics, at their minimal inhibitory concentration (MIC) levels, were strongly bactericidal against species of Enterobacteriaceae, but weakly bactericidal against Pseudomonas aeruginosa. Their bactericidal activity was not increased by increasing the antibiotic concentration above the MICs. In contrast to this potent bactericidal activity, the bacteriolytic activity of carumonam and aztreonam was low and limited to enteric bacterial species like Escherichia coli. Filamentation was the major morphological change of Gram-negative bacilli after exposure to carumonam and aztreonam. E. coli and Serratia marcescens, but not P. aeruginosa, were converted to ghosts after prolonged incubation with carumonam.

Anti-Bacterial Agents↗

Appearance of uridine 5'-diphospho-N-acetylglucosamine-4-epimerase during sporulation of Bacillus megaterium.

In a biosynthetic study of the spore coat of Bacillus megaterium ATCC 12872 spore with galactosamine phosphate as a major component of the outer coat, high-performance liquid chromatography (HPLC) and enzyme immunoassay were applied for the measurement of UDP-N-acetylglucosamine-4-epimerase [EC 5.1.3.7] activity and the enzyme protein concentration, respectively. The new HPLC system using an ion-pair (or anion-exchange) column allowed us to determine successfully the enzyme activity and its application, proving that the specific activity of the enzyme in the cells increased at the later stage of sporulation. This increase in activity was parallel to the induction of enzyme protein synthesis, which was detected by sandwich enzyme immunoassay using antiserum to the purified enzyme. These results suggested that the regulation of this enzyme is at the genetic level and it plays an important role in the outer coat synthesis in the later sporulation stage of B. megaterium.

Bacillus megaterium↗

Novel morphological changes in gram-negative bacteria caused by combination of bulgecin and cefmenoxime.

The mode of action of bulgecin was investigated by examining its bactericidal and bacteriolytic activities, its effect on bacterial morphology, and its interaction with penicillin-binding proteins (PBPs). Bulgecin alone did not show any antibacterial activity against Escherichia coli and Serratia marcescens, but in concert with cefmenoxime, it induced potent growth-inhibitory and bactericidal activities. Electron microscopic examination of E. coli cells exposed to bulgecin combined with cefmenoxime revealed that a bulge developed in the middle of the cell, and additional smaller bulges were formed halfway between the central bulge and the polar ends. At the site of bulge development, vesicular mesosomelike structures appeared in the cytoplasm, the peptidoglycan layer facing them became faint, and the outer membrane protruded to form blebs. These morphological changes were quite different from those caused by the mecillinam-cefmenoxime combination that produces big bulges in E. coli. When S. marcescens was exposed to the combination of bulgecin and cefmenoxime, not only bulge formation, but also branching of the cells was observed. Bulgecin neither showed affinity for any PBPs of E. coli nor affected the binding of cefmenoxime or mecillinam to the PBPs.

Bacterial Proteins↗

Properdin factor B frequencies in four Asian populations.

The distribution of Properdin factor B (Bf) phenotypes and their gene frequencies were investigated in four Asian populations (Chinese, Filipino, Thai and Japanese). The frequency of the BfS phenotype in Filipinos (0.717) was significantly lower than that in Chinese (0.900) and Thai (0.889) (p less than 0.01), but not different from the Japanese (0.840). One variant, BfF 0.65 S, was identified in a Japanese subject. Thus, in the Asian populations studied, Bfs frequencies were high and the frequency of variants other than F and S were low.

China↗

Clinical features of aluminum-associated bone disease in long-term hemodialysis patients.

We encountered 11 patients with aluminum-associated bone disease (AABD), and treated them with deferoxamine (DFO). In 3 patients, a second bone biopsy was done during DFO treatment. Clinical features of AABD were compared with surgically proven secondary hyperparathyroidism (2 degrees HPT) with osteitis fibrosa on X-ray. Patients with AABD had disabling bone pain. This disease showed radiological signs ranging from normal, localized bone atrophy, to multiple fractures. It was characterized by increased soft tissue activity and localized abnormal uptake of 99mTc-MDP, detected by skeletal scintigrams. Patients with AABD had low levels of parathyroid hormone and alkaline phosphatase, but high aluminum (Al) levels compared to those with 2 degrees HPT. Serum Al increased after DFO administration, and the patients improved both clinically and histologically. 1-alpha-Hydroxyvitamin D3 (1-alpha-OH D3) was not effective for AABD. We concluded that the administration of antacids containing Al should be minimized in dialysis patients.

Adult↗

Elevated pancreatic oncofetal antigen levels measured by enzyme immunoassay in pure pancreatic juice of patients with pancreatic cancer.

Pancreatic oncofetal antigen (POA) was measured by enzyme immunoassay in pancreatic juice from patients with pancreatic cancer, chronic pancreatitis, or other diseases. POA levels in pancreatic cancer were significantly higher than in other disorders, and POA was seen by immunofluorescence to be in the cancerous tissues of pancreatic cancer. Assay of POA in the pancreatic juice may be more reliable than serum POA, and could contribute to the diagnosis of pancreatic cancer.

Antigens, Neoplasm↗

Influence of human serum on bactericidal activity of ceftizoxime sodium.

The influence of normal human serum on bactericidal activity of ceftizoxime sodium (CZX) was studied in vitro against Escherichia coli and Staphylococcus aureus. Subminimal inhibitory concentrations of CZX inhibited the growth of bacteria. Normal human serum as a source of complement and low doses of CZX, such as 1/20 or 1/10 the minimal inhibitory concentration, had a strong synergic action on the gram-negative bacteria E. coli, but not on the gram-positive bacteria S. aureus. However, the combination of CZX and fresh human serum had a stronger inhibitory effect on the growth of S. aureus than CZX alone. It is concluded that subminimal inhibitory concentrations of CZX inhibited the growth of bacteria in vitro in the presence of human serum, indicating that smaller dosages of CZX may act to eliminate the invading bacteria in vivo together with serum complement.

Bacteriological Techniques↗

Combination of cefmenoxime and cefsulodin in the treatment of complicated urinary tract infections caused by Pseudomonas aeruginosa.

The clinical efficacy of the combination therapy with cefmenoxime plus cefsulodin was studied in patients with complicated urinary tract infections caused by Pseudomonas aeruginosa. Patients received 1 g of CMX and 1 g of CFS concomitantly twice a day by 1-hour intravenous drip infusion. Of a total of 127 patients who received medication, 82 patients were evaluated on the 5th day. The overall clinical efficacy of treatment was evaluated by the criteria proposed by the UTI Committee, Japan, as excellent, moderate or poor. It was excellent in 15%, moderate in 55% and poor in 30%. Of the 143 strains isolated from 82 patients, 115 strains (80%) were eradicated. The eradication rate of P. aeruginosa was 83%. Subjective side effects were observed in 3 (2.4%) of the patients. Drug-related aggravations in laboratory test results were observed in 8 (7.5%), but most of them were minimal and reversible. The results of this study suggest that a combination of cefmenoxime and cefsulodin might be useful in the treatment of complicated urinary tract infections caused by P. aeruginosa.

Candidiasis↗

Diabetes due to secretion of a structurally abnormal insulin (insulin Wakayama). Clinical and functional characteristics of [LeuA3] insulin.

We have identified a non-insulin-dependent diabetic patient with fasting hyperinsulinemia (90 microU/ml), an elevated insulin:C-peptide molar ratio (1.68; normal, 0.05-0.20), normal insulin counterregulatory hormone levels, and an adequate response to exogenously administered insulin. Insulin-binding antibodies were absent from serum, erythrocyte insulin receptor binding was normal, and greater than 90% of circulating immunoreactive insulin coeluted with 125I-labeled insulin on gel filtration. The patient's insulin diluted in parallel with a human standard in the insulin radioimmunoassay, confirming close molecular similarity. The patient's insulin was purified from serum and shown to possess both reduced binding and ability to stimulate glucose uptake and oxidation in vitro. Analysis of the patient's insulin by high-performance liquid chromatography (HPLC) revealed two products: 7.3% of insulin immunoreactivity coeluted with the human standard, while the remaining 92.7% eluted as a single peak with increased hydrophobicity. Family studies confirmed the presence of hyperinsulinemia in four of five relatives in three generations, with secretion of an abnormal insulin documented by HPLC in the three tested. Leukocyte DNA was harvested from the propositus and the insulin gene cloned. One allele was normal, but the other displayed a thymine for guanine substitution at nucleotide position 1298 from the putative cap site, resulting in a leucine for valine substitution at position 3 of the insulin A chain. Insulin Wakayama is therefore identified as [LeuA3] insulin.

Adipose Tissue↗

Measurement of DNA content in single cells morphologically identified on smears.

A method was developed for measuring the nuclear DNA content in single cells previously identified on a bone marrow smear stained by the Wright-Giemsa method. The smear was first photographed and the location of individual cells, identified by morphology, was recorded on a cell map. The smear was then bleached with 50% acid ethanol and absolute methanol, and re-stained by the Feulgen method in 0.05% pararosaniline Schiff's reagent (pH 2.3) at 7 degrees C for 10 min. Nuclear red fluorescence was observed and the intensity of this fluorescence was proportional to the amount of DNA after prior irradiation of smears with green light for 9 hr. The method is useful for measuring cell DNA content in heterogeneous cell populations when morphological cell identification is required.

Bone Marrow↗

Ectopic adrenocorticotropin syndrome caused by lung cancer that responded to corticotropin-releasing hormone.

ACTH responses to corticotropin-releasing hormone (CRH) were studied in three patients with the ectopic ACTH syndrome caused by lung cancer. Plasma ACTH responded to synthetic CRH in two of three patients. Tumor tissues obtained from these two patients contained CRH and ACTH. In one patient, tumor ACTH secretion was stimulated by CRH in vitro. Tumor CRH was immunologically, chromatographically, and biologically similar to hypothalamic CRH. In addition, multiple forms of immunoreactive beta-endorphin were present in plasma and the tumor extracts. From these results, we conclude that some patients with the ectopic ACTH syndrome have tumors that produce both ACTH and CRH and that CRH can stimulate ACTH secretion by such tumors. Other patients with the ectopic ACTH syndrome do not have ACTH responses to CRH. Therefore, procedures other than CRH testing are needed to differentiate patients with Cushing's syndrome due to ectopic ACTH/CRH production from those with Cushing's disease, since the latter also usually have ACTH responses to CRH.

ACTH Syndrome, Ectopic↗

Dopamine release and presynaptic dopaminergic regulation in guinea pig spinal cord.

Using pharmacological approaches, we obtained evidence for the release of dopamine (DA) and its dopaminergic regulation in the guinea pig spinal cord. Electrical stimulation of the cord pieces increased the endogenous DA release and the efflux of [3H]dopamine [( 3H]DA) from tissues preloaded with [3H]DA. The evoked release of [3H]DA was current- and frequency-dependent and was prevented by tetrodotoxin (10(-6) M) or Ca2+-free medium containing EGTA (10(-4) M), while benztropine allowed a recovery of a more extensive amount of [3H]DA in the superfusing medium by inhibiting the reuptake process. The stimulated [3H]DA release was reduced by LY-171555, but not by SKF-38393 and 8-Br-cAMP. (-)Sulpiride enhanced the stimulated endogenous DA and [3H]DA release. (-)Sulpiride reversed the inhibition of evoked [3H]DA release induced by LY-171555, while SKF-38393 and 8-Br-cAMP did not affect LY-171555-induced inhibition of evoked [3H]DA release. These findings provide additional evidence for the neurotransmitter role of DA in the spinal cord of the guinea pig, and they strongly suggest the presence of presynaptic regulation of DA release via the dopamine receptor which is the D2 type.

Animals↗

[Toxicological studies on sophorolipid derivatives. (I). Acute toxicity, eye irritation, primary skin irritation, skin sensitization, phototoxicity, photosensitization, mutagenicity of polyoxypropylene (12) [(2'-0-beta-D-glucopyranosyl-beta-D-glucopyranosyl)oxy-] fatty acid ester-].

Acute toxicity, eye irritation, primary skin irritation, skin sensitization, phototoxicity, photosensitization and mutagenicity of sophorolipid derivatives were studied in rats, mice, rabbits, guinea pigs and Salmonella typhimurium strains. The acute oral toxicity of sophorolipid (SL) which Torulopsis bombicola produces, and its derivatives (PSL, Ethyl-SL and Oleyl-SL) were shown to be very low. The LD50 values of PSL ranged from 10 g/kg to 16 g/kg on oral administration in rats and mice, and from 5.8 g/kg to 6.6 g/kg on subcutaneous administration in mice. The oral LD50 values of Ethyl-SL and Oleyl-SL were estimated to be greater than 15 g/kg and that of SL was 12.5 g/kg. In eye irritation study, PSL failed to produce any reactions at 50% concentration even when the rabbit eye was not subsequently washed. SL, Ethyl-SL, Oleyl-SL and Tween 20 were "no irritant" or "slight irritant" to the rabbit eye at 20% concentration. PSL showed no irritancy to both the intact and abraded guinea pig skin at 50% concentration. And in other examinations, it was also indicated that PSL had no potentials of skin sensitization, phototoxicity and photosensitization in guinea pigs and had no potentials of mutagenicity in Salmonella typhimurium TA98 and TA100.

Animals↗