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Biomedical subjects

M Kondoh

Publications and source records attributed to M Kondoh.

At least 55 records · Page 3Linked to original sources

A novel nonenzymatic pathway for the generation of nitric oxide by the reaction of hydrogen peroxide and D- or L-arginine.

Nitric oxide (NO) is a biologically active molecule known to be enzymatically synthesized from L-arginine in the presence of NO synthetase (NOS). In this study, we demonstrate a novel non-enzymatic pathway for NO synthesis involving hydrogen peroxide and D- or L-arginine. We employed two measures of NO generation. The first consists in the demonstration of the oxidative metabolites of NO (NO2 + NO3 = NOx) and the second is the confirmatory finding of chemiluminescence derived from NO. The results show that NOx increases in the incubation mixture containing hydrogen peroxide coupled with D-arginine, L-arginine, L-canavanine, and even the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). However, chemiluminescence was detected only from the reactions of hydrogen peroxide and D- or L-arginine and was diminished by the addition of carboxy-2-phenyl-4, 4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (PTIO), a specific scavenger of NO, confirming NO generation in the reaction.

Amino Acids↗

Acyl amino acid derivatives as novel inhibitors of influenza neuraminidase.

We searched our chemical collection to identify non-N-acetylneuraminate (NeuAC) inhibitors of influenza neuraminidase (NA). Of the 62 acyl derivatives tested, several acyl amino acids, but not acyl alkanolamine derivatives, were effective and inhibited the NA activity in a dose-dependent manner. N-3-Hydroxymyristoyl D-cysteine and N-myristoyl-O-caproyl-D-serine were the more potent compounds and inhibited the enzyme in a noncompetitive manner (Ki = 102 and 125 microM, respectively) without respect to the substrate. An important consideration for the choice of inhibitor is the selectivity of the inhibition. These compounds were selective inhibitors of viral NA and effective for any variant enzyme, but the enzymes from V. cholerae and human placenta were insensitive. Accordingly, the acyl amino acid derivatives may be expected to be inhibitors without cellular toxicity and may serve as lead compounds for anti-influenza agents.

Acylation↗

Mucinous adenocarcinoma of the male urethra.

We report a case of primary mucinous adenocarcinoma arising in the bulbomembranous urethra. The patient underwent radical cystectomy and total penectomy, followed by systemic chemotherapy. Metastases in lungs, skin, and lymph nodes (inguinal, iliac, para-aortic, and tracheobronchial) were found within 2 months after operation. We reviewed 37 cases of primary adenocarcinomas of the male urethra.

Adenocarcinoma, Mucinous↗

A quantity of stereotyped behavior of ddY mice induced by low-dose methamphetamine.

It is reported that high-dose methamphetamine (8 mg/kg) induces stereotyped behavior in ddY mice in an open field, but it is still not certain that low-dose methamphetamine (less than 2 mg/kg) can induce the stereotyped behavior in ddY mice in a narrow space. In order to investigate the problem, we evaluated the quantity of stereotyped behavior of ddY mice by using a mouse wheel-running apparatus. In this method, we have come to recognize an increase in the stereotyped behavior depending on the dose of methamphetamine and the reverse-tolerance phenomenon as a decrease in the wheel-revolution counts. The present findings indicate that low-dose methamphetamine can promote stereotyped behavior in ddY mice under conditions in which the ambulation is restricted to a narrow wheel space.

Animals↗

Primary hemostasis during women's life cycle measured by Thrombostat 4000.

The Thrombostat 4000 was used to investigate primary hemostasis in women during different stages of their life cycle. Nonpregnant females were studied during their proliferative and luteal phases; pregnant women were investigated during their 28-35th weeks of gestation and some women between the ages of 70-84. Data were compared to those obtained from male volunteers injected with 40 mg estrogen. No significant differences between proliferative and luteal phases were found, but BT2 was prolonged in the elderly women. In the pregnant women extremely short BT2 values were measured. Shortening of BT2 was also seen in the males injected with estrogen.

Adult↗

Correlation of the clinical manifestations and gene mutations of Japanese xeroderma pigmentosum group A patients.

The gene responsible for xeroderma pigmentosum (XP) group A has recently been cloned and designated XPA gene. Previous studies have shown that most Japanese XPA patients have homozygous mutations for the splicing site of intron 3 of the XPA gene, which was recognized by restriction endonuclease (RE) AlwNI (AlwNI mutation). Other mutations found to date have been the nonsense mutation at codon 228 in exon 6, recognized by RE HphI (HphI mutation), and at codon 116 in exon 3, recognized by RE MseI (MseI mutation). Using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis, we examined the point mutations of the XPA gene in 16 XPA patients, their parents, and their four asymptomatic siblings. We found that eight patients were homozygous for the AlwNI mutation, two were compound heterozygotes for the AlwNI mutation and the HphI mutation, one was a compound heterozygote for the AlwNI mutation and the MseI mutation, three were compound heterozygotes for the AlwNI mutation and an unidentified mutation, and two were compound heterozygotes for the HphI mutation and an unidentified mutation. Investigation of their clinical features suggested that the four patients who were heterozygous for the HphI mutation and the AlwNI or an unidentified mutation had milder clinical manifestations such as later development of skin cancers and milder neurological deterioration, than those patients who were either homozygous for the AlwNI mutation or heterozygous for the AlwNI mutation and MseI mutation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Computer-aided clinical laboratory diagnosis in conjunction with the electronic medical textbook.

1. INTRODUCTION. Medical knowledge has been increasing and diversifying on a worldwide scale, while the specialization of physicians has been extended vigorously. Under this environment, it may be natural that mistakes are made in a comprehensive diagnosis, as the physician cannot master all of this dramatically increasing volume of knowledge. The knowledge has extended beyond the memory of human beings, thereby causing the deterioration of service; this is called the "Knowledge crisis." To tackle this problem, the Electronic Medical Textbook (EMT) has been conceived and set up as a medical knowledge base for physicians to optimize both their specialties and activities in clinical practice. Meanwhile, laboratory information systems were widely introduced. However, there are few systems which allow interpretation of the findings obtained. With this in mind, we have improved the utility of the EMT by enhancing its function with laboratory information follow-up, thesaurus back-up, Japanese language support, and online access. 2. SYSTEM DESCRIPTION. The knowledge database for medical decision-making consists of three categories: 1) Medical domain knowledge (including approximately 3500 diseases) from the AMA's "The Current Medical Information & Terminology (CMIT)"; 2) Knowledge on relationship between laboratory testing results and diseases from "The Effects of Disease on Clinical Laboratory," compiled by the AACC; and 3) Clinical testing knowledge from Otsuka's laboratory test handbook "Kensa-Kojien." These categories are connected by links in the process of cross-reference. In actual use, the first is to select the supporting system bringing up clinical signs and findings on CRT from which users can then choose any representations corresponding to the patient's clinical state. Once the relevant objects have been selected, the system presents the correlated investigative tests to be performed, along with a scope of laboratory tests ordering for its initial investigative task. The required tests against the data objects denoted by "High," "Low," or "Abnormal" are linked to possible diagnoses, which appear on CRT in order of likelihood. Similarly, the possible diagnoses can be obtained directly by consulting the patient's laboratory test results in linkage, by way of automated data transformation into the corresponding data object using the reference interval. If necessary, additional information relative to clinical signs can be added. With the repetition of this procedure, clinically useful tests can be located, thus increasing the likelihood of an appropriate diagnosis. The proposed diseases can be confirmed through cross-reference to the patient's clinical signs from the description in the Textbook on CRT. In order to bolster the efficiency of cross-checking on CRT, the sentences including hit-words are highlighted in red. Moreover, with regard to specific keywords for disease, those sentences are highlighted in green to emphasize differences in between. In parallel, the description points out an active behavior of laboratory test results in the progression of the disease and is also able to display applicable laboratory test listings. Furthermore, this knowledge-based interpretation system is directly accessible via online network services in referring to laboratory test results. 3. CONCLUSION. A combination of the CMIT and laboratory diagnostic information in the knowledge database allows the narrowing down of proposed diagnoses due to its flexible approach, which depends not only on clinical signs and findings, but also on applicable test-ordering support and suggestions. This enhances the potential usefulness of the EMT. The system contributes to the support of the diagnostic procedures and assists in educational setting, because the process can be operated in reverse based on clinical signs and laboratory findings in a dialogue style on CRT. The related disease description highlighted in color has won a good reputation dur

Artificial Intelligence↗

The measurement of gastric emptying in conscious rats by monitoring serial changes in serum acetaminophen level.

A method for evaluation of gastric emptying via monitoring serial serum levels of acetaminophen (APAP) as an indicator, without involving animal sacrifice, has been developed in conscious rats. We administered orally suspended test meals of 0.5, 1, 2, or 4 mL/rat each, containing 20 mg APAP. The animals were repeatedly bleed at 15, 30, 45, 60, or 90 min after APAP treatment. Serum APAP level was determined by a high-performance liquid chromatography. As a result, a 2-mL meal was found optimal to attain continuous levels of APAP in serum. The APAP method showed a close correlation (r = 0.77) with the phenol red method, a standard procedure for quantitative detection of gastric emptying entailing rat sacrifice. The blood loss (approximately 2 mL) resulting from the APAP method did not significantly modify the rate of gastric emptying. In addition, data was presented to substantiate the validity of the APAP method in demonstrating enhancement and inhibition of gastric emptying using cisapride and cholecystokinin-octapeptide (CCK), respectively. These results suggest that the APAP method is easy, versatile, and reliable, and requires only a minimal number of animals for the evaluation of sequential changes in gastric emptying.

Acetaminophen↗

Siblings with xeroderma pigmentosum complementation group A with different skin cancer development: importance of sun protection at an early age.

BACKGROUND: For patients with xeroderma pigmentosum (XP), strict protection from UV light exposure is the only way to prevent and retard skin cancer formation. OBJECTIVE: Our purpose was to learn how the timing of sun protection influences the clinical findings in patients with XP. METHODS: We studied two siblings with XP group A (XPA) who showed a significant difference in the age at onset of skin cancer development and in neurologic abnormalities. RESULTS: The elder sister had had her first basal cell carcinoma (BCC) at 13 years of age and had had multiple BCCs by 25 years of age. Her younger sister had her first BCC at 23 years of age. Neurologic impairment of the younger sister was much milder. The elder sister started strict sun protection at 4 years of age, whereas the younger began at 2 years of age. Analysis of the XPA complementing gene revealed that both patients had the identical mutation. CONCLUSION: In patients with XP the earlier sun protection begins the later skin cancer develops. Neurologic deterioration may also be reduced by earlier sun protection.

Adolescent↗

Anti-proliferative effects of benidipine hydrochloride in porcine cultured vascular smooth muscle cells and in rats subjected to balloon catheter-induced endothelial denudation.

Using the [3H]thymidine incorporation technique, the anti-proliferative effects of benidipine, a long-acting calcium antagonist, on porcine cultured vascular smooth muscle cells (VSMCs) were determined and compared with those of other calcium antagonists. Benidipine inhibited serum-stimulated [3H]thymidine incorporation into VSMCs (IC50, 0.2 microM), and this inhibitory effect was significantly more potent than that of nitrendipine, felodipine, nisoldipine, manidipine, amlodipine, nifedipine, verapamil and diltiazem. When growth-arrested cells were stimulated with platelet-derived growth factor followed by insulin, benidipine, administered with either stimulation, inhibited [3H]thymidine incorporation into VSMCs. This suggests that it acts in both the G0/G1 and G1/S phases. In another series of experiments, the anti-proliferative effect in vivo was investigated using rats subjected to balloon catheter-induced endothelial denudation of the aorta. Benidipine (5 mg/kg, p.o., b.i.d.) significantly reduced the incorporation of [3H]thymidine into aortic DNA 48 h after balloon injury, whereas it did not affect incorporation into bone marrow, suggesting that it inhibits arterial DNA synthesis. From our results, benidipine was shown to exert antiproliferative effects on VSMCs in vivo as well as in vitro. The drug may be useful for the treatment of vascular proliferative diseases such as restenosis following percutaneous transluminal angioplasty and atherosclerosis.

Animals↗

Inhibitory action of benidipine on balloon catheterization-induced intimal thickening of the carotid artery in rats.

We examined the effect of benidipine, a long lasting Ca2+ channel blocker, on balloon catheterization-induced intimal thickening of the carotid artery in rats. In the carotid arteries of vehicle-treated rats, neo-intima formation and elevation of DNA content was observed at 14 days after the surgery. Benidipine (5 mg/kg, p.o., b.i.d.) halved the intimal thickening and suppressed the elevated DNA-content in the balloon catheter-injured artery. These results suggest that benidipine may be useful for the treatment of vascular proliferative diseases like restenosis following percutaneous transluminal angioplasty.

Animals↗

A new methionine antagonist that has antifungal activity: mode of action.

A new antifungal, azoxybacilin (an unusual amino acid with an azoxy moiety) was identified from Bacillus cereus, and its in vitro antifungal activity and mode of action were investigated. Azoxybacilin was active against a broad spectrum of fungi. It was especially active against mycelial fungi, such as Aspergillus, and did not show antibacterial activity. No cross-resistance with antifungals currently on the market was observed. The IC50 values of azoxybacilin antifungal activity against Saccharomyces cerevisiae were significantly greater when amino acids containing sulfur were added to the growth medium, whereas other amino acids were not effective at all. We, therefore, tested the effect of the intermediates involved in the synthetic pathway of these amino acids. The activity markedly diminished when one of the following four intermediates was present in the medium:homocysteine, cysteine, cystathionine or methionine. These four intermediates were the same as those required for the growth of the O-acetylhomoserine sulfhydrylase mutant, S. cerevisiae ONO726, indicating that azoxybacilin would inhibit a step or steps in the sulfur-fixation pathway.

Amino Acids↗

[MEP (methotrexate, etoposide and cisplatin) and M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for advanced uroepithelial cancer--a preliminary report of MEP as second line chemotherapy for recurrence after M-VAC].

Combination chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC regimen) or with methotrexate, etoposide and cisplatin (MEP regimen) was administered to 32 patients with advanced measurable uroepithelial cancers. Fifteen patients among them were adequately treated with M-VAC regimen, and 11 with MEP regimen. Complete remission was not achieved clinically in any patients. Partial remission occurred in 73.3% (11/15) of M-VAC patients and 72.7% (8/11) of MEP patients. Of eleven MEP patients, six were treated with MEP therapy as second line chemotherapy for the recurrence after other chemotherapy (5 cases after M-VAC, 1 case after intraarterial cisplatin). They showed a considerable response (4 patients, PR; 2 patients, MR) and an appreciable remission period, not inferior to those of first line chemotherapy with M-VAC regimen. The present study shows that MEP may be a promising regimen for advanced uroepithelial cancers, especially as a second line chemotherapy for relapsed cases after M-VAC therapy.

Adult↗

Flow cytometric analysis of nuclear DNA content of renal cell carcinoma correlated with histologic and clinical features.

BACKGROUND: The prognostic value of flow cytometric analysis of DNA content is contradictory in renal cell carcinoma (RCC). METHODS: Flow cytometric analysis was performed on 72 patients with RCC, and the relationship between the DNA content and pathologic or clinical features was investigated. RESULTS: Aneuploidy was observed in 36 (50%) of these patients. Two tissue samples from primary tumors of 12 patients were analyzed, and heterogeneity was found in 7 (58%) of these patients. The incidence of aneuploidy was significantly higher in high-grade than in low-grade tumors (P = 0.0328). All five tumors with a maximum diameter of 2.5 cm or smaller (T1N0M0) were diploid, and a trend for more aneuploid tumors among high-stage diseases was observed. The survival rate of patients with diploid tumors was not significantly different from that of those with aneuploid tumors in the low- or high-stage group. CONCLUSIONS: DNA ploidy assessed with one sample is not a prognostic factor, and heterogeneity between different samples of a given tumor indicates that one sample is not enough for DNA flow cytometry in RCC.

Adult↗

Case report: left ventricular apical hypertrophy in progressive limb-girdle muscular dystrophy.

Cardiac involvement is uncommon in patients with limb-girdle muscular dystrophy. This report describes a patient in whom concentric hypertrophy localized to the apical left ventricle was revealed during a long clinical course of skeletal muscular dystrophy, with evolving electrocardiographic changes also compatible with apical hypertrophic cardiomyopathy. Endomyocardial biopsy revealed similar histologic changes in the skeletal muscle biopsy specimen, characterized by muscle fiber atrophy and hypertrophy with a mild degree of interstitial fibrosis. The pathogenesis of cardiac hypertrophy in this case is unclear. However, the pathologic findings suggest that the myocardium may be involved in the same dystrophic process as the skeletal muscles.

Cardiomyopathy, Hypertrophic↗