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Biomedical subjects

S Kondo

Publications and source records attributed to S Kondo.

At least 145 records · Page 8Linked to original sources

Male reproductive defects caused by puromycin-sensitive aminopeptidase deficiency in mice.

Male reproductive performance is composed of two principal elements, copulation and spermatogenesis. A wealth of literature has described the intricate web of endocrine events underlying these biological processes. In the present study we show that puromycin-sensitive aminopeptidase (Psa)-deficient mice are infertile, lack copulatory behavior, and have impaired spermatogenesis. The reproductive deficits of the mutants are not restored by androgen administration, although no aberrant localization of the sex steroid receptors was detectable in their brains and testes. Considering the strong expression of the Psa gene in the brain and Sertoli cells and the degenerative morphology of Sertoli cells in Psa-deficient mice, Psa may participate in testosterone-mediated reproductive signal pathways in the brain and testis.

Aminopeptidases↗

Possible existence of a novel receptor for uridine analogues in the central nervous system using two isomers, N3-(S)-(+)- and N3-(R)-(-)-alpha-hydroxy-beta-phenethyluridines.

Uridine analogue binding sites, the so-called uridine receptor, were observed in the experiments on specific [3H]N3-phenacyluridine binding to bovine synaptic membranes using two isomers, N3-(S)-(+)- and N3-(R)-(-)-alpha-hydroxy-beta-phenethyluridine, as ligands. The potent hypnotic, N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine, but not the (R)-isomer, strongly inhibited [3H]N3-phenacyluridine binding. The racemate had inhibitory activity intermediate between that of the two alpha-hydroxy-beta-phenethyluridines ((R)- or (S)-isomers). The inhibitory constants of these compounds were determined. The Ki values of N3-phenacyluridine, alpha-hydroxy-beta-phenethyluridine (racemate), N3-(R)-(-)-, and N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine were 0.65, 397.4, 1908, and 10.2 nM, respectively. The present results indicate the existence of uridine receptors in the central nervous system in relation to their hypnotic activities reported previously.

Animals↗

Hypnotic action of N3-substituted arabinofuranosyluracils on mice.

Methyl (2), ethyl (3), propyl (4), butyl (5), allyl (6), benzyl (7), o-, m-, p-xylyl (8-10), and alpha-phenylethyl (11) derivatives of arabinofuranosyluracil (1) were synthesized and their pharmacological effects in mice were examined by using hypnotic activity and synergism with pentobarbital as indices for the CNS depressant effects. At a dose of 2.0 micromol/mouse by intracerebroventricular injection, the values of mean sleeping time induced by 7-11 were 144, 154, 117, 33, and 34 min, respectively, whereas the alkyl (2-6) derivatives did not cause any hypnotic activity. N3-o-Xylylarabinofuranosyluracil (8) displayed the most potent hypnotic activity among the derivatives tested. Certain derivatives (6-11) significantly prolonged the pentobarbital-induced sleeping time compared to control. The present study indicated that substitution with benzyl and/or related groups on the N3-position of arabinofuranosyluracil produced CNS depressant effects.

Animals↗

A new drug delivery system using plasma-irradiated pharmaceutical aids. VIII. Delayed-release of theophylline from double-compressed tablet composed of eudragit as wall material.

The rapid release from a double-compressed tablet containing theophylline as a core drug with the pH-dependent water-soluble polymers, Eudragit L100, S100 or L100-55 used as a wall material was suppressed by argon plasma-irradiation due to an effect of inter-segmental cross-link reactions on the decrease in the surface polymer solubility of outer layer. In addition, the rapid theophylline release from the double-compressed tablet of Eudragit L100-55 with a lower glass transition temperature (Tg) has converted into the delayed-release system under a set of plasma operational conditions due to an additional effect of plasma heat flux on softening of Eudragit L100-55 surface resulting in the formation of the film-like surface with a particle-particle interlinking of the outer layer.

Delayed-Action Preparations↗

A new drug delivery system using plasma-irradiated pharmaceutical aids. IX. Controlled-release of theophylline from double-compressed tablet composed of cellulose derivatives as wall material.

The rapid release from a double-compressed tablet containing theophylline with the water-soluble polymer, hydroxypropylmethylcellulose (HPMC) or hydroxypropylmethylcellulose phthalate (HPMCP), used as a wall material can be suppressed by argon plasma-irradiation and changed into the sustained-release system due to a decrease in solubility of the outer layer. It was shown that the release profiles can be varied so as to cause theophylline release at different rates, depending on the set of conditions chosen for tablet manufacture and for plasma operation.

Argon↗

[Estimation of radiation exposed area by the nuclear accident occurred at Tokai village using ESR measurements of household sugar].

The area of radiation exposure by the nuclear accident occurred at Tokai village in 1999 was estimated by the ESR measurement of 95 household sugar samples collected from the accident area. These samples were roughly classified into three types of sugar, fine white sugar, fine brown sugar and coarse brown sugar. The control fine white sugar showed no radical in the ESR spectrum, while those of fine brown sugar and coarse brown sugar showed the presence of a small amount of radicals. It was also shown that, among these three kinds of sugar, the radical concentration of fine white sugar sampled from wooden houses at the area similar to each other did not vary much with the samples, while those of fine brown sugar and coarse brown sugar varied to a considerable extent. Thus, the fine white sugar is considered to be more suitable for the estimation of the level of radiation exposure. The radical concentration of each fine white sugar sample was plotted against the distance from the site of the nuclear accident with a correction of the difference in the shielding effect between concrete houses and wooden houses. The samples obtained at more than 2 km north of the site of nuclear accident showed no ESR spectral signal to a detectable extent. On the other hand, the ESR spectra were observed from the samples obtained within 10 km south and 4 km west of the accident site. These results suggest that the radiation exposure by the contaminant blown by the northeast wind blowing on the day of the accident may occur at the south and west areas.

Electron Spin Resonance Spectroscopy↗

Antihypertensive effects of acetic acid and vinegar on spontaneously hypertensive rats.

To clarify the possibility of a preventive effect of dietary vinegar on blood pressure, long-term administration of vinegar or the acetic acid to SHR was examined. As a result, it was observed that acetic acid itself, the main component of vinegar, significantly reduced both blood pressure (p<0.05) and renin activity (p<0.01) compared to controls given no acetic acid or vinegar, as well as vinegar. There were no significant differences in angiotensin I-converting enzyme activity in various organs. As for the mechanism of this function, it was suggested that this reduction in blood pressure may be caused by the significant reduction in renin activity and the subsequent decrease in angiotensin II. From this study, it was also suggested that the antihypertensive effect of vinegar is mainly due to the acetic acid in it.

Acetic Acid↗

Solitary true cyst of the pancreas in an adult: report of a case.

BACKGROUND: Solitary true cyst of the pancreas is rare in adults, and the differential diagnosis of cystic lesions of the pancreas is challenging. AIM OF THE STUDY: To describe a solitary true cyst of the pancreas in an adult and discuss the differential diagnosis. METHODS: A 50 yr old woman presented with a mass lesion in the right upper quadrant of the abdomen. Abdominal computed tomography showed a cystic lesion, with a maximum diameter of 12 cm, between the inferior surface of the liver and the ascending colon. The cyst was homogenous and had smooth edges. On magnetic resonance imaging, a unilocular cyst was seen that was low intensity on T1-weighted images and very high intensity on T2-weighted images. No connection between the cyst and the pancreatic ductal system was demonstrated on endoscopic retrograde cholangiopancreatography. Laparotomy was performed with a presumptive diagnosis of cystic tumor of the pancreas. RESULTS: On pathologic examination, the cyst was serous and was lined with a single layer of normal cuboidal epithelium that was periodic acid Schiff stain negative. Meticulous examination failed to identify honeycomb-like microcysts characteristic of serous cystadenoma. The final diagnosis was a solitary true cyst of the pancreas. CONCLUSION: The differential diagnosis of solitary true cyst from other cystic lesion of the pancreas usually is based on histology. Particular care must be taken to distinguish this lesion from macrocystic serous cystadenoma.

Diagnosis, Differential↗

Standardization of laboratory data and establishment of reference intervals in the Fukuoka Prefecture: a Japanese perspective.

Standardization of 22 clinical chemistry analytes and five serum protein constituents has been performed in the Fukuoka Prefecture, which has a population of approximately five million. The standardization project was established to determine reference intervals for these analytes by educating physicians, medical technologists and staff of medical institutions, and by daily or monthly monitoring the use of common control samples through e-mail. Standardization extended to 97% of the institutions in the prefecture. Results for 14 of the 22 clinical chemistry analytes have become highly reliable and differences between institutions decreased. Standardization of other analytes is now in progress. Regional collaboration based on international guidelines led to a significant improvement in interlaboratory comparability. Areas where further improvements are needed have been identified.

Adolescent↗

Combination therapy of 2-5A antisense against telomerase RNA and cisplatin for malignant gliomas.

2',5'-Oligoadenylate (2-5A) linked to an antisense oligonucleotide against human telomerase RNA (2-5A-anti-hTR) is a novel therapeutic modality we have recently developed. We designed the oligonucleotide to target telomerase which maintains chromosome integrity in cancer cells. We have already demonstrated the efficacy of this new therapy in malignant glioma cells with telomerase activity. In the present study, we investigated the effect of 2-5A-anti-hTR in combination with cisplatin, an anti-cancer drug commonly used for malignant glioma patients. Six human malignant glioma cell lines with telomerase activity were treated with 0.5 microM 2-5A-anti-hTR and/or cisplatin (0, 0.1, 1, 5, 10, or 20 microg/ml) for three days, and cell viability was measured using the MTT colorimetric assay. The combination therapy showed synergistic effect at 1 microg/ml cisplatin and additive effect at 5 microg/ml cisplatin. TUNEL staining of the treated cells showed significantly increased apoptotic cells after the combination therapy. Furthermore, tumor growth of subcutaneous xenografts of human malignant glioma cells in nude mice was effectively reduced after the combination therapy for seven days. Our study shows that the tumor-killing effects of the combined treatments are, at least in part, due to induction of apoptosis. 2-5A-anti-hTR is a promising therapy not only when used alone, but also in combination with cisplatin.

Animals↗

A novel treatment of human malignant gliomas in vitro and in vivo: FADD gene transfer under the control of the human telomerase reverse transcriptase gene promoter.

Telomerase activity has a close relationship with malignancies in many cell types and it is tightly regulated at the transcriptional level of human telomerase reverse transcriptase (hTERT). Utilizing the hTERT promoter, the authors developed a gene delivery system of Fas associated protein with death domain (FADD) (hTERT/FADD). FADD is a protein which plays an important role in the apoptotic pathway of Fas. Over-expression of FADD induces apoptosis in the cells regardless of Fas expression on the cell surface. We hypothesized that we might be able to restrict the expression of FADD in malignant glioma cells if we use the gene transfer system under the control of hTERT promoter. This study was designed to investigate whether the hTERT/FADD construct induces apoptosis effectively in malignant glioma cells while keeping normal cells intact. First, using the reverse transcription-polymerase chain reaction (RT-PCR) technique, we confirmed that hTERT mRNA was expressed in human malignant glioma cells (U373-MG, A172 and GB-1), but not in cultured astrocytes (TEN) or fibroblasts (MRC5). After transient transfection with the hTERT/FADD construct, a significant number of FADD-positive cells and apoptotic cells were detected in hTERT-positive malignant glioma cells. In contrast, hTERT-negative astrocytes and fibroblasts remained intact. Furthermore, subcutaneously implanted U373-MG tumors treated with the hTERT/FADD construct reduced in volume significantly compared to the conrol treatment (p=0.0001). Gene transfer of FADD under the control of the hTERT promoter may be a novel and promising therapy to kill hTERT-positive malignant glioma cells while sparing normal brain cells lacking hTERT.

Animals↗

Purification of proplatelet formation (PPF) stimulating factor: thrombin/antithrombin III complex stimulates PPF of megakaryocytes in vitro and platelet production in vivo.

In this study, the protein which stimulates proplatelet formation (PPF) of megakaryocytes was purified from normal human plasma using 7 steps procedures. Two different protease inhibitors were identified based on their amino acid sequences, i.e. antithrombin III (AT III) and C1 inhibitor. They were included in high density lipoprotein (HDL). HDL was necessary for AT III to be active in PPF in vitro. The biological effects of the AT III/HDL or thrombin-AT III (TAT)/HDL were studied in vitro. PPF of murine megakaryocytes was stimulated by negative control (BSA) (1.8 +/- 0.3%), AT III (2.0 +/- 0.4%), HDL (1.2 +/- 0.9%), AT III/HDL (14.8 +/- 2.1%) or TAT/HDL (23.3 +/- 3.5%), respectively. TAT/HDL also had a synergistic effect with the mpl ligand, judging by the acetylcholinesterase (AchE) expression of murine megakaryocytes (2.7 fold increase). In vivo subcutaneous administration of AT III alone or TAT for 3 days significantly stimulated thrombocytosis (136% and 144%, respectively, p<0.05) and AT III/HDL showed rapid and further stimulation (150%, p <0.01). These results and the previous studies indicate that megakaryocytopoiesis is regulated by the mpl ligand, while a protease/protease inhibitor complex such as TAT, which is involved in the coagulation cascade associated with platelet consumption, might be one of the regulators in platelet production.

Amino Acid Sequence↗

Concentration and localization of YKL-40 in hip joint diseases.

OBJECTIVE: YKL-40 is a major secretory protein from human chondrocytes and synovial fibroblasts. We evaluated the concentrations and localization of YKL-40 in hip joint diseases, and analyzed the possibility of YKL-40 as a new inflammatory joint marker. METHODS: The concentration of YKL-40 in synovial fluid (SF) was measured by a sandwich-type ELISA. SF samples were collected from 19 hips with osteoarthritis (OA) of the hip joint, 21 hips with osteonecrosis of the femoral head (ONFH), and 5 hips with failed total hip arthroplasty (failed THA). In all cases of failed THA, cartilage tissue in hip joints was removed completely during the previous THA. The localization of YKL-40 was determined through immunohistochemical analysis using a specific antibody. RESULTS: The mean SF concentration of YKL-40 was significantly higher in ONFH and failed THA than in OA. Comparison by OA grade was not significantly different. In staging of ONFH, Ficat stage III with collapsed femoral head showed significantly higher YKL-40 concentrations than the other stages. Immunohistochemical studies showed that YKL-40 was localized in chondrocytes in the superficial and middle layers of the cartilage. In the synovium, YKL-40 was localized in fibroblasts and macrophages. CONCLUSION: YKL-40 reflects the degree of inflammation rather than cartilage metabolism. YKL-40 may be a useful inflammatory marker of hip joint diseases.

Adipokines↗

Studies of tin ethyl etiopurpurin photodynamic therapy of the canine prostate.

PURPOSE: Previous studies have demonstrated the technical feasibility of destroying prostate tissue using photodynamic therapy for benign and malignant disease. A series of canine studies was performed to evaluate the systemic uptake and distribution of the photosensitizer tin ethyl etiopurpurin (SnET2) in the prostate and surrounding tissues, and determine the optimal combination of drug dose, light dose and time interval between drug and light administration using transurethral and transperineal interstitial light delivery. MATERIALS AND METHODS: Adult male mongrel source dogs received intravenous bolus injections of 0.5 or 1.0 mg./kg. SnET2 in 4 studies. In the first study the concentration of SnET2 in the prostate and surrounding tissue was measured at various time points after dosing. In the second study a tissue dose response relationship of SnET2-PDT was studied after transperineal interstitial light application. The third and fourth studies evaluated the tissue effects of combined transurethral and transperineal interstitial light application on SnET2 sensitized prostates. RESULTS: Substantial amounts of SnET2 were measured in the prostate between 24 and 168 hours after infusion. Drug and light dose dependent prostatic tissue necrosis and volume reduction were documented in the dose response relationship study. The combination of transurethral and transperineal light resulted in the extensive destruction of glandular epithelium with minimal damage to surrounding structures. Average prostate volume decreased 52%. Transperineal interstitial light delivery with multiple diffusers resulted in substantial glandular destruction of the prostate. An average volume reduction of more than 60% was achieved. CONCLUSIONS: SnET2-PDT is a viable minimally invasive treatment modality for prostate tissue destruction.

Animals↗

[Clinical laboratory data and reference intervals standardized in Fukuoka].

In Fukuoka whose population is approximately five million inhabitants, surveys on the accuracy of laboratory data have been performed by the Fukuoka Prefecture Medical Association for the last 30 years. We have been attempting to evaluate the data for routine use since 1988, and it has become possible to share laboratory data between all institutions in Fukuoka prefectures. As a result, reference intervals for 23 clinical chemistry analytes were established in 1995, to which were added in 1996 five serum protein constituents that have been utilized for clinical examinations. Methods for documentations and monitorings the data obtained in the prefecture were also established, standardization of the above analytes extended to 97% of the institutions in the prefecture. Results for 14 of the 23 clinical chemistry analytes have become highly reliable and clinically useful as differences between institutions in terms of results have narrowed. Standardization of other analytes is now in progress.

Aged↗

[Infants 12 month-old or less as a high risk group in tuberculosis--comparison of clinical data with those in children aged one to two years].

A number of tuberculosis (TB) infants 12 month-old or less is larger than the ones of any other age groups with childhood TB in our hospital. This study was undertaken to elucidate clinically why infants 12 month-old or less suffered from TB most among infants and early children. We studied tuberculin skin reaction, isolation frequency of Mycobacterium tuberculosis (MTB) in gastric aspirates, and frequency of systemic dissemination of TB among 45 TB infants 12 month-old or less, and compared the results with those of 31 control TB infants and children aged 13 to 35 month-old. The frequency distribution of tuberculin skin reaction size among the studied infants was significantly smaller than that among the controls (p < 0.05). MTB was positive among 33 out of the 45 studied infants (73%) while 12 out of the 31 controls (39%), and the difference was significant (p < 0.005). Miliary TB and/or TB meningitis were seen among 8 out of the 45 studied infants (18%) while 1 out of the 31 controls (3%), and there was marginally significant difference between them (p = 0.054). These results suggest that delayed-type hypersensitivity and cell-mediated immunity to MTB among infants 12 month-old or less may be lower than those among infants and children aged 13 to 35 month-old, and the studied infants may be inferior in their capacity to kill mycobacteria and to encapsulate mycobacteria by granuloma formation.

Child, Preschool↗

Detection of antinuclear antibodies by use of an enzyme immunoassay with nuclear HEp-2 cell extract and recombinant antigens: comparison with immunofluorescence assay in 307 patients.

BACKGROUND: A new enzyme immunoassay (EIA) for automated detection of antinuclear antibodies (ANAs) uses a mixture of HEp-2 cell extracts and multiple recombinant nuclear antigens immobilized on beads. We compared this EIA and an immunofluorescence (IF) assay in a large group of patients and controls. METHODS: We studied 492 healthy individuals and 307 patients with connective tissue diseases (CTDs). Sera were tested by an automated EIA (COBAS Core HEp2 ANA EIA; Roche Diagnostics) and IF. Samples were also tested for eight disease-specific antibodies, including antibodies against U1RNP, Sm, SSA/Ro, SSB/La, Scl-70, Jo-1, dsDNA, and centromere. RESULTS: Areas under ROC curves for the EIA were greater than (P = 0.008-0.012) or numerically identical to areas for the IF method for each of six CTDs studied. ROC areas for EIA were 0.98 (95% confidence interval, 0.95-0.99), 0.99 (0.96-1.00), and 0.99 (0.98-1.00) in systemic lupus erythematosus (n = 111), systemic sclerosis (n = 39), and mixed connective tissue disease (n = 33), respectively. For all 258 CTD patients with conditions other than rheumatoid arthritis (RA), the sensitivity and specificity of the IF method at a cutoff dilution of 1:40 were 92% and 65%, respectively, vs 93% and 79% for the EIA at a cutoff of 0.6. For the IF method at a cutoff dilution of 1:160, sensitivity and specificity were 81% and 87%, respectively, vs 84% and 94%, respectively, for the EIA at a cutoff of 0.9. For 207 sera containing at least one of eight disease-specific ANAs, positivities for the EIA and the IF method were 97.1% and 97.6%, respectively, at cutoffs of 0.6 and 1:40 (P = 0.76). CONCLUSIONS: An EIA that can be performed by a fully automated instrument distinguishes CTDs (except RA) from healthy individuals with both higher sensitivity and specificity than the IF method when the cutoff index was set at 0.9. Moreover, it can be used to exclude the presence of disease-specific ANAs by setting the cutoff index at 0.6 with almost the same efficacy as the IF method.

Adolescent↗

[Intentional limited operation for minute peripheral adenocarcinoma of the lung].

The purpose of this report is to evaluate the limited operation for peripheral minute adenocarcinoma of the lung. Firstly, 44 cases (47 lesions) of surgically resected minute peripheral lung adenocarcinoma, 10 mm or less in diameter, were reviewed using Noguchi's classification, and the correlation between high resolution CT (HRCT) images and the clinicopathological features was examined retrospectively. All type A and B adenocarcinomas (n = 14) had no recurrence and all cases were the air containing type by HRCT. Lymph node metastasis and lymphatic/vascular involvement were detected with type C, D, E, F and 3 cases among them were died for recurrence. Based on those results, from April 2000, intentional limited operation was prospectively performed for 14 patients (16 lesions) with peripheral nodule showing ground-glass opacity on HRCT. The pathological findings were type A (n = 9), type B (n = 5), and atypical adenomatous hyperplasia was one case (If the findings were confirmed type C, D, E, F by permanent section diagnosis, VATS lobectomy will be performed). We recommend limited operation should be performed in only type A or B adenocarcinoma and permanent section diagnosis is necessary to determine whether or not.

Adenocarcinoma↗