Biomedical subjects

Y Kondo

Publications and source records attributed to Y Kondo.

At least 145 records · Page 8Linked to original sources

PubMed2000

Combination therapy of malignant glioma cells with 2-5A-antisense telomerase RNA and recombinant adenovirus p53.

Malignant gliomas of astrocytic origin have commonly expressed several features such as alterations in the tumor-suppressor gene p53 or p16 or the acquisition of telomerase activity, which are distinctive from astrocytes. Therefore, restoration of the tumor-suppressor gene or telomerase inhibition is expected to provide a cure for malignant gliomas. We have recently demonstrated that the treatment with a 19-mer antisense oligonucleotide against human telomerase RNA linked to a 2',5'-oligoadenylate (2-5A-anti-hTR) inhibited the growth of malignant glioma cells. From a therapeutic point of view, it is very important to investigate the antitumor efficacy of 2-5A-anti-hTR combined with the restoration of p53 or p16 gene. In this study, we evaluated the antitumor effect of 2-5A-anti-hTR in combination with recombinant adenoviruses bearing p53, its associated p21WAF1/CIP1, or p16CDKN2 gene (Ad5CMV-p53, Ad5CMV-p21, or Ad5CMV-p16) against malignant glioma cells in vitro and in vivo. Five malignant glioma cell lines expressing the mutant p53 gene (A172, GB-1, T98G, U251-MG and U373-MG) were more sensitive to the combination of 2-5A-anti-hTR and Ad5CMV-p53 than to other combinations. The additive effect of the combination therapy was due to induction of caspase-dependent apoptosis and cell growth arrest. Furthermore, the 2-5A-anti-hTR treatment when combined with Ad5CMV-p53 showed greater efficacy against subcutaneous U251-MG tumors in nude mice. In contrast, U87-MG cells expressing the wild-type p53 gene were insensitive to Ad5CMV-p53, although the treatment with 2-5A-anti-hTR was significantly effective. These results indicate that combining 2-5A-anti-hTR with Ad5CMV-p53 has the most therapeutic potential for malignant gliomas with mutant p53. For tumors exhibiting wild-type p53, it may be useful to treat with 2-5A-anti-hTR. Gene Therapy (2000) 7, 2071-2079.

Adenoviridae↗

PubMed2000

Is autonomic dysfunction a necessary condition for chronic peptic ulcer formation?

BACKGROUND: The relationship between 1/f fluctuation of the heart rate variability and Helicobacter pylori infection was evaluated, in order to clarify whether autonomic nervous dysfunction is a necessary condition for chronic peptic ulcer formation. METHODS: The subjects were 11 patients with recurrent chronic peptic ulcer and 20 age-matched normal subjects. Holter ECGs were recorded over 24 h, and the 1/f(-x) fluctuation of the heart rate was computed. The 1/f(-x) fluctuation of the heart rate is a novel index of autonomic function that has been shown to reflect a patient's pleasant mood. For 1/f(-x) fluctuation, the slope of the regression line (-x) was determined and cosine fitting of the absolute slope of the regression line over a 24-h period was performed. RESULTS: For the normal group, the absolute slope of the regression line during daytime and night-time were 0.53 +/- 0.16 and 1.05 +/- 0.18, respectively. For the peptic ulcer group, the corresponding values during daytime and night-time were 0.94 +/- 0.15 and 1.84 +/- 0.18, respectively. The mean value of the cosine curve was 0.76 +/- 0.23 in the normal group and 1.12 +/- 0.25 in the peptic ulcer group. Thus, these values were significantly higher for the latter group than for the former group (P<0.05). No statistically significant difference in H. pylori infection between the two groups was observed. CONCLUSIONS: Autonomic nervous dysfunction as well as H. pylori infection appears to be a necessary condition for chronic peptic ulcer formation.

Aged↗

PubMed2000

Evaluation of autonomic nervous function in patients with essential hypertension complicated with peptic ulcer.

BACKGROUND AND AIMS: The relationship between peptic ulcer, autonomic activity and the incidence of Helicobacter pylori infection in untreated hypertensive patients complicated with peptic ulcer were evaluated. METHODS: Ten hypertensive patients with peptic ulcer (HT-PU group), 15 untreated essential hypertensive patients without peptic ulcer (HT group) and 10 normal subjects (N group) were enrolled, and a power spectral analysis was performed in each subject. A biopsy urease test was used to detect infection by H. pylori. RESULTS: No significant differences were observed in the values of mean low-frequency (LF) power between the three groups. However, the mean high-frequency (HF) power in the HT-PU group was significantly greater than those of the HT and N groups (P<0.01). The mean LF/HF ratios in the HT-PU and HT groups were significantly greater than that of the N group (P<0.01). With respect to H. pylori infection, no significant differences between the three groups were observed. Sympathetic activity (LF power) was increased in the HT and HT-PU groups. Furthermore, parasympathetic activity (HF power) was increased in the HT-PU group. CONCLUSIONS: These findings suggest the participation of increased parasympathetic activity in peptic ulcer patients. Therefore, it is suggested that new techniques, such as spectral analysis of heart rate variability, as used in this study, will clarify the relationship between peptic ulcer and autonomic nervous function.

Autonomic Nervous System↗

PubMed2000

Role of neutrophils in sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats.

BACKGROUND AND AIMS: The authors have shown previously that sinusoidal endothelial cell injury developed concomitantly with the accumulation of neutrophils in the hepatic sinusoidal space in cholestatic rats after extensive hepatectomy. The aim of the present study was to investigate the role of neutrophils in the development of this kind of endothelial cell injury. METHODS: Rats underwent 78% partial hepatectomy after 2 weeks of cholestasis, and subsequent external biliary drainage for 5 days. To decrease the number of neutrophils, antirat neutrophil serum was administered intraperitoneally. Some serum parameters and histological specimens were examined 48 h after partial hepatectomy. RESULTS: Anti-neutrophil serum significantly reduced the number of accumulated neutrophils in the hepatic sinusoids. Although the purine nucleoside phosphorylase: alanine aminotransferase ratio, a marker of non-parenchymal cell injury, was increased in cholestatic-hepatectomized rats, this abnormality was significantly attenuated by the treatment with antineutrophil serum. Electron microscopically, focal detachment of cytoplasms of sinusoidal endothelial cells was observed occasionally in cholestatic-hepatectomized rats, but was not found in the antirat neutrophil serum-treated rats. CONCLUSION: These results indicate that accumulated neutrophils might be important effector cells in the pathogenesis of sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats, even after appropriate external biliary drainage.

Alanine Transaminase↗

PubMed2000

Spontaneously regressed Kaposi's sarcoma and human herpesvirus 8 infection in a human immunodeficiency virus-negative patient.

Kaposi's sarcoma occurring in a 78-year-old woman, with the absence of the human immunodeficiency virus infection, was correctly diagnosed by immunohistochemistry using anti-human herpesvirus 8 (HHV8) antibody (PA1-73N) for the first time. The patient suffered from chronic respiratory failure and was treated with a low dose of steroids for 2.5 years. After her medication dosage was increased for the exacerbation of the respiratory failure, multiple skin tumors in her feet and legs suddenly developed. Histopathologically, skin tumors were suspected as Kaposi's sarcoma at the first biopsy and reactive angiomatosis at the second biopsy. Polymerase chain reaction and immunohistochemistry, however, revealed the presence of HHV8 DNA fragment and positive staining in the majority of spindle cells in the skin tumors. Serological examination confirmed the positivity of anti-HHV8 antibodies. HHV8 infection and steroid-induced immunosuppression, as well as environmental factors played a role in the development of Kaposi's sarcoma in this patient, because she was born in Okinawa, which is a well-known endemic area of Kaposi's sarcoma in Japan. As her general condition improved, the skin lesions regressed without any specific treatment, and disappeared completely 8 months later, in which regression may be associated with evidence of numerous CD8 cell infiltration in the second biopsy tissues. No recurrence was observed during the following 6 month follow up.

Aged↗

PubMed2000

Aberrant expression of beta-catenin and mutation of exon 3 of the beta-catenin gene in renal and urothelial carcinomas.

The present study attempted to clarify the significance of aberrant expression of beta-catenin protein and mutation of exon 3 of the beta-catenin gene in renal and urothelial carcinogenesis. beta-Catenin expression was examined immunohistochemically and mutation of the beta-catenin gene was analyzed by polymerase chain reaction-single strand conformation polymorphism (SSCP) and direct sequencing. beta-Catenin immunoreactivity was observed at the cell membrane in all 30 renal cell carcinomas (RCC) examined, and no RCC showed a mobility-shifted SSCP band. Of 46 transitional cell carcinomas (TCC) examined, there was reduced expression of beta-catenin, as compared with its expression in non-cancerous transitional epithelium, in 22 cases (48%) and beta-catenin accumulation in the nucleus in five cases (11%). Of four renal pelvis TCC examined, point mutation of exon 3 of the beta-catenin gene at codon 45 resulting in amino acid substitution (Ser to Phe) was detected in one (25%). The incidence of reduced expression of beta-catenin correlated significantly with the growth pattern (superficial type vs invasive type) of TCC (P < 0.05). These data indicate that: (1) aberrant beta-catenin expression may be at least partly involved in urothelial carcinogenesis, but less significantly so in renal carcinogenesis, and (2) it may be associated with the progression of TCC showing invasive growth.

Adult↗

PubMed2000

Genetic instability and aberrant DNA methylation in chronic hepatitis and cirrhosis--A comprehensive study of loss of heterozygosity and microsatellite instability at 39 loci and DNA hypermethylation on 8 CpG islands in microdissected specimens from patients with hepatocellular carcinoma.

A study was conducted to examine the significance of genetic instability and aberrant DNA methylation during hepatocarcinogenesis. Genomic DNA was extracted from 196 microdissected specimens of noncancerous liver tissue that showed no marked histologic findings or findings compatible with chronic hepatitis or cirrhosis, and 80 corresponding microdissected specimens of hepatocellular carcinoma (HCC) from 40 patients. Loss of heterozygosity (LOH) and microsatellite instability (MSI) were examined by polymerase chain reaction (PCR) using 39 microsatellite markers, and DNA methylation status on 8 CpG islands was examined by bisulfite-PCR. In noncancerous liver tissues, LOH, MSI, and DNA hypermethylation were found in 15 (38%), 6 (15%), and 33 (83%) of 40 cases, respectively. The incidence of DNA hypermethylation in histologically normal liver was similar to that in chronic hepatitis and cirrhosis, although neither LOH nor MSI was found in histologically normal liver. In cancerous tissues, LOH, MSI, and DNA hypermethylation were found in 39 (98%), 8 (20%), and 40 (100%) of 40 cases, respectively. CpG islands of the p16 gene and methylated in tumor 1, 2, 12, and 31 clones were frequently methylated in cancerous tissues, although neither the thrombospondin-1 nor the human Mut L homologue (hMLH1) gene was methylated. Absence of silencing of the hMLH1 gene by DNA hypermethylation is consistent with the low incidence of MSI in HCCs. The results of this study indicate that LOH and aberrant DNA methylation contribute to hepatocarcinogenesis; DNA hypermethylation in particular, which precedes or may even cause LOH, is as an early event during hepatocarcinogenesis.

Adult↗

PubMed2000

Observation of coherent cerenkov radiation from a solid dielectric with short bunches of electrons

Short bunches of 150-MeV electrons of a linear accelerator passed along the surface of a crystal quartz or a teflon and coherent Cerenkov radiation from the solid dielectrics has been observed in the wavelength range from 0.5 to 4 mm. Properties of the radiation have been experimentally investigated. The angular distribution of the observed radiation showed a maximum peak in the direction of the Cerenkov angle with several satellite peaks. The intensity increased linearly with increasing the length of the medium and was proportional to the square of the number of electrons in the bunch. The spectral intensity was enhanced by almost five orders of magnitude in comparison with the theoretical calculation of incoherent radiation.

Journal Article↗

PubMed2000

The presence and role of the dopamine DA-2 receptor in the human decidua.

OBJECTIVES: Our objectives were to identify the presence of the dopamine DA-2 receptor in human decidua and to study its function in human parturition. METHODS: Human term decidual tissues were obtained during vaginal delivery and then homogenized. The P3 fraction was prepared for a radiolabeled receptor assay with [3H] spiperone as the ligand. Human decidual tissues obtained at cesarean section before the onset of labor were incubated in Krebs-Ringer buffer at 37 degrees C for 30 minutes in the presence of dopamine with or without (-)-sulpiride. The level of prostaglandin (PG) F in the medium was measured with a RIA kit. Differences were assessed with the Wilcoxon non-parametric test. RESULTS: Scatchard analysis showed a single class of binding sites having an equilibrium dissociation constant (Kd) of 2.25 +/- 0.59 nM (mean +/- SD) and a maximum binding capacity (Bmax) value of 166.5 +/- 77.7 fmol/mg protein (n = 3). Dopamine significantly increased the production of PGF. This stimulatory effect of dopamine was suppressed by (-)-sulpiride (p < 0.05; n = 7). CONCLUSION: The DA-2 receptor was demonstrated in the human decidua. Dopamine can stimulate PGF production via this receptor.

Decidua↗

PubMed2000

Reproducibility of cystometry in overactive detrusor.

OBJECTIVE: To examine the reproducibility of cystometry in the overactive detrusor. METHODS: The study sample involved 30 patients of the placebo arm in double-blind clinical trials for an overactive detrusor. They had demonstrated detrusor overactivity and underwent the second cystometry after 2-4 weeks. Nonparametric tests for paired data were used to examine the reproducibility of four variables: volume at first desire to void, volume at first involuntary contraction, cystometric capacity, and the maximum pressure of involuntary contraction. Percent change and within-subject standard deviation were calculated to assess intraindividual variability. RESULTS: The second test results showed a significant and systematic change for the better. Volume variables increased by 10-13% (p<0.01), involuntary contraction was not elicited in 3 cases (10%), and the maximum contraction pressure decreased by 18% in the remaining cases. Intraindividual variability was not small. Seventeen patients (57%) demonstrated > or = 25% change in one or more variables, and the 95% confidence interval of cystometric capacity, for example, was calculated as (x -57, x +57), where x is a test result. No specific patients' demographics were found related to variability. CONCLUSION: Repeat cystometry in the overactive detrusor is not highly reproducible and may be subject to a systematic effect for the 'better'. Whether this is due to the placebo effect or the learning effect could not be determined.

Double-Blind Method↗

PubMed2000

Successful treatment of a neonate with vein of Galen aneurysmal malformation.

We present a follow-up study on a 5-year-old boy who was born with vein of Galen aneurysmal malformation (VGAM) accompanied by extreme cardiovascular distress. He was successfully treated by the staged endovascular technique during the neonatal stage. Postoperative angiographic study confirmed complete occlusion of the VGAM and the establishment of normal brain perfusion. At 5 years of age, the child is growing normally without neurological deficits or developmental retardation. We suggest that the restoration of normal brain perfusion in neonates with VGAM can cause normal brain development.

Cardiomegaly↗

PubMed2000

An occipital encephalocystocele involving both sides of the lateral ventricles.

We reported a rare case of an occipital encephalocystocele linked by bilateral posterior horns of the lateral ventricles. The subject was a newborn girl with a large occipital cephalocele (6 x 9 cm in diameter) covered with alopetic skin. Cerebrospinal fluid leakage was not observed. The fontanel was soft, but a characteristic flat forehead was noted. Neither neurological deficits nor cardiopulmonary dysfunctions were evident at birth. Magnetic resonance images revealed that the sac contained the occipital lobes and that the cavity was linked by bilateral posterior horns. Agenesis of the corpus callosum and dysgenesis of the falx cerebri were associated. Fifteen days after birth, the cephalocele was removed surgically. Cutting sections revealed that the cephalocele contained enlarged bilateral posterior horns and cerebral hemispheres. The postoperative course was uncomplicated by hydrocephalus or infection, and the patient was discharged without any neurological deficit 22 days after surgery. Her milestone was survival; and at present 12 months after surgery, she is alive with moderate developmental retardation.

Abnormalities, Multiple↗

PubMed2000

Low molecular weight chitosan prevents the progression of low dose streptozotocin-induced slowly progressive diabetes mellitus in mice.

The present study was designed to clarify the effect of low molecular weight (LMW) chitosan (chitosan lactate, average MW: 20000) on the progression of slowly progressive non-insulin-dependent diabetes mellitus (NIDDM) induced by a single i.p. injection of low dose (100 mg/kg) streptozotocin (STZ) to 8-week-old male ICR mice. The non-fasting serum glucose levels of STZ-treated control mice continued to rise throughout the experimental period until 23 weeks after STZ treatment. The 0.2% or 0.8% chitosan (water solution), given as drinking water from prediabetic stage (2 weeks after STZ treatment), markedly prevented the time course-related rise of serum glucose levels of diabetic mice. In addition, the reduction of relative numbers of insulin-immunoreactive cells (beta-cells) in the islets of diabetic mice at 24 weeks after STZ treatment was markedly prevented by 0.2% or 0.8% chitosan administration. However, the progression of hyperglycemia in diabetic mice was not affected by 0.2% glucosamine, a monosaccharide of chitosan. The glucose levels of normal mice were not affected by 0.8% chitosan administration. When 0.2% chitosan administration was stopped at 20 weeks, these animals had still maintained significantly lower serum glucose levels, compared to control animals, even at 5 weeks after stopping the administration. These results indicate that LMW chitosan prevents the progression of low dose STZ-induced slowly progressive NIDDM.

Administration, Oral↗

PubMed2000

Chemical constituents of Avicennia alba. Isolation and structural elucidation of new naphthoquinones and their analogues.

Three new naphthoquinones and their analogues, named avicequinone-A (1), -B (2), -C (3), and avicenol-A (4), -B (5), -C (6), respectively, were isolated from the stem bark of Avicennia alba (Avicenniaceae) collected in Singapore, and their structures were elucidated by means of spectral methods. Gillan and co-workers have proposed that the structures of the new phytoalexins isolated from Avicennia marina are 1,2-naphthoquinones 8 and 9. Our synthetic and spectrometric studies showed that these structures should be revised respectively to 1,4-naphthoquinones 2 and 3, named avicequinone-B and -C by us.

Magnetic Resonance Spectroscopy↗

PubMed2000

Chemical constituents of Glycosmis citrifolia (Willd.) Lindl. Structures of four new acridones and three new quinolone alkaloids.

The structures of two new dimeric acridone alkaloids, glycobismine-D (1) and -E (2), having a novel linkage as binary acridones, three monomeric acridones, glycocitrine-IV (3), -V (4), and -VI (5), and three quinolone alkaloids, glycocitlone-A (6), -B (7), and -C (8) from Glycosmis citrifolia (Willd.) Lindl. (Rutaceae) have been elucidated by spectrometric studies.

Acridines↗

PubMed2000

The cyclization reaction of ortho-ethynylbenzaldehyde derivatives into isoquinoline derivatives.

In order to elucidate the reaction mechanism of the cyclization between an ethynyl group and an imino group at the ortho-position on an aromatic ring to afford isoquinolines, reaction of 2-ethynylbenzaldehydes under various conditions was examined. It is concluded that reaction proceeds via an ionic process and the isoquinoline 4-hydrogen atom derives from the solvent. In addition, it was found that 2-ethynylbenzaldehyde O-methyloximes underwent cyclization in the presence of primary and secondary alcohols to give 3-substituted isoquinolines.

Benzaldehydes↗

PubMed2000

Activation of cerebral function by CS-932, a functionally selective M1 partial agonist: neurochemical characterization and pharmacological studies.

A newly synthesized agonist for muscarinic acetylcholine (ACh) receptors CS-932, (R)-3-(3-iso-xazoloxy)-1-azabicyclo-[2.2.2]octane hydrochloride, showed a relatively higher affinity for M1 than M2 receptors expressed in Chinese hamster ovary (CHO)-cells in comparison with ACh. CS-932 elevated the intracellular Ca2+ level only in M1-CHO cells, although ACh increased the level in both M1- and M3-CHO cells. CS-932 and ACh reduced forskolin-stimulated accumulation of cAMP in M2-CHO cells by 20% and 80%, respectively. This neurochemical profile of CS-932 indicates that the compound can activate M1-receptor-mediated functions selectively. CS-932 increased firing of cholinoceptive neurons in rat hippocampal slices, and this excitation was antagonized by pirenzepine, but not by AF-DX 116. CS-932 increased awake and decreased slow wave sleep episodes of daytime EEG in free-moving rats. It counteracted scopolamine-induced slow waves in rat cortical EEG. CS-932 also increased the power of alpha- and beta-waves, but decreased delta-wave of the cortical EEG in anesthetized monkeys. It ameliorated scopolamine-induced impairment of working memory in rats. Orally administered CS-932 had the best penetration into the brain among the muscarinic agonists tested and caused the least salivary secretion among the cholinomimetics examined. These results indicate that CS-932 has potential as a cognitive enhancer with fewer side effects in therapy for Alzheimer disease.

Animals↗

PubMed2000

[Bone mineral density of the calcaneus and related factors in men].

In this cross-sectional study, the bone mineral density of the calcaneus was investigated in healthy young (n = 35, 22-33 years) and middle-aged (n = 49, 45-59 years) men. The relationships among the bone mineral density, body fatness, physical fitness, physical activity in recent and past days, smoking, alcohol, and sex hormones (free testosterone, estradiol, and dehydroepiandrosterone-sulfate; DHEA-S) and sex hormone binding globulin were evaluated. The speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness were measured by ultrasonic measurement. There was no association between age and bone density in each group. In the young group, there was a positive correlation between the body mass index (BMI) and BUA and between the training time during junior high school and BUA, and an inverse correlation between alcohol consumption and SOS after adjustment for the confounding factors using partial correlation analysis. The level of DHEA-S was weakly but not significantly associated with BUA. In the middle-aged group, there was an inverse correlation between the waist to hip ratio and SOS, and between the height of jump and SOS after adjustment for the confounding factors using partial correlation analysis. These results suggest that different factors may affect bone density in the young and middle-aged men. In young men, the higher BMI and the longer training time during boyhood may have a positive effect, and heavy alcohol consumption may have a negative effect on bone density. In middle-aged men, abdominal fat accumulation has a negative effect and leg muscle power has a positive effect on bone density.

Adipose Tissue↗