Search PubMed⌕ Search

Biomedical subjects

K Matsubara

Publications and source records attributed to K Matsubara.

At least 253 records · Page 14Linked to original sources

Analysis of hprt gene mutation following anti-cancer treatment in pediatric patients with acute leukemia.

We evaluated the genotoxic effect of cancer therapy on somatic cell mutation by isolating 6-thioguanine-resistant mutants in peripheral lymphocytes. The study population comprised 45 children with acute lymphoblastic leukemia (ALL), 13 children with acute myelogenous leukemia (AML) and 28 age-matched healthy controls. The geometric mean mutant frequency for ALL patients was 7.8 x 10(-6), which was significantly higher than that for AML patients (1.7 x 10(-6)) or for healthy controls (1.1 x 10(-6)). Fifteen patients with ALL showed a high mutant frequency above 10 x 10(-6), although 10 of them had completed their treatment at least 24 months earlier. Moreover, repeated measurements of mutant frequency at intervals of 12 or more months revealed that the values were very stable. Structural hypoxanthine-guanine phosphoribosyl transferase (hprt) gene alterations, as determined by Southern blot analysis, were seen in 23% (12/52) of mutant clones derived from ALL patients, but not in those from the controls. These results suggest that intensive anti-cancer therapy of children may produce persistent somatic mutations, which could be related to the appearance of second neoplasms.

Adolescent↗

Toxicological index of paraquat: a new strategy for assessment of severity of paraquat poisoning in 128 patients.

A new assessment of the severity of paraquat poisoning in 128 patients has been developed. It involves toxicological index of paraquat and discriminant function score. This system not only allows a more accurate assessment of severity of the poisoning, but also provides a more reliable prediction of the outcome in an early stage for the purpose of forensic and clinical toxicology.

Discriminant Analysis↗

Effects of oral theophylline on sick sinus syndrome.

OBJECTIVES: We sought to determine the effect of theophylline on cardiac pauses in sick sinus syndrome. BACKGROUND: Sick sinus syndrome, a relatively benign condition, is usually treated with pacemaker implantation without any proved effectiveness. Thus, an appropriate pharmacologic therapy would be useful. METHODS: Theophylline (200 to 400 mg/day for 1 month) was initially administered orally to 17 patients with sick sinus syndrome, which is manifested by sinus pauses of > 2.5 s. Eleven of the 17 patients subsequently received theophylline for an additional 8 to 37 months. Twenty-four-hour Holter recordings were obtained before treatment, at the end of 1 month of treatment and then at 6-month intervals. RESULTS: Theophylline decreased the frequency of sinus pauses from 256 +/- 230 to 23 +/- 62 pauses per 24 h and decreased the duration of the longest pauses from 4.7 +/- 1.8 to 2.2 +/- 0.97 s after 1 month of treatment. Subjective symptoms associated with cardiac pauses disappeared in 16 of 17 patients. Ventricular premature beats increased in frequency but did not last longer than two beats. Three patients experienced adverse effects. Nine of the 11 patients receiving long-term treatment had a good outcome, but 2 patients required a pacemaker because of the reappearance of long sinus pauses. CONCLUSIONS: The results suggest that oral theophylline may be beneficial for the treatment of patients with sick sinus syndrome.

Administration, Oral↗

Identification of new genes by systematic analysis of cDNAs and database construction.

The large-scale collection of partial cDNA sequences is becoming a powerful tool in biology. Similarity or motif searches in DNA databases using these partial cDNA sequences have facilitated the discovery of new genes of interest. By collecting and registering large numbers of partial sequences with a well designed non-biased cDNA library, an expression profile of active genes in a particular tissue can be obtained. Tissue-specific or stage-specific genes can be discovered by comparing the profiles from different tissues or from a tissue at different stages of development, respectively. The compilation of such expression profiles enables genes to be mapped to the tissue(s) where they are actively transcribed. The large-scale collation of gene sequences actively expressed in the body into databases complements efforts directed towards the structural analysis of the genome, with the ultimate aim of decoding all the genetic information carried in the human genome. This cDNA strategy is also being widely applied to organisms other than man.

Animals↗

A clomiphene citrate and tamoxifen citrate combination therapy: a novel therapy for ovulation induction.

OBJECTIVE: To assess the efficacy of a clomiphene citrate (CC) and tamoxifen citrate (CC/tamoxifen) combination therapy in ovulation induction by comparing with a CC alone therapy. DESIGN: A randomized cross-over study with CC alone and CC/tamoxifen combination therapies for 20 normoprolactinemic anovulatory women. Randomly selected 10 of the 20 women (group A) underwent a CC alone therapy (100 mg CC during cycle days 5 to 9) for the initial three consecutive treatment cycles and a CC/tamoxifen combination therapy (50 mg CC and 20 mg tamoxifen during cycle days 5 to 9) for the subsequent three consecutive treatment cycles. The remaining 10 (group B) were treated similarly but with the inverse sequence. Ovulation was documented when a high BBT phase persisted for 11 days or more, when midluteal serum P levels exceeded 7 ng/mL (22.3 nmol/L), or when pregnancy ensued. RESULTS: The rates of ovulatory/treated, pregnant/treated, and pregnant/ovulatory cycles were 42 of 56 (75.0%), 3 of 47 (6.4%), and 3 of 35 (8.6%) for CC/tamoxifen, respectively. Those were 25 of 57 (43.9%), 1 of 48 (2.1%), and 1 of 21 (4.8%) for CC, respectively. Clomiphene citrate/tamoxifen was more effective in ovulation induction than CC. All the pregnancies were normal and single. None of the treatments was accompanied by any remarkable side effects. CONCLUSION: Clomiphene citrate/tamoxifen is a novel treatment modality of ovulation induction with high efficacy.

Adult↗

Molecular biology and life science.

Molecular biology has made the transition from phase 1, dealing with prokaryotic genes and DNA, to phase 2, dealing with genes of eukaryotic multicellular organisms. This transition came about because of the DNA technology that has evolved since the early 1970s. Now we are at the beginning of the transition to phase 3, through the emerging human genome project. The background of the development of this project, its current state, and its possible impact on the life sciences is briefly outlined and discussed.

Human Genome Project↗

Mechanism of enhancement of neutrophil survival by granulocyte colony-stimulating factor and adenine.

An in vitro study was performed on the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and adenine on the survival of purified human neutrophils. The addition of rhG-CSF (1 to 100 ng/mL) or adenine (100 microM) enhanced the survival of neutrophils. The maintenance of O2- production in response to N-formylmethionyl-leucyl-phenyl-alanine (FMLP) suggested that these neutrophils were functionally alive. Neutrophils in cultures had shown two distinct biochemical changes during cell death: DNA fragmentation and depletion of cellular adenosine triphosphate (ATP) pools. Treatment with rhG-CSF (10 ng/mL) significantly delayed the appearance of DNA fragmentation as measured quantitatively by diphenylamine or by agarose gel electrophoresis. On the other hand, adenine had no effect on the generation of DNA fragmentation. The decrease of ATP during incubation for 12 hours was similar in control and rhG-CSF-treated neutrophils, while rhG-CSF prevented the further decline of ATP seen in control cultures. In contrast, adenine (100 microM) preserved ATP at levels significantly higher than in controls at both 12 hours and 24 hours of incubation. Our results suggest that rhG-CSF and adenine promote the survival of neutrophils in vitro by different mechanisms.

Adenine↗

Role of protein kinase C in neutrophil survival enhanced by granulocyte colony-stimulating factor.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) (10 ng/mL) prolonged human neutrophil survival in culture by at least 36 hours. The addition of H-series compounds at concentrations that are considered to inhibit both protein kinase C (PKC) and cyclic adenylate monophosphate (cAMP)-dependent protein kinase (PKA) counteracted the effect of rhG-CSF. Concomitantly, the inhibition of nucleosomal DNA fragmentation by rhG-CSF was canceled. At lower concentrations, presumably capable of inhibiting only PKA, however, the compounds exhibited marginal effects on rhG-CSF-mediated increase of cell survival. These PKC inhibitors did not influence the priming effect of rhG-CSF significantly, as determined by O2- production stimulated by N-formyl-L-methionyl-L-leucyl phenylalanine (fMLP). Our results suggest that PKC plays an important role in the mechanism by which rhG-CSF promotes neutrophil survival, in striking contrast with the priming effect elicited by rhG-CSF.

Adult↗

Intravenous injection of adenosine triphosphate for assessing sinus node dysfunction in patients with sick sinus syndrome.

The clinical value of rapid intravenous injection of adenosine triphosphate (ATP, Adephos Kowa # L3, CAS 56-65-5) for assessing sinus node function was examined in 5 patients with sick sinus syndrome (SSS) and 6 normal controls. All patients with SSS showed cardiac pauses longer than 3 s on a 24-h Holter ECG monitoring. First, after prophylactic insertion of a temporary pacemaker in the right ventricle, overdrive suppression test was conducted using the standard technique, and sinus node recovery time (SNRT) was observed to evaluate the sinus node function. Then, 10 min later, 10 mg of ATP was rapidly injected intravenously, and body surface and intracavitary ECG were continuously recorded until the basal state was regained. The rapid injection of ATP resulted in a slight inhibition of sinus node automaticity in normal subjects, but marked inhibition was in patients with SSS associated with suppression of AV conduction. The longest post ATP atrial cycle (AA interval in the intracavitary ECG showed a close inverse relationship with SNRT corrected for basal sinus length (CSNRT), according to the following formula: longest AA interval (ms) = 3.32 x CSRT (ms) +254.4 (r = 0.91, p < 0.001). The results suggest that rapid intravenous injection is a useful tool for the diagnosis of SSS.

Adenosine Triphosphate↗

[Basic study of CA125 measurement using a newly developed "SD-8729" IRMA kit].

"SD-8729" is a one-step IRMA kit employing OC125 antibody as 125I-labeled tracer and M-11 antibody as an immunoadsorbent. Higher bound-radioactivity to beads was observed with shorter incubation time than that of a currently used CA125 IRMA kit which employed OC125 antibody both as 125I-labeled ligand and immunoadsorbent attached to beads. Almost identical CA125 values were obtained by using two kits. The antigenic nature recognized by the M-11 antibody seems substantially different from those of 130-22 or 145-9 antibodies recognizing CA130 antigen.

Antibodies, Monoclonal↗

[Trans-activating function of integrated hepatitis B virus].

HBV DNAs are often found in integrated form in human hepatocellular carcinoma (HCC). Since transactivation of the X gene has been shown, surveys of collections of HBV integrants with flanking cellular sequence were performed to clarify whether they might exhibit a transactivation. The majority of integrants showed transactivation effect which may to be due to the virus-cell fusion products derived from the 3' truncated X gene. Additionally, it has been found that 3' truncated preS2/S gene in the integrant encodes a transactivator to which C terminal truncation is essential. These results suggest that the transactivating effect of integrated HBV DNAs plays a role in hepatocarcinogenesis by activating cellular genes.

Carcinoma, Hepatocellular↗

Genomic analysis of human hepatocellular carcinomas using Restriction Landmark Genomic Scanning.

Restriction Landmark Genomic Scanning (RLGS) was used to examine the multiple alterations of genomic DNAs that occur in association with transformation and development of malignancy in primary hepatocellular carcinoma (HCC). Genomic DNAs from HCC and its normal counterpart were cleaved by the restriction enzyme NotI, radiolabeled at the cleavage sites, and then size-fractionated by two-dimensional electrophoresis using HinfI as the second cleavage enzyme. About 2000 spots were recognized, whose position and intensity reflect the locus and the copy number of the corresponding restriction sites. Using this system in combination with micromanipulation of HCC to eliminate possible carry-over of nonmalignant cells, we detected six spots that were decreased in intensity in common to three different HCCs, along with five that were intensified spots. In addition, several spots showed changes that were nonoverlapping among different tumors.

Carcinoma, Hepatocellular↗

[Glaucoma-like disc without increased intraocular pressure or visual field loss and early stage normal-tension glaucoma disc].

The optic disc topography of 11 eyes of 11 glaucoma-like discs without increased intraocular pressure or visual field loss was compared with that of 11 eyes of 11 relative early stage normal-tension glaucomas. There were no statistically significant differences between the two groups in terms of optic disc parameters measured with a Rodenstock Optic Nerve Head Analyzer Plus, except that the inferior quadrant of the neuroretinal rim area of the normal-tension glaucoma discs was significantly smaller than that of the glaucoma-like discs. Also, in the Humphrey automated visual field, only the superior part of the Total Deviation score of normal-tension glaucoma eyes corresponding to the inferior disc changes was significantly lower than that of glaucoma-like discs. When the data of the two groups were pooled, the inferior quadrant of the neuroretinal rim area significantly correlated with the visual field loss in the group of eyes with a rim area smaller than 0.198 mm2. These results seem to suggest that some of the glaucoma-like discs might be early normal-tension glaucoma.

Female↗

[A case of an idiopathic enlargement of the right atrium, lacking in prominent right atrium contour and mimicking left pericardial defect on the chest X ray].

A 47-year-old man was admitted for evaluation of heart murmur in 1982. On admission, two-dimensional echocardiogram showed a giant right atrium with mild tricuspid regurgitation, but a chest X ray showed no prominent right atrium contour. Echocardiographic finding at various postures and chest X ray with artificial pneumothorax indicated little likelihood of left pericardial defect. An angiocardiogram and computed tomography showed the dilated right atrium with clockwise rotation. There was no indication of right atrial overload. Therefore, we made the diagnosis of an idiopathic enlargement of the right atrium. For about 10 years after discharge, we have followed up this patient. He has received no treatment and has been asymptomatic. On the other hand, echocardiography shows that the right atrium has gradually enlarged. Electrocardiogram has clearly revealed only a tall and slender peaked P wave in chest leads for the last 5 years. This may indicate not only an increasing load on the right atrium but also that the enlarged atrium is getting closer to the walls of the chest. We report this case of an idiopathic enlargement of the right atrium lacking in prominent right atrium contour, and mimicking left pericardial defect on chest X ray.

Cardiomegaly↗

Purification of forensic specimens for the polymerase chain reaction (PCR) analysis.

Purification methods of deoxyribonucleic acid (DNA) from degraded and contaminated forensic samples were investigated for polymerase chain reaction (PCR) analysis. DNA extracted from putrefied tissue or bloodstains sometimes contained the copurified contaminant, that was identified as the porphyrin compound (hematin). When contaminated but less degraded DNA was analyzed by PCR, it was necessary to eliminate the impurity by anion exchange column chromatography or chelating resin preparation, and ultrafiltration using Centricon microconcentrators. When highly degraded DNA was analyzed, trace amounts of high molecular weight DNA was recovered by electroelution method, and then further purified by both column chromatography and ultrafiltration. From thus purified samples, the amelogenin gene for sex determination could be amplified by dual PCR technique.

Adipose Tissue↗