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Biomedical subjects

K Murayama

Publications and source records attributed to K Murayama.

At least 19 recordsLinked to original sources

Schedule-dependent synergistic action of tiazofurin and dipyridamole on hepatoma 3924A cells.

Tiazofurin is an oncolytic nucleoside analog that has shown therapeutic activity in end-stage acute non-lymphocytic leukemia and in chronic granulocytic leukemia in blast crisis. Tiazofurin is anabolized to the active metabolite, TAD, which inhibits IMP dehydrogenase activity, leading to a reduction in guanylate pools and to the cessation of neoplastic cell proliferation. The drug exhibits potent cytostatic and cytotoxic activity against hepatoma 3924A cells in culture. In growth-inhibition and clonogenic assays, the 50% inhibitory concentration of tiazofurin was 3.8 and 4.2 microM, respectively. Dipyridamole, an inhibitor of nucleoside transport, curtails the salvage of nucleosides and bases for nucleotide biosynthesis. Dipyridamole exhibited cytotoxicity against hepatoma 3924A cells, with an LC50 of 24 microM and an IC50 of 29 microM being recorded. A combination of tiazofurin and dipyridamole provided synergistic cytotoxicity in hepatoma 3924A cells in culture. This synergistic activity was dependent on the order of addition of the drugs. Simultaneous addition of the two drugs produced antagonism, whereas preincubation of cells with tiazofurin or dipyridamole followed by addition of the second drug resulted in synergy. TAD concentrations were significantly higher (129% and 135%) in cells that had been pretreated with tiazofurin or dipyridamole before the addition of the second agent as compared with cells that had been treated simultaneously (113%). These studies indicate the importance of the order of the addition of drugs to obtain a synergistic response in combination chemotherapy and suggest the need for a careful selection of drug modulation in clinical trials of tiazofurin and dipyridamole.

Animals

[A study of bladder function in benign prostatic hyperplasia].

A study of bladder function was performed on 106 patients with benign prostatic hyperplasia (BPH), 21 of whom had cerebrovascular disease (CVD). The incidence of overactive bladder in 21 patients with CVD was 57% and was significantly higher than the 25% in 86 patients without CVD. The incidence of cases having residual urine of over 100 ml, was in the order of low compliance bladder, overactive bladder and normal bladder. The mean value of maximum voiding pressure in overactive bladder was higher than that in normal bladder. The high pressure was improved after the operation for BPH. Improvement of overactive bladder after the operation was seen in 9 of 13 patients without CVD while in 2 of 6 patients with CVD.

Aged

[Clinical effects of distigmine bromide (Ubretid), a cholinesterase inhibitor, on micturition disturbance by benign prostatic hypertrophy--comparative study of distigmine bromide and the combination of distigmine bromide and adrenergic blocker].

We report the results of a comparative study on the clinical efficacy of the single use of distigmine bromide and its combined use with prazosin hydrochloride in the treatment of benign prostatic hypertrophy. The single use and combined use groups were administered 10 mg/day of distigmine bromide and the same with 1 mg/day of prazosin hydrochloride for a period of 8 weeks respectively. In the single administration group, marked improvement was found in one patient (9%), moderate improvement in 4 patients (36.3%), slight improvement in 3 patients (27.2%) and aggravation in 3 patients. In the combined use group, marked improvement was found in one patient (11.0%), moderate improvement in 5 patients (55.5%), and slight improvement in 3 patients (33.3%). No significant differences were found in the improvement rate between the two groups. However, significant improvements were found in both groups for the subjective symptoms of urinary disturbance, diurnal and nocturnal frequency. As a result of the examination of objective findings, a significant decrease in residual urine ratio was also shown in both groups, while significant improvement for average flow and maximum flow rates were found in only the combined use group. In conclusion, distigmine bromide and distigmine bromide+prazosin hydrochloride are considered very useful for the treatment of miturition disturbance due to benign prostatic hypertrophy.

Aged

[The relationship between pathological spreading factors and tumor size in 45 patients with renal cell carcinoma].

The relationship between pathological spreading factors (T3,4 V+, N+, M+) and tumor size was studied in 45 patients with renal cell carcinoma during the past 10 years from 1982. The incidence of having one or more factors was 0% for the 17 tumors smaller than 5 cm, but 75% for the 28 tumors over 5 cm. The mean diameter of the tumors having a T, V, N or M factor was significantly larger than that of tumors having no factor (T1,2V0N0M0). These findings suggest that they have a higher tendency of having spreading factors once the tumors have exceeded a certain size.

Adult

Phylogenetic affiliation of ancient and contemporary humans inferred from mitochondrial DNA.

Nucleotide sequence analysis of the major non-coding region of human mitochondrial DNA (mtDNA) from three major races was extended with data from 27 contemporary Mongoloids (20 from southeast Asia, seven from America) and 11 Ancient Japanese bones (five from Jomon Age; 3000-6000 years BP, six from the early modern Ainu; 200-300 years BP). In both cases, the sequence was determined directly from the polymerase chain reaction products. Based on a comparison of the 482 base pair sequences from a total of 128 contemporary humans, the nucleotide diversity is estimated to be 1.46%, which is three times higher than the corresponding value estimated from restriction-enzyme analysis of the whole mtDNA genome. The phylogenetic tree revealed that all lineages are classified into at least five clusters designated as C1-C5. C1 consists exclusively of Africans, and most Asians and Europeans formed C2, C3, C5 and C4, respectively. Phylogenetic analysis also indicated that part of the Asians, including the Japanese, subsequently diverged from the majority of Africans, and that Asians can therefore be separated into two distinct groups. Native Americans, however, appeared only in C3 and C5, suggesting that the size of the founder population was not so large during the peopling of American. Nucleotide sequences derived from ancient bones in a highly polymorphic region were also compared with those of contemporary humans. The nucleotide diversity among the 139 sequences in the region was estimated to be 2.26%. A group of ancient Japanese, including both Jomon peoples and the Ainu, showed a close phylogenetic affiliation with one group of contemporary Japanese and southeast Asians.(ABSTRACT TRUNCATED AT 250 WORDS)

Asian People

Neurological aspects of del(1q) syndrome.

We have studied three children with de novo terminal deletion of the long arm of chromosome 1 (46,XX,del(1)(q43)). They all have minor anomalies and neurological signs (severe psychomotor developmental delay, generalized hypotonia, and seizures) that have been described previously. In addition, all of these three patients have autistic-like behavior. They avoid eye contact, show no interest in people, express little emotion, and repeat stereotypic movements such as head nodding and purposeless finger manipulation. They also spend excessive time in making unusual sounds consisting of a high-pitched shrill cry with little intonation in infancy and a harsh, strained, and glottal stridency in later life. They make no labial, lingual, or nasal sounds. We suggest that these observations may be unique clinical manifestations of certain terminal 1q deletions.

Autistic Disorder

Host range mutant of human immunodeficiency virus type 1: modification of cell tropism by a single point mutation at the neutralization epitope in the env gene.

We have isolated a variant of human immunodeficiency virus type 1 (HIV-1) which is highly infectious to fibroblastlike cells (BT cells) derived from human brain as well as CD4-positive T cells. This variant HIV-1, named HIV[GUN-1V], was obtained by infecting BT cells with a prototype HIV-1 isolate, named HIV[GUN-1WT], which is highly infectious to T cells but barely infectious to BT cells. HIV[GUN-1V] infects BT cells productively and this infection appeared to be mediated by CD4. To elucidate the viral gene responsible for the host range difference between the variant and prototype HIV-1s, we cloned and analyzed the provirus genomes of the two viruses. Examination of the infectivities of BT cells by various recombinant viruses and analyses of the nucleotide sequences of HIV[GUN-1V] and HIV[GUN-1WT] showed that a single nucleotide exchange was responsible for their difference in infectivity of BT cells: HIV[GUN-1V] contains a thymine residue instead of the cytosine residue in HIV[GUN-1WT] at position 931 of the env coding sequence. Replacement of cytosine by thymine at this position of the env coding sequence of the HIV[GUN-1WT] genome induced the ability to infect BT cells. The base exchange at this position was expected to change amino acid 311 of the envelope glycoprotein, gp120, from proline to serine, which is located in a variable region containing type-specific immunodominant epitopes. Thus, HIV[GUN-1V] acquired a wider host range than HIV[GUN-1WT] by a single point mutation in the env gene.

Amino Acid Sequence

[Clinical study of voiding disorders in patients with cerebrovascular accidents].

Cystometry and urethral pressure profile were determined in 41 patients (29 males and 12 females) with voiding disorders resulting from cerebrovascular accidents within one year after the episode. By clinical symptoms, they were classified into 3 groups, urge incontinence (14 patients, 34%), pollakisuria (10 patients, 24%) and dysuria (17 patients, 41%). Cystometrogram were classified into 3 types, hyperactive bladder (31 patients, 76%), normal bladder (5 patients, 12%) and hypoactive bladder (5 patients, 12%). All patients in both groups of incontinence and pollakisuria showed hyperactive bladder except one normal bladder, while in the group of dysuria 3 types of cystometrograms were observed. Bladder capacity in incontinence group showed tendency to be smaller than that in dysuria group who had hyperactive bladder. Maximum urethral pressure in incontinence group was significantly lower than that in pollakisuria group and dysuria group who had hyperactive bladder. Ten patients with cerebral cortical lesions (80%) showed hyperactive bladder and 60% of them showed incontinence. In patients with cerebral lesions who had hyperactive bladder, the maximum urethral pressure of patients with incontinence showed tendency to be lower than that of patients with pollakisuria and dysuria. The majority of 7 patients with thalamic lesions showed hyperactive bladder and normal urethral pressure, and had dysuria. Two patients with pontine lesions showed hypoactive bladder. These findings suggested that urge incontinence resulting from cerebrovascular accidents was due not only to hyperactive bladder but also to lower urethral pressure.

Aged

[Clinical studies of terodiline hydrochloride and clenbuterol hydrochloride for urinary frequency and incontinence].

The clinical effectiveness and safety of terodiline hydrochloride and clenbuterol hydrochloride were studied on 51 patients with neurogenic bladder, stress incontinence, unstable bladder and others, the chief complaints of which were urinary frequency or urinary incontinence. Overall improvement was graded as marked in 6 patients (11.8%), moderate in 20 patients (39.2%), slight in 11 patients (21.6%), unchanged in 13 patients (25.5%) and aggravated in one. The patients impression was "good" or better in 56.9%. There were a total of 13 cases (25.5%) of adverse reactions, namely, 7 cases of finger tremor, 3 cases of dry mouth and others. These reactions disappeared rapidly after the discontinuance of drug administration. The clinical efficacy in the treatment of subjective symptoms was 71.4% for urinary incontinence, 56.4% for diurnal pollakisuria. The examination of lower urethral functions demonstrated a significant (p less than 0.01) increase in bladder capacity at first desire and maximum desire to void. However, we found no significant increase in urethral clossure pressure. The findings of this study suggest that terodiline hydrochloride and clenbuterol hydrochloride are very useful for the treatment of urinary frequency and incontinence.

Aged

[A study on lipid peroxidation in neonates--(2). Perioperative changes in serum lipid peroxide and superoxide dismutase activity].

Pre-, intra-, and post-operative changes in serum lipid peroxide: malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were studied in 10 neonates aged from 15 hours to 26 days. The results are summarized as follows: 1) Preoperative serum MDA levels were significantly lower than those of normal neonates. No significant difference was found between pre- and post-operative values, although much fluctuations were observed in neonates within 7 days of age. All the individual values returned to the normal range during the early postoperative period with different respiratory management. 2) Changes in serum SOD activity were similar to those in MDA values. The activity seemed to be higher and more sensitive to oxygen concentration in younger neonates, which may suggest the specific antioxidant properties of the neonates. 3) Postoperatively, serum MDA levels tended to increase following intravenous administration of lipid emulsion. 4) There was a positive correlation between the values of serum MDA and SOD activity, especially in neonates within 7 days of age.

Female

[A study of lipid peroxidation in neonates--(1) Daily change of serum lipid peroxides in full term neonates].

Lipid peroxide has been highlighted as a possible marker of cell destruction by oxygen derived free radical reactions. We, therefore, examined serum lipid peroxides, malondialdehydes (MDA) in 106 healthy full term neonates (aged 0.5 to 317 hrs, averaged 79.3 +/- 69.9 hrs). Their lipid peroxides in capillary blood were determined by the luminescence method (Yagi method). Based on our data, we conclude as follows: 1) MDA concentrations were influenced by the serum bilirubin concentrations. We, therefore, adjusted our data according to the serum bilirubin concentrations. 2) We found significantly higher values of MDA (4.76 +/- 1.35 nmol.ml-1) than those in adult (3.12 +/- 0.35 nmol.ml-1). In fact, these values increased gradually on the second day, and the high values were maintained until the fifth day. 3) The values of MDA and total bilirubin concentrations in the vaginally delivered neonates were significantly higher than those delivered by Cesarean section (P less than 0.05). 4) There were no correlations between the values of MDA and values of other serum lipid and bilirubin.

Humans

Capillary gas chromatography/negative ion chemical ionization mass spectrometry for the quantification of bile acids including 1 beta-hydroxylated and unsaturated bile acids in serum and urine.

12 bile acids, including 1 beta-hydroxylated and unsaturated bile acids, have been quantified by capillary gas chromatography/negative ion chemical ionization mass spectrometry, using the trimethylsilyl(TMS) ether derivatives of bile acid pentafluorobenzyl(PFB) esters. The analysis time is 12 min and the minimum measurable amount is 100 fg for each bile acid. Bile acids in 200 microL of serum and 50 microL of urine from healthy human adults were measured. These small sample sizes enhance the practicality of using this method as a screening test for bile acids in the serum and urine of human infants, where small sample size is a major problem.

Adult

Identification of 17-hydroxyprogesterone and other steroid hormones in saliva from a normal child and patients with congenital adrenal hyperplasia by plasmaspray liquid chromatography/mass spectrometry.

A very sensitive, selective and simultaneous method for the analysis of salivary steroid hormones was examined by discharge-assisted thermospray liquid chromatography mass spectrometry (plasmaspray LC/MS). Plasmaspray LC/MS gave [M + H]+ or [MH - H2O]+ as a predominant ion in most of the steroids in this work and in some cases fragment ions were also observed. Eight salivary steroid hormones, pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, aldosterone, and testosterone were identified within 10 minutes using the selected ion monitoring technique in conjunction with plasmaspray LC/MS. Progesterone, 17-hydroxyprogesterone, cortisol, aldosterone and testosterone were detected in 1 mL of saliva from a normal child and two patients with congenital adrenal hyperplasia.

17-alpha-Hydroxyprogesterone

Electroretinograms and pattern visually evoked cortical potentials in central areolar choroidal dystrophy.

We describe three patients with central areolar choroidal dystrophy whose electroretinograms (ERGs) and pattern visually evoked cortical potentials (VECPs) confirmed their macular dysfunction. Visual fields measured by Goldmann perimetry showed central relative scotomata corresponding to a dystrophic lesion. Dark adaptation curves were slightly abnormal either in the first curve or in the second curve, depending on the visual acuity. Color vision was disturbed irregularly. Fluorescein angiography revealed a loss of the choriocapillaries, and a hyperfluorescent border outlined the dystrophic lesion. Single-flash dark-adapted ERGs and scotopic ERGs were almost normal, while photopic and flicker ERGs showed slightly attenuated amplitudes. Conversely, VECPs to pattern reversal stimulation were greatly affected for both transient and steady-state stimuli. We conclude that, in central areolar choroidal dystrophy, pattern VECPs can provide more information on macular dysfunction than does the ERG.

Adult

[Dural arteriovenous malformation in the posterior fossa presenting with multiple intracerebral hematomas. Case report].

A 59-year-old female was hospitalized because of disturbance of consciousness and convulsive seizures. She had taken a hormonal drug for 15 months after breast cancer surgery. A computed tomography scan revealed multiple high-density areas in the left temporal and frontal and the right parietal lobes. Angiography showed a dural arteriovenous malformation (AVM) in the posterior fossa fed by the occipital and the middle meningeal arteries and draining into the transverse sinus. It also demonstrated occlusion of the left sigmoid sinus in the venous phase. She complained of headache in the occipital region and dizziness. On day 13, the left occipital artery was ligated and cut, and then abnormal arterial anastomoses around the lesion were coagulated. After surgery, clinical symptoms disappeared. The etiology of dural AVM is controversial, but in this case it is suspected that sinus thrombosis due to the drug caused the dural AVM. The authors discuss the etiology and treatment of dural AVM in the posterior fossa.

Arteriovenous Malformations