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Biomedical subjects

K Yamaoka

Publications and source records attributed to K Yamaoka.

At least 19 recordsLinked to original sources
PubMed1992

Semiquantitative analysis of immunoreactivities of tyrosine hydroxylase and aromatic L-amino acid decarboxylase in the locus coeruleus of desipramine-treated mice.

The influence of antidepressant drugs on catecholaminergic neuron groups of the mouse brain was studied immunohistochemically, using a microphotometric semiquantitative method. The immunoreactive level of tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) in the locus coeruleus (LC) was significantly decreased after 2 weeks of antidepressant administration. Our results suggest that long-term exposure to an antidepressant drug, desipramine, significantly affects intracellular catecholamine-synthesizing enzymes. These results may suggest some significant roles of the catecholaminergic neuronal groups to the action of the tricyclic antidepressant drugs.

Animals↗
PubMed1992

Mitochondrial tRNA(Ile) mutation in fatal cardiomyopathy.

A patient with mitochondrial encephalomyopathy who died from progressive intractable cardiac failure at the age of 18 is reported. At the age of 4, he presented with short stature, but multiorgan disorders including deafness, focal glomerulosclerosis, epilepsy and dilated cardiomyopathy appeared later in his clinical course. Laboratory tests showed hyperlactatemia and hyperpyruvatemia. Histopathological findings demonstrated mitochondrial myopathy with ragged red fibers and focal cytochrome C oxidase-deficient fibers in skeletal and cardiac muscles. The activity of cytochrome C oxidase was 30% less than the control level in skeletal muscle. Sequencing of the entire mitochondrial tRNA genome revealed a novel point mutation in the tRNA(Ile) region (nt 4269). This A-to-G substitution was found in none of the 30 controls by screening using mispairing PCR and Ssp I digestion methods, suggesting that this new mutation was pathogenic in our case.

Adolescent↗
PubMed1992

Isolation and sequence of a developmentally regulated putative novel gene, priA, from the basidiomycete Lentinus edodes.

Screening for gene(s) homologous to v-Ha-ras (Harvey rat sarcoma viral ras gene) in the basidiomycete, Lentinus edodes, resulted in the isolation of a novel gene (designated priA), in addition to a ras gene homologue [Hori et al., Gene 105 (1991) 91-96]. The priA gene has a coding capacity of 258 amino acids (aa) interrupted by two short putative introns. The 5'-upstream region of priA contains GGGCGG box, CCAAT box, TATAAA box and CT sequence elements in 5'----3' order. One transcription start point (tsp) was located 10 nucleotides upstream from a TATAAA box and another tsp just in a CT sequence. The deduced PRIA protein (26.7 kDa), rich in Ser (42 residues), Pro (29 residues) and Thr (27 residues), contained different types of putative zinc-binding motifs. It initiated with a hydrophobic aa sequence and terminated with the unique sequence, Cys-Aaa-Aaa-Xaa (where Aaa is aliphatic aa and Xaa is any aa), implying an association with the inner membrane surface via acylation of the Cys residue. The priA gene expression was found to be developmentally regulated with primordia/immature fruiting bodies having much higher levels of priA transcript. Preprimordial mycelia and mature fruiting bodies, however, contain very low levels of priA transcript. The priA gene may play a role during the beginning of fruiting.

Amino Acid Sequence↗
PubMed1992

Regulation of cell division of mature B cells by ionomycin and phorbol ester.

The growth of a human B lymphoma cell line B104, an experimental model for mature B cells, was inhibited by ionomycin but not 12-O-tetradecanoylphorbol-13-acetate (TPA). Ionomycin inhibited B104 cells from entering into the M phase of the cell cycle without affecting DNA synthesis. The inhibition of cell division of B104 cells by ionomycin occurred within 24 h after stimulation. Because such a mode of action resembles that of anti-IgM antibodies, signals transduced by Ca2+ may be responsible for the inhibition of cell division of B104 cells by anti-IgM antibodies. Indeed, EGTA suppressed the inhibition of cell division of B104 cells caused not only by ionomycin, but also by anti-IgM antibody. Although TPA itself did not have any ability to promote the growth of B104 cells, it could cancel the inhibition of cell division of B104 cells by ionomycin and increase the proportion of B104 cells entering into the M phase of the cell cycle. Staphylococcus aureus Cowan I causes the greatest proliferation of normal human peripheral blood B cells during the period from 48 to 72 h after stimulation. When ionomycin was added to S. aureus Cowan I-stimulated peripheral blood B cells at 48 h of culture, it inhibited cell division during this period without affecting DNA synthesis. In the presence of TPA, this activity of ionomycin was suppressed, and the proportion of M-phase cells increased. These results suggest that cell division of mature B cells is regulated by the signals mediated by Ca2+ and protein kinase C in a mode quite different from that of regulation of DNA synthesis.

B-Lymphocytes↗
PubMed1992

Anti-IgM but not anti-IgD antibodies inhibit cell division of normal human mature B cells.

Insolubilized anti-IgD antibody markedly increased DNA synthesis in and cell division of normal peripheral blood B cells (PBL-B) when used in combination with IL-4. Anti-IgM antibodies also induced DNA synthesis of PBL-B, but their ability to induce cell division was less than that of anti-IgD antibodies even when used in combination with IL-4. Moreover, anti-IgM antibodies inhibited cell division of PBL-B stimulated with insolubilized anti-IgD antibody plus IL-4 without affecting DNA synthesis. Anti-IgM antibodies also inhibited Staphylococcus aureus Cowan I-induced cell division of PBL-B without affecting DNA synthesis. These results indicate that cross-linkage of surface IgM (sIgM) in mature B cells generates negative signals to inhibit cell division of mature B cells. Because anti-IgD antibodies did not inhibit cell division at all, the role of sIgD in the regulation of cell division of mature B cells may be quite different from that of sIgM. IFN-alpha/beta promoted cell division of PBL-B stimulated with insolubilized anti-IgD antibody plus IL-4. They also counteracted the inhibitory effect of anti-IgM antibody on cell division of PBL-B.

Antibodies, Anti-Idiotypic↗
PubMed1992

Evaluation of vitamin D-binding protein and vitamin D metabolite loss in children on continuous ambulatory peritoneal dialysis.

We measured the serum concentration of vitamin D-binding protein (DBP) in children with chronic renal failure (CRF). We also evaluated the relationships between the peritoneal loss of vitamin D metabolites, DBP and albumin in nine children on continuous ambulatory peritoneal dialysis (CAPD). The serum levels of DBP in children with CRF were significantly higher than in normal children. The mean serum DBP level in CRF children undergoing CAPD was slightly lower than in CRF patients who were not on dialysis. In patients on CAPD, the peritoneal loss of 25-hydroxyvitamin D (25OHD) showed a significant positive correlation with the DBP concentration in the dialysate (r = 0.855, P less than 0.005). In contrast, the peritoneal loss of 1,25-dihydroxyvitamin D (1,25(OH)2D) showed a significant correlation with the loss of albumin in the dialysate (r = 0.779, P less than 0.01). The synthesis of 1,25(OH)2D3 is reduced in advanced renal failure, and the peritoneal losses of the active vitamin D sterols in patients on CAPD may aggravate this deficiency. We recommend that supplementation of active form of vitamin D, such as 1 alpha-hydroxyvitamin D3 or 1,25(OH)2D3, is important in CAPD patients, particularly those with elevated peritoneal loss of DBP and/or albumin.

Adolescent↗
PubMed1992

1,25-Dihydroxyvitamin D3 does not up-regulate vitamin D receptor messenger ribonucleic acid levels in hypophosphatemic mice.

The effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) administration on duodenal vitamin D receptor (VDR) mRNA levels in hypophosphatemic (Hyp) mice, a murine homologue of human X-linked hypophosphatemic rickets, was examined. Basal levels of VDR mRNA in Hyp mice were similar to those of normal littermates and, in normal mice, VDR mRNA levels were up-regulated 1.8-2.7-fold after injection of 1 microgram/kg 1,25(OH)2D3. In contrast, no significant change in VDR mRNA was observed in Hyp mice treated with 1,25(OH)2D3. To determine the effect of phosphate repletion on VDR mRNA levels, high-phosphate diet was fed to Hyp mice. Although plasma phosphorus concentration was restored to normal, up-regulation of VDR mRNA was not recovered with phosphate supplementation. These results indicate that the vitamin D-resistance in Hyp mice is not caused by hypophosphatemia, per se, and may result from a fundamental molecular defect in vitamin D action at the intestine which could be related to ineffective up-regulation of VDR mRNA by 1,25(OH)2D3.

Animals↗
PubMed1992

Comparing postgraduate medical education at university and non-university hospitals in Japan.

In 1988 the authors surveyed all the teaching hospitals in Japan to evaluate the present status of postgraduate medical education (PGME); they received responses from 67 (84%) of the university and 172 (89%) of the non-university teaching hospitals. It was found that a large proportion of residents had spent two years in a residency without having had a single experience of some of the basic clinical skills. Consequently the residents' confidence in their abilities to perform these skills was low. The residents at the university hospitals, in particular, had had fewer experiences and were less confident about their clinical skills than were the residents at the non-university hospitals. The lack of standard and minimum requirements for PGME in Japan may be the cause of the poor level of acquisition of clinical skills of residents during PGME. Other possible causes are the tendency in Japanese medical society to attach greater importance to academic attainment than to clinical competence and the excessive gravitation of residents toward university hospitals. The authors suggest their results show the necessity to improve the training in basic clinical skills in PGME in Japan, especially in university hospitals.

Clinical Competence↗
PubMed1992

Temperature dependence of electrophysiological properties of guinea pig and ground squirrel myocytes.

The effects of changing temperature on the electrophysiology of isolated cardiac myocytes of the guinea pig and Richardson's ground squirrel were studied by patch-clamp techniques. In cells from both species, the resting membrane potential declined on cooling from 36 to 12 degrees C by approximately 6 mV. The duration of the plateau of the action potential in guinea pig cells increased monotonically on cooling. In contrast, the action potential of ground squirrel cells showed a biphasic response, increasing in duration from 36 to 24 degrees C and then decreasing on cooling from 24 to 12 degrees C. From voltage-clamp studies, the properties of L-type calcium currents (ICa) on cooling were compared in the two species and were found to be similar: In both cases, ICa decreased in amplitude from approximately 2 nA peak current at 36 degrees C to less than 400 pA at 12 degrees C. The Q10 of both the maximum amplitude and time to peak for ICa in both species was approximately 1.8. The time for half inactivation had a greater Q10 of 2.5-3. It is concluded that, surprisingly, factors affecting the resting membrane potential and properties of L-type calcium channels are not major contributors to cardiac dysfunction on cooling. Rather, it is sarcoplasmic reticulum calcium release and reuptake that are likely to be the most important cold-sensitive processes.

Animals↗
PubMed1992

[Disposition analysis by fast inverse Laplace transform (FILT)].

A curve fitting program, MULTI (FILT), in which an algorithm of fast inverse Laplace transform is incorporated, was introduced into the area of drug disposition. The reliance of MULTI (FILT) was verified by the Monte Carlo simulation based on compartment models. MULTI (FILT) was applied to the analysis of the local dispositions of drugs through the liver, including the construction of new dispersion model, the effect of albumin in perfusate, and the effect of perfusion rate. The elimination in the lung and the enterohepatic circulation were also evaluated using MULTI (FILT) in a simple manner.

Computer Simulation↗
PubMed1992

Identical 24-hour intragastric pH response to low continuous infusion doses of famotidine in active gastric ulcer patients.

UNLABELLED: In order to establish the therapeutic plasma concentration of famotidine, the 24-h intragastric pH response to low-dose intravenous (i.v.) continuous infusion of 40 (group A) or 20 mg/day (group B), administered over more than two days, was studied in 10 adult patients with active gastric ulcers (GU). In group A, the mean age was 64.8 years and in group B, 54.2 years. On the second day, 4 blood samples were collected for famotidine assay and 24 h intragastric pH monitoring was performed. RESULTS: the mean 24 h pH did not differ significantly (P less than 0.01) between group A at 6.9 and group B at 7.2. In group A, the percentage of time with pH above 6.0 and above 7.0 were 94.8 and 59.0, respectively, and the mean famotidine dose and plasma concentration were 0.81 mg/kg/day and 140.89 ng/ml. In group B, the percentage of time with pH above 6.0 and 7.0 were 97.6 and 65.4, and the mean dose and famotidine concentration were 0.34 mg/kg/day and 45.42 ng/ml. In conclusion, in fasting patients with active gastric body ulcers, continuous infusions of low-dose famotidine maintain both the therapeutic plasmatic concentration and the intragastric pH to near anacidity level.

Adult↗
PubMed1992

Block of sodium channels by tyramine and its analogue (N-feruloyl tyramine) in frog ventricular myocytes.

Pharmacological effects of tyramine and its analogue, N-feruloyl tyramine (NFT), on sodium and calcium currents in frog ventricular myocytes were examined using the whole-cell voltage-clamp technique. To improve the temporal and spatial control of the membrane potential, sodium currents (INa) were recorded in 45.5 mM [Na+]o at 10 degrees C. Both tyramine and NFT (1-100 microM) induced a concentration-dependent decrease in INa evoked from a holding potential of -80 mV without affecting a change in either the time to peak or the time constant for the falling phase of INa. Similarly the reversal potential for INa remained unchanged at a value close to that predicted from the Nernst equation. The finding that both tyramine and NFT decreased INa when activated maximally, from a holding potential of -120 mV, indicates that the amplitude of INa can be reduced independently of a change in the kinetics of the current. In addition, tyramine (100 microM) shifted the membrane potential for half maximal inactivation (Vh) of the steady-state inactivation (h infinity)-curve from -74 to -84 mV without affecting its slope. In contrast, NFT failed to affect the h infinity-curve. The calcium current (ICa) recorded in the presence of 0.3 microM TTX was not affected by either 100 microM tyramine or NFT. We concluded that tyramine directly blocks Na channel by shifting h infinity-curve and by suppressing maximum Na channel conductance, while NFT suppresses only maximum Na channel conductance.

Animals↗
PubMed1992

"Swimming-induced head twitching" in rats in the forced swimming test induced by overcrowding stress: a new marker in the animal model of depression?

We have used overcrowding stress to study the pathogenesis of depression and the action of antidepressant drugs. In the present study, the influence of overcrowding on behavior was assessed by the forced swimming test. All the stressed rats revealed highly characteristic head twitching movement, which was not inhibited by repeated administration of diazepam and haloperidol, but was markedly suppressed by repeated administration of desipramine and mianserine. A significant positive correlation in the number of twitching episodes in each stressed rat between the first and second forced swimming test was seen. These findings support the use of overcrowding of rats as a stressor in the animal depression model because it fulfills the criteria of the model; face validity, construct validity and predictive validity. We propose the adoption of "swimming head twitching" as a new marker in the animal model of depression.

Animals↗
PubMed1992

Synergistic effect of 1,25-dihydroxyvitamin D3 and retinoic acid in inducing U937 cell differentiation.

We examined the effects of retinoic acid (RA), 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), and its synthetic analogue, 22-oxa-1,25-(OH)2D3, on differentiation of U937 cells by studying the cellular growth, surface marker expression and cytosolic free Ca2+ concentration ([Ca2+]i). RA inhibited cellular growth but did not induce expression of Mo2 (CD14), a monocyte/macrophage specific surface marker. To the contrary, 1,25-(OH)2D3 did not inhibit cellular growth, but increased CD 14-positive cells. Simultaneous addition of 1,25-(OH)2D3 and RA had no additive effect on cellular growth inhibition or CD14 expression. With regard to [Ca2+]i, however, 5 days' incubation with either of them increased the basal [Ca2+]i level and induced U937 cells to respond to formyl-methionyl-leucyl-phenylalanine (FMLP). When the cells were incubated with both 10(-6) M RA and 10(-8) M 1,25-(OH)2D3, basal [Ca2+]i was higher and FMLP caused a greater increase in [Ca2+]i than when only RA or 1,25-(OH)2D3 was added. These data suggest that RA and 1,25-(OH)2D3 induce monocytoid differentiation in U937 cells through different pathways and act synergistically in the differentiation process. The 22-oxa-1,25-(OH)2D3 induced CD14 expression, basal [Ca2+]i increase and [Ca2+]i response to FMLP, but did not cause cellular growth inhibition in U937 cells, and in these points, 22-oxa-1,25-(OH)2D3 exhibited no significantly different effects from 1,25-(OH)2D3. Thus, 22-oxa-1,25-(OH)2D3 has the same potent activity as 1,25-(OH)2D3 in inducing differentiation of U937 cells.

Antigens, CD↗
PubMed1992

[Flow cytometric analysis of cellular DNA content in epithelial ovarian cancer].

Tumor DNA content (ploidy) was determined by flow-cytometry (FCM) on tissue from 32 epithelial ovarian cancer patients. Staining for DNA analysis was achieved with Propidium Iodide. Peripheral blood lymphocytes were used as reference diploid cell population. Of the 32 patients, 26 (81.3%) had tumors which were aneuploid, whereas 6 (18.7%) were diploid. DNA aneuploid cell lines were found in 100% of serous adenocarcinoma, in 57% of mucinous adenocarcinoma, in 67% of endometrial adenocarcinoma, in 88% of clear cell carcinoma and in 75% of undifferentiated carcinoma. The DNA ploidy abnormalities differed in each histologic characteristic of epithelial ovarian cancer.

Adenocarcinoma↗
PubMed1992

[Behavioral assessment of antidepressants (1)--The forced swimming test: a review of its theory and practical application].

Forced swimming test is now widely used as a screening method for antidepressant drugs since it was proposed by Porsolt in 1977. In this article, we at first reviewed its theoretical background and then pointed out various factors which could possibly affect the results. These include the apparatus used for the test (quality and size of cylinder), experimental animals (breeding condition, body weight, age and strain), method of drug administration and evaluation of animal's behavior (criteria for counting the immobility time and those for excluding variety of orienting or escape behaviors, such as jumping, climbing, diving, circling and extended sniffing behaviors). Finally, potential pitfalls and difficulty of the test were discussed based on our own experiences. We concluded that the various factors discussed in this article should be carefully controlled for the pertinent application of the forced swimming test.

Animals↗
PubMed1992

[Flow cytometric evaluation of DNA ploidy pattern in uterine cancer].

The distribution of DNA ploidy levels and its prognostic significance in cervical cancer (including squamous cell carcinoma and adenocarcinoma) and endometrial cancer is discussed. DNA aneuploidy was observed in most of the cases with either the histological type of cervical cancer and in half of those with endometrial cancer. The DNA ploidy level of the tumor showed a characteristic distribution according to its histological type or grade. Although several investigators have already reported that patients with DNA diploid uterine tumors had a better survival than those with DNA aneuploid uterine tumors, further research is required before a definite conclusion can be attained on the prognostic value of the degree of DNA ploidy measurement in uterine cancer.

Adenocarcinoma↗