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Biomedical subjects

K Sugimoto

Publications and source records attributed to K Sugimoto.

At least 487 records · Page 27Linked to original sources
PubMed1990

G1-specific cyclins of S. cerevisiae: cell cycle periodicity, regulation by mating pheromone, and association with the p34CDC28 protein kinase.

The S. cerevisiae CLN genes encode cyclin homologs essential for progression from G1 to S phase. The CLN2 gene encodes a 62 kd polypeptide that accumulates periodically, peaking during G1 and decreasing rapidly thereafter, and is rapidly lost following exposure of cells to mating pheromone. Cln2 abundance can be explained by the G1-specific accumulation of the CLN2 transcript coupled with instability of the Cln2 protein. The abundance of the CLN1 and CLN2 transcripts increases greater than 5-fold during the G1 interval, decreasing dramatically as cells enter S phase. Both transcripts decrease in cells responding to mating pheromone. Finally, we demonstrate that the Cln2 polypeptide interacts with p34CDC28 to form an active protein kinase complex. This physical interaction is consistent with the genetic interaction between the CLN genes and CDC28 and suggests that Cln proteins are an essential component of the active protein kinase complex required for the G1 to S transition.

Cell Cycle↗
PubMed1990

Circadian influence on effect of propranolol on exercise-induced tachycardia in healthy subjects.

Following a cross-over design propranolol 20 mg p.o. was given to 7 healthy subjects at 09.00 h and 21.00 h at an interval of 1 week. Heart rate (HR) during submaximal ergometer exercise was measured at four intervals during 10 h after treatment. Plasma propranolol concentrations were also determined. The suppressive effect (%R) of propranolol on the rise in HR during exercise after the morning dosage was significantly greater at 1.5 h and tended to be greater 3 h after administration than at comparable times in the evening trial. Mean plasma propranolol concentrations during the early phase were higher after the morning than the evening dose. The maximum plasma concentration (Cmax), area under the plasma concentration-time curve from 0 to 10 h (AUC (0-10] and absorption rate constant (ka) were significantly greater after the morning dose. The time to maximum concentration (tmax) and elimination half-life (t 1/2) of the morning and evening dosages did not differ. A significant correlation was observed between plasma propranolol concentration and %R in HR during exercise in the morning (r = 0.74) and evening (r = 0.63) trials, and the regression lines of the morning and evening treatments did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Stress fibers in the mesenteric mesothelial cells of the large intestine of the bullfrog, Rana catesbeiana.

Actin-containing cytoplasmic fibers were visualized in the mesenteric mesothelial cells of the large intestine of bullfrog tadpoles by rhodamine-phalloidin staining of en face preparations of mesothelial cells. These fibers were concurrently stained by immunofluorescence using antibodies to myosin or alpha-actinin. Electron microscopy showed the presence of bundles of microfilaments in the basal cytoplasm of the cells. Such fibers in the mesothelial cells may be comparable to the stress fibers present in cultured cells. The mesothelial cells initially formed axially oriented stress fibers when they changed from a rhombic to a slender spindle-like shape. On the other hand, stress fibers disappeared as cells transformed from elongated to polygonal shapes during the period of metamorphic climax. Expression of stress fibers in these cells appears to be related to the degree of tension loaded on the mesentery, which may be generated by mesenteric winding. These stress fibers in the mesothelial cells may serve to regulate cellular transformation. They may also help to maintain cellular integrity by strengthening the cellular attachment to subepithelial tissue against tensile stress exerted on the mesentery.

Actin Cytoskeleton↗
PubMed1990

Depressor effects and pharmacokinetics of single and consecutive doses of delapril in hypertensive patients with normal or impaired renal function.

The antihypertensive effects and pharmacokinetic properties of delapril, an angiotensin-converting enzyme (ACE) inhibitor, were investigated in hypertensive patients with normal renal function (NRF; n = 6) and in those with impaired renal function (IRF; n = 5). A 15-mg oral dose of delapril was given once on the first and last days, and twice daily on the other days. The measurement of blood pressure and sampling were done at 0, 1, 2, 4, 6, 12, and 24 hours postdose on the first and last days of treatment. Plasma and urinary concentrations of delapril and its metabolites were measured by HPLC. ACE activity was suppressed from 1 hour after the first dose to 24 hours after the last dose of delapril in both the NRF and IRF groups. During the consecutive dosing, significant BP falls were observed from 1 hour postdose of delapril to 24 hours in the NRF group and to 6 hours in the IRF group. Peak plasma concentrations of 5-hydroxydelapril diacid and areas under the plasma concentration-time curve (AUC) of both delapril diacid and 5-hydroxydelapril diacid in the IRF group were significantly higher (p less than 0.001 or 0.05) than in the NRF group. No significant increase of pharmacokinetic parameters in repeated dosing was observed in both the NRF and IRF groups. Significant positive correlations (p less than 0.001) were found between the inverse of creatinine clearance and the AUCs of the active diacid metabolites in single and consecutive doses.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Quantitation of vitamin K in human milk.

A quantitative method was developed for the assay of vitamin K in human colostrum and milk. The procedure combines preparative and analytical chromatography on silica gel in a nitrogen atmosphere followed by reversed phase high performance liquid chromatography (HPLC). Two HPLC steps were used: gradient separation with ultraviolet (UV) detection followed by isocratic separation detected electrochemically. Due to co-migrating impurities, UV detection alone is insufficient for identification of vitamin K. Exogenous vitamin K was shown to equilibrate with endogenous vitamin K in the samples. A statistical method was incorporated to control for experimental variability. Vitamin K1 was analyzed in 16 pooled milk samples from 7 donors and in individual samples from 15 donors at 1 month post-partum. Vitamin K1 was present at 2.94 +/- 1.94 and 3.15 +/- 2.87 ng/mL in pools and in individuals, respectively. Menaquinones, the bacterial form of the vitamin, were not detected. The significance of experimental variation to studies of vitamin K in individuals is discussed.

Adult↗
PubMed1990

Age-related decrease in the number of hemopoietic stem cells and progenitors in senescence accelerated mice.

Senescence accelerated mice (SAM-P) were used for the study of the possible aging of hemopoiesis. The number of peripheral leukocytes decreased significantly with age, whereas hematocrit showed only a slight decrease. Although the number of total nucleated cells in the bone marrow increased, the number of hemopoietic stem cells (CFU-S) as well as that of granulocyte-macrophage colony forming cells (GM-CFC) showed a decrease in old mice. A significant decrease in the number of GM-CFC was observed in the spleen of old SAM-P mice, whereas no decrease was found in the number of CFU-S. Such a profound reduction of the recruitment of GM-CFC from CFU-S in the spleen together with a reduction of bone marrow hemopoiesis may be responsible for the decrease in the number of peripheral leukocytes in the old mice. SAM-P mice could provide a good model for the study of the aging of hemopoietic system.

Aging↗
PubMed1990

Presence of an activity indispensable for the granulocyte/macrophage colony-stimulating activity of interleukin 3 in bovine serum albumin.

Media conditioned by an interleukin 3 (IL-3)-producing T-cell line, STIL-3, as well as recombinant mouse IL-3 showed granulocyte/macrophage (GM) colony-stimulating activity in the semi-solid culture medium containing horse serum (HS) or bovine serum, but the activity was not apparent when fetal calf serum (FCS) was used. No such serum-dependency of GM colony formation was observed when abdominal wall conditioned medium or L-cell conditioned medium containing GM colony-stimulating factor was used. Although the levels of albumin and total protein were lower in FCS than HS, increase of FCS concentration did not affect the GM colony-stimulating activity of IL-3. Addition of bovine serum albumin (BSA) preparation to FCS, however, increased the number of GM colonies to the same level as that observed with HS. The levels of bacterial lipopolysaccharide (LPS) in sera and BSA and the effect on the bone marrow cells from LPS-nonresponsive C3H/HeJ mice indicated that the observed effect of BSA was not due to the contaminating LPS. The activity of BSA was not substituted by IL-1, IL-2, IL-4, IFN-gamma, TNF, NGF or erythropoietin. The present study suggests the presence in BSA of co-factor(s) of IL-3 in stimulating GM colony formation.

Animals↗
PubMed1990

Distribution of IL-3 activity in mice transplanted with IL-3 producing T cells (STIL-3): abrogation of the distribution of STIL-3 cells into the liver and liver hemopoiesis by splenectomy.

Distribution of IL-3 producing T cells, STIL-3, in splenectomized mice after intravenous injection was studied in order to determine the site of IL-3 production in the splenectomized mice. Hematological features of STIL-3-inoculated mice after splenectomy were also studied. Splenectomy prior to inoculation of STIL-3 cells resulted in a slight increase in the level of IL-3 activity in most lymphohemopoietic tissues, but resulted in a slight decrease in the level of IL-3 activity in the plasma. The splenectomy also abrogated granulocytosis which was evident in sham-operated host mice. Hepatomegaly and a number of granulocytic foci in the liver were observed in STIL-3 inoculated mice, but this was again abrogated completely by the splenectomy. These results suggest that the spleen is the major site of granulopoiesis in response to the stimulus with IL-3, and also that the spleen is essential for the migration or metastasis of STIL-3 cells to the liver.

Animals↗
PubMed1990

Colony promoting activity: differences from interleukin-3 and similarities to interleukin-6.

The supernatant of long-term bone marrow culture contains colony promoting activity (CPA) which does not have granulocyte-macrophage colony stimulating activity (CSF) but which enhances granulocyte-macrophage (GM) colony formation in the presence of CSF. CPA might consist of IL-3 or IL-3-like activity, since CPA stimulates proliferation and differentiation of more immature cells to CSF-responding granulocytes-macrophage progenitors (GM-CFC), and since IL-3 also stimulates immature hemopoietic cells to proliferate and differentiate to functional blood cells. IL-1 and IL-6 are also known to enhance GM colony formation. One or both of these molecules can accordingly be another candidate for CPA. In the present study, GM-CSF activity of IL-3 was dependent on the batch of serum: it was negative in the presence of fetal calf serum, but positive in the presence of horse serum. In contrast, GM-CSF and CPA showed no such dependence on the batch of serum. The addition of IL-3 to GM colony assay system did not enhance but rather suppressed GM colony formation. The supernatant of long-term bone marrow culture which contains substantial levels of CPA did not stimulate proliferation of IL-3 dependent DA-1 cells, but facilitated the proliferation of IL-6 dependent, MH60.BSF2 cells. No detectable level of IL-1 activity was found in the supernatant. These results indicate that CPA is different from IL-1, IL-3 or GM-CSF, but similar to or the same as IL-6.

Animals↗
PubMed1990

Voltage-dependent ionic currents in taste receptor cells of the larval tiger salamander.

Voltage-dependent membrane currents of cells dissociated from tongues of larval tiger salamanders (Ambystoma tigrinum) were studied using whole-cell and single-channel patch-clamp techniques. Nongustatory epithelial cells displayed only passive membrane properties. Cells dissociated from taste buds, presumed to be gustatory receptor cells, generated both inward and outward currents in response to depolarizing voltage steps from a holding potential of -60 or -80 mV. Almost all taste cells displayed a transient inward current that activated at -30 mV, reached a peak between 0 and +10 mV and rapidly inactivated. This inward current was blocked by tetrodotoxin (TTX) or by substitution of choline for Na+ in the bath solution, indicating that it was a Na+ current. Approximately 60% of the taste cells also displayed a sustained inward current which activated slowly at about -30 mV and reached a peak at 0 to +10 mV. The amplitude of the slow inward current was larger when Ca2+ was replaced by Ba2+ and it was blocked by bath applied CO2+, indicating it was a Ca2+ current. Delayed outward K+ currents were observed in all taste cells although in about 10% of the cells, they were small and activated only at voltages more depolarized than +10 mV. Normally, K+ currents activated at -40 mV and usually showed some inactivation during a 25-ms voltage step. The inactivating component of outward current was not observed at holding potentials more depolarized -40 mV. The outward currents were blocked by tetraethylammonium chloride (TEA) and BaCl2 in the bath or by substitution of Cs+ for K+ in the pipette solution. Both transient and noninactivating components of outward current were partially suppressed by CO2+, suggesting the presence of a Ca2(+)-activated K+ current component. Single-channel currents were recorded in cell-attached and outside-out patches of taste cell membranes. Two types of K+ channels were partially characterized, one having a mean unitary conductance of 21 pS, and the other, a conductance of 148 pS. These experiments demonstrate that tiger salamander taste cells have a variety of voltage- and ion-dependent currents including Na+ currents, Ca2+ currents and three types of K+ currents. One or more of these conductances may be modulated either directly by taste stimuli or indirectly by stimulus-regulated second messenger systems to give rise to stimulus-activated receptor potentials. Others may play a role in modulation of neurotransmitter release at synapses with taste nerve fibers.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1990

Inducible and non-inducible factors co-operatively activate the GM-CSF promoter by interacting with two adjacent DNA motifs.

The upstream region of the mouse granulocyte macrophage colony stimulating factor (GM-CSF) gene between positions -95 and -73 is required for phorbol-12-myristate-13-acetate (PMA)- and calcium ionophore (A23187)-inducible transcriptional activity in vivo. To study the mechanism of GM-CSF gene activation in T cells, nuclear extracts from non-stimulated and PMA/A23187-stimulated Jurkat cells were used in DNA binding assays. DNA mobility shift assays with wild type and mutant oligonucleotides revealed that this region contains at least two DNA binding motifs. One is the binding sequence GGTAGTTCCCC (positions -91 to -81), recognized by NF-GM2 (nuclear factor of GM-CSF 2), and the other is a GC-rich sequence (GC-box). NF-GM2, induced in Jurkat cells by PMA/A23187 stimulation, effectively competed with DNA containing the NF-kappa B binding sequence, suggesting that it has NF-kappa B-like activity. By UV cross-linking analysis, three cross-linked bands, corresponding to Mr 165, 70, and 60 kd for NF-GM2, and 110 and 130 kd for A1 and A2, respectively, were identified. Transfection experiments showed that activation of the GM-CSF gene in response to PMA/A23187 stimulation was abolished by point mutations in either the GC-box or the NF-GM2 site; these mutations also abolished binding of the respective proteins. These results indicate that constitutive (GC-box binding factor) and inducible (NF-GM2) factors regulate the GM-CSF promoter co-operatively in a PMA/A23187-inducible manner in vivo.

Animals↗
PubMed1990

Measurement of plasma active renin by solid phase radioimmunoassay using monoclonal antibodies.

A direct radioimmunoassay (RIA) for plasma active renin concentration (ARC) was evaluated by using plasma samples obtained from hospitalized normal volunteers and hypertensive patients. The direct renin RIA was performed by using a pair of anti-renin monoclonal antibodies and a sandwich method. It is suggested that an agitator should be used during the incubation, because the magnetic solid phase was precipitated and could not be suspended well in plasmas. Further, the thawed reagents should not be used for the assay. A highly significant correlation (r = 0.96, p less than 0.01) was found between ARC and enzymatic activity of renin (PRA) in plasma samples obtained from hypertensive patients. The mean values of ARC were 22.8 +/- 3.6 pg/ml in normal subjects, 22.5 +/- 5.3 in patients with EH having medium levels of PRA, 113.7 +/- 11.7 in patients with renovascular hypertension, and undetectable in patients with primary aldosteronism. The results indicated good and reliable performance of the direct renin RIA, which is clinically useful to investigate the renin-angiotensin system.

Antibodies, Monoclonal↗
PubMed1990

Effects of diltiazem on the pharmacokinetics of nifedipine.

To evaluate the effect of diltiazem pretreatment (60 mg three times a day for 3 days) on pharmacokinetics and pharmacodynamic effect of nifedipine, six healthy subjects received 20 mg nifedipine orally on two occasions using a double-blind cross-over, placebo-controlled method. Diltiazem induced a marked increment of the area under the plasma concentration-time curve (AUC) for nifedipine by a mean of 140% and reduced the total body clearance (Cl) from 0.0043 +/- 0.0019 to 0.0017 +/- 0.0006 ml/min/kg (p less than 0.05, mean +/- SD). The biological half-life (t1/2) of nifedipine was prolonged from 2.46 +/- 0.65 to 3.21 +/- 0.92 h (p less than 0.05) without any changes in indocyanine green (ICG) clearance. Diltiazem did not produce significant changes of AUC, Cl, and t1/2 for the acid metabolite of nifedipine. Blood pressure (BP) after nifedipine administration with diltiazem pretreatment was more decreased than that without diltiazem. Both a decreased hepatic clearance and an increased bio-availability of nifedipine by diltiazem probably explain the significant changes in pharmacokinetics and hemodynamics of nifedipine. A clinically important drug interaction may occur with nifedipine when diltiazem is administered concurrently.

Adult↗
PubMed1990

Glucose and lipid metabolism during long-term treatment with cilazapril in hypertensive patients with or without impaired glucose metabolism.

The effects of long-term cilazapril therapy on glucose tolerance and serum lipid profiles were investigated in 19 hypertensive patients: seven with normal glucose tolerance and 12 with glucose intolerance (including three patients with noninsulin-dependent diabetes). Cilazapril was administered once daily for a mean duration of 6.4 months. A 75-g oral glucose tolerance test was performed before and during long-term therapy with cilazapril. Cilazapril produced satisfactory control of blood pressure in both patient groups during long-term therapy. It was well tolerated by all patients. Neither fasting nor postglucose-load venous plasma glucose levels were altered in either group of patients, and no patients with normal glucose tolerance developed diabetes mellitus during the study. There were no significant changes in the insulinogenic index (delta IRI/delta BS at 30 min postglucoseload) in patients with normal or impaired glucose tolerance. No significant changes in fasting levels of serum cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides were observed in either group. These results suggest that effective long-term cilazapril therapy does not compromise glucose or lipid metabolism in hypertensive patients. Cilazapril may have a clinical advantage in that it can be given to hypertensive patients without concern that it might alter their serum lipid concentrations or impair glucose tolerance.

Adult↗
PubMed1990

Pharmacokinetics and antihypertensive effects of lisinopril in hypertensive patients with normal and impaired renal function.

The antihypertensive effects and pharmacokinetic properties of lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, were investigated in hypertensive patients with normal renal function (NRF, mean serum creatinine 1.0 mg/dl, n = 9) and those with impaired renal function (IRF, mean serum creatinine 1.7 mg/dl, n = 8). Lisinopril was administered orally (10-mg dose once daily for 5 or 8 days). Measurement of blood pressure (BP) and sampling of blood specimens were made on the first and last days of treatment. During consecutive dosing of lisinopril, its antihypertensive effects were sustained for greater than or equal to 12 h with less diurnal variation of BP. Serum ACE activity was markedly suppressed for 24 h. Plasma levels of lisinopril in the IRF group were higher than those in NRF with significant differences in the peak levels and areas under the plasma concentration time curve (AUC). A significant inverse correlation was found between the creatinine clearance and the AUC for lisinopril. These results suggest that lisinopril has a long-lasting action and that it is a useful antihypertensive agent for controlling BP in patients with either NRF or mild IRF. When administered for an extended period, however, more careful consideration should be given to the dose in patients with IRF than in patients with NRF to minimize the possibility of untoward side effects.

Adult↗
PubMed1990

The effects of haematocrit, plasma protein concentration and temperature of drug-containing blood in-vitro on the concentrations of the drug in the plasma.

Factors which influence the plasma drug concentrations in whole blood have been investigated in-vitro using human blood containing radio-labelled phenytoin or chlorpromazine. Phenytoin (3.55 micrograms mL-1, 0.01 mM) or chlorpromazine (2.74 micrograms mL-1, 0.01 mM) was mixed with normal or modified blood and the plasma drug level was measured. Plasma phenytoin and chlorpromazine levels decreased with decrease in the protein concentration of plasma, but were not influenced by addition of gamma-globulin to the blood specimen. Plasma phenytoin levels increased with an increase in haematocrit from 20 to 45%, whereas the chlorpromazine level remained constant. The partition coefficients of phenytoin and chlorpromazine between blood cells and plasma were almost the same at various haematocrit values. By cooling the blood containing each drug to 4 degrees C, plasma phenytoin and chlorpromazine levels were higher compared with those at 37 degrees C. Similar temperature effects on the drug levels in plasma were obtained when the washed erythrocytes were resuspended in albumin medium, but not when resuspended in saline.

Adult↗
PubMed1990

[Three cases of meningitis due to Listeria monocytogenes type Ib].

Three infants having Listeria monocytogenes meningitis were admitted to our hospital in the last ten years. They were a nineteen-month-old boy, a two-year-old girl and a five-year-old girl. They were all healthy infants. The two female patients survived, while the male patient died. At autopsy, arachnoid turbid, swollen brain substance and slight bleeding under the cerebellar tent were observed. Judging from the minimal inhibitory concentration of antibiotics against the isolated L. monocytogenes, antibacterial activity of penicillin G and ampicillin was good, whereas that of cefotaxime and latamoxef was poor. In conclusion, for therapy of bacterial meningitis due to unknown origin, the combination of ampicillin and cephalosporins is necessary.

Ampicillin↗