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Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 973 records · Page 54Linked to original sources

Synthesis of a novel cytokine and its gene (LD78) expressions in hematopoietic fresh tumor cells and cell lines.

The gene coding for the protein LD78 was isolated from stimulated human tonsillar lymphocytes by differential hybridization. The gene product consisted of 92 amino acids with characteristics of cytokines. LD78 gene transcripts were detected in eight of eight fresh samples of cells from patients with acute nonlymphocytic leukemia (ANLL) by Northern blot analysis. ANLL cells with monocytic features gave the strongest bands. RNA transcripts were found in two of three samples of cells from patients with adult T cell leukemia (ATL), eight of nine samples from patients with acute lymphocytic leukemia (ALL) of B cell lineage, and one of the three samples from patients with T cell ALL. KG-1, HL-60, HUT 102, MT-2, and MJ cell lines expressed the LD78 gene constitutively. The LD78 protein was detected in culture supernatants and cell lysates of HUT 102, MT-2, MJ, and fresh ATL cells by Western blot analysis. This protein was not found in culture supernatants or cell lysates of monocytic leukemia cells and HL-60 cells, although LD78 transcripts were found in those cells. The discrepancy between gene and protein expression might be explained by the stability of the mRNA. Thus, the protein may be involved in the neoplastic transformation of hematopoietic cells.

Biological Factors↗

Development of a ceramic heart valve.

A durable and thromboresistant ceramic heart valve comprised of a single crystal alumina disk and titanium nitride (TiN) valve ring has been developed. Blood compatibility was examined by scanning electron microscopy (SEM) examinations of the valves implanted in sheep for 35 (#1), 26 (#2), 20 (#3), 23 (#4), and 26 (#5) days. The single crystal alumina and TiN surfaces were free of platelet aggregation or fibrin networks, except for some depositions of fibrin and platelets on the outflow TiN ring in #3, and isolated red cells on the outflow TiN ring in #5. Durability testing under high pressure (1750 mmHg = 233 KPa) pulsatile conditions showed that the safety factor of the ceramic valve was more than seven times greater than anticipated. The ceramic valve is promising as an artificial heart valve.

Animals↗

Structure and permeability of dialysis membranes sterilized by various methods.

Appropriate design of dialysis membranes requires correct values of structural parameters such as pore radius, surface porosity, water content and tortuosity. It is impossible, however, to find the pore radius of dialysis membranes using a mercury porosimeter or an electron microscope because the pores are only several tens of angstroms in radius. Consequently, diffusional and convectional procedures such as the Lw method that uses both pure water permeability and water content, the Lw and Pm method which uses both solute and pure water permeability, and the sigma method which uses the reflection coefficient, have been employed extensively to determine the pore radius of dialysis membranes. The structural parameters of symmetric membranes are determined from water content, solute and pure water permeability data based on the Lw and Pm method combined with the tortuous pore model we have proposed. Determination of the structural parameters of microfiltration membranes for plasma separation having huge pores by various methods is required to verify the method of characterizing dialysis membranes based on the tortuous pore model. A dyeing method is also suitable for characterizing dialysis membranes of regenerated cellulose. Pore model studies using permeability and water content data for sterilized and treated membranes facilitate optimal design of dialysis membranes for clinical applications.

Animals↗

Effect of water extracts of aloe and some herbs in decreasing blood ethanol concentration in rats. II.

Oral administration of ethanol to rats at a dose of 3 g/kg decreased alcohol dehydrogenase (ADH) activity and metabolism of lactate to pyruvate in the liver. The effects of water extracts of Aloe and some other herbs on blood ethanol concentration and on ADH activity in liver cytosol were examined. The water extracts of these herbs caused a faster elimination of ethanol from blood of normal rats when administered orally 30 min before oral administration of ethanol. The rapid elimination of ethanol seems to be due to a protection of ADH activity and the supply of nicotinamide dinucleotide, both of which are reduced by high ethanol concentration. The effects of ethanol in decreasing the enzyme activities relating to its own metabolism occur when high concentrations of ethanol pass through the liver, and thus may primarily appear during the absorption of alcohol from the gastrointestinal tract, when portal concentration of ethanol are very high.

Aloe↗

Effect of extracts of Zingiberaceae herbs on gastric secretion in rabbits.

Some of the Zingiberaceae herbs are known to be useful as stomachics. Water extracts and methanol extracts of eight such herbs were examined in intact unanesthetized rabbits for their effect on gastric secretion. Oral administration of either water extracts or methanol extracts caused a significant decrease in gastric secretion. A significant effect of these extracts appeared at 3 h after administration. The effect of water extracts on gastric secretion was very similar to that of cimetidine, with a significant decrease in acid output. The effect of the methanol extracts was primarily observed as decreased pepsin output.

Animals↗

Characterization of a novel alpha 1-adrenoceptor antagonist, SGB-1534, in contractile response of isolated canine arterial and venous smooth muscle to exogenous noradrenaline: comparison with prazosin, phentolamine and yohimbine.

The pharmacological properties of SGB-1534, 3-[2-[4-[(o-methoxyphenyl)-1-piperazinyl]ethyl]-2,4(1H,3H)- quinazolinedione monohydrochloride, a selective alpha 1-adrenoceptor antagonist, compared with prazosin, phentolamine and yohimbine, were examined in contractile responses of isolated canine mesenteric arteries and veins and femoral arteries and veins to exogenous noradrenaline. The arteries and veins concentration-dependently contracted when exposed to noradrenaline. The sensitivity to noradrenaline, when compared in terms of pD2 values, was significantly higher in the veins than in the arteries. Phentolamine and yohimbine were competitive antagonists against noradrenaline in the arteries and the veins. SGB-1534 and prazosin caused a parallel shift to the right of the concentration-response curves for noradrenaline only in the arteries: the two antagonists were less effective in the veins than in the arteries when low concentrations of noradrenaline were applied. The pharmacological characteristics of SGB-1534 resemble those of prazosin. The pA2 values for SGB-1534 against noradrenaline in the arteries were much higher than those for prazosin, phentolamine and yohimbine. The result indicates that SGB-1534 may predominantly act upon arterial resistance vessels rather than the venous side, resulting in potent hypotension.

Adrenergic alpha-Antagonists↗

Neurokinin A-induced bronchial hyperresponsiveness to methacholine in Japanese monkeys.

The present study was designed to investigate whether neurokinin A (NKA) and substance P (SP) increase bronchial responsiveness to methacholine (MCh). Before and 1, 2, 3 and 4 weeks after three Japanese monkeys had inhaled 10(-8) M NKA and 10(-8) M SP for 2 min, bronchial responsiveness to inhaled MCh was evaluated. Pulmonary flow resistance (R1) and dynamic lung compliance (Cdyn) were used as pulmonary function tests. Dose-response curves of R1 to inhaled MCh were shifted to the left 1 to 4 weeks after NKA treatment, compared with that obtained before treatment. However, SP treatment did not change the R1 dose-response curve. Thus, bronchial responsiveness to MCh was increased by inhalation of 10(-8) M NKA in Japanese monkeys.

Airway Resistance↗

Urinary and biliary metabolites of mephentermine in male Wistar rats.

1. Excretion of urinary and biliary radioactivity, and metabolites of [3H]mephentermine (MP), after i.p. or subcutaneous administration of [3H]MP to male Wistar rats, were determined by preparative t.l.c.-liquid scintillation counting. 2. About 45% of the radioactivity administered i.p. was excreted in the 24 h urine. The major urinary metabolite was conjugated p-hydroxymephentermine (p-hydroxy-MP), which accounted for about 18% of the administered radioactivity in the 24 h urine. 3. About 4.2% of the radioactivity administered subcutaneously was excreted in bile during 24 h. The major biliary metabolite was conjugated p-hydroxy-MP, which accounted for about 39% of the radioactivity excreted in the bile in 24 h. 4. Urinary and biliary minor metabolites detected were phentermine (Ph), p-hydroxyphentermine (p-hydroxy-Ph), N-hydroxyphentermine (N-hydroxy-Ph), N-hydroxymephentermine (N-hydroxy-MP) and their conjugates, and conjugated MP. 5. The conjugates were considered to be glucuronides from the inhibitory effect of saccharic acid 1,4-lactone on their hydrolysis with beta-glucuronidase. 6. Biliary excretion rates of conjugated p-hydroxy-Ph and p-hydroxy-MP reached maxima at 3 to 4 h, and non-conjugated metabolites were maximal at 1 to 2 h, after administration. 50% of the biliary metabolites was excreted within 5 h.

Animals↗

Age-related decreases in cardiac receptor control of forearm vascular resistance in humans.

We examined 1) the relationship between the magnitudes of reflex forearm vasoconstriction during lower body negative pressure (LBNP) at -10 mmHg and ages in 59 subjects whose ages ranged from 24 to 77 years old, and 2) the slopes of the regression lines relating changes in forearm vascular resistance and those in central venous pressure in the three age-groups; those younger than 35 years old (n = 15), those between 35 and 55 years old (n = 12) and those older than 55 years old (n = 12). Forearm blood flow was measured using a strain gauge plethysmograph and forearm vascular resistance was calculated from forearm blood flow and mean blood pressure. There was a significant negative correlation (r = -0.512, p less than 0.01) between age and the magnitude of reflex forearm vasoconstriction during LBNP at -10 mmHg. The slope of the regression line in the old age-group was less (p less than 0.05) than that in the young or middle age-group. Forearm vascular responses to the cold pressor test did not differ among the three age-groups. These results suggest that cardiac receptor control of forearm vascular resistance decreases with aging in humans.

Adult↗

[The desensitization therapy in children with nasal allergy to house dust].

A study about the desensitization therapy carried out on children with nasal allergy to house dust who were under 15 years old. The good effect was seemed in 35.7% of patients with the desensitization for 3 months, and 62.7% for 6 months, 90.0% for 12 months, 92.7% for 24 months. The patients with the desensitization for over 6 months had a considerable effect, as if they dropped out. In the questionnaire to patients who dropped out with no contact to us, the effect of this therapy was seemed on 83.3% in those who answered questions, as so we considered that the sensitization for children with nasal allergy was very important as the basic therapy. Refer to the efficacy of this therapy, it was seemed to be recommended to children who were about from 7 to 9 years old, or those who had allergic rhinitis for a long time. At the point of 6 months after starting HD desensitization, the patients who reacted intensively to the provocation test had not significantly the efficacy compared with those who reacted slightly, but other clinical data were not significantly concerned with the efficacy of this therapy.

Adolescent↗

[Evaluation of renal scarring in children with primary VUR by 99mTc-DMSA renoscintigraphy].

Renal scarring in 271 kidneys of 172 children with primary vesicoureteral reflux (VUR) was evaluated by 99mTc-DMSA renoscintigraphy. 58% of refluxing kidneys were with renal scar by the initial DMSA renoscintigraphy. Only 52% of these kidneys showed good correlation between the findings on IVP and DMSA renoscintigram. Of the 144 refluxing kidneys with normal IVP, 41% had renal scarring on DMSA renoscintigram. DMSA renoscintigram revealed widespread renal scarring in 28% of kidneys with only calyceal clubbing and in 60% of those with segmental cortical thinning on IVP. It is realized that IVP was an in-sensitive method to evaluate renal scarring of refluxing kidneys and such kidneys with segmental renal scar on IVP accompanies more widespread scar on DMSA renoscintigram. These cases were allocated to 2 age groups, younger than 3 years and older than 4 years. In the former group less than 10% of kidneys with low grade VUR and about 40% with high grade UVR had widespread renal scarring. On the contrary, in the latter group severe renal scar was recognized in more than 20% of kidneys with low grade VUR and in about 60% with high grade UVR.

Adolescent↗

Cyclic adenosine 3',5'-monophosphate metabolism in activated T-cell clones.

The role of cAMP in lymphocyte proliferation was investigated in the response of a monoclonal T-cell population to a specific antigen and compared to the response to interleukin-2 (IL-2) and allogeneic cells. Myelin basic protein (MBP)-reactive and encephalitogenic T-cell clones were established from long-term lines derived from SJL/J (H-2s) mice. The clone 4b.14a recognizes the peptide sequence 89-101 of the MBP molecule in association with 1-As products of the major histocompatibility complex (MHC). Incubation of 4b.14a cells with syngeneic antigen-presenting cells, previously pulsed with the 89-101 synthetic peptide or with 80 U/ml of IL-2, or allogeneic H-2Ik cells, resulted in a significant increase in the accumulation of intracellular cAMP. This increase was preceded by a peak in membranal adenylate cyclase (AC) activity. Parallel time kinetics but significantly higher cAMP production and AC activity were observed when the cells were treated with pertussis toxin. At the same concentrations the toxin inhibits cellular proliferative responses, assayed by [3H]thymidine incorporation. Our results indicate the involvement of cAMP as a positive signal in the activation of the 4b.14a clone.

Animals↗

Combined effect of disopyramide and bethanechol: use of bethanechol to prevent anticholinergic side effects of disopyramide without reduction of antiarrhythmic efficacy.

Because bethanechol chloride (B) relieves the anticholinergic side effects of disopyramide (D), we examined the combined effects of D and B on the heart and urinary bladder. B was confirmed to counteract dose dependently the effect of D on the dog bladder. In the ventricular muscle, the combined electrophysiological effects (D + B) were additive, with no reduction in the effect of D. With the control value set as 100%, the decrease in the maximum rate of depolarization with 5 X 10(-6) g/ml D (90 +/- 6%) was not affected by the same dose of B (D + B: 84 +/- 14%). Moreover, the effective refractory period (ERP) was larger with D + B (128 +/- 12%) than with either B (109 +/- 9%, p less than 0.01) or D (115 +/- 11%, p less than 0.05). In contrast, in the atrial muscle and AV and SA nodes, B had marked acetylcholine-like effects. These were completely suppressed by the addition of D except for the atrial ERP with the highest tested concentration of B (5 X 10(-6) g/ml). In the latter case, the prolongation of ERP was minimal (B + D: 105 +/- 14%) as compared with D alone (130 +/- 15%). Since the plasma concentration of B after oral administration of a clinical dose is expected to be on the order of 10(-7) g/ml, no practical effect is anticipated. We conclude that B can be expected to counteract urination disorders caused by D without reducing D's antiarrhythmic efficacy.

Anesthesia↗

[MR imaging of large heterotopic gray matter].

One and a half year-old boy was admitted to our hospital with a history of intractable myoclonic epilepsy. Seizures were fairly controlled on carbamazepine, phenobarbital, diphenylhydantoin and clonazepam, but still occurred several times per month. Neurological examination showed mild psychomotor retardation. The CT and MR imaging studies showed both large heterotopic gray matter and supracerebellar arachnoid cyst. No enhancement was noted after the administration of contrast medium. No calcification was present. In the MR image, a large nodule in the right hemisphere showed almost the same signal intensity as the cortical gray matter. The right lateral ventricle was absent for a portion of the anterior horn. The sulci on the right parietal lobe were almost absent, suggesting the region of agyria.

Brain↗

[A fatal case of pemphigus vulgaris with interstitial pneumonia occurring during gold therapy].

We report a case of a 52-year-old female with therapy-resistant pemphigus vulgaris. She was treated with prednisone, azathioprine and gold sodium thiomalate. After administration of a total dose of 110 mg gold sodium thiomalate, she suddenly developed pityriasis rose-like drug eruptions and interstitial pneumonia and died despite intensive care including pulse therapy. In Japan, there have been 8 reported cases of pemphigus or bullous pemphigoid that developed interstitial pneumonia during gold therapy. In these 7 cases, interstitial pneumonia occurred after administration of 110 to 430 mg gold sodium thiomalate, and 4 cases died. This rate of death is higher than those with other diseases: i.e., 9 dead cases among 99 cases of interstitial pneumonia developing in patients with rheumatoid arthritis or asthma under treatment with gold sodium thiomalate. We think that it is necessary to reevaluate the combined treatment of sodium thiomalate and other immunosuppressive drugs such as azathioprine in pemphigus, because we also found 2 other fatal cases among the 4 reported ones with interstitial pneumonia.

Azathioprine↗

[Mass-screening for acid mucopolysaccharidosis using urine samples by modified HCl-albumin turbidity method].

To establish a method for screening acid mucopolysaccharidosis (AMPS), the HCl-albumin turbidity method was reexamined and modified for semiquantitative analysis. Mucopolysaccharide samples and HCl-albumin in buffer solution were incubated at 37 degrees C for 30 minutes, and the optical density at 600 nm (OD 600) of the reaction mixtures were measured. When the same amount of the samples were tested, OD 600 of dermatan sulfate and hyaluronic acid were higher than that of keratan sulfate. When the cut-off point of OD 600 was set at 0.100 based on the values obtained from randomly selected subjects, only 3 of 328 urine samples (0.9%) showed value higher than the cut off value. The values in five patients with AMPS were all above 0.800 without overlapping those of the control subjects. These results suggest that mass-screening for AMPS using urine sample is possible by the partially modified HCl-albumin turbidity method with the cut-off point of OD 600 set at 0.100.

Adolescent↗

[Measurement of portal blood flow in man by a continuous local thermodilution method. III. Effects of dopamine on systemic and portal hemodynamics after hepatectomy].

We gave dopamine (3 micrograms/kg/min, 30 min) intravenously on the third day after hepatectomy to 19 patients, and studied the effects of the drug on systemic and portal hemodynamics. In another 42 patients, administration of dopamine at the same rate was started soon after hepatectomy and continued for about 2 weeks; the clinical results were evaluated. After hepatectomy, the systemic hemodynamics were hyperdynamic and the portal hemodynamics were hypodynamic. After 30 min of dopamine administration, the oxygen pressure in portal blood increased, and because portal blood flow also increased, the oxygen delivery to the liver increased. The mechanism involved an increased proportion of portal venous flow to cardiac output, and a decrease in the splanchnic resistance, not portal venous resistance. Probably, specific dopamine receptors played important role in the increase in the superior mesenteric arterial blood flow. Among 42 patients given small dosage of dopamine, the clinical symptoms of five of seven who had developed liver failure improved. None of the other 35 patients given dopamine preventively developed liver failure. Dopamine in small doses is useful for the management of liver failure after liver resection.

Adult↗