Biomedical subjects

K Shiba

Publications and source records attributed to K Shiba.

At least 145 records · Page 8Linked to original sources

PubMed1992

Evaluation of N-alkyl derivatives of radioiodinated spiperone as radioligands for in vivo dopamine D2 receptor studies: effects of lipophilicity and receptor affinity on the in vivo biodistribution.

A series of radioiodinated spiperone (2'-ISP) derivatives bearing amide N-alkyl substituents (N-methyl-2'-ISP, N-ethyl-2'-ISP, and N-propyl-2'-ISP) were synthesized and evaluated as potential singlet photon emission computed tomographic radiopharmaceuticals for visualizing dopaminergic receptors. The lipophilicity of these ligands (i.e., the partition coefficient for octanol-phosphate buffer) increased as the chain length increased. Investigation of blood-brain barrier permeability in rats showed a parabolic relationship between the brain uptake index and the partition coefficient. In vitro competitive binding studies showed that the relative affinity for the dopamine D2 receptor was in the order of N-propyl-2'-ISP greater than 2'-ISP greater than N-methyl-2'-ISP approximately N-ethyl-2'-ISP. In vivo biodistribution studies showed that the initial brain uptake correlated fairly well with the brain uptake index and that the kinetics of the radioactivity specifically bound to the striatum were strongly influenced by the dopamine receptor binding affinity of the compounds. Thus, the in vivo behavior of these N-alkylated 2'-ISP derivatives involved a complex interplay between receptor affinity, lipophilicity, and blood-brain barrier permeability.

Animals↗

PubMed1992

[Methicillin-resistant Staphylococcus aureus (MRSA) isolated in hospitals in Fukuoka City area].

Bacteriological and clinical studies were carried out on 280 strains of Staphylococcus aureus isolated in hospitals in Fukuoka city area from September 1990 to March 1991. Of all S. aureus strains studied 116 (41.4%) were methicillin-resistant. The proportion of MRSA in S. aureus isolates from outpatients was 10% (11/109), 69.2% (90/130) in those from inpatients. The average age of patients with isolated MRSA was 70.5 +/- 16.9 years and that of patients with isolated MSSA, 44.2 +/- 29.3. MRSA strains were recovered mainly from sputum and pus. The isolation rate did not vary significantly with hospitals of different size (number of beds). Of all MRSA strains 48 (41.3%) produced coagulase type VII. As for drug susceptibility, MRSA strains with coagulase type VII were more sensitive to clindamycin and more resistant to minocyclin compared to MRSA with other coagulase types.

Age Factors↗

PubMed1991

Positive and negative regulations of plasmid CoLIb-P9 repZ gene expression at the translational level.

Expression of the repZ gene involved in DNA replication of the ColIb-P9 plasmid depends on translation of a transcribed repZ leader sequence (repY) and is negatively regulated by Inc RNA, the product of the inc gene and a countertranscript to RepZ mRNA. To further understand the regulatory loop of repZ expression, we isolated and characterized replication-defective ColIb-P9 mutants that affected the level of repZ expression. Here we report that mutations occurring in two complementary sequences, one (5'GGCG3') in the inc region and one in the repY region, reduce the level of repZ expression without affecting transcription. The mutations in one complementary sequence were suppressed by compensatory base changes in the other sequence, restoring the ability of repZ expression. These results indicated that interaction by base pairing between the two complementary sequences of RepZ mRNA was essential for repZ translation. The two sequences, separated by 107 bases from each other, have a potential to form a novel pseudoknot in the RepZ mRNA leader. We also found that some mutations in the 5'GGCG3' sequence altered the specificity of Inc RNA, thereby reducing significantly its regulatory activity. Thus, this single specific sequence is involved in both positive and negative regulations for repZ expression. Possible regulatory mechanisms of repZ expression are discussed.

Amino Acid Sequence↗

PubMed1991

Sequence determination and modeling of structural motifs for the smallest monomeric aminoacyl-tRNA synthetase.

Polypeptide chains of 19 previously studied Escherichia coli aminoacyl-tRNA synthetases are as large as 951 amino acids and, depending on the enzyme, have quaternary structures of alpha, alpha 2, alpha 2 beta 2, and alpha 4. These enzymes have been organized into two classes which are defined by sequence motifs that are associated with specific three-dimensional structures. We isolated, cloned, and sequenced the previously uncharacterized gene for E. coli cysteine-tRNA synthetase (EC 6.1.1.16) and showed that it encodes a protein of 461 amino acids. Biochemical analysis established that the protein is a monomer, thus establishing this enzyme as the smallest known monomeric synthetase. The sequence shows that cysteine-tRNA synthetase is a class I enzyme that is most closely related to a subgroup that includes the much larger methionine-, isoleucine-, leucine-, and valine-tRNA synthetases, which range in size from 677 to 951 amino acids. The amino-terminal 293 amino acids of the cysteine enzyme can be modeled as a nucleotide-binding fold that is more compact than that of its closest relatives by virtue of truncations of two insertions that split the fold. This smaller nucleotide-binding fold accounts for much of the reduced size of the cysteine enzyme and establishes the limit to which the structure of this domain is contracted in the five members of this subgroup of class I enzymes.

Amino Acid Sequence↗

PubMed1991

Evaluation of the densitometric method of ejection fraction by direct digital subtraction left ventriculography.

The aim of the present study was to test the hypothesis that the densitometric ejection fraction (EF) could be calculated by direct contrast digital subtraction left ventriculography in a single heartbeat. Thirty patients underwent direct contrast digital subtraction left ventriculography and biplane conventional left ventriculography. The values of EF were obtained from digital subtraction ventriculograms of the first cardiac cycle after completion of the injection of the contrast medium by the videodensitometric technique and were compared with those obtained from conventional ventriculograms by the area-length method in the same patients. There was a close correlation between the densitometric EF from digital subtraction ventriculograms and the volumetric EF from conventional ventriculograms (r = 0.78). Densitometric EF measured in the 30 degree right anterior oblique projection highly correlated with densitometric EF measured in the 60 degree left anterior projection (r = 0.98). These data suggest that this densitometric technique is available in any projection and is a simple procedure for the accurate measurement of left ventricular EF.

Absorptiometry, Photon↗

PubMed1991

Synthesis and characterization of 99Tcm-p-halophenethyl diaminodithiol analogs.

In an effort to develop new, clinically useful 99Tcm-diaminodithiol (99Tcm-DADT) complexes for the evaluation of regional cerebral perfusion, basic diaminodithiols (DADT-TM, DADT-HM and DADT-MHM) and three diaminodithiol ligands functionalized with p-iodophenethyl (DADT-IPE), N-ethyl-p-fluorophenethyl amine (DADT-EFPE) or N-ethyl-p-iodophenethyl amine (DADT-EIPE), whose chemical structures are analogous to N-isopropyl-p-iodoamphetamine (IMP), were synthesized, labelled with 99Tcm and evaluated comparatively in experimental animals. In addition, the relationships between the chemical properties of the derivatives and their brain uptake and retention were investigated. The results were: (1) Isomeric configuration of 99Tcm-DADT complexes has an influence on uptake and retention in the rat brain. (2) In basic 99Tcm-DADT complexes, a correlation exists between initial brain uptake and lipophilicity, but in 99Tcm-DADT complexes containing a chemical structure similar to that of IMP, no correlation exists. (3) 99Tcm-DADT-IPE has relatively high uptake and long retention in the rat brain.

Animals↗

PubMed1991

Optic tract syndrome with relative afferent pupillary defect.

Two cases are reported of optic tract lesions with complete homonymous hemianopia, characteristic optic atrophy and retinal nerve fiber bundle defect, and relative afferent pupillary defect (RAPD). RAPD was 0.6 log units in both cases. Infrared pupillography revealed pupillary light response of the ipsilateral side to be 1.2 or 1.3 times higher than that of the contralateral side. We confirmed that the detection of RAPD is helpful in differentiating optic tract lesions from suprageniculate lesions in cases of complete homonymous hemianopia.

Fundus Oculi↗

PubMed1991

[Analysis of left ventricular pulsus alternans in hypertrophic cardiomyopathy].

We analyzed left ventricular (LV) pulsus alternans in 49 patients with hypertrophic cardiomyopathy during cardiac catheterization. LV pulsus alternans was noted in 6 of 17 patients with hypertrophic obstructive cardiomyopathy, 5 of whom already showed intraventricular pressure gradient at rest. No patient with hypertrophic non-obstructive cardiomyopathy had LV pulsus alternans. Pulsus alternans was neither observed in the right ventricle nor in the pulmonary artery. There was little, if any, pulsus alternans in a low pressure LV chamber (subaortic portion) and peripheral artery during LV pulsus alternans in a high pressure chamber. LV end-diastolic pressure also remained unchanged during LV pulsus alternans, except in one case. It is suggested that LV pulsus alternans in hypertrophic obstructive cardiomyopathy may imply LV dysfunction associated with increased afterload.

Adult↗

PubMed1991

[Development and clinical evaluation of a new urinary protein test paper (URINE-TP)].

Because standard urinary protein test paper reacts more strongly to albumin than to globulin, we attempted to develop a test paper sensitive to globulin by applying chromatic analysis principles used in quantitative analysis of urinary protein. We developed a new urinary protein test paper (URINE-TP) containing a reagent of ACID VIOLET 17. It was found that URINE-TP reacts with the same strength to gamma-globulin as to albumin. This new test paper therefore allows accurate detection of Bence Jones protein, which was formerly detectable with standard test paper. There was a correlation between values for urinary protein obtained with URINE-TP and those obtained by quantitative analysis. As with standard test paper, URINE-TP indicates urinary protein values in the normal range by a lack of reaction, but on URINE-TP positive and negative results are more clearly distinguishable than on standard test paper. From these results, we conclude that URINE-TP enables detection of both gamma-globulin and albumin in the urine, and that is as sensitive as the analytical method in the screening of urinary proteins.

Bence Jones Protein↗

PubMed1990

A novel role for accessory cells in T cell-dependent B cell differentiation.

The monocyte requirement for pokeweed mitogen-induced T cell-dependent B cell activation was reexamined. We report a dichotomy in the requirement for accessory cells in B cell proliferation and differentiation. Adherent cell-depleted human peripheral blood mononuclear cells which contained only 5% monocytes generated sufficient T cell help for optimal B cell proliferation. However, the presence of 10 to 20% monocytes were required during the last 5 days of culture for stimulated B cells to become IgG-secreting cells. Similar numbers of monocytes were also needed for anti-CD3-induced B cell differentiation. Moreover, monocytes alone added to previously activated B cells could support B cell differentiation in the absence of T cells. To determine the role of cytokines in this system, we demonstrated that supernatants of adherent cell-depleted PBMC contained decreased IL-6 activity in comparison with unseparated PBMC, but not IL-1, IL-2, or BCGF. Recombinant IL-6, however, added back either alone or with other cytokines could not replace the effects of intact monocytes on B cell differentiation. Physical interaction between the accessory cells and the responder cells was also required. As a minimum, paraformaldehyde-fixed monocytes, IL-6, and IL-1 were needed to reconstitute maximal IgG secretion. These studies suggest that accessory cells capable of producing IL-1 and IL-6 can have direct effects on the terminal differentiation of stimulated B cells.

Antibody Formation↗

PubMed1990

Characteristics of the binding of N-isopropyl-p-[125I]iodoamphetamine in the rat brain synaptosomal membranes.

N-isopropyl-p-[125I]iodoamphetamine (125I-IMP) binding to crude synaptosomal membranes of rat brain was saturable and pharmacologically displacable. Scatchard analysis of binding data revealed an apparent dissociation constant, KD of 56.2 +/- 5.2 microM, and the estimated maximum number of binding sites, Bmax of 7.5 +/- 1.1 nmoles mg-1 protein; and competition studies demonstrated structure activity relationships among structural analogues of arylalkylamines. These findings suggest that the retention mechanism of IMP in the brain is probably associated with saturable binding of IMP to extreme high-density, relatively low-affinity binding sites rather than any of the well-known amine receptors.

Amphetamines↗

PubMed1990

Renal handling of fleroxacin in rabbits, dogs, and humans.

The renal handling of fleroxacin was studied by renal clearance and stop-flow techniques in rabbits and dogs and by analyzing the pharmacokinetics with and without probenecid in humans. In rabbits the excretion ratios (fleroxacin intrinsic renal clearance/glomerular filtration rate) were greater than unity (2.01) without probenecid and were decreased to a value below unity (0.680) with probenecid. In dogs, on the other hand, the excretion ratios were less than unity (0.608 and 0.456) both without and with probenecid, and so were not affected by probenecid. This fact suggested that fleroxacin was excreted into urine by both glomerular filtration and renal tubular secretion in rabbits, but only by glomerular filtration in dogs, accompanied by partial renal tubular reabsorption in both species; these mechanisms were also supported by stop-flow experiments. In humans probenecid treatment induced increases in the elimination half-life and area under the serum concentration-time curve and decreases in apparent serum clearance, renal clearance, and urinary recovery of fleroxacin. The excretion ratio without probenecid was 1.13, which was significantly decreased to 0.750 with probenecid. These results indicated that both renal tubular secretion and reabsorption contributed to renal excretion of fleroxacin in humans. The contribution of tubular secretion was species dependent and was extensive in rabbits, minimal in dogs, and moderate in humans. Renal tubular reabsorption was commonly found in every species. The long elimination half-life of fleroxacin in humans might be explained by its small total serum clearance and small renal clearance, which are attributed to less tubular secretion and more tubular reabsorption.

Adult↗

PubMed1990

Posttranscriptional control of plasmid ColIb-P9 repZ gene expression by a small RNA.

The replication frequency of plasmid ColIb-P9 depends on the level of repZ gene expression, which is negatively regulated by the action of the inc gene (C. Hama, T. Takizawa, H. Moriwaki, Y. Urasaki, and K. Mizobuchi, J. Bacteriol. 172:1983-1991, 1990). To further understand the mechanism of this regulation, we analyzed transcripts of the ColIb-P9 replication control region. Four RNA species, designated RNAI to RNAIV, were observed in plasmid pCH11, which contained the whole inc gene region and the 5' portion of the repZ gene. RNAII, RNAIII, and RNAIV, with sizes of approximately 200, 500, and 1,500 bases, respectively, were identified as rightward transcripts that shared common transcription initiation sites; RNAIV was determined to be equivalent to a part of repZ mRNA, which was observed in pCH10, a plasmid that contained sufficient information for replication and control of ColIb-P9. Conversely, RNAI, with a size of about 70 bases, was transcribed leftward and was identified as the product of the inc gene and hence equivalent to inc RNA detected by in vitro RNA synthesis. This small RNA was found to be complementary to a part of repZ mRNA. These results and quantitative analyses of the transcripts in Inc- mutants indicate that the inc RNA negatively regulates repZ expression mainly at the posttranscriptional level through the possible formation of an inc RNA-repZ mRNA hybrid in the host cells.

Bacterial Proteins↗

PubMed1990

A mutation that enhances synthesis of sigma 32 and suppresses temperature-sensitive growth of the rpoH15 mutant of Escherichia coli.

The rpoH15 mutant cannot grow at or above 34 degrees C, because it produces an altered sigma 32 protein that is largely deficient in the transcription of the heat shock genes. Extragenic suppressor mutations (suhB) located at 55 min on the Escherichia coli chromosome endowed the mutant cell with the ability to grow at 40 degrees C and the inability to grow at 25 degrees C. One such mutation (suhB2), studied in detail, markedly enhanced the rate of sigma 32 synthesis and the rpoH mRNA level during steady-state growth at 37 to 40 degrees C but little affected the cellular content of sigma 32 or the induction of heat shock proteins. In the isogenic rpoH+ strain, neither sigma 32 synthesis nor the rpoH mRNA level was enhanced by the suhB suppressor. Furthermore, expression of the rpoH-lacZ gene fusion, but not the operon fusion, was much higher in the suhB mutant than in the wild type or the suhB rpoH+ strain, indicating that suhB affects rpoH expression primarily at the level of translation. suhB probably acts to increase sigma 32 synthesis by affecting the regulatory circuit of rpoH expression or by modulating certain parameters in protein synthesis. Consistent with these findings, overproduction of the mutant (rpoH15) sigma 32 by multicopy plasmid enabled the rpoH15 or delta rpoH (deletion) mutant to grow at up to 40 degrees C. Plasmids containing an E. coli DNA segment of 1.0 kilobase could complement the cold-sensitive phenotype of the suhB2 mutant. Nucleotide sequence analysis revealed that the segment contained an open reading frame encoding a protein of 29,128 daltons.

Amino Acid Sequence↗

PubMed1990

[Effects of breathing high concentrations of oxygen on changes in blood indices during bicycle exercise].

The purpose of this study is to examine effects of hyperoxic gas mixtures on changes of blood indices during bicycle exercise of human. Oxygen-enriched gases (30% O2) were inspired during the ramp load exercise of 25 watt/min. Changes of blood indices were analyzed with Sequential Multiple Analyzer with the computer (SMAC). The improvement of exercise performance were discussed about relationship between function of hyperoxic gas and physiological mechanism. Three experimental conditions were set as follows (I) 30% O2 +N2 gases balance, (II) air (21% O2), and (III) 30% O2 +2% CO2 +N2 gases balance. Arterial blood were sampled from the radial artery of the forearm in order to analyze following items; 1) pH level, PaO2, PaCO2, and HCO3 of these blood gases, 2) Blood sugar, TG, and F-CH of the blood contents, 3) red blood corpuscle, white blood corpuscle, Hb, and Ht values, 4) LDH, CK, GOT, and GPT of the blood enzymes, 5) TP, ALB, Na, K, Ca and Cl of the electric ions. In the case of inspiring hyperoxic gases, the recovery rate of blood indices increased after this ramp load exercise remarkably, and the whole exercise metabolism were removed from acidosis tendency to alkalosis value of the resting condition significantly. At hyperoxic experimental conditions, the blood sugar and oxygen consumption were much more decreased than these at normal oxygen content one during both states of exercise and recovery times. These data of the blood indices would support strongly to the hypothesis that improvement of oxygen delivery should be depended upon the enhanced performance with the hyperoxic gases. There might be effects of the hyperoxia on the cellular metabolism and on function of the vascular muscle during those aerobic exercise.

Administration, Inhalation↗

PubMed1990

[Serum level of vascular basement membrane associated collagen by the sandwich ELISA with monoclonal antibodies and its clinical significance in various diseases].

A sandwich ELISA system for detecting vascular basement membrane associated collagen (BAC) was developed. Serum levels of BAC were determined in patients with liver diseases (N = 53), various cancers (N = 65) and other diseases (399). Serum levels of procollagen type III (PIIIP) amino propeptide, type IV collagen.7s domain (7s domain) and other parameters (TP, ALB, GOT, GPT, CHE, gamma-GTP, ALP, LDH, CHE, TG, GLU) were also determined in those patients. In the whole patients, serum concentrations of BAC showed a weak correlation with GOT, GPT, ALB and CHE but not with gamma-GTP and ALP. There was no correlation between BAC and PIIIP or 7s domain. Although serum levels of BAC were elevated in both liver diseases and cancers, the increase in liver diseases was more marked. Markedly increased serum levels of BAC with low levels of CHE were found only in liver cirrhosis and liver cirrhosis plus hepatocellular carcinoma. Increased BAC may reflect capillarization of the liver sinusoid or remodeling of the vascular basement membrane which is observed in the progression of liver fibrosis. Serum BAC is thought to be a promising new marker, different from PIIIP or 7s domain for diagnosing fibrosis state in the organs, particularly in the liver.

Antibodies, Monoclonal↗

PubMed1990

[Comparison of effects of intravenous versus intramuscular famotidine on pH and volume of gastric juice].

Famotidine, an H2-antagonist, is frequently used for prevention of acid aspiration in surgical patients. Intravenous as well as intramuscular administration of famotidine has proved effective to reduce gastric acid secretion during anesthesia. However, the onset and duration of action of famotidine following intravenous administration has not been extensively investigated. In the present study on 89 patients undergoing elective surgery, the effects of famotidine 20 mg administered intravenously 5-30 min before endotracheal intubation on pH and volume of gastric contents aspirated 0, 1, 2, and 4 hrs after tracheal intubation and immediately after extubation through nasogastric tube were compared with the effects of the drug administered intramuscularly one hour before endotracheal intubation. Famotidine administered intramuscularly 5-14 min before endotracheal intubation produced inadequate suppression of gastric secretion after tracheal intubation. In contrast, intravenous famotidine given 15-30 min before tracheal intubation, as well as the intramuscular administration of famotidine as premedication, effectively decreased gastric fluid volume and increased gastric pH. Suppression of gastric secretion by intravenous and intramuscular famotidine continued for over 4 hours. Intravenous famotidine has a rapid onset and a long duration of depressant action on gastric secretion, thus reducing the risk of aspiration pneumonitis during and after general anesthesia.

Adult↗

PubMed1990

[Effects of antacids on absorption, excretion and metabolism of cefteram pivoxil].

Effects of various antacids (sodium bicarbonate, aluminium hydroxide gel) and an H2-blocker (cimetidine) on the absorption and excretion of a new cephem drug for oral use, cefteram pivoxil (CFTM-PI), were studied in healthy adult volunteers. 1. No significant differences were found in serum levels of CFTM and CFTM-A (an inactive isomer of cefteram (CFTM)) or their urinary excretion levels (concentration, recovery rate) between the group given CFTM-PI in combination with sodium bicarbonate and that given CFTM-PI alone. 2. There were no significant differences in serum levels of CFTM and CFTM-A or their urinary excretion levels (concentration, recovery rate) between the group given CFTM-PI in combination with aluminium hydroxide gel and that given CFTM-PI alone. 3. In contrast, serum levels of CFTM and its urinary recovery rate were significantly less in the group given the drug in combination with cimetidine than in that given a single administration 2-3.5 hours and 2-4 hours after administration, respectively. Clinical considerations remain.

Absorption↗