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Biomedical subjects

S Hiraga

Publications and source records attributed to S Hiraga.

At least 109 records · Page 6Linked to original sources
PubMed1993

[Pharmacokinetics of MX2, a new morpholino anthracycline, in CSF following intravenous injection].

MX2 x HCl is a new morpholino anthracycline derivative with molecular weight 622.07, and highly lipophilic. In the animal experiments, MX2 was found to cross the blood brain barrier after i.v. injection. Its distribution into the brain was increased by intracarotid injection. In the present study, we examined the distribution of MX2 into the cerebrospinal fluid (CSF) after i.v. administration (5 mg/kg) in normal rabbits. Five min after injection, plasma concentration of MX2 reached to the maximum level (4344.5 ng/ml). CSF concentration of MX2 was at the highest level (75.8 ng/ml) 10 min after injection, and thereafter decreased gradually in parallel with plasma concentration. At 5 hrs after injection, CSF concentration became 26.7 ng/ml, AUC half time of elimination, and mean residence time were 3093.8 ng.hr/ml, 4.57 hrs and 5.10 hrs in plasma and 212.3 ng.h/ml, 5.23 hrs and 7.14 hrs in CSF, respectively. These results indicate that MX2 is able to distribute into CSF after i.v. injection, and expected to be a new anticancer drug for brain and leptomeningeal tumors.

Animals↗
PubMed1993

[In vitro ENU-induced carcinogenesis of rat fetal astroglia--biological character of mutant glial cell].

To investigate glial carcinogenesis in vitro, fetal rat brain cells were cultured and exposed to ENU (approximately 200 micrograms/ml). The cells were passaged weekly thereafter. Morphological changes were observed under the phase contrast microscope. When mutant colonies where the cells lost contact inhibition and grew in a multilayer fashion appeared, the cells were cloned. To assess the biological characters of cells, expression of GFAP, vimentin, A2B5 and p53 product were determined by immunohistochemistry and flow cytometry. Tumor forming ability of the cells was evaluated by both colony forming efficiency in low serum medium (LSM; 2% FBS, 300 cells/100 mm dish) and transplantability to nude mice. Both primary cultured and ENU-treated cells were positive for GFAP and vimentin, but population of A2B5 positive cells was less than 5%, thus indicating that these cells were astroglial in origin. The mutant colonies appeared 7 weeks after ENU treatment. These cells grew rapidly with cell doubling time ranging between 18 to 26 hours, while non-ENU-treated astroglias had a longer cell doubling time (48 to 55 hours). The cloned mutant glial cell lines formed large colonies in LSM (efficiency 20-40%), but astroglial cells did not. The mutant astroglial cells also developed tumors in nude mice. p53 protein was never detected in normal astroglia, however, some glial cells treated by ENU abruptly became p53 positive after several passages. These p53 positive cells formed stratified colonies thereafter. These results indicate that mutant astroglial cells can be induced by a single dose of ENU in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Evaluation of renal graft function with radionuclide dynamic images--application of modified Rutland's analytical method].

An uptake coefficient (UC) is estimated with applying the method proposed by Rutland to the renal dynamic images with 99mTc-diethyltriamine pentaacetate (DTPA). UC estimated with this method is proportional to glomerular filtration rate in the original Rutland's method the cardiac and renal time-activity curves (TAC) were used for input and output functions, respectively. In this paper, our method of estimating an input and output function by applying factor analysis method to renal dynamic images and it's clinical application are presented. In 11 patients, U"s estimated by this modified method revealed good correlations between the UCs and CCr (r = 0.75), between UCs and effective renal plasma flow (r = 0.67), and inverse correlations between UCs and serum creatinine values (r = 0.65). The results showed that UC in this method can be a useful parameter for grafted renal function. This method is simple in technique and applicable for the evaluation of split renal function in renal transplant donors.

Creatinine↗
PubMed1992

Plasmin stimulates the release of dermatan sulfate from vascular smooth muscle cells in culture.

We investigated the effect of plasmin on the release of sulfated glycosaminoglycans (GAG) from cultured vascular smooth muscle cells. Confluent cultures of vascular smooth muscle cells from bovine aorta were labelled with [35S]sulfate and incubated at 37 degrees C for principally 60 min in a serum-free medium in the presence of plasmin. Plasmin at 10 mU/ml (approximately 2.7 micrograms/ml) and above significantly increased the release of [35S]sulfate-labeled GAG (35S-GAG) from the cell layer after a 60 min incubation. A time course study showed that plasmin at 10 mU/ml significantly increased the 35S-GAG release after 20 min and longer. However, plasminogen at 100 mU/ml and below did not cause a significant change of the 35S-GAG release after a 90 min incubation. A characterization of 35S-GAG revealed that plasmin increased both dermatan sulfate and the other 35S-GAG in the medium. Plasmin at 100 mU/ml enhanced the cell detachment significantly but only slightly. From these results, it was suggested that a endogenous thrombin inhibitor heparin cofactor II may be activated in the liquid phase by dermatan sulfate released from plasmin-stimulated vascular smooth muscle cells when the vascular is disrupted and plasma is exposed to extravessel.

Animals↗
PubMed1992

E.coli MukB protein involved in chromosome partition forms a homodimer with a rod-and-hinge structure having DNA binding and ATP/GTP binding activities.

mukB mutants of Escherichia coli are defective in the correct partitioning of replicated chromosomes. This results in the appearance of normal-sized anucleate (chromosome-less) cells during cell proliferation. Based on the nucleotide sequence of the mukB gene, the MukB protein of 177 kDa was predicted to be a filamentous protein with globular domains at the ends, and also having DNA binding and nucleotide binding abilities. Here we present evidence that the purified MukB protein possesses these characteristics. MukB forms a homodimer with a rod-and-hinge structure having a pair of large, C-terminal globular domains at one end and a pair of small, N-terminal globular domains at the opposite end; it tends to bend at a middle hinge site of the rod section. Chromatography in a DNA-cellulose column and the gel retardation assay revealed that MukB possesses DNA binding activity. Photoaffinity cross-linking experiments showed that MukB binds to ATP and GTP in the presence of Zn2+. Throughout the purification steps, acyl carrier protein was co-purified with MukB.

Acyl Carrier Protein↗
PubMed1992

Characterization of high molecular weights of complexes and polymers of cytoplasmic proteins in Escherichia coli.

To search for filamentous polymers of cytoplasmic proteins of Escherichia coli, high molecular weights (> 670 kDa) of protein complexes of cell extracts were fractionated by gel filtration and ion-exchange column chromatography. Proteins of 100, 77 and 52 kDa were co-purified. The 100- and 52-kDa proteins were identified to be pyruvate dehydrogenase and lipoamide dehydrogenase, respectively, by determining the N-terminal amino acid sequences. Experimental results indicate that the 77-kDa protein is identical to dihydrolipoamide acyltransferase. The 100-kDa protein was found to be identical to the 100-kDa protein described by Tomioka (1991), and was related to the formation of filaments and sheets in the presence of 100 mM KCl. However, neither long filaments nor sheets were observed in our sample containing these enzymes, which was not consistent with Tomioka's conclusion. Another 100-kDa protein which forms spirosome-like particles was purified and identified to be alcohol dehydrogenase based on the N-terminal sequence.

Acyltransferases↗
PubMed1992

Identification and characterization of the smbA gene, a suppressor of the mukB null mutant of Escherichia coli.

The mukB gene encodes a protein involved in chromosome partitioning in Escherichia coli. To study the function of this protein, we isolated from the temperature-sensitive mukB null mutant and characterized 56 suppressor mutants which could grow at 42 degrees C. Ten of the mutants also showed cold-sensitive growth at 22 degrees C. Using one of the cold-sensitive mutants as host, the wild type of the suppressor gene was cloned. The cloned suppressor gene complemented all of the 56 suppressor mutations. DNA sequencing revealed the presence of an open reading frame of 723 bp which could encode a protein of 25,953 Da. The gene product was indeed detected. The previously undiscovered gene, named smbA (suppressor of mukB), is located at 4 min on the E. coli chromosome, between the tsf and frr genes. The smbA gene is essential for cell proliferation in the range from 22 to 42 degrees C. Cells which lacked the SmbA protein ceased macromolecular synthesis. The smbA mutants are sensitive to a detergent, sodium dodecyl sulfate, and they show a novel morphological phenotype under nonpermissive conditions, suggesting a defect in specific membrane sites.

Amino Acid Sequence↗
PubMed1992

Intracranial and intraspinal dissemination of an ACTH-secreting pituitary tumor.

A case of a 29-year-old man with an ACTH-producing pituitary tumor disseminated into the subarachnoid space is described. After total adrenalectomy for Cushing's disease at the age of 15, Nelson's syndrome developed. Transsphenoidal adenomectomy at 17 and 21 years of age, pituitary irradiation and medical therapies with sodium valproate, baclofen and bromocriptine failed to lower his plasma ACTH level. Multiple intracranial and intraspinal tumors associated with the symptoms of left hemiparesis developed. The removal of a tumor grown at the level of C1-3 was performed with successful palliation of his symptoms. Histologically, the tumor cells showed sinusoidal, papillary and diffuse patterns with a preponderance of the former over the latter two, although the papillary pattern predominated in the primary pituitary tumor. Immunohistochemical analysis demonstrated most cells to be positive for ACTH in the metastatic tumor as well as the primary adenoma. The clinical significance of his course is discussed with a review of 11 reported cases with metastatic ACTH-producing pituitary tumors.

Adrenocorticotropic Hormone↗
PubMed1992

[Usefulness and safety of bunazosin hydrochloride in neurogenic bladder after prolonged administration].

Bunazosin hydrochloride (Ea-0643), a selective alpha 1-blocker, was administered to 14 patients with neurogenic bladder over prolonged periods of time in order to determine its efficacy and safety. Subjective symptoms were classified into 4 grades, and their response assessed after 12 weeks of treatment. The proportion of patients showing improvement by at least one grade was 50.0% for retarded urination, 16.7% for prolonged urination, 25.0% for urinary stream condition, 25.0% for abdominal pressure at voiding, and 28.6% for residual urine. Objective symptoms were also assessed after 12 weeks of treatment, and a statistically significant improvement was recognized in the volume of spontaneously voided urine, the maximum and mean flow rates on uroflowmetry. It should be noted that both of those flow rates had improved significantly only 2 weeks into the treatment. The degree of improvement in subjective and objective symptoms and the degree of general improvement were all higher at week 12 than at week 2 of treatment. Current knowledge of the mechanism of action of this drug, coupled with the observations made in this study, suggests that, once it has improved the urodynamics, it exhibits a sustained effect for prolonged periods of treatment. However, further studies are warranted concerning the mechanisms of the pharmacological action of the drug from a pathological viewpoint. The proportion of patients in whom Ea-0643 was judged to be useful at 12 weeks of treatment was 41.7%, but when the assessment of 'slightly useful' was taken into consideration, the usefulness rate rose as high as 91.7%. Stomatitis was observed in only one case as a side effect of this drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1992

Plasmapheresis in the Tokai University Medical Center, 1983-1989.

There were 634 instances of plasmapheresis performed on 152 patients in the Kidney Center, Tokai University Hospital, in the seven year period from Jan. 1983 to Dec. 1989. The average number of plasmapheresis treatments per patient was highest for those with neurological and dermatological disease (6.7), followed by liver disease (5.6), and drug intoxication (1.2). The major treatment modalities for the liver, collagen, drug intoxication, hematologic, neurologic and hyperlipidemic disorders were plasma exchange (PE) and double filter plasmapheresis (DFPP). Recently, however, the use of plasma perfusion (PP) and immunoadsorbent plasma perfusion (IPP) has been increasing because of their ability to selectively adsorb various pathologic macromolecules.

Collagen Diseases↗
PubMed1991

Participation of the histone-like protein HU and of IHF in minichromosomal maintenance in Escherichia coli.

The closely related Escherichia coli genes, hupA, hupB, himA and himD (hip), encode the bacterial histone-like protein subunits, HU-2, HU-1, IHF chi and IHF beta, respectively. We report here that E. coli minichromosomes [plasmids (2.7-12.2 kb) with oriC] carrying the intact mioC region were unable to transform mutants deficient in both HU and integration host factor (IHF), whereas they could transform mutants deficient in either HU or IHF as efficiently as the wild-type strain. Minichromosomes carrying a deletion of the proximal part of mioC or a DnaA box just upstream from mioC could not transform cells deficient in IHF, but could transform cells deficient in HU. These results suggested that HU and IHF participate in minichromosomal replication from oriC in E. coli.

Bacterial Proteins↗
PubMed1991

The new gene mukB codes for a 177 kd protein with coiled-coil domains involved in chromosome partitioning of E. coli.

An Escherichia coli temperature sensitive mutant which produces spontaneously normal size anucleate cells at low temperature was isolated. The mutant is defective in a previously undescribed gene, named mukB, located at 21 min on the chromosome. The mukB gene codes for a large protein (approximately 180 kd). A 1534 amino acid protein (176,826 daltons) was deduced from the nucleotide sequence of the mukB gene. Computer analysis revealed that the predicted MukB protein has distinct domains: an amino-terminal globular domain containing a nucleotide binding sequence, a central region containing two alpha-helical coiled-coil domains and one globular domain, and a carboxyl-terminal globular domain which is rich in Cys, Arg and Lys. A 180 kd protein detected in wild-type cell extracts by electrophoresis is absent in mukB null mutants. Although the null mutants are not lethal at low temperature, the absence of MukB leads to aberrant chromosome partitioning. At high temperature the mukB null mutants cannot form colonies and many nucleoids are distributed irregularly along elongated cells. We conclude that the MukB protein is required for chromosome partitioning in E. coli.

Amino Acid Sequence↗