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Biomedical subjects

T Hirose

Publications and source records attributed to T Hirose.

At least 739 records · Page 41Linked to original sources

Mechanism of renal excretion of FK027 in dogs and rabbits.

The mechanism of renal excretion of FK027, a new oral cephalosporin, was investigated in dogs and rabbits. In dogs, FK027 was mainly cleared by glomerular filtration, and approximately 50% of the filtered drug was reabsorbed through the proximal tubules. This tubular reabsorption and a high binding ratio to serum protein lead to the exceptionally long serum half-life of the drug. The facts that the clearance ratio of FK027 declined slightly from 58.0 to 49.2% by the addition of probenecid, and that the effect of probenecid was less marked in the stop-flow study, along with no significant change in serum half-life, may account for the scarcely detectable secretion from the renal tubules. In rabbits, the addition of probenecid caused a decrease of the clearance ratio of FK027, disappearance of FK027 peak in the stop-flow study, and extended the serum half-life. These facts are evidence that FK027 is excreted by both tubular secretion and glomerular filtration in rabbits.

Absorption↗

Pharmacokinetics of FK027 in rats and dogs.

The pharmacokinetics of FK027, a new oral cephalosporin, were investigated in rats and dogs and compared with those of cefaclor, cephalexin and amoxicillin. Upon oral administration to either rats or dogs, FK027 produced higher and more sustained serum levels than the reference drugs, hence a longer half-life. After both oral and intravenous administration, the half-life of FK027 in dogs was approximately three fold that in rats. Although the concentrations of FK027 in rat kidney, liver and spleen were lower than those of cephalexin and amoxicillin, they were sustained similarly to the serum levels. The 24-hour urinary and biliary recovery rates of FK027 in rats after oral dosing with 100 mg/kg were 34.1 and 21.9%, respectively. The urinary excretion of FK027 was significantly lower than that of the reference drugs, however, the biliary excretion was higher. In dogs, 23.4 and 0.2% of the given dose of 40 mg/kg of FK027 was excreted in the 24-hour urine and bile, respectively. Bioavailability of FK027 after oral dosing was 38% in rats and 47% in dogs, as calculated from intravenous data. Binding of FK027 to serum protein in all species was the highest of the test drugs: 63% for human, 93% for dog, 61% for rat serum.

Animals↗

Polypoid traumatic neuroma of the gallbladder.

We report a case of polypoid traumatic (amputation) neuroma incidentally found in a gallbladder resected for cholelithiasis. This traumatic neuroma may have developed as the result of injury to the gallbladder during an unsuccessful cholecystectomy performed 20 years previously. Traumatic neuromas are known to arise at the stump of the cystic bile duct after cholecystectomy, but, to our knowledge, there seem to be no previous reports of traumatic neuromas arising in the gallbladder.

Cholecystectomy↗

Record form for eye examination under anesthesia.

We designed a record sheet for eye examination under anesthesia, which is often required in children or babies with suspected ocular pathology and in adults with severe mental retardation. The form is both complete and concise, allows for schematic illustrations, and has proven very helpful in more than 200 examinations performed over the past year.

Adult↗

Bilateral endogenous Escherichia coli endophthalmitis.

Bilateral endogenous endophthalmitis developed in a 68-year-old woman with diabetic ketoacidosis and Escherichia coli septicemia secondary to a urinary tract infection. She was started on large doses of ampicillin, and later, during her hospitalization, she received steroids. When the vitreous cleared, the fundus revealed extensive bilateral occlusion of retinal arterioles that showed the appearance of white threads. The electroretinogram was nonrecordable in both eyes except for a very small a-wave in the left eye when tested with a strong photic stimulus. The septicemia was controlled, but vision did not recover in either eye.

Aged↗

[Solid and cystic tumor of the pancreas--report of a case in a 13-year-old girl].

A case of adenocarcinoma of the body of the pancreas in a 13-year-old girl is reported. The gross appearance of the tumor revealed apparent encapsulation, cystic degeneration and hemorrhagic necrosis. Microscopically, the tumor resembled an islet cell tumor, but immunohistochemically there was no evidence of endocrinic activities. Ultrastructurally, tumor cells contain numerous mitochondria but no secretory or zymogen granules. This peculiar type of tumor usually arises in young women and shows a favorable prognosis. Diagnosis should be established immunohistochemically and ultrastructurally.

Adolescent↗

Laurence-Moon-Bardet-Biedl syndrome: electrophysical and psychophysical findings.

Four cases of Laurence-Moon-Bardet-Biedl syndrome were studied through electrophysiological and psychophysical examinations, and findings were correlated with those of fluorescein angiography. In all cases the macula showed degenerative changes, including a bull's eye appearance. The fundus periphery could be devoid of clumps of pigmentation, but all cases showed profound functional abnormalities that affected the macula and the periphery, impairing both the cone and rod systems equally. Bull's eye macula associated with severe, diffuse functional abnormality of the macula and peripheral retina, along with obesity and mental retardation, help establish the diagnosis of Laurence-Moon-Bardet-Biedl syndrome.

Adolescent↗

[Cooperative phenomena in the membrane potential of parathyroid cells induced by divalent cations].

Membrane potentials of mouse parathyroid cells were measured by means of the intracellular microelectrode method. The membrane potential in external Krebs solution containing 2.5 mM of Ca++ was -23.6 +/- 0.4 mV (mean +/- standard error of mean). The low concentration of Ca++ (1.0 mM) caused hyperpolarization of the membrane potential to -61.7 +/- 0.8 mV. The membrane potential was proportional to the logarithm of the concentration of K ion in the solution of low Ca ion. The concentration of external Na+, C1- and HPO4-- had no effect on the membrane potential. The sigmoidal transition of membrane potentials was induced by the change of Ca ion concentration in the range from 2.5 to 1.0 mM. The change of the membrane potentials in low Ca ion is originated from increase in potassium permeability of the cell membrane. The similar sigmoidal changes of the membrane potentials were observed in the solution containing 4 to 3 mM of Sr ion. The Mg and Ba ion showed smaller effect on the membrane potential. The Goldman equation was extended to divalent ions. Appling the extended membrane potential equation, ratios of the permeability coefficients were obtained as follows: PK/PCa = 0.067 for 2.5 mM Ca++, 0.33 for 1.0 mM Ca++; PK/PSr = 0.08 for 4 mM Sr++ and 0.4 for 3 mM Sr++; PK/PMg = 0.5; PK/PBa = 0.67 for all range of concentration. The Hill constants of Sr ion and Ca ion were 20; the relationship between Sr ion and Ca ion was competitive. The Hill constants of Mg and Ba ion were 1 each. The Hill constant of Ca ion was depend of the temperature; nmax = 20 at 36 degrees C, n = 9 at 27 degrees C, n = 2 at 22 degrees C. The enthalpy of Ca-binding reaction was obtained from the Van't Hoff plot as 0.58 kcal. The activation energies of the K+ permeability increase were obtained from the Arrhenius plots as 3.3 kcal and 4 kcal. The difference, 0.7 kcal, corresponds to the enthalpy change of this reaction, of which value is close to that of the Ca-binding reaction.

Animals↗

Primary structure of beta subunit precursor of calf muscle acetylcholine receptor deduced from cDNA sequence.

Clones harbouring cDNA sequences for the beta subunit precursor of the acetylcholine receptor from calf skeletal muscle have been isolated. Nucleotide sequence analysis of the cloned cDNA has disclosed the primary structure of this polypeptide, which consists of 505 amino acids including a hydrophobic prepeptide of 24 amino acids. The beta subunit of the calf muscle acetylcholine receptor, like the alpha and gamma subunits of the same receptor and the alpha subunit of its human counterpart, exhibits structural features common to all four subunits of the Torpedo electroplax receptor, apparently being oriented across the membrane in the same manner as proposed for the fish receptor subunits. The degree of sequence homology between the calf and Torpedo beta subunits (59%) is comparable to that between the gamma subunits (56%), but is lower than that between the alpha subunits of the two species (81%). Some regions of the beta subunit molecule, including the region corresponding to the putative acetylcholine binding area on the alpha subunit and the region encompassing the clustered putative transmembrane segments M1, M2 and M3, are relatively well conserved between the two species.

Amino Acid Sequence↗

Primary structure of gamma subunit precursor of calf-muscle acetylcholine receptor deduced from the cDNA sequence.

Clones carrying cDNA sequences for the gamma subunit precursor of the acetylcholine receptor from calf skeletal muscle have been isolated. Nucleotide sequence analysis of the cloned cDNA has revealed the primary structure of this polypeptide, which consists of 519 amino acids including a hydrophobic prepeptide of 22 amino acids. The gamma subunit of the calf muscle acetylcholine receptor, like the alpha subunit of the calf as well as the human muscle receptor, shares features characteristic of all four subunits of the Torpedo electroplax receptor, such as the putative disulphide bridge corresponding to that in the alpha subunit proposed as being in close proximity to the acetylcholine binding site and the four putative, hydrophobic transmembrane segments M1-M4. Thus, the calf gamma subunit molecule apparently exhibits the same transmembrane topology as proposed for the fish receptor subunits. The degree of sequence homology between the calf and Torpedo gamma subunits (56%) is lower than that between the alpha subunits of the two species (81%). Some regions of the gamma subunit molecule, including the region encompassing the putative disulphide bridge and the region containing the putative transmembrane segments M1, M2 and M3, are relatively well conserved between the two species.

Amino Acid Sequence↗

Adenocarcinoma of the ciliary body pigment epithelium in a child.

Tumors arising from the pigment epithelium of the ciliary body are rare and most commonly occur in white adults. We describe a tumor that was clinically indistinguishable from a melanoma or medulloepithelioma occurring in a 7-year-old Japanese boy. Three months after initial evaluation, the eye was enucleated because of intractable intraocular pressure elevation and pain. On pathologic examination the tumor was found to fill approximately one third of the anterior chamber. Light microscopic and ultrastructural findings were consistent with an adenocarcinoma of the ciliary body pigment epithelium. To our knowledge, this is the youngest patient described with this tumor.

Adenocarcinoma↗

Molecular cloning and nucleotide sequence of cDNA for mRNA of mitochondrial cytochrome P-450(SCC) of bovine adrenal cortex.

We have isolated cDNA clones of the mRNA for cytochrome P-450(SCC), which catalyzes the side-chain cleavage reaction of cholesterol in bovine adrenal cortex mitochondria, by using synthetic oligonucleotides as probes. Sequence analysis of the cloned cDNAs enabled us to deduce the primary structure of the precursor form of P-450(SCC), which consisted of 520 amino acids and contained an extrapeptide of 39 amino acids at the NH2 terminus. The amino acid sequence from the 40th to 55th amino acid residue in the predicted structure completely coincided with the sequence of the NH2-terminal portion of purified P-450(SCC). The amino acid composition calculated from the predicted structure showed an excellent agreement with that determined with the purified protein. The extrapeptide of the precursor molecule resembles those of a few nuclear-encoded yeast mitochondrial proteins reported so far. Although P-450(SCC) is a component of mitochondria, comparison of its primary structure with those of other forms of cytochrome P-450 shows that P-450(SCC) is structurally more related to microsomal cytochrome P-450s than to a bacterial cytochrome P-450, P-450cam. A homologous sequence observed with various forms of cytochrome P-450 is also highly conserved in the P-450(SCC) molecule. Only two cysteinyl residues are present in the mature form of P-450(SCC), one of which is located in the middle of the conserved sequence, confirming the function of this cysteinyl residue as the fifth ligand of the heme.

Adrenal Cortex↗

Contact points between transcription machinery and the fibroin gene promoter deduced by functional tests of single-base substitution mutants.

An efficient method for oligonucleotide-directed mutagenesis was developed to construct a set of site-specific mutations by using a mixture of oligodeoxyribonucleotides. With this method, as high as 40% of the tested clones turned out to be desired mutants. Seven single-point mutants were isolated in the "TATA" box region of the fibroin gene. In vitro transcription experiments showed that single-base transversions at the TATA box (A----T at position -29, T----A or G at -28, A----T at -27, and A----T at -26) resulted in decreased promoter activities, whereas A----G transitions at positions -24 and -23 had no effect. The initiation site of transcription was normal in three down-promoter mutants at positions -28 and -26, but the A----T transversions at positions -29 and -27 induced an additional transcription start from position +4. Using 10 single-point mutants obtained as above or by nitrous acid-induced mutagenesis, we have prepared a pair of heteroduplex DNAs consisting of a mutant strand and the wild-type one. The molecules heterozygous at positions -30, -21, and -20 showed reduced transcription activities when the noncoding strand bears the mutation, whereas that at position -26 gave a low activity when the coding strand carries the mutation. Both types of heteroduplex at positions -29, -28, -27, and -17 exhibited decreased activities. These results suggest a transcription machinery contact to a major groove of the DNA helix at the TATA box and region of position -20.

Animals↗

Some evidence suggesting the existence of P2 and B3 sites in the active site of bovine pancreatic ribonuclease A.

In order to clarify the subsite structure of ribonuclease A (RNase A), the interactions of pdTp, pAp, dTpdAp, and pdTpdAp with RNase A were investigated by means of kinetic studies and 31P NMR spectroscopy. The pH profile of the 31P NMR spectrum of RNase A-pdTp complex indicated the interaction of the 3'- and 5'-phosphates with RNase A. The signal of 3'-phosphate of pdTp in the presence of RNase A gave a characteristic titration curve indicating the participation of more than 2 ionic groups in the P1 subsite. A similar 31P NMR titration was observed in the case of 5'-phosphate of pAp in the presence of RNase A. The results indicated that pAp interacted with RNase A at the P1, B2, and P2 sites. dTpdAp and pdTpdAp inhibited RNase A action more markedly than dTpdA, indicating the contribution of 3'- and 5'-terminal phosphate groups attached to dTpdA to the affinity of RNase A. The 31P NMR spectra of RNase A-dTpdAp and pdTpdAp complexes excluded the possible interaction of the monoester type phosphate of the inhibitors with the P1 site of RNase A, thus indicating the binding of the 3'-side phosphates with the P2 subsite of RNase A.

Animals↗