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Biomedical subjects

S Ohashi

Publications and source records attributed to S Ohashi.

At least 127 records · Page 7Linked to original sources
PubMed1995

[Clinical study of photodynamic therapy for laryngeal cancer].

Photodynamic therapy (PDT) is an innovative treatment involving the use of a photosensitizer and low powered laser to selectively destroy tumor cells. In the head and neck, its application to laryngeal papilloma, metastatic tumor and oral cancer have been reported but our report on PDT for laryngeal cancer is the only clinical report in Japan. At present, we treat laryngeal cancer by PDT using argon and excimer dye lasers such as the HpD. In the present study, we assessed the utility and safety of PDT and investigated long-term prognosis after this therapy. The subjects were 12 patients with laryngeal cancer who underwent PDT between February 1988 and October 1993. Among them, ten with cancer of the vocal cords underwent PDT as the primary treatment and two underwent PDT because of recurrence after radiotherapy. Under local anesthesia, PDT was performed using a video endoscope (Pentax EB2000). The optimal dose from an argon dye laser was set at 200-500 mW/cm2 of continuous waves for 20 minutes and that from the excimer dye laser was set at 200 J/cm2 of pulse waves (3-4 mJ/pulse, 30-40 Hz). The argon dye laser used was the Fujinon PDT developed by Fuji Photo Optical Co., Ltd. The excimer dye laser used was a product of Hamamatsu Photonics Co., Ltd. 1) Effect of PDT The effect of PDT as a primary treatment for ten patients was classified as CR in eight and PR in two cases, the CR rate being 80.0%. When evaluated only for T1 patients, the results were classified as CR in eight and PR in one. The patient whose response was classified as PR had refused repeated PDT. CR was maintained for five and 13 months in the two patients who underwent PDT as a secondary treatment after radiotherapy. CR was obtained in 83.3% of all patients studied. 2) Duration of the effect of PDT and long-term prognosis The patients were followed up for 14 to 71 months. The longest duration of CR achieved by PDT monotherapy was 65 months. Among the patients who underwent PDT as a primary treatment, one developed local recurrence and underwent radiotherapy. However, the prognosis was uneventful in all other patients. CR after PDT monotherapy was maintained for 42 months in one T3 patient. Two patients with a history of previous treatment thereafter relapsed and underwent total laryngectomy. The larynx could be conserved in 83.3% of all patients. However, it could be conserved in 100% of patients who underwent PDT as a primary treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1994

Alpha-helical assembly of biologically active peptides and designed helix bundle protein.

The formation of alpha-helical assembly by complexing biologically active peptides with de novo designed protein is described. The de novo designed protein described here is a cystine-linked 4-helix bundle protein constructed with 80 amino acid residues and forms a hydrophobic core region surrounded by 4 helices in an aqueous solution. The biologically active peptides, such as melittin and human growth hormone releasing factor, contain the sequences that are able to form amphiphilic helices. These peptides alone do not form the alpha-helix structure in a diluted solution with low ion strength. But on mixing with the designed helix bundle protein, the peptides are strongly bound to the protein with the induction of alpha-helical structure in the biologically active peptides. The content of induced alpha-helix is in accord with that estimated from the amphiphilic sequence. The results mean that a novel architecture composed of alpha-helices is formed. Fluorescent and temperature-scanning measurement revealed that the alpha-helical assembly is constructed with hydrophobic interaction. Also, it is shown by means of fluorescence depolarization that the assembly has a compact globular form corresponding to 1:1 complex.

Amino Acid Sequence↗
PubMed1994

Pituitary adenylate cyclase-activating polypeptide: effects on pancreatic-adrenal hormone secretion and glucose-lipid metabolism in normal conscious dogs.

The effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on plasma insulin, glucagon, catecholamine, cortisol, glucose, triglyceride (TG), free fatty acid (FFA), cholesterol, and cyclic adenosine monophosphate (cAMP) concentrations were examined in unanesthetized normal dogs. A bolus injection of 6 pmol/kg PACAP27 elicited a transient increase in plasma insulin, epinephrine, and norepinephrine concentrations, with a peak value at 2 minutes after injection. Injections of 60 and 600 pmol/kg caused greater increases in these hormone concentrations in a dose-dependent manner. The plasma cortisol concentration was not changed by a bolus injection of 6 pmol/kg PACAP27, and was gradually increased by injections of 60 and 600 pmol/kg. Significant increases were observed from 10 and 5 minutes after the injection of 60 and 600 pmol/kg, respectively. The plasma glucagon concentration was not changed by either 6, 60, or 600 pmol/kg. The plasma glucose concentration decreased with 60 pmol/kg PACAP27 and increased with 600 pmol/kg. The plasma FFA concentration was increased gradually, with a peak value at 10 minutes after the injection, in a dose-dependent manner. The plasma TG concentration was slightly increased with 600 pmol/kg with a peak value at 10 minutes, although plasma cholesterol did not change. The plasma cAMP concentration increased significantly with 600 pmol/kg PACAP27, but not with 6 or 60 pmol/kg. These effects of PACAP27 were observed with a bolus injection of PACAP38 of an equal potency. Infusion of graded doses of PACAP27 (1, 3, and 10 pmol/kg/min every 20 minutes) caused a gradual increase in plasma cortisol, catecholamine, FFA, and cAMP concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Solid-phase synthesis of human osteocalcin by using a gamma-carboxyglutamic acid derivative.

Human osteocalcin, also called bone Gla protein (BGP), consisting of 49 amino acids with two or three gamma-carboxyglutamate residues, was chemically synthesized for the first time by a novel solid-phase peptide synthesis. An L-enantiomer of N-tert-butyloxycarbonyl-gamma,gamma'-dicyclohexyl-gamma-carboxyglutamic acid was designed, prepared and utilized as a monomeric compound and proven to be useful for the solid-phase peptide synthesis of human osteocalcin. The synthesis and optical resolution of the gamma-carboxyglutamic acid (Gla) derivative are first described, followed by the synthesis and characterization of Gla17-human osteocalcin.

1-Carboxyglutamic Acid↗
PubMed1994

Effects of du-zhong leaf extract on serum and hepatic lipids in rats fed a high-fat diet.

We evaluated the effects of Du-Zhong leaf extract on the serum and liver lipids in rats fed a high-fat diet supplemented with animal fat, cholesterol and cholate. The Du-Zhong leaf extract suppressed significantly the high-fat diet-induced increases in total serum cholesterol, serum triacylglycerol and hepatic triacylglycerol but not the total hepatic cholesterol. The Du-Zhong leaf extract also suppressed the high-fat diet induced increases in very-low density lipoprotein and low density lipoprotein without affecting high density lipoprotein cholesterol. These results suggest that Du-Zhong leaf extract may be beneficial for the regulation of hyperlipidemia.

Animals↗
PubMed1994

Structure-activity relationships of glucagon-like peptide-1(7-36)amide: insulinotropic activities in perfused rat pancreases, and receptor binding and cyclic AMP production in RINm5F cells.

To examine the structure-activity relationships in the insulinotropic activity of glucagon-like peptide-1(7-36) amide (GLP-1(7-36)amide), we synthesized 16 analogues, including eight which were designed by amino acid substitutions at positions 10 (Alal0), 15 (Serl5), 16 (Try16), 17 (Arg17), 18 (Lys18), 21 (Gly21), 27 (Lys27) and 31 (Asp31) of GLP-1(7-36)amide with an amino acid of GH-releasing factor possessing only slight insulinotropic activity, and three tentative antagonists including [Glu15]-GLP-1(8-36)amide. Their insulinotropic activities were assessed by rat pancreas perfusion experiments, and binding affinity to GLP-1 receptors and stimulation of cyclic AMP (cAMP) production were evaluated using cultured RINm5F cells. Insulinotropic activity was estimated as GLP-1(7-36)amide = Tyr16 > Lys18, Lys27 > Gly21 > Asp31 >> Ser15, Arg17 > Ala10 >> GRF > [Glu15]-GLP-1(8-36) amide. Displacement activity against 125I-labelled GLP-1(7-36)amide binding and stimulatory activity for cAMP production in RINm5F cells correlated well with their insulinotropic activity in perfused rat pancreases. These results demonstrate that (1) positions 10 (glycine), 15 (aspartic acid) and 17 (serine) in the amino acid sequence of GLP-1(7-36)amide, in addition to the N-terminal histidine, are essential for its insulinotropic activity through its binding to the receptor, (2) the amino acid sequences for the C-terminal half of GLP-1(7-36)amide also contribute to its binding to the receptor, although they are less important compared with those of the N-terminal half, and (3) [Glu15]-GLP-1(8-36)amide is not an antagonist of GLP-1(7-36)amide as opposed to des-His1 [Glu9]-glucagon amide which is a potent glucagon antagonist.

Animals↗
PubMed1994

Regulation of the growth hormone (GH) receptor and GH-binding protein mRNA.

In fasting rats, a transient increase in growth hormone-binding protein (GHBP) mRNA levels was observed after 1 day, in muscle, heart, and liver, but not in fat tissues. The liver GH receptor (GHR) mRNA level was significantly increased after 1 day (but not after 5 days) of bovine GH (bGH) treatment in fed rats. Both the liver GHR mRNA level and the net increment of plasma IGF-I markedly decreased after 5 days of bGH administration in fasting rats. These findings suggest that GHR and GHBP mRNAs in the liver are expressed in a different way and that the expression of GHBP mRNA is regulated differently between tissues, at least in rats. The results also suggest that refractoriness to GH in a sustained fasting state might be beneficial in preventing anabolic effects of GH. In humans, GHR mRNA in lymphocytes, from subjects with either GH-deficiency or acromegaly, could be detected by the reverse transcription-polymerase chain reaction method. In one patient with partial GH insensitivity, a heterozygous missense mutation (P561T) was identified in the cytoplasmic domain of GHR.

Animals↗
PubMed1993

Cholangioscopic extraction of intrahepatic stones associated with biliary strictures using a rendezvous technique.

Two patients with a severe biliary stricture of one intrahepatic duct and associated intrahepatic stones were successfully treated after dilatation of their stricture by a new endobiliary rendezvous technique with the aid of percutaneous transhepatic cholangioscopy (PTCS). The strictured bile duct was approached from a contralateral percutaneous tract via PTCS and from the diseased duct by introducing a guidewire. This guidewire was then extracted through the other side using a PTCS-guided biopsy forceps to form a communication between both sides which could be used as a pathway for subsequent dilatation. Our technique allows the extraction of intrahepatic stones even in the presence of biliary strictures.

Adult↗
PubMed1993

Immunological application of the dihydrofolate reductase handle carrying a small peptide, leucine enkephalin.

The "dihydrofolate reductase (DHFR) handle" [Iwakura, M. et al. (1992) J. Biochem. 111, 37-45; Iwakura, M. & Tanaka, T. (1992) J. Biochem. 111, 638-642] fused with a pentapeptide, leucine enkephalin (LEK), has been applied in immunoassays for LEK and for the preparation of anti-LEK monoclonal antibody. DHFR fused with LEK (DHFR-LEK) was first utilized as an immobilized antigen in an enzyme-linked immunosorbent assay for LEK. By using a commercially available anti-LEK and peroxidase-linked anti-IgG, LEK could be quantified in the range between 0.1 ng/ml and 10 micrograms/ml. By using a commercially available anti-LEK and the DHFR-LEK as an enzyme-labeled antigen, LEK was quantified in the range between 0.1 ng/ml and 1 microgram/ml by monitoring the recovery of the DHFR activity from the immuno-precipitates. By using the DHFR-LEK as an immunogen, three mouse monoclonal antibodies against LEK, but not DHFR, were isolated. All three monoclonal antibodies were of IgG1 kappa type. The large-scale preparation of two of these monoclonal antibodies, designated as anti-LEK-36 and anti-LEK-74, was carried out and their recognition specificities were studied by competitive binding assays. The IC50 values of LEK for the anti-LEK-36 and anti-LEK-74 were 3.74 x 10(-6) and 4.66 x 10(-6) M, respectively. The competitive binding assays showed that recognition specificities of the two monoclonal antibodies were high and restricted to LEK and leucine-enkephalin (sulfated form). These results strongly suggest that the DHFR handle is useful in several immunological applications.

Amino Acid Sequence↗
PubMed1993

Stimulatory effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on insulin and glucagon release from the isolated perfused rat pancreas.

Rat pancreas perfusion was performed to study the effects of pituitary adenylate cyclase activating polypeptide (PACAP) on pancreatic hormone release. Under the perfusate glucose concentration of 5.5 mmol/l, 0.1 nmol/l PACAP27 significantly stimulated both insulin and glucagon release. The degree of stimulation was in a dose dependent manner. The stimulation of insulin release was clearly dependent on the perfusate glucose concentration, when compared with 2.8, 5.5 and 8.3 mmol/l. The potency of PACAP38 on the stimulation of insulin release was greater than that of PACAP27 at 5.5 mmol/l of perfusate glucose concentration, but not at 8.3 mmol/l. No differences for glucagon and cAMP release were found between the two peptides. PACAP's stimulatory effects on insulin and glucagon release were completely abolished by an equimolar and ten times lower concentration of somatostatin, respectively. The physiologic significance of these potent effects of PACAP's islet hormones release must be clarified by further studies.

Analysis of Variance↗
PubMed1993

[The utility of endoscopic ultrasonography (EUS) in endoscopic mucosal resection of early gastric cancer].

The utility of EUS was evaluated in 27 patients with early gastric cancer undergoing endoscopic mucosal resection over the past 2 years. Accuracy of the assessment of depth of cancerous invasion was studied in 16 patients undergoing EUS before endoscopic mucosal resection. Patients showing no changes in the submucosal (sm) layer or below on EUS included 15 with mucosal (m) cancer and one with sm cancer showing very slight infiltration. Seven patients with m cancer, a negative stump, and no ulcer in the cancer focus at endoscopic mucosal resection, were followed up for more than 1 year after endoscopic mucosal resection. On EUS, four patients showed Ul-IIs changes resembling benign ulcers, two showed Ul-IIIs changes and two showed no changes in the sm layer or below. All patients were negative for cancer in follow up biopsies. No lymphadenopathy was observed. EUS was effective in diagnosing the depth of cancerous invasion in patients undergoing endoscopic mucosal resection and also in clarifying changes in the sm and deeper layers during follow up.

Aged↗
PubMed1993

[Examination of cholangiogram of obstructive jaundice using MRI--compared with PTC and ERCP].

PTC and ERCP are most often used in diagnosis of obstructive jaundice. We studied the possibility of clinical diagnosis using MRI in 33 cases of obstructive jaundice. A clinical diagnosis of malignant tumors could be given in 17 cases out of 20 (85%) using MRI if respiratory standstill was possible. An MRI cholangiogram was particularly effective in describing tearful parting bile ducts and was clearer than PTC in describing negative gallbladders. Choledochal stones could be diagnosed in 58% of cases, which was less than the rate for malignant tumors. MRI is not an invasive examination, can be used in diagnosis of obstructive jaundice, and helps in selecting treatment methods such as PTCD and ERBD.

Adult↗
PubMed1993

Effect of heparin on hemagglutination by pseudorabies virus.

Heparin inhibited hemagglutination (HA) by pseudorabies virus (PRV), but not HA by Akabane virus, bovine adenovirus type 7, Fukuoka virus, Getah virus, Japanese encephalitis virus, and parainfluenza virus type 3 belonging to the families Bunyaviridae, Adenoviridae, Rhabdoviridae, Togaviridae, Flavivi-idae, and Paramyxoviridae, respectively. The minimal inhibitory concentration of heparin required to inhibit 8 HA U of PRV ranged from 0.005 to 0.01 U/ml. Mouse erythrocytes failed to combine with the HA inhibitory factor of heparin. On the other hand, mouse erythrocytes treated with heparinase had greatly reduced agglutinability by PRV. Virus-heparin complex formation could be observed by sedimenting heparin with the virus particles.

Animals↗