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Biomedical subjects

K Koyama

Publications and source records attributed to K Koyama.

At least 19 recordsLinked to original sources

Expression of the cell surface antigen detected by the monoclonal antibody A7 in pancreatic carcinoma cell lines.

In a previous study, we used a murine monoclonal antibody, A7, against human colon carcinoma as a drug-carrier to treat colorectal cancer. In the present study, we found that MAb A7 also reacted immunohistochemically with 73% of human pancreatic carcinoma cell lines, with the A7 antigen mainly being detected on the cell surface. However, the A7 antigen was found in only 9% of the spent media of these human pancreatic carcinoma cell lines by ELISA. On the other hand, the positive incidence of CA19-9, POA, ferritin, CEA, DU-PAN-2 and SLX in those spent media was 100%, 64%, 64%, 55%, 55% and 36%, respectively. These results suggest that the A7 antigen may only rarely be shed into the sera of pancreatic cancer patients, in which case MAb A7 could be a suitable drug-carrier in targeting chemotherapy for pancreatic cancer patients.

Antibodies, Monoclonal

A prostacyclin analogue reduces free radical generation in heart-lung transplantation.

The mechanism by which prostacyclin acts to prevent in vivo reperfusion injury is still uncertain. This study was therefore undertaken to assess the effect of a stable prostacyclin analogue (OP 41483-alpha-CD [OP]) on oxygen-derived free radicals after heart-lung transplantation. OP was administered to the heart-lung graft through the pulmonary artery for 25 minutes encompassing the reperfusion process. Free radicals were directly measured by electron spin resonance spectroscopy. The radical intensities of pulmonary venous blood were significantly lower in the OP group than in the control group, suggesting that fewer free radicals were generated in the lungs of the OP group. The cardiac and respiratory function were better in the OP group than in the control group. The lung is the primary source of oxygen free radical attack, and the beneficial action of OP on free radical generation is almost exclusively restricted to the lung and does not apply to the heart. This result suggested that OP probably is effective in inhibiting free radical generation from the endothelium.

Adenosine Diphosphate

Antifertility effect of active immunization with ZP4 glycoprotein family of porcine zona pellucida in hamsters.

Female golden hamsters were immunized with solubilized porcine zona pellucida (s-PZP) or ZP4 glycoprotein family isolated from s-PZP by preparative SDS-PAGE. Both antigen preparations induced production of antibodies which reacted not only with porcine zona pellucida but also with the hamster zona pellucida. The hamsters immunized with solubilized porcine zona pellucida mainly produced antibodies reactive to ZP3, while the hamsters immunized with ZP4 mainly produced antibodies reactive to ZP4. The former animals became permanently infertile but the infertility in the latter animals was temporary and they became pregnant later. Histological studies revealed that the ovarian follicles in hamsters immunized with s-PZP were completely destroyed leaving only atrophic follicle-like cell clusters, while in the ovaries of hamsters immunized with ZP4 a number of small follicles with oocytes remained intact. These observations are encouraging for the further characterization of the ZP4 antigens as candidates for the development of a contraceptive vaccine.

Animals

Arachidonic acid metabolites and alpha 2-adrenoceptor-mediated glucagon secretion in rats.

Effects of phospholipase A2 inhibitor, cyclooxygenase inhibitor and lipoxygenase inhibitor on glucagon secretion induced by the alpha 2-adrenergic agonist clonidine were studied in the isolated perfused rat pancreas. The phospholipase A2 inhibitor mepacrine at 25 and 50 mumol/l significantly inhibited glucagon secretion induced by 0.1 mumol/l clonidine (P less than 0.01, respectively), whereas 5 mumol/l mepacrine did not affect clonidine-induced glucagon secretion. Also, both 100 mumol/l acetylsalicylic acid (cyclooxygenase inhibitor) and 100 mumol/l caffeic acid (lipoxygenase inhibitor) significantly inhibited clonidine-induced glucagon secretion (P less than 0.01, respectively), whereas neither 10 mumol/l acetylsalicylic acid nor 10 mumol/l caffeic acid affected clonidine-induced glucagon secretion. None of the drugs at the tested concentrations affected insulin secretion at a glucose concentration of 5.5 mmol/l. These results suggest that not only cyclooxygenase metabolites but also lipoxygenase metabolites are involved in the stimulation of glucagon secretion mediated through the alpha 2-adrenergic receptors in perfused rat pancreas.

Animals

Isolation and mapping of 88 new RFLP markers on human chromosome 8.

To obtain new RFLP markers for construction of a high-resolution map of human chromosome 8, a cosmid library was constructed from a somatic hybrid cell that contained chromosome 8 as the only human component in mouse genomic background. Eighty-eight new RFLP markers were isolated and characterized, and 71 of them were sublocalized to chromosomal bands by fluorescent in situ hybridization (FISH). Of these, 36 were localized to the short arm, 34 to the long arm, and 1 to the centromeric region. Five markers defined VNTR loci. This work represents the first extensive isolation and physical mapping of RFLP markers on human chromosome 8. These new markers will serve as useful resources for linkage mapping of loci for inherited diseases and for efforts to identify a putative tumor suppressor gene(s) on chromosome 8.

Autoradiography

Comparative studies of the antigens recognized by sperm-immobilizing monoclonal antibodies.

Characteristic properties of the antigens recognized by sperm-immobilizing monoclonal antibodies (SI-mAbs) from different sources were compared by ELISA competitive inhibition assay, Western blot analysis, chromatographic analysis, and enzymatic digestion studies. Among 9 SI-mAbs, human mAb H6-3C4 and three mouse mAbs--2C6, 2B6, and 2E5--also possessed strong sperm-agglutinating activity. Binding of human mAb H6-3C4 to sperm was strongly inhibited by the three mouse mAbs (2C6, 2B6, and 2E5), but not by the rat or the other four mouse mAbs. SDS-PAGE revealed that mAb H6-3C4 and three mouse mAbs recognized the same antigen molecules of 15-25 kDa present in both sperm extracts and seminal plasma. Chemical treatments with trifluoromethanesulfonic acid and sodium metaperiodate destroyed the antigen determinants recognized by the above four mAbs, as detected by both ELISA and antibody absorption tests. Western blot analysis revealed that the antigens were susceptible to treatments with papain, proteinase K, and N-glycanase, but resistant to trypsin, V8 protease, and thermolysin. These results indicate that one of the major antigens recognized by mAbs with sperm-immobilizing action may be a sperm membrane-associated glycoprotein of 15-25 kDa and the epitope may involve N-linked oligosaccharides.

Amidohydrolases

Alpha-2 adrenergic agonism stimulates islet glucagon release from perfused rat pancreas: possible involvement of alpha-2A adrenergic receptor subtype.

Although insulin release is known to be inhibited by alpha-2 adrenergic agonism, the effect of alpha adrenergic agonism on islet glucagon release remains controversial. Alpha-2 adrenoceptors are subdivided into alpha-2A and alpha-2B subtypes using receptor binding methods or cloning methodology. This study was designed to confirm the involvement of the alpha-2 adrenoceptor and its subtypes in glucagon release from the isolated, perfused rat pancreas. Both the alpha-2A preferential agonist oxymetazoline and the non-subtype-selective alpha-2 agonist clonidine induced concentration-dependent stimulation of glucagon release, starting at 10(-8) and 10(-7) mol/l, respectively (p < 0.01). In contrast, neither of the two alpha-1 selective agonists, methoxamine and phenylephrine, at concentrations up to 10(-6) mol/l affected glucagon release. Furthermore, the non-subtype-selective alpha-2 antagonist rauwolscine at concentrations of 10(-6) and 10(-5) mol/l and the alpha-1 and alpha-2A selective antagonist WB-4101 at 10(-5) mol/l showed significant antagonism of 10(-7) mol/l clonidine-induced glucagon release versus corresponding controls. Neither the alpha-1 and alpha-2B selective antagonist prazosin nor the alpha-2B preferential antagonist chlorpromazine, at concentrations up to 10(-5) mol/l, antagonized the effects of clonidine. None of the eight drugs, at the concentrations tested, affected insulin release with 5.5 mmol/l glucose. These results suggest that in rats islet glucagon release induced by alpha adrenoceptor agonism is mediated through alpha-2 adrenoceptors, possibly the alpha-2A subtype.

Adrenergic alpha-Agonists

Interstitial nephritis associated with glomerulonephritis in a patient with Hashimoto's disease and idiopathic portal hypertension.

A middle-aged women with hypothyroidism, idiopathic portal hypertension and nephrotic syndrome is presented. This unusual clinical appearance could not be explained as SLE by serological examinations. Pathohistological examinations showed "Banti's liver", Hashimoto's thyroiditis and diffuse proliferative glomerulonephritis with severe tubulo-interstitial nephritis. Immunohistochemical studies revealed IgA deposits in glomeruli. Electron microscopic study disclosed peculiar lucent areas of rarefaction with osmiophilic particles in tubular basement membranes. This tubulointerstitial nephritis was considered to be related to the immunological mechanism involving thyroid gland, liver and kidney disorders. This case thus had a clinically rare combination of these three.

Female

[Evaluation of the timing principle with vecuronium].

We evaluated the usefulness of the timing principle with vecuronium in 60 patients who underwent elective surgery, and divided into two groups according to the dose of vecuronium (0.15 and 0.2 mg.kg-1). First, we studied the interval between vecuronium and thiopental administration in 40 patients. The time after vecuronium administration to onset of clinical muscle weakness was 57.6 +/- 7.8 sec in 0.15 mg.kg-1, and 42.2 +/- 2.2 sec in 0.2 mg.kg-1 group. Then, we made and examined the protocol of the timing principle for the rapid tracheal intubation. Induction of anesthesia with 4-5 mg.kg-1 thiopental was done 40 sec after 0.15 mg.kg-1 in 10 patients, and 30 sec after 0.2 mg.kg-1 vecuronium administration in 10 patients. Intubating conditions were almost excellent 70 sec after thiopental administration. In our study, there were no patients who experienced discomfort during induction. We conclude that the timing principle with vecuronium is useful for rapid-sequence tracheal intubation.

Adult

[Evaluation of the timing principle with small priming doses of vecuronium].

The intubating conditions using the timing principle combined with small priming doses of vecuronium were evaluated in forty patients who underwent elective surgery. They were randomly assigned to one of two groups: 1) timing, 2) timing with priming. In timing group, vecuronium 0.15 mg.kg-1 was administered, and at the onset of clinical muscle weakness, thiopental 4-5 mg.kg-1 was given promptly. Sixty seconds after thiopental, patients were intubated. In the timing with priming group, vecuronium 0.005 mg.kg-1 was administered as priming doses. Four minutes later vecuronium 0.15 mg.kg-1 was given. The administration of thiopental and the intubation were done in the same way as in timing group. The time to onset of clinical weakness after the administration of vecuronium 0.15 mg.kg-1 was significantly shorter in the timing with priming group than that in the timing group (46.1 +/- 4.8 vs. 57.6 +/- 7.8, P < 0.01). There were no significant differences in intubating score, T1, TR, onset time, and duration between the two groups. We conclude that the timing principle combined with small priming doses of vecuronium might be safe and useful for rapid tracheal intubation.

Adult

Familial juvenile nephronophthisis and renal transplantation in two siblings.

Familial juvenile nephronophthisis (FJN) is a hereditary renal disease, characterized by a juvenile onset and the development of medullary cysts and progressive renal damage. The pathogenesis of FJN remains unknown, and at present, no rational therapy other than renal transplantation is available. We describe two cases in siblings in whom there were no extrarenal complications, such as retinopathy or central nervous system involvement. Both patients display juvenile onset of the disease and end-stage renal failure. The brother received a kidney from his father, and the sister received a kidney from her mother. Recurrence of the underlying disease has not so far been found in the transplanted kidney.

Adolescent

Damage and repair of hepatocyte nuclear DNA after hepatic inflow occlusion.

Recent reports emphasize that ischemic tissue damage is caused mainly by superoxide produced at the reperfusion rather than by ischemia itself. In this paper, the damage and repair of hepatocyte nuclear DNA of is investigated using rats with portasystemic shunt. Hepatic inflow was occluded for 30, 60 and two times 30 (with a 10-minute interval) minutes. Extent of DNA damage and repair were measured by nick-translation and 3H-thymidine incorporation, respectively. Superoxide, GOT and endotoxin were also measured. The results are as follows. 1. Sixty minutes of ischemia produced more serious DNA damage of the hepatocyte nucleus and a significant delay in repair as compared with 30 minutes of ischemia. 2. Intermittent ischemia for two times 30 minutes produced milder damage to DNA, and earlier recovery than a single ischemia of 60 minutes. 3. Serum and tissue peroxide increased after reperfusion in 60 minutes and intermittent ischemia, but not after 30 minutes of ischemia. Endotoxin level increased only in 60-minute ischemia. Histological change, neutrophilic cell infiltration, was most prominent in 60-minute ischemia. On the basis of these data, insofar as the duration of ischemia is not so long that cell damage becomes irreversible, damage by superoxide after reperfusion will be negligible. Therefore, intermittent short-term inflow occlusion is preferable in hepatic surgery.

Animals

Postoperative chemotherapy and follow-up program in colon cancer with high serum CEA level.

We present a patient with colon cancer who had a high serum CEA level without detectable liver metastases at surgery. He underwent hepatic arterial infusional chemotherapy for suspicious liver metastasis concomitant with colon resection at the initial operation. He was followed closely by monitoring the serum CEA levels as well as abdominal US and CT. Five months after the first operation, a small but apparent metastatic lesion was detected in the liver, for which curative resection was performed. The importance of postoperative management with chemotherapy for occult metastases in the liver and close follow-up by CEA monitoring is discussed for such a patient.

Adenocarcinoma

[Prednisolone and aspirin therapy for habitual abortion associated with anti-cardiolipin antibody].

Anti-phospholipid antibody syndrome (APS) is characterized by thrombocytopenia, thrombosis and/or abortion. Steroid and aspirin therapy has been reported useful for habitual abortion associated with APS. Eleven patients, whose prior pregnancies resulted in habitual abortion (41 abortions), were received a intentional prednisolone (40 mg/day) and aspirin (81 mg/day) therapy before further pregnancies and both agents were decreased gradually. We maintained prednisolone (10-15 mg/day) and aspirin (40.5 mg/day) during pregnancy period. After the treatment, the outcome of pregnancy was successful in 7 of 10 pregnancies. The weight of newborn infants ranged from 1980 to 2980 g and apgar score ranged from 4 to 9 points. No side effect was observed, and fetal malformation and/or adrenal insufficiency was not recognized in any infants. In conclusion, an intentional prednisolone plus aspirin therapy is useful to prevent habitual abortion in patient with APS.

Abortion, Habitual