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Biomedical subjects

Y Akutsu

Publications and source records attributed to Y Akutsu.

88 records · Page 5Linked to original sources

Morphological changes of platelets during the process of platelet aggregation in gray platelet syndrome.

Morphological changes of platelets during the process of platelet aggregation in gray platelet syndrome were observed by means of light microscopy, and scanning and transmission electronmicroscopy. Light microscopic examinations showed normal platelets and slightly enlarged, gray colored ones due to a deficiency in alpha-granules by May-Giemsa stain. At the time of maximum aggregation, normal platelets aggregated completely to form a mass by addition of ADP. On the other hand, patient's platelets only aggregated loosely and each platelet could be recognized separately, resembling primary aggregation of normal platelets. When collagen was added, almost no aggregation was noted in the patient's platelets. Scanning electronmicroscopic examinations revealed the same results as seen by light microscopy. Centralization of platelet organelles and almost complete aggregation and degranulation of platelets were noted immediately after 30 sec and 3-4 min after addition of ADP and collagen on the transmission electronmicrographs in normal platelets, whereas most patient's platelets remained to be unchanged. From these results, we concluded that these morphological changes were consistent with the changes of "release abnormalities" as shown in the functional examinations. Although some relationships between alpha-granule deficiency and functional abnormalities are considered, there is no definitive opinion.

Adenosine Diphosphate↗

[Coagulation studies in patients after abdominal surgery].

Coagulation studies were performed in patients who underwent abdominal surgery. One hundred and twenty six patients with cholelithiasis, peptic ulcer and gastric cancer were examined. Although fibrinogen increased up to 560 mg/dl postoperatively, DIC did not occur among these patients, at all. For 30 patients who underwent hepatectomy, esophageal transection or pancreatoduodenectomy, HPT, PT, fibrinogen, platelet count, alpha 2-PI, AT-III, plasminogen and DIC score were investigated until 10 postoperative days. As for 13 patients without liver cirrhosis in this group, deterioration of HPT, PT and AT-III was noted on the second postoperative day, however these parameters improved on the fifth postoperative day and all patients recovered uneventfully. On the contrary, as to patients with liver cirrhosis, changes of coagulation parameters were drastic. Significant decrease of HPT, PT, AT-III, plasminogen and increase of FDP and DIC score were noted after operation and these values deteriorated with time in certain cases. Seven patients out of 17 died of DIC and multiple organ failure. More than half of these patients received Gabexate Mesilate (GM) injection in a dose of 1200 mg/day postoperatively for more than 5 days to prevent DIC. In patients who underwent hepatectomy due to hepatocellular carcinoma with liver cirrhosis, the increase of FDP and DIC score seemed to be inhibited by GM on the fifth postoperative day.

Abdomen↗

Development and characterization of a mouse monoclonal antibody, MoAb HMSA-1, against a melanosomal fraction of human malignant melanoma.

To characterize the biological property unique to melanocytes and to utilize this property to establish laboratory diagnostic tools for malignant melanoma, monoclonal antibody (MoAb) human melanosome-associated antigen-1 (HMSA-1), a mouse monoclonal antibody, was developed against purified melanosomal fractions of human melanoma. MoAb HMSA-1 belongs to an IgG1 (kappa) subclass. Fractionation of cell organelles combined with enzyme linked immunosorbent assay analysis indicated that the antigen(s) reactive with MoAb HMSA-1 is localized in melanosome and endoplasmic reticulum fractions and that it is related to melanosomal protein and its precursor forms. The localization of the antigen in the melanosome and endoplasmic reticulum was also confirmed by immunoelectron microscopy. Characteristically, MoAb HMSA-1 reacted with formalin-fixed and paraffin-processed tissues of melanocytic nevi and malignant melanoma, including amelanotic lesions. It did not react with normal melanocytes, normal tissues and organs from fetuses and adults, or most non-melanocytic tumors. Thus MoAb HMSA-1 identifies the differentiation antigen for the melanosome-associated property in neoplastic melanocytes and is a useful adjunct for immunohistological diagnosis of melanocytic lesions on routine paraffin sections.

Animals↗

Distribution and organelle specificity of melanoma-associated antigens identified by Mo 465.12 in human malignant melanoma.

Mo 465.12 (Mo 465) is a unique monoclonal antibody that detects cytoplasmic antigens highly restricted to the cells of human malignant melanoma (MM). As yet, it is not known which cytoplasmic components are reactive with Mo 465 within MM cells. This study, using the enzyme-linked immunosorbent assay (ELISA) technique, examines the distribution and specificity of Mo 465-reactive proteins in MM tissues that were isolated by cell fractionation and solubilized by a nonionic detergent (Brij 35). Light microscopically, Mo 465 bound strongly to the cytoplasm of MM cells, being localized as patchy or microgranular, but not to the normal epidermal melanocytes. When the cultured MM cells were fractionated, Mo 465 reacted with both soluble and membrane fractions and with the spent culture medium. To further identify the organelle specificity of Mo 465-reactive proteins, metastatic human MM and normal human liver tissues were separated into the fractions of large granules, small granules, Golgi apparatus, mitochondria, rough endoplasmic reticulum (ER), smooth ER, microsomes, and melanosomes. Mo 465-reactive proteins were detected in the fractions of crude homogenate, microsomes, and rough ER of MM tissue, and their reactivities were in parallel to the concentration of solubilized protein. the findings indicate that Mo 465-reactive proteins are localized in rough ER, that they are released into the cytoplasm, and that in the in vitro condition they are shed into the culture medium.

Antibodies, Monoclonal↗

Comparison of the antinociceptive effects of intracerebroventricular injection of kyotorphin, cyclo (N-methyl-Tyr-Arg) and Met-enkephalin in mice.

Intracerebroventricular (i.c.v.) administration of kyotorphin (L-Tyrosine-L-Arginine) or Metenkephalin (Met-ENK) to conscious mice resulted in a dose-dependent antinociceptive effect as measured by three pain tests. Cyclo(N-methyl-L-Tyrosine-L-Arginine) (cyclo NMTA), an analogue of kyotorphin, increased the reaction time in the tail-pressure and tail-flick tests. Both dipeptides also decreased writhing induced by acetic acid. However, the antinociceptive activity of cyclo NMTA was substantially greater than that of kyotorphin or Met-enkephalin. At the maximum effective dose of 62.7 nmol/mouse, this cyclic dipeptide produced a more long-lasting antinociceptive effect than did kyotorphin or Met-enkephalin. Antinociception induced by cyclo NMTA or kyotorphin was significantly reversed by pretreatment with naloxone (2 or 8 mg/kg, i.p.), though naloxone was not as effective an antagonist of the antinociceptive action of these peptides as it was against Met-enkephalin. The results indicate that the antinociceptive effect induced by cyclo NMTA may in part involve the endogenous opioid system in mice.

Analgesia↗

Potentiation of cyclo (N-methyl-Tyr-Arg)-induced antinociceptive activity by thyrotropin-releasing hormone in mice.

The effect of thyrotropin-releasing hormone (TRH) and its metabolite, cyclo(His-Pro) (C.HP), on cyclo(N-methyl-Tyr-Arg) (C.NMTA)-induced antinociception as measured by the tail-pressure test in mice has been examined. C.NMTA-induced antinociception was significantly potentiated by simultaneously intracerebroventricular or intraperitoneal injection of TRH (approximately 20-50%) in a dose-dependent manner, whereas the effect of morphine was not influenced significantly by TRH. C.HP had no significant effect on the antinociceptive response induced by C.NMTA or morphine. It is concluded that the mechanism of C.NMTA-induced antinociception may be involved in TRH neuronal system in the brain.

Analgesics↗

Comparison of the antinociceptive effect between the cyclic dipeptide cyclo[Tyr(Et)-homoarginine] and the linear dipeptide Boc-Tyr(Et)-homoarginine-OMe in rats.

The antinociceptive effect of the cyclic dipeptide cyclo[Tyr(Et)- homoarginine] (C.TEHA) was examined utilizing the tail flick test and the digitus pinching test in rats in comparison with the linear dipeptide Boc-Tyr(Et)-homoarginine-OMe (B.TEHM). Though both dipeptides administered into the lateral, 3rd and 4th cerebroventricles produced antinociceptive effects equipotent to morphine, except for the 4th cerebroventricular administration of B.TEHM, the administration into the spinal subarachnoid space was without effect. The effect of B.TEHM was completely antagonized by the pretreatment of naloxone (i.p.) when administered into the 3rd cerebroventricle where its effect was demonstrated to be the most potent. However, naloxone had no significant effect on C.TEHA administered into the 3rd cerebroventricle in both tests. It was concluded that both dipeptides act on the upper brain stem, especially around the 3rd cerebroventricle. Moreover, it was also thought that the effect of B.TEHM may be involved in the brain opioid system, and that of C.TEHA can be produced via a naloxone-resistant opioid system or a non-opioid system.

Analgesics↗

Antinociceptive effect of centrally administered cyclo(N-methyl-L-Tyr-L-Arg) in the rat.

The tail-flick test was used to test cyclo(N-methyl-L-Tyr-L-Arg) (C.NMTA), kyotorphin (L-Tyr-L-Arg) and morphine for antinociceptive effects following injection into the cerebroventricles (lateral ventricle (VL), third ventricle (V3) and fourth ventricle (V4)) and into the spinal subarachnoid space in the rat. When injected into the VL, V3 and V4, but not into the spinal subarachnoid space, C.NMTA produced a dose-dependent inhibition of the tail-flick response to thermal stimulation. The ED50 values for each site were 61.0 (48.0-77.5), 40.0 (27.4-58.4) and 163.0 (86.7-306.4) nmol/rat, respectively. Behavioral sedation was seen when C.NMTA was injected into the VL, V3 and V4, but not into the spinal subarachnoid space. Kyotorphin was without antinociceptive effect when given by all routes. However, weak sedation was seen after injection into the cerebroventricles. Naloxone (2, 4 and 20 mg/kg), an opiate antagonist, injected intraperitoneally (i.p.) 20 min before C.NMTA injection, did not significantly alter the C.NMTA-induced antinociceptive effect. Additionally, naloxone (2, 4 and 20 mg/kg i.p.) did not abolish the sedative effect of this peptide. It is suggested that C.NMTA produced a naloxone-resistant antinociceptive effect mainly on the upper brain stem.

Analgesics↗

Actions of intracerebroventricular administration of kyotorphin and an analog on thermoregulation in the mouse.

Intracerebroventricular (ICV) administration of kyotorphin (L-Tyr-L-Arg) and cyclo (N-methyl-L-Tyr-L-Arg), its analog, produced significant dose-dependent hypothermic responses in mice at an ambient temperature of 24 degrees C. The hypothermic action of kyotorphin was much greater than that of Met-enkephalin (Met-ENK) but less than that of cyclo NMTA. This action was slightly but not significantly reversed by intraperitoneally administered naloxone (8 mg/kg), an opioid receptor antagonist. Met-ENK utilized as a control peptide in this study also produced a dose-dependent hypothermia which was slightly antagonized by naloxone (8 mg/kg, IP). Thyrotropin releasing hormone (TRH) injected ICV produced hyperthermia dose-dependently. The hypothermia induced by kyotorphin, its cyclic analog and Met-ENK was prevented by a small dose of TRH (0.18 microgram = 0.5 nmol/animal) which by itself had little effect on body temperature. A TRH neuronal system in the brain may explain the mechanism of kyotorphin-induced hypothermia. However, there was little evidence of involvement of opioid receptors. The present study demonstrates a potent action of kyotorphin and its analog on thermoregulation.

Analgesics↗

Exercise-induced ST-segment changes permit prediction of improvement in left ventricular ischemic dysfunction after revascularization: evaluation with positron emission tomographic measurements of regional myocardial blood flow and cardiac output.

BACKGROUND: Prediction of the recovery of left ventricular (LV) ischemic dysfunction after revascularization is important in patients with coronary artery disease (CAD). We investigated whether the improvement in LV ischemic dysfunction after revascularization could be predicted preoperatively by exercise-induced ST-segment changes. METHODS AND RESULTS: Regional myocardial blood flow (RMBF) and cardiac output were measured with nitrogen 13-ammonia positron emission tomography at rest and during low-level exercise in 28 patients with angiographically proven CAD before and after successful revascularization and in 9 normal subjects. Before revascularization, exercise-induced upsloping ST-segment depression <1 mm 80 msec after the J-point was observed in 11 patients (group 1), horizontal depression of 1 to 1.5 mm was observed in 9 patients (group 2), and downsloping depression > or =1.5 mm was observed in 8 patients (group 3). The number of regions of critical CAD was greater in group 3 than in groups 1 and 2 (3.6 +/- 1.4 vs 1.6 +/- 0.7 and 2.2 +/- 1.1, p < 0.001, p < 0.02). Increase of RMBF in regions of critical CAD with exercise was lower in group 3 than in groups 1 and 2 (0.15 +/- 0.01 vs 0.22 +/- 0.01 and 0.18 +/- 0.02 ml/min per gram, p < 0.0001, p < 0.01). After revascularization, RMBF in regions of critical CAD both at rest and during exercise improved in groups 1 (0.49 +/- 0.15 to 0.60 +/- 0.18, 0.70 +/- 0.26 to 0.86 +/- 0.33 ml/min per gram, both p < 0.05) and 2 (0.50 +/- 0.15 to 0.62 +/- 0.19, 0.67 +/- 0.26 to 0.89 +/- 0.31 ml/min per gram, both p < 0.02), but was unchanged in group 3 (0.47 +/- 0.09 to 0.47 +/- 0.15, 0.62 +/- 0.17 to 0.64 +/- 0.23 ml/min per gram, both p = NS). Cardiac output at rest improved in groups 1 (4.98 +/- 0.43 to 5.35 +/- 0.50 L/min, p < 0.02) and 2 (5.08 +/- 0.52 to 5.53 +/- 0.28 L/min, p < 0.02), but was unchanged in group 3 (4.76 +/- 0.48 to 4.88 +/- 0.82 L/min, p = NS). CONCLUSIONS: Our results suggest that marked downsloping ST-segment depression induced by preoperative low-level exercise may predict a lack of improvement in LV ischemic dysfunction after revascularization.

Ammonia↗