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Biomedical subjects

J Asai

Publications and source records attributed to J Asai.

At least 91 records · Page 5Linked to original sources

Islet amyloid polypeptide response to glucose, insulin, and somatostatin analogue administration.

We determined islet amyloid polypeptide (IAPP) response in plasma to oral and intravenous glucose administration and intravenous insulin injection in nondiabetic subjects. Moreover, we studied the effect of somatostatin analogue SMS 201-995 on glucose-induced IAPP secretion in nondiabetic subjects. Plasma IAPP concentration was determined by radioimmunoassay. Oral administration of 75 g glucose (n = 8) significantly increased plasma IAPP levels from 4.5 +/- 0.7 to 14.0 +/- 1.7 pM (P less than 0.01) 60 min after administration. Intravenous administration of 10 g glucose (n = 7) also caused a significant increase in plasma IAPP from 5.0 +/- 0.4 to 11.6 +/- 0.9 pM (P less than 0.01) 5 min after injection. Plasma IAPP significantly decreased from 5.1 +/- 0.4 to 2.9 +/- 0.4 pM (P less than 0.01) 60 min after intravenous insulin injection (n = 8). Pretreatment with SMS 201-995 completely abolished IAPP and insulin secretion to intravenous glucose injection. A significant correlation was found between plasma IAPP and insulin levels in oral and intravenous glucose administration and between plasma IAPP and C-peptide levels during insulin-induced hypoglycemia. These results suggest that IAPP is cosecreted with insulin in response to a glucose load and secretion of IAPP is inhibited by hypoglycemia and somatostatin. IAPP may serve as a novel pancreatic hormone to control carbohydrate metabolism.

Administration, Oral↗

Oncogenicity of the ret transforming gene in MMTV/ret transgenic mice.

We have successfully produced transgenic mice that carry the ret oncogene driven by a mouse mammary tumor virus promoter/enhancer. Mammary and salivary gland adenocarcinomas were developed in a stochastic fashion in these mice. Moreover, premalignant tumors with hyperplastic and dysplastic lesions of Harderian glands and male reproductive tracts frequently occurred at young ages. High expression of the transgene was closely associated with the development of these tumors although the levels of the transgene expression were variable among individuals. In addition, large amounts of phosphotyrosine-containing proteins were detected in cell lysates from mammary and salivary adenocarcinomas by immunoblotting with the anti-phosphotyrosine antibody.

Animals↗

Generation and characterization of monoclonal antibodies against rat microglia and ontogenic distribution of positive cells.

We have generated two mouse IgM monoclonal antibodies against rat microglia. The RMG-1 antibody recognized a 46-kilodalton cell-membrane antigen of ameboid microglia and cross-reacted with perivascular cells, monocytes/macrophages, and capillary endothelial cells of various organs but not with ramified microglia. In the normal brain, RMG-1-positive cells were found in the choroid plexus, periventricular area, corpus callosum, subarachnoid space and white matter of the cerebrum. The RMG-2 antibody recognized a 78-kilodalton cytoplasmic and cell-membrane antigen of ameboid and ramified microglia and cross-reacted with perivascular cells and monocytes/macrophages of various organs but not with endothelial cells. A small number of RMG-2-positive cells were found in the choroid plexus and subarachnoid space on embryonic day 17. On postnatal day 1, RMG-2-positive cells appeared in the periventricular area and corpus callosum and then migrated to the internal capsule and thalamic nucleus. Thereafter, the number of RMG-2-positive cells increased, reaching a maximum on postnatal day 10 to 14, and gradually decreasing by postnatal day 28. These observations show that microglia are cells of monocytic lineage that enter the brain parenchyma late in embryogenesis or early in the postnatal period and lose at least some monocytic antigens to differentiate into ramified microglia. These monoclonal antibodies will provide useful tools to investigate the relation between microglia, perivascular cells, and endothelial cells in the brain and the kinetics of these cells in normal or pathologic conditions.

Aging↗

Establishment of radioimmunoassay for human islet amyloid polypeptide and its tissue content and plasma concentration.

Using a synthetic C- terminal tetradecapeptide of human islet amyloid polypeptide (IAPP), we prepared an antiserum for human IAPP [24-37] and established a highly sensitive radioimmunoassay (RIA) for human IAPP. Analyses of human pancreatic extract using reverse-phase high performance liquid chromatography coupled with the RIA revealed that the antiserum specifically detects human IAPP. The content of IAPP in the pancreas of two non-diabetic patients was 604.0 and 1447.7 pg/mg wet weight, and a small amount of IAPP-immunoreactivity was detected in the stomach, duodenum, and jejunum. The mean plasma concentration of IAPP in 10 normal individuals was 13.5 +/- 4.8 (SD) pg/ml. The RIA established in this study provides a useful tool to elucidate the physiological function of IAPP and its pathophysiological significance in non-insulin-dependent diabetes mellitus (NIDDM).

Adult↗

Isolation and sequence determination of rat islet amyloid polypeptide.

Rat islet amyloid polypeptide (IAPP) was isolated from the pancreata of normal rats by utilizing cross-reactivity of a radioimmunoassay system for human IAPP with rat IAPP. Rat IAPP was a 37-amino acid polypeptide with tyrosine amide at the C-terminus, as was the case with human IAPP. Amino acid sequences of rat and human IAPPs were 84% identical, and the most highly conserved sequences were found in the N- and C-terminal regions. Rat IAPP sequence was also 51% identical to those of alpha and beta rat calcitonin gene-related peptide sequences.

Amino Acid Sequence↗

Observations on the fine structure of interdigitating cell sarcoma.

In this histo-pathological follow-up study of a case of interdigitating cell sarcoma, intracytoplasmic membrane complexes were seen by electron microscopy within the neoplastic cells. These complexes might correspond to the eosinophilic inclusions seen in the tumour cells by light microscopy; they were not identified in the initial lymph node lesion. Recently, these structures have been found to be a variation of microtubuloreticular complexes. To our knowledge, they have not been previously described in interdigitating cell sarcoma. Their significance remains obscure.

Dendritic Cells↗

Histological evaluation of mast cells in rat gastric mucosal lesions induced by compound 48/80.

Repeated intraperitoneal administration of compound 48/80 to rats produced gastric lesions, a decrease in connective tissue mast cells (CTMCs) and an increase in gastric mucosal mast cells (MMCs). The ratio of MMC to CTMC was significantly correlated with lesion formation. A mast cell stabilizer, MAR-99 (50 mg/kg), prevented lesion formation and changes in the mast cells. Omeprazole (20 or 60 mg/kg) significantly reduced the gastric lesions, but mast cell changes persisted. Cimetidine (50 mg/kg) could not inhibit compound 48/80-induced lesions nor a decrease in CTMCs, but did prevent an increase in MMCs. These facts suggest that in compound 48/80-induced gastric lesions chemical mediators released from CTMCs might be trigger factors, while intraluminal gastric acid might be an aggravating factor. Furthermore, the increase in MMCs might be regulated by histamine released from the CTMCs via H2 receptors and have no causal relation to lesions formation.

Animals↗

Interdigitating cell sarcoma. A morphologic, immunohistologic, and enzyme-histochemical study.

A 58-year-old man presented with an unusual sarcoma of the cervical lymph node. The tumor also involved the mesenteric lymph node and jejunum. Tumor cells possessed intracytoplasmic S100 protein, Leu-3a (T4), and HLA-DR antigens. The neoplastic cells also showed membranous ATPase activity. LeuM1, T6, Leu1, Leu2a, B1, lysozyme, and immunoglobulin were not recognized. Their fine structure was similar to that of interdigitating cells. These data are consistent with derivation from lymph node interdigitating reticulum cell.

Antineoplastic Combined Chemotherapy Protocols↗

Distribution of atrial natriuretic polypeptide (ANP)-containing cells in the rat heart and pulmonary vein. Immunohistochemical study and radioimmunoassay.

The distribution of atrial natriuretic polypeptide (ANP) was immunohistochemically surveyed in the rat heart and lung using an antiserum raised against alpha-human ANP. The ANP-immunoreactive cells were seen to be distributed in the atrial walls and proximal portions of the pulmonary vein and venae cavae, but were absent from the aorta, pulmonary arteries, trachea, bronchus, and alveolar cells. The immunoreactive cells were present in a narrow region just beneath the endothelium of the pulmonary vein and vena cavae, and, ultrastructurally and immunocytochemically, were seen to be striated muscle cells with ANP-containing specific granules similar to those seen in atrial cardiocytes. A radioimmunoassay for ANP revealed a content of 604 +/- 51 pg/mg wet weight in the pulmonary vein, and 3343 +/- 1620 pg/mg wet weight in the venae cavae. In addition to the atrial wall, the proximal portion of both the pulmonary vein and venae cavae are suggested to be constituents of an ANP-producing organ.

Animals↗

Developmental expression of C3 receptor on murine epidermal Langerhans cells during ontogeny.

The developmental expression of C3 receptor, an important surface marker of murine epidermal Langerhans cells (LCs), was quantitatively studied using an immunohistochemical technique on epidermal sheets and then compared with developmental expression of Ia antigen and membrane ATPase. Anti-Mac-1 monoclonal antibody associated with CR3 was used for detecting C3 receptor and proved positive for LCs by immunoelectron microscopy. Mac-1 positive (Mac-1+) cells showed quite a different distribution from those of ATPase+ and Ia+ cells. Almost the same number of Mac-1+ and ATPase+ cells were present during the embryonic period. The number of Mac-1+ cells gradually decreased from day 1 to day 5 of postnatal life, after which they increased again. Using the double-labeling technique on epidermal sheets at day 1 of postnatal life, it was shown that Ia+ cells possessed membrane ATPase activity and some Mac-1+ cells expressed Ia antigen. On days 4 and 7 of postnatal life all Mac-1+ cells expressed Ia antigen. These findings suggest that Mac-1 antigen observed during the embryonic period gradually fades after birth and is re-expressed after day 5 of postnatal life.

Adenosine Triphosphatases↗

Neutrophil-derived epoxide, 9,10-epoxy-12-octadecenoate, induces pulmonary edema.

We have observed that neutrophils biosynthesize linoleate epoxide, 9,10-epoxy-12-octadecenoate, and have named it leukotoxin because of its cytotoxic effect. In this experiment, the effect of leukotoxin on the lung was investigated. Acute effect of leukotoxin: Using Wistar rats, leukotoxin (100 mumol/kg) was injected intravenously for the leukotoxin group, and linoleate (100 mumol/kg) for the linoleate group. Physiological saline was injected as the control. Ten min after injection, rats were divided into 3 groups: (1) lungs were isolated, and lung wet weight, and dry weight were measured; (2) lung lavages were performed, and albumin concentration and activity of angiotensin converting enzyme (ACE) were measured; (3) morphological changes were studied by light and electron microscope. After administration of leukotoxin, lung wet weight/body weight ratios and dry weight/wet weight ratios were increased. Albumin concentration and ACE activity in lung lavages were also increased. Pulmonary edema was also confirmed by light microscopic findings. Alveolar epithelial cell damage and endothelium damage were also observed. Linoleate had no significant effect on these biochemical parameters and morphological findings. Subacute effect of leukotoxin: Twelve hr after administration of leukotoxin (50 mumol/kg) or linoleate (50 mumol/kg), the same studies were performed as in the acute experiments. Immediately after administration of leukotoxin, no significant effect was observed. However, 12 hr later similar changes were observed as in the acute experiments. Linoleate did not show any significant effect 12 hr after injection. These results indicate that leukotoxin biosynthesized by neutrophils might be closely related to the genesis of inflammatory edema.

Animals↗

The role of leukotoxin (9,10-epoxy-12-octadecenoate) in the genesis of coagulation abnormalities.

This study was designed to clarify whether or not leukotoxin (9, 10-epoxy-12-octadecenoate), which is biosynthesized by neutrophils, might be involved in the genesis of coagulating abnormalities. Twelve dogs were divided into 2 groups. In the test group (n = 6), 100 mumol/kg of leukotoxin was injected intravenously, and in the control group (n = 6), 100 mumol/kg of linoleate was injected. In each group, a series of blood samples were collected and used for coagulation studies. After the end of the experimental period, a histological study was performed on organs removed from the dogs. In the leukotoxin group, fibrin and fibrinogen degradation products (FDP) was increased time-dependently. Fibrinogen was decreased, and prothrombin time and activated partial thromboplastin time were prolonged in parallel with the increase in FDP. A decrease in number of platelets was also observed. Intravascular coagulation was observed in sections of lung. These data were compatible with a diagnosis of disseminated intravascular coagulation (DIC). No significant changes in these parameters were observed in the linoleate group. Leukotoxin has been confirmed to show antifungal and antibacterial activity, and its production might be a defensive response to infection. Over-production of leukotoxin associated with severe infection might therefore account for infection-induced DIC.

Animals↗

Identification of secretory immunoglobulin A in human sweat and sweat glands.

Secretory immunoglobulin A (sIgA) plays an important role in local immune defense mechanisms. Although skin is always exposed to external antigens, the role of local immune defenses involving sIgA in the skin has not been adequately studied. In order to evaluate the presence of sIgA in sweat, we have measured the concentration of sIgA in human sweat by enzyme immunoassay and have localized the components of sIgA in the sweat glands of human axillary skin. The concentration of sIgA in sweat was found to be 10 times higher in men than in women (13.0 +/- 0.9 micrograms/ml versus 1.6 +/- 0.9 micrograms/ml). Secretory component (SC) was localized immunohistochemically in protein synthetic organelles, such as the perinuclear spaces and Golgi complex, in cytoplasmic vesicles, and along the external surface membranes of mucous cells on the terminal segment of eccrine sweat glands. IgA and J chain were present in plasma cells in the protein synthetic organelles. The luminal aspects of eccrine sweat ducts also strongly express SC, as well as IgA and J chain. Neither SC, IgA, or J chain were identified in epithelial cells of apocrine sweat glands. These findings are consistent with the theory that J chain complexed with dimeric IgA is synthesized in plasma cells and is transported by SC-mediated endocytosis transfer across mucous cells of eccrine sweat glands and thus into sweat.

Adult↗

Two cases of acquired toxoplasmic lymphadenitis. Light and electron microscopic and immunohistochemical studies.

We report two cases of acquired toxoplasmic lymphadenitis, one with toxoplasmic cysts and the organisms of Toxoplasma gondii and the other with the organisms only. These cysts and organisms were observed in paraffin-embedded sections, touch smears and ultrathin sections for electron microscopy. Touch smears were especially valuable for the quick and accurate diagnosis of toxoplasmic lymphadenitis. We also studied immature sinus histiocytosis (ISH) in these cases. The predominant cells of ISH were confirmed to be B lymphocytes immunohistochemically, the majority being positive for polyclonal surface IgM. ISH was observed in the perifollicular and paracortical areas surrounding post-capillary venules (PCV), whereas the sinuses were only partially involved.

Adolescent↗

A case of ovarian granulosa cell tumor with invasive adenocarcinoma of the endometrium. A case report and review of the Japanese literature.

A 47-year-old woman was admitted complaining of irregular uterine bleeding. On surgery, an ovarian tumor was found together with a broad-based polypoid endometrial mass. These lesions were histologically diagnosed as granulosa cell tumor with invasive adenocarcinoma of the endometrium. To our knowledge, only four other cases of granulosa cell tumor with adenocarcinoma of the endometrium have been reported in Japan, although our case was unique in showing invasion to the uterine myometrium.

Adenocarcinoma↗

[Ultrastructural changes in the jejunal mucosa of the dog after dissection of the cranial mesenteric plexus].

Ultrastructural change was investigated in the small intestinal mucosa of dogs after experimental dissection of the cranial mesenteric plexus and/or obstruction of the lymphatics. In group with a combination of dissection of the plexus and obstruction of the lymphatics (Group A): Marked mucosal edema and dilatation of intercellular spaces of epithelial cell were observed after the 6th postoperative hours (POH), and numerous pinocytotic vesicles appeared after 24th POH. After the 5th postoperative days, rough glycocalyx and irregular microvilli were recognized in epithelial cells. As a characteristic change, pinocytotic vesicles fused together and formed a complex. However, no lipid droplet were accumulated in epithelial cells. In group with obstruction of lymphatics (Group B): Epithelial cells were full in lipid droplets. Based on these evidences, it was suggested that diarrhea and nutritional disorder were mainly caused by the disturbance of absorption and water transport in epithelial cells, involving severe pathological changes in their ultrastructure.

Animals↗

[A case of ovarian granulosa cell tumor with invasive adenocarcinoma of the endometrium].

A case of an ovarian granulosa cell tumor with an invasive adenocarcinoma of the endometrium, and a review of the relevant Japanese literature is reported. A 47-year-old woman was admitted to Ichinomiya Citizens' Hospital complaining of irregular uterine bleeding. On operating, an ovarian tumor was found with a broad-based polypoid mass extending into the endometrium. These lesions were histologically diagnosed as a granulosa cell tumor with an invasive adenocarcinoma of the endometrium. We have found 4 cases of a granulosa cell tumor with adenocarcinoma of the endometrium in the Japanese literature and have determined that our case with an endometrial cancer showing an invasion to the myometrium of the uterus is unique among previously reported cases.

Adenocarcinoma↗

Presence of atrial natriuretic polypeptide in the pulmonary vein and vena cava.

Striated muscle cells and storage granules observed in the atria were found in main branches of the pulmonary veins and superior and inferior venae cavae of the rat, pig, and ox. The presence of atrial natriuretic polypeptide (ANP) in these veins was examined by reverse-phase high-performance liquid chromatography coupled with a radioimmunoassay for ANP. The veins contained 0.6 to 8.0 ng ANP/mg wet tissue with the major molecular form being gamma-ANP. ANP was detected in the peripheral lung tissue in a small quantity, but was not detected in the pulmonary artery. The identification of gamma-ANP and storage granules stained with an anti-ANP antiserum in the pulmonary vein and vena cava suggest that the veins may participate in regulating volume status, blood pressure, and cardiovascular homeostasis through the release of ANP.

Animals↗