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Biomedical subjects

S Baba

Publications and source records attributed to S Baba.

At least 541 records · Page 30Linked to original sources
PubMed1990

Natural regulatory mechanisms of insulin degradation by insulin degrading enzyme.

Insulin-degrading enzyme (IDE) accounts for most of the insulin degrading activity in extracts of several tissues and plays an important role in the intracellular degradation of insulin. Using newly developed sandwich radioimmunoassay for rat IDE, this enzyme was detectable in all tissues we examined and liver had the highest level of IDE. The ratio of insulin degrading activity to IDE concentration was roughly the same in liver, brain and muscle, however, twice as high in kidney as compared with other tissues. On the contrary, its degrading activity in these tissue extracts, including kidney, was completely lost after immunoprecipitation of IDE. These results suggest that IDE degrades insulin in the initial step of cleavage and that there are some mechanisms to regulate insulin degrading activity by IDE in the tissues.

Animals↗
PubMed1990

Detection of Epstein-Barr virus genome in benign polyclonal proliferative T cells of a young male patient.

Epstein-Barr virus (EBV) DNA was detected in polyclonal T cells that proliferated transiently in a 21-year-old male (referred to as H.J.) who underwent an apparently benign lymphocytosis (white blood cells, 31 x 10(6)/microL; lymphocyte, 79%) with fever, tonsillar swelling, lymphadenopathy, and hepatosplenomegaly. The symptoms and signs subsided mostly within a month of hospitalization. The major population of the lymphocytes at admission was positive for CD3, CD8 (4/8 ratio, 0.16), WT31, and DR antigen. Eight percent of the leukocytes were too blastoid to be classified as atypical lymphocytes of infectious mononucleosis (IM). The blastoid lymphocytes and the duration and degree of the lymphocytosis and hypergammaglobulinemia appeared inconsistent with IM, whereas the EBV serology indicated either EBV primary infection or a secondary alteration of normal seropositive EBV immunity. The genomic analysis of T-cell receptor beta chain in the peripheral blood mononuclear cells (PBMC) at admission with a C beta probe did not show a monoclonal rearrangement. EBV genome was detected in these cells, using the BamHI W and K probe, but not in the cells after discharge. Analysis of the EBV terminal repeat junctional sequence, using Xho I fragment of the latent membrane protein (LMP) probe binding with the terminus, did not show monoclonal or oligoclonal populations. EBV-associated nuclear antigen (EBNA) was detected in 36% of the PBMC at admission, but not in the later cells. These EBNA-positive cells were found to form rosette with sheep erythrocytes. The PBMC of six acute IM patients contained neither EBV DNA nor EBNA-positive cells. The observations in this case show a unique type of EBV infection in T cells that has not been previously reported.

Adult↗
PubMed1990

Neutrophil chemotactic activity of N-terminal peptides from the calpain small subunit.

On the basis of previous findings that N-acetyl nonapeptide from the human calpain I large subunit has chemotactic activity for neutrophils, a series of peptides with the N-terminal sequence of the calpain small subunit were synthesized and their chemotactic activity was examined. Potent activity was found in N-acetyl tetra, hepta, octa, nona and a larger peptide of 13 residues, although N-acetyl tripeptide showed only weak activity and N-acetyl penta and hexa peptides showed almost no activity. Since the small subunit is identical in calpains I and II, the results indicate that both calpains could be precursor proteins of chemotactic factors for neutrophils.

Amino Acid Sequence↗
PubMed1990

[The effect of neuropeptide Y on the hypothalamic-pituitary-adrenal axis in the dog].

There is increasing evidence that neuropeptide Y (NPY) affects the release of pituitary hormones, including adrenocorticotropic hormone (ACTH). The present study was designed to clarify the mechanism by which NPY activates the hypothalamic-pituitary-adrenal (HPA) axis in the dog. Mongrel dogs were equipped with a chronic cannula allowing intra-third (i.t.v.) or intra-lateral (i.l.v.) cerebroventricular administration. A 1.19 nmol, i.t.v. dose of NPY produced as great an ACTH and cortisol response as did equimolar ovine corticotropin releasing factor (CRF). This action of NPY was dose-dependent and shared by peptide YY (PYY) and pancreatic polypeptide (PP), other members of the PP family peptide. Intravenously (i.v.) administered NPY (1.19-11.9 nmol) was much less potent than i.v. CRF in stimulating ACTH and cortisol secretion. However, i.v. NPY significantly increased plasma ACTH and cortisol concentrations, raising the possibility that NPY may modulate the activity of corticotrophs. We next investigated the possible relationship between NPY and CRF on the HPA axis. Pretreatment with a novel CRF antagonist, alpha-helical CRF9-41 (130.9 nmol i.t.v. or 261.5 nmol i.v.), partly but significantly attenuated the ACTH and cortisol responses to i.t.v. NPY (1.19 nmol). Furthermore, adding a subthreshold dose of i.t.v. NPY (0.119 nmol) to i.t.v. CRF (1.19 nmol) or i.v. NPY (2.38 nmol) to i.v. CRF (0.595 nmol) resulted in the potentiation of CRF-induced ACTH secretion. These results indicate that NPY may activate the HPA axis in concert with CRF probably at hypothalamic and/or pituitary levels. The present findings that NPY evokes ACTH secretion and potentiates the effectiveness of CRF as a secretagogue, together with high concentrations of NPY in the hypothalamus and pituitary portal blood, suggest the NPY is involved in the multihormonal control of ACTH release.

Adrenocorticotropic Hormone↗
PubMed1990

Brain neuropeptide Y in the control of adrenocorticotropic hormone secretion in the dog.

An immunoneutralization technique with specific antibodies was used to explore the role of endogenous neuropeptide Y (NPY) in the adrenocorticotropic hormone (ACTH) release after hypoglycemic stress in the dog. Dogs received injections of rabbit antihuman NPY gamma-globulin (anti-NPY) or normal gamma-globulin (NGG) into the third cerebral ventricle, which was followed by i.v. injection of insulin. Hypoglycemia of a 40% fall in systemic glucose levels occurred in anti-NPY-treated dogs as well as NGG-treated animals. An intraventricular administration of anti-NPY significantly inhibited the ACTH and cortisol release to hypoglycemia, but had no effect on the pancreatic polypeptide (PP) response. These findings suggest involvement by endogenous NPY in the ACTH secretion induced by hypoglycemia.

Adrenocorticotropic Hormone↗
PubMed1990

Determination of the enantiomers of suprofen and [2H3]suprofen in plasma by capillary gas chromatography-mass spectrometry.

A method for the stereoselective assay of the (+)- and (-)-enantiomers of suprofen and [2H3]suprofen in human plasma was developed using gas chromatography-mass spectrometry-selected-ion monitoring. (+/-)-[2H7]Suprofen was used as an internal standard. The method involved diethyl ether extraction and chiral derivatization with S-(-)-1-(naphthyl)ethylamine to form diastereomeric amide. The diastereoisomers were separated on a capillary gas chromatograph-mass spectrometer. Quantitation was achieved by selected-ion monitoring of the quasi-molecular ions of the diastereoisomers. The sensitivity, specificity, accuracy and reproducibility of the method were demonstrated to be satisfactory for application to pharmacokinetic studies of suprofen enantiomers.

Gas Chromatography-Mass Spectrometry↗
PubMed1990

Stable isotope coadministration methodology for the estimation of the fraction of imipramine metabolized to desipramine.

The application of a stable isotope coadministration technique for estimating the fraction (fm) of imipramine (IP) that is converted to desipramine (DMI) is described. Four healthy male subjects received 25 mg of IP-d4 hydrochloride orally with 25 mg of DMI hydrochloride. The plasma concentrations of IP-d4, DMI-d4, and DMI were determined by capillary gas chromatography-mass spectrometry-selected ion monitoring using d8 analogues as internal standards. The fm values, calculated from the ratio of the area under the plasma concentration-time curve of DMI-d4 to that of DMI, varied from 0.54 to 0.85.

Adult↗
PubMed1990

Anti-interleukin 2 receptor antibody attenuates low-dose streptozotocin-induced diabetes in mice.

Recent evidence indicates that activated T cells and macrophages play an important role in the induction of insulitis and diabetes in certain strains of mice treated with multiple subdiabetogenic doses of streptozotocin. In the present study, we treated C57BL/6J mice with five daily doses of 40 mg/ml streptozotocin and examined the prophylactic effect of an anti-interleukin 2 receptor monoclonal antibody (PC61). In mice treated with streptozotocin, interleukin 2 receptor-positive mononuclear cells were shown to infiltrate into the islets and soluble interleukin 2 receptors in the sera were significantly increased compared with control mice. The administration of PC61 to the mice attenuated the insulitis, and diminished interleukin 2 receptor-positive cells from islets and soluble interleukin 2 receptors in the sera. Moreover, the administration of PC61 significantly reduced the development of hyperglycaemia shown in these mice (12.8 +/- 1.1 mmol/l vs 18.5 +/- 0.7 mmol/l, p less than 0.005). As judged by flow cytometric analysis, this antibody did not cause any changes in either spleen cell counts or T cell subsets. Interleukin 2 receptors were expressed on a minor population of spleen cells regardless of treatment with PC61 (STZ + normal rat IgG: 2.1 +/- 0.3%, STZ + PC61: 2.4 +/- 0.3%). Even after stimulation of spleen cells with concanavalin A or alloantigen, interleukin 2 receptor expression was not significantly different between the two groups. Our studies suggest that interleukin 2 receptor-positive activated T cells or macrophages are important in the development of multi-low-dose streptozotocin diabetes and that an anti-interleukin 2 receptor antibody can attenuate this process.

Animals↗
PubMed1990

Importance of retinal pigmentation as a subclinical marker in familial adenomatous polyposis.

Surgery was performed in 35 patients with familial adenomatous polyposis (FAP) from 22 family trees. To clarify retinal pigmentation as an important subclinical marker in patients with FAP, precise retinal examinations were performed in 41 cases (82 eyes), including 23 patients and 18 family members including 12 second-generation and third-generation possible carriers. In 27 patients, precise studies were done on accompanying lesions, and the number of polyps was counted at the time of surgery in each patient in every family tree. The overall incidence of retinal pigmentation in patients was 82.6 percent. The incidence of retinal pigmentation in possible carriers was found to be 50 percent, which is comparable with the calculated expressibility of the polyps. The shape and distribution of pigmentations were classified into two categories--large and small. A total of 1984 control retinal examinations were performed, which revealed only six retinal pigmentations (0.3 percent). In the control group, all pigmentation was solitary and unilateral. No large pigmentations in bilateral eyes were found in the control group. In large pigmentation, the sensitivity and specificity were calculated as 0.652 and 0.999, respectively, and in small pigmentation, the sensitivity and specificity were calculated as 0.783 and 0.997, respectively. Small pigmentation appears to increase in number around the age of the appearance of the polyp. Earliest recognition of the pigmentation in this series was one year of age.

Adenomatous Polyposis Coli↗
PubMed1990

Stable isotope methodology in the pharmacokinetic studies of androgenic steroids in humans.

The use of stable isotopically labeled steroids combined with gas chromatography/mass spectrometry (GC/MS) has found a broad application in pharmacologic studies. Initially, stable isotopically labeled steroids served as the ideal analytic internal standard for GC/MS analysis; however, their in vivo use has expanded and has proven to be a powerful pharmacokinetic tool. We have successfully used stable isotope methodology to study the pharmacokinetic/bioavailability of androgens. The primary advantage of the technique is that endogenous and exogenous steroids with the same basic structure can be differentiated by using stable isotopically labeled analogs. The method was used to examine the pharmacokinetics of testosterone and testosterone propionate, and to clarify the influence of endogenous testosterone. Another advantage of the isotope methods is that steroidal drugs can be administered concomitantly in two formulations (e.g., solution and solid dosage). A single set of blood samples serves to describe the time course of the formulations being compared. This stable isotope coadministration technique was used to estimate the relative bioavailability of 17 alpha-methyltestosterone.

Androgens↗
PubMed1990

Endourologic management of filling defect in renal pelvis: limited value of cold cup biopsy.

A fifty-six-year-old woman underwent transurethral ureterorenoscopy and cold cup biopsy for evaluation of a filling defect of the left renal pelvis. The pathology indicated a benign lesion, and percutaneous resection was done with the nephroresectoscope. However, the pathologic diagnosis of the resected tissue showed it to be transitional cell carcinoma, grade I. Consequently we performed a nephroureterectomy with excision of a cuff of bladder and the nephrostomy tract. Residual tumor was found in deep layer of the renal pelvis. The implication from this case in defining the indications for endourologic management of tumors is considered.

Biopsy↗
PubMed1990

Heterogeneity of islet cell autoantibodies in terms of insulin release from rat islets and insulinoma cells.

The clinical significance of cytoplasmic islet cell autoantibodies (ICA) has been studied since their discovery by Bottazzo et al. in 1974. Some ICAs destroy pancreatic B cells in the presence of complement, whereas others take no part in this destruction. This suggests that islet function varies with the amount of ICA produced. In the present investigation we report the heterogeneity of monoclonal islet cell antibodies produced by one of us in terms of insulin release from isolated rat islets as well as from rat insulinoma cells (RINr).

Adenoma, Islet Cell↗
PubMed1990

Relationship between age and autonomic neuropathy in diabetes mellitus.

The influence of age on diabetic autonomic neuropathy was studied. In the present study autonomic neuropathy was assessed by cardiac beat-to-beat variation during deep breathing (BBV) and pupil area prior to photic stimulus (A1). In the studies on BBV a total of 440 subjects (11-82 years in age) were divided into three groups: those with a duration of diabetes of less than 5 years and without obvious diabetic complications; those with a duration of diabetes of longer than 5 years and with diabetic complications; and non-diabetic, healthy subjects. The relationship between BBV and age was examined in each group. In the studies on A1 a total of 101 subjects (22-75 years in age) were investigated in the same way. The results were as follows: (1) The autonomic nerve function of young diabetics corresponds to that of old non-diabetics in terms of cardiac beat-to-beat variation and pupil area prior to photic stimulus; (2) in young diabetics duration of diabetes and the complications influence the autonomic nerve function; (3) autonomic nerve function is related to age. Age is more influential than duration of diabetes and diabetic complications, especially in the older subjects.

Adult↗
PubMed1990

Heterogeneity of human islet cell antibodies in terms of cross-species reactivity.

There has been no consistent view about the cross-species reactivity of islet cell antibodies (ICA), and no report about their target antigens in the pancreatic islet cells of different species. Therefore, we examined the cross-reactivity of human ICA against rodent pancreatic islet cells, and found at least two types of ICA, one having a comparatively strong cross-reactivity and the other lacking it. Furthermore, using human as well as some rodent pancreatic tissues that had been modified chemically, we came to suspect that the target antigens of ICA were sialic acid residues of glycolipids. Therefore, we suggest that there are at least two types of ICA recognizing sialic acid residues of glycolipids, one reacting with antigen(s) commonly present in human and rat islets, and the other with antigen(s) only present in human islets.

Animals↗
PubMed1990

Possible involvement of cholinergic nicotinic receptor in insulin release from isolated rat islets.

Insulin release is influenced by the autonomic nervous system. Regarding parasympathetic control, previous reports have shown that regulation of insulin release is executed exclusively through muscarinic receptors in the pancreatic islets. In the present study, however, we examined the effect on insulin release at the islet level of various agents affecting the parasympathetic nervous system, especially nicotinic receptor blockers. Pancreatic islets isolated from adult Wistar male rats were incubated with these agents and insulin release in the media was measured. Acetylcholine chloride (10(-5) M), as well as distigmine bromide (10(-6), 10(-5) M), both of which are cholinesterase inhibitors, stimulated insulin release, whereas atropine (5 x 10(-6), 5 x 10(-5) M) suppressed it. On the other hand, serum and IgG from myasthenia gravis patients, containing anti-acetylcholine receptor antibodies, affected insulin release, and alpha-bungarotoxin (10(-9)-10(-7) M), a nicotinic receptor blocker, stimulated insulin release dose-dependently. The present observations suggest that insulin release is influenced by the parasympathetic nervous system, mediated via not only muscarinic but also nicotinic receptors.

Acetylcholine↗