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Biomedical subjects

J Chan

Publications and source records attributed to J Chan.

At least 271 records · Page 15Linked to original sources
PubMed1987

Cyclical edema and hypokalemia due to occult episodic hypercorticism.

Yearly episodes of edema, hypokalemia, anxiety, and depression were found to be due to cortisol and deoxycorticosterone surges secondary to a pituitary adenoma in a woman without any of the usual clinical features of Cushing's syndrome. During the long clinical remissions, she had no recognizable laboratory abnormality. She had two episodes in the year following incomplete transphenoidal pituitary tumor resection, but has had none in 2 yr since receiving radiotherapy. The episodes were caused by mineralocorticoid actions of large ACTH-induced increases in cortisol and deoxycorticosterone secretion. A history of episodic edema and hypokalemia, often attributed in women to surreptitious diuretic abuse, requires a careful search for hypercorticism even in the absence of clinical Cushing's syndrome.

Adenoma↗
PubMed1987

TSH receptor structure.

When solubilized, radiolabelled membrane preparations from FRTL-5 rat thyroid cells are applied to TSH affinity columns, two separate peaks of protein can be eluted by high salts/high pH and low pH buffers, respectively. Immunoprecipitation with monoclonal antibodies to the TSH receptor shows that both peaks contain proteins related to the TSH receptor. If extracts were from cells grown without TSH, one peak has a approximately 300 K and the other a approximately 70 K protein the 70 K protein can be derived from the purified 300 K protein in vitro. A 50 and 20 K protein can be derived from the 70 K protein. If extracts are from cells grown with TSH, the peaks contain a multiplicity of additional immuno-precipitable bands of approximately 200, 175, 130, 90, 50, 20 K etc. These bands are shown to result from the ability of TSH to increase the synthesis (3-4-fold) and degradation (2-3-fold) of the 300 and 70 K proteins. The 300/70 K protein fractions are reactive with monoclonal autoimmune thyroid stimulating antibodies and contain a specific disialo ganglioside. The ganglioside migrates near GM2, i.e., like a lower order ganglioside, and contains fucose. In translation experiments, the monoclonal antibodies to the TSH receptor identify a single mRNA component which produces a protein of approximately 220 K. This protein is not present in thyroid cells which have no functional TSH receptor and which cannot be surface labelled with monoclonal antibodies to the TSH receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The diagnostic accuracy of preoperative CT scanning in the evaluation of pituitary ACTH-secreting adenomas.

Between 1980 and 1985, 35 patients (26 women and nine men) who had coronal CT scans of the sella turcica for suspected ACTH-secreting pituitary adenoma underwent transsphenoidal exploration. The CT examinations were performed with a fourth-generation EMI scanner (CT 7070). The reports of the preoperative CT examinations were compared with the findings at transsphenoidal exploration; in cases with negative CT scans, the decision to operate was based on biochemical evidence of Cushing's disease. In 27 patients, distinct adenomas were found at surgery; in the eight others, total hypophysectomy (four cases) or resection of the central core of the pituitary gland (four cases) was performed. Three patients had macroadenomas, all of which had been identified correctly on preoperative CT scan. Among the 24 microadenomas (less than 10 mm diameter), 14 had been correctly identified on preoperative CT scan while 10 were found in patients with negative scans. The CT examinations in these 35 patients showed probable adenomas in 20 cases, of which 17 (85%) were confirmed at surgery. In the other three cases (15%), adenomas were not found. Among the 15 patients with negative CT scans, 10 (66.6%) had distinct adenomas found at surgery. Coronal CT scans for ACTH-secreting adenomas had a sensitivity of 63%, a specificity of 62.5%, and an overall accuracy rate of 62.8%. Thus, in our experience, CT scanning with current state-of-the-art equipment has poor diagnostic accuracy in Cushing's disease. The possible reasons for this are that most of the adenomas in this series were microadenomas less than 6 mm in diameter, and that ACTH microadenomas probably show almost the same degree of enhancement with contrast medium as the surrounding normal pituitary tissue.

Adenoma↗
PubMed1987

Leu-M1 antigen as a marker of acute nonlymphoid leukemia.

The monoclonal antibody Leu-M1 was originally described as a marker of myeloid/monocytic cells and their precursors. Its usefulness as a myeloid marker in bone marrow specimens was further supported by a limited number of studies using flow cytometry and cell suspensions. Recent reports on its utility in paraffin sections for the diagnosis of acute leukemia have not shown it to be an effective marker of myeloid differentiation. To further evaluate the diagnostic usefulness of Leu-M1 in acute leukemia, we investigated the immunoreactivity of Leu-M1 antigen in a series of 100 plastic-embedded bone marrow biopsies from patients with acute leukemia and compared these results to those obtained in a series of 30 paraffin-embedded specimens. We also investigated the usefulness of neuraminidase pretreatment of sections to enhance the sensitivity of Leu-M1. In plastic sections, we were able to demonstrate positive Leu-M1 staining in 48 of 50 (96%) cases of acute nonlymphoid leukemia (ANL) (FAB classification M1-M5) and 0 of 50 cases of acute lymphocytic leukemia (ALL). Comparatively, Leu-M1 stained positively in 10 of 20 (50%) cases of ANL and 0 of 10 ALL embedded in paraffin. In both plastic and paraffin sections, pretreatment with neuraminidase enhanced the sensitivity of Leu-M1 reactivity, but markedly decreased its specificity. Our study suggests Leu-M1 is both a reliable marker of myelomonocytic differentiation and a useful diagnostic tool in the differentiation of ANL from ALL in plastic sections, and confirms its limited usefulness in paraffin-embedded material.

Antibodies, Monoclonal↗
PubMed1987

High incidence of anticardiolipin antibodies in relatives of patients with systemic lupus erythematosus.

Anticardiolipin antibodies (aCL) were measured in the serum of 22 patients with systemic lupus erythematosus (SLE) and 101 of their first degree relatives. Four patients' sera (18%) were positive. Eight sera from relatives were strongly positive (7.9%). All 8 relatives came from different families, and only 3 of them were related to a positive positive proband. All 8 had clinical and/or other serological abnormalities, compared with only 30% of the aCL negative relatives (p less than 0.05). There were no reports or evidence of thrombosis, thrombocytopenia or spontaneous abortion among the aCL positive relatives. Our data indicate a strikingly higher incidence of aCL among relatives of lupus patients compared with controls. This may be associated with an increased incidence of abnormal clinical or serological findings in these individuals, and constitute a feature of a genetic predisposition to SLE.

Adult↗
PubMed1987

Tumor progression in vitro: the paradoxical natural antibody and complement-selected phenotype.

An in vitro model of tumor progression was employed to investigate the contribution of natural antibody (NAb) to antitumor resistance in vivo. Repeated cycles of L5178Y-F9 and SL2-5 tumor growth in the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) followed by the selective elimination of sensitive variants through complement-dependent syngeneic NAb lysis yielded tumors with a reduced sensitivity to NAb and complement, natural killer (NK) cells and the rapid elimination assay of natural resistance (NR). A dissection of the resistant phenotype revealed a reduction in the binding capacity of complement-fixing NAb and NK cells, a reduced susceptibility to hypotonic lysis and, paradoxically, increased fluorescence-detected NAb binding that correlated inversely with a reduced tumor frequency of threshold subcutaneous tumor inocula. The data distinguish tumor binding of NAb that leads to complement activation from other NAb binding and expose a difference between NR measured as the tumor frequency of threshold tumor inocula versus the rapid radiolabelled tumor elimination assay. Complement-dependent NAb lysis may not contribute significantly to the defense against small tumor foci; however, NAb-mediated processes associated with high fluorescence-detected NAb binding likely provide resistance.

Animals↗
PubMed1986

Behavioral effects of neurotensin in the open field: structure-activity studies.

The behavioral effects of intracerebroventricularly administered neurotensin (NT), some NT fragments and two synthetic NT analogs were investigated in the open field. Each peptide was studied in both a 'novel' (no pre-exposure) and a 'familiar' (with pre-exposure) environmental situation. Neurotensin decreases locomotor activity in the periphery but increases the time spent in the central area of the apparatus. Of the congeners tested, D-Phe11-NT has similar effects to NT whereas the NT fragments were generally inactive. These findings indicate that the intact peptide or stable substituted NT analogs, but not small C- and N-terminal fragments of NT, are behaviorally active after intraventricular administration.

Animals↗
PubMed1986

Demonstration of T-cell dysfunction during acute toxoplasma infection.

Mice were infected with the virulent RH and the relatively avirulent C56 strains of Toxoplasma gondii (TG). The concanavalin A (Con A)-stimulated lymphoproliferative response of these animals and interleukin-2 (IL-2) production by their lymphocytes were assessed 3 and 6 days postinfection. The proliferative response of splenocytes (SC) and T-enriched cells from all infected groups was significantly (P less than 0.05-0.005) depressed. Partial removal of macrophages (m phi) or addition of indomethacin had no effect on the depressed proliferative response of SC from mice infected with the RH strain of TG for 6 days (RH6), and only partially improved that from the other infected groups. IL-2 production of T-enriched cells, obtained by scrupulously removing m phi using sequential adherence of SC to plastic and nylon wool, was markedly decreased in all infected mice. These data indicate that both m phi and T cells are involved in the immunodepression in toxoplasmosis. Except for the RH6 group, the depressed lymphoproliferative responses of all infected groups were entirely reconstituted by exogenous IL-2, but their peak response never reached that of the control group. Therefore, the decreased lymphoproliferation could not be explained solely by a defect in IL-2 production. The proliferative response of the RH6 lymphocytes, in the presence of Con A, was significantly lower than without Con A at each IL-2 concentration added. This suggests the presence of an active suppressor factor inducible by Con A. The RH strain of TG caused a greater degree of immunodepression than the C56 strain, suggesting an association between the virulence of different strains of TG with their ability to immunosuppress.

Acute Disease↗
PubMed1986

Ultrastructural localization of phenylethanolamine N-methyltransferase in sensory and motor nuclei of the vagus nerve.

The ultrastructural localization of phenylethanolamine N-methyltransferase (PNMT), the enzyme used in the final step in the synthesis of adrenaline, was examined in the medial nuclei of the solitary tracts (m-NTS) and in the dorsal motor nuclei of the vagus. Adult rats were anesthetized with Nembutal (50 mg/kg intraperitoneally), and the brains were fixed by vascular perfusion with a solution containing 3.75% acrolein and 2% paraformaldehyde in 0.1 M phosphate buffer. Coronal Vibratome sections were collected through the intermediate portions of the m-NTS at the level of the area postrema. These sections were immunocytochemically labeled employing a rabbit polyclonal antiserum against PNMT and the peroxidase-antiperoxidase method. Immunoreactivity was detected in perikarya, dendrites, and axon terminals in the intermediate portion of the m-NTS. The labeled perikarya were either small (10-15 microns diameter) and oval or large 20-30 microns) with two or more proximal processes. The PNMT-containing dendrites received synaptic input from unlabeled, small (0.5-1.0 microns) and large (2-3 microns) vagal-like afferents as well as from a few terminals, which also showed PNMT immunoreactivity. Axons and axon terminals containing immunoreactive PNMT were more frequently observed than the perikarya or dendrites in the m-NTS and were the only labeled profiles in the dorsal motor nuclei. In both regions the PNMT-labeled terminals formed principally symmetric synapses with unlabeled dendrites. However, a few asymmetric axodendritic and symmetric axosomatic synapses also were detected. These findings indicate that the adrenergic neurons may have multiple, but principally inhibitory, actions on other neurons within cardiovagal portions of baroreflex pathways.

Animals↗
PubMed1986

Antinutritional and biochemical properties of winged bean trypsin inhibitors.

The trypsin inhibitors (TI) of winged bean (Psophocarpus tetragonolobus) isolated by affinity chromatography consisted of 8 protein bands by disc polyacrylamide electrophoresis. All the bands exhibited trypsin inhibitor activity (TIA) with two of the major bands also exhibiting chymotrypsin inhibitor activity (CIA). Electrofocusing separated the TI into 5 protein bands. Two bands with dual TIA/CIA activities had acidic pI while 3 bands with TIA only had alkaline pI. The TI belonged to two molecular weight groups of 20,900 and 16,600, as determined by NaDodSo4 polyacrylamide electrophoresis. Sufficient quantities of TI were isolated by affinity chromatography for rat feeding. Raw winged bean was toxic to rats, causing death after 12 days of feeding. Autoclaved winged bean was not toxic but caused growth inhibition. When fed with casein, the isolated inhibitor caused slight growth inhibition, pancreatic and spleen hypertrophy. It was concluded that TI in winged bean was not primarily responsible for the toxicity of raw winged bean.

Amino Acids↗
PubMed1986

Thyroglobulin-treated blood dendritic cells induce IgG anti-thyroglobulin antibody in vitro in Hashimoto's thyroiditis.

Nonadherent, low density cells of dendritic morphology from the blood of patients with Hashimoto's thyroiditis were treated with human thyroglobulin (Tg) in vitro and cultured under serum-free conditions with autologous patient B cells and irradiated T cells. The patients were selected for high serum levels of IgG antithyroglobulin antibody (anti-Tg IgG). In 2 out of 12 patients the Tg-treatment induced production of anti-Tg IgG in excess of that secreted spontaneously. The amount of antibody produced in vitro (whether increased by Tg or not) correlated with the serum levels of antibody. In 5 patients (including the 2 who responded to Tg) the ratio of supernatant IgG anti-Tg antibody to total IgG was reduced when polyclonal stimulation was done with BCGF (10%). Antibody production was absent in cultures of cells from 2 patients with Graves disease and 4 normal individuals. Thus, in some patients with Hashimoto's thyroiditis, an extrinsically added autoantigen (Tg) on blood-derived dendritic cells can induce IgG anti-Tg antibody in vitro. These data suggest that "professional" antigen-presenting cells may play a role in autoimmune thyroid disease.

Aged↗
PubMed1986

Clear cell sarcoma of the penis.

The case of a 10-year-old boy in whom clear cell sarcoma occurred at the root of the penis is reported. The tumor cells were positive for S-100 protein, and ultrastructural examination showed the presence of melanosomes.

Child↗
PubMed1986

Activity of roxithromycin (RU 28965), a macrolide, against Toxoplasma gondii infection in mice.

Roxithromycin (RU 28965), an ether oxime derivative of erythromycin, protected mice against a lethal infection with the virulent RH strain of Toxoplasma gondii. Therapy begun 24 h before, 2 h after, and 24 h after infection with 2 X 10(3) tachyzoites protected 90, 80, and 50% of the mice, compared with 0% of untreated controls (P less than 0.05 to 0.001). Toxoplasma was isolated in less than 20% of surviving roxithromycin-treated mice.

Animals↗
PubMed1986

Autoradiographic detection of [125I]-secondary antiserum: a sensitive light and electron microscopic labeling method compatible with peroxidase immunocytochemistry for dual localization of neuronal antigens.

We examined whether autoradiographic localization of [125I]-antirabbit immunoglobulin (IgG) was suitable for light and electron microscopic detection of a rabbit antiserum to the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), and whether autoradiographic and peroxidase labeling could be combined for simultaneous immunocytochemical identification of TH and neuropeptides in brain. Adult rat brains were fixed by aortic arch perfusion with acrolein and paraformaldehyde. Vibratome sections of the fixed tissues were incubated with various dilutions of TH antiserum followed by [125I]-secondary IgG. These sections were then directly processed for autoradiography or were incubated with rabbit antiserum to substance P (SP) or methionine [Met5]-enkephalin (ME). These latter sections were then processed by the peroxidase-antiperoxidase (PAP) or conjugated peroxidase methods followed by autoradiography. Exposure periods of 12-20 days for light microscopy or 90 days for electron microscopy yielded substantial accumulations of silver grains even at the highest (1:30,000) dilution of TH antiserum. At this dilution, immunoreactivity for TH was virtually nondetectable by PAP and conjugated peroxidase methods. The differential sensitivities of the autoradiographic versus peroxidase methods provided a means for separable identification of rabbit antiserum to TH and to SP or ME. Ultrastructural analysis of the catecholaminergic neurons in the medial nuclei of the solitary tract (NTS) showed selective cytoplasmic localization of silver grains for [125I]-labeling of TH in perikarya, dendrites, and terminals. Within single thin sections prepared for dual labeling, the peroxidase marker for SP and for ME was differentially localized with respect to autoradiographic labeling of TH.

Animals↗
PubMed1986

New monoclonal antibodies against colon cancer-associated antigens.

Established human colon cancer cells with distinct degrees of differentiation (LoVo, well-differentiated; SW620, intermediate differentiation; and SW1116, poorly differentiated) were used to produce monoclonal antibodies (MoAbs) by standard hybridoma techniques. Specificity was tested by an enzyme-linked immunosorbent assay against human foreskin cells, 7 established human colon cancer lines, a panel of 17 established human tumor lines of different histological origins, purified carcinoembryonic antigen, panels of red blood cells, and a suspension of lymphocytes obtained from 30 random normal donors. MoAb LoVo-F4 3E4/1A1/2E10 (MoAb F4/2E10) reacted with five colon cancer lines and only slightly with MCF-7 cells (estrogen receptor positive breast carcinoma). MoAb LoVo-F4 3E4/1A1/5C10 also reacted with the previous five colon cancer lines and with two gastric cancer lines. A MoAb obtained with a LoVo 3 M KCl membrane extract reacted exclusively with LoVo cells. MoAb SW620-F1 4E5/1A3 reacted with only three colon cancer cell lines and an estrogen receptor negative breast cancer line. MoAb SW1116-F2 1E3/1A1 reacted with four colon carcinoma cell lines, one gastric cancer line, MCF-7 cells, and a lung cancer line. MoAb SW1116-F2 1F3/1B1 reacted intensely with purified carcinoembryonic antigen and with every carcinoembryonic antigen-producing cell line available in our laboratory. Further studies concentrated on the immunoglobulin G1 MoAb F4/2E10. We demonstrated that the purified MoAb did not inhibit binding of MoAb CA19-9 to any colon Ca lines and reacted with fresh human colon carcinoma specimens regardless of whether they were processed by cryostat or paraffin embedding after fixation in formalin for 24 through 96 h. Using the peroxidase-antiperoxidase technique, MoAb F4/2E10 did not react with 23 normal adult and 18 fetal (less than 3 months old) human tissue specimens. When tested on 312 specimens of diverse histological origins and diseases, the MoAb was positive in 57 of 62 colorectal cancers, in 12 of 19 villous adenomas, in 5 of 7 adenomatous polyps, and in 10 of 12 cases of ulcerative colitis. With the exception of 2 of 15 cases of Crohn's disease that were slightly positive, all tissues from nonmalignant diseases (regardless of histological origin) were consistently negative. There was only weak reactivity in 2 of 18 breast cancers, 7 of 21 squamous cell carcinomas, 4 of 27 lung tumors, 1 of 13 kidney carcinomas and in 7 miscellaneous tumors.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1986

Dual peroxidase and colloidal gold-labeling study of angiotensin converting enzyme and angiotensin-like immunoreactivity in the rat subfornical organ.

The cellular relationships between angiotensin converting enzyme (ACE) (EC 3.4.14.1) and angiotensin-like immunoreactivity (AGLI) were examined in the subfornical organ (SFO). Brains from adult rats were fixed by vascular perfusion with 3.75% acrolein and 2% paraformaldehyde. The region containing the SFO was then sectioned on a vibrating microtome. Partially permeabilized sections were immunocytochemically labeled using the peroxidase-antiperoxidase (PAP) or combined PAP and immunogold methods. Goat antiserum to ACE was localized to both non-neuronal and neuronal cells within the SFO. Intense peroxidase immunoreactivity for ACE was associated with the ventricular and basal surface of ependymal cells, the luminal surface of the vascular endothelium, portions of glial membranes exposed to extracellular spaces, and membranous organelles within neuronal processes. Two antisera raised in rabbits against angiotensin II showed peroxidase immunoreactivity within the extracellular spaces and throughout the cytoplasm of numerous axon terminals and a few perikarya and dendrites in the SFO. Axon terminals and dendrites also showed aggregates of AGLI in smooth membranes and vesicles near the plasmalemma. Gold labeling for AGLI was evident in only 6% of the axon terminals and in a smaller number of dendrites containing peroxidase immunoreactivity for ACE. The low incidence of terminals containing both markers appeared to at least partially reflect limited penetration of the 10 nm gold particles. These results provide the first ultrastructural evidence that ACE is associated with the plasmalemma and membranous organelles strategically located for interaction with precursors of angiotensin II or other peptides within the cerebrospinal fluid, extracellular spaces and neurons of the SFO.

Angiotensin I↗