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Biomedical subjects

T Kwan

Publications and source records attributed to T Kwan.

At least 55 records · Page 3Linked to original sources

Human natural resistance-associated macrophage protein: cDNA cloning, chromosomal mapping, genomic organization, and tissue-specific expression.

Natural resistance to infection with unrelated intracellular parasites such as Mycobacteria, Salmonella, and Leishmania is controlled in the mouse by a single gene on chromosome 1, designated Bcg, Ity, or Lsh. A candidate gene for Bcg, designated natural resistance-associated macrophage protein (Nramp), has been isolated and shown to encode a novel macrophage-specific membrane protein, which is altered in susceptible animals. We have cloned and characterized cDNA clones corresponding to the human NRAMP gene. Nucleotide and predicted amino acid sequence analyses indicate that the human NRAMP polypeptide encodes a 550-amino acid residue membrane protein with 10-12 putative transmembrane domains, two N-linked glycosylation sites, and an evolutionary conserved consensus transport motif. Identification of genomic clones corresponding to human NRAMP indicates that the gene maps to chromosome 2q35 within a group of syntenic loci conserved with proximal mouse 1. The gene is composed of at least 15 exons, with several exons encoding discrete predicted structural domains of the protein. These studies have also identified an alternatively spliced exon encoded by an Alu element present within intron 4. Although this novel exon was found expressed in vivo, it would introduce a termination codon in the downstream exon V, resulting in a severely truncated protein. Northern blot analyses indicate that NRAMP mRNA expression is tightly controlled in a tissue-specific fashion, with the highest sites of expression being peripheral blood leukocytes, lungs, and spleen. Additional RNA expression studies in cultured cells identified the macrophage as a site of expression of human NRAMP and indicated that increased expression was correlated with an advanced state of differentiation of this lineage.

Alternative Splicing↗

Bedside assessment of skin-fold thickness. A useful measurement for distinguishing Cushing's disease from other causes of hirsutism and oligomenorrhea.

BACKGROUND: The known catabolic effects of glucocorticoid excess on protein metabolism prompted us to devise a method to assess this measure in reproductive-aged females with Cushing's disease. Since collagen protein is a major component of skin, decreased abundance of this protein should cause a reduction in skin-fold thickness. To determine whether skin-fold thickness is useful as an added tool in the diagnosis of Cushing's disease, we compared this value in female patients with Cushing's disease with those who presented with a similar set of symptoms. METHODS: This open prospective study was conducted in an endocrinology clinic at a tertiary care center. The study population consisted of 88 females in the reproductive age group who presented to the clinic with hirsutism, oligomenorrhea, and/or obesity. Measurement of skin-fold thickness, body mass index, Ferriman-Gallwey index, and serum testosterone were performed in all patients. RESULTS: Skin-fold thickness in the patients with Cushing's disease was 1.5 +/- 0.2 mm (range, 1.0 to 1.8 mm). This value was significantly (P < .01) lower than that in controls or subjects with other disorders that have a similar set of presenting symptoms. CONCLUSIONS: Bedside assessment of skin-fold thickness is an easy, low-cost, and noninvasive test for distinguishing Cushing's disease from disorders with similar presenting symptoms in females of reproductive age. Assessment of skin-fold thickness should be used as an adjunct to current physical and biochemical study of patients with symptoms suggestive of Cushing's disease.

Adolescent↗

Multiple balloon rupture during coronary angioplasty. A case report.

The authors report a case of coronary angioplasty of the left anterior descending artery complicated by multiple balloon rupture. Various balloon types including polyethylene terephthalate and PE 600 (ACS) ruptured at low atmospheric pressure. During balloon rupture, a septal side branch was dissected with severe intimal staining. The authors postulate that a particular lesion morphology was responsible for balloon rupture. Approaches to such lesions using alternative coronary angioplasty techniques and newer technologies are discussed.

Aged↗

Late neovascularization of longstanding left ventricular mural thrombus--a case report.

Serial coronary angiography done in a patient with left ventricular mural thrombus demonstrated abnormal neovascularity from the coronary artery to the left ventricle occurring eight to eighteen months after thrombus formation. This is the first case report describing such late neovascularization of left ventricular mural thrombus. The formation of coronary neovascularity to left ventricular mural thrombus need not occur in the early stage of the thrombus.

Chronic Disease↗

Cardiac tamponade in patients infected with HIV. A report from an inner-city hospital.

Thirty-seven consecutive cases of cardiac tamponade occurring over a 6-year period were retrospectively studied from January 1986 to December 1991 in an inner-city public teaching hospital. All episodes were secondary to medical illnesses. Thirteen (35 percent) of 37 patients had HIV infection. Significant differences (HIV vs non-HIV) in clinical presentation were noted in the following parameters: (1) age (34 +/- 7 years vs 56 +/- 14 years, p < 0.001); (2) febrile presentation (62 percent vs 17 percent, p < 0.02); and (3) presence of pulmonary infiltrates (54 percent vs 17 percent, p < 0.03). All but two patients underwent pericardiocentesis or had operative creation of a pericardial window. Two patients had purulent pericarditis; two patients had tuberculous pericarditis. In the remaining patients, there was no evidence of opportunistic infection or malignancy based on cultures of pericardial fluid and histopathologic analysis of tissue. Six of 13 patients with HIV infection survived to be discharged from the hospital following hospitalization for the illness. We conclude the following: (1) HIV infection is frequently found in patients with cardiac tamponade at inner city hospitals; (2) when young patients present with cardiac tamponade, the coexistence of fever and pulmonary infiltrates is suggestive of underlying HIV infection; and (3) the etiology of the pericardial effusion is not confirmed in the majority of patients with HIV infection.

AIDS-Related Opportunistic Infections↗

Digitalis toxicity caused by toad venom.

A case of toad venom-induced digitalis toxicity is presented. A pause of 13.5 s was noted in the patient taking a Chinese medication which contained toad venom. This is the first case report of clinical digitalis toxicity related to toad venom in Western society.

Aged↗

Systematic underreporting of cutaneous malignant melanoma in Massachusetts. Possible implications for national incidence figures.

An independent tabulation of incidence of cutaneous malignant melanoma in Massachusetts indicates that 12% and perhaps as many as 19% of new cases of cutaneous malignant melanoma in Massachusetts are not recorded in the Massachusetts Cancer Registry, significantly more than the expected 5% (p = 0.0001). The increasing number of nonhospital medical settings in which melanomas can be diagnosed and/or treated appears to account for this discrepancy. We suspect that these findings in Massachusetts also apply to cancer reporting systems in other regions of the United States. We suggest that the true incidence of cutaneous malignant melanoma in Massachusetts, and perhaps in the United States, may be significantly higher than reported.

Humans↗

Transcapillary oncotic pressure in the edema of congestive heart failure.

Tissue fluid and plasma oncotic pressure levels were measured in an unselected group of 13 patients presenting with congestive heart failure. Patients had a mean serum albumin of 3.6 g/dl +/- (SD) 0.35; serum oncotic pressure was 22.23 +/- 1.8 mm Hg; tissue fluid (lower leg) oncotic pressure was 0.985 +/- 0.34 mm Hg. The oncotic pressure gradient between plasma and tissue fluid was 21.25 Hg +/- 1.7. This is about 10 mm Hg greater than delta pi in normal man. The high value in congestive heart failure is a mechanism to protect against the formation of edema. The possible mechanisms responsible for the formation of edema in congestive heart failure are discussed.

Aged↗

Oedema protein concentrations for differentiation of cellulitis and deep vein thrombosis.

The differentiation between cellulitis and deep vein thrombosis was investigated in a series of patients with acutely swollen, painful, red legs. Oedema-fluid protein concentrations (as mean [SD]) were significantly higher in patients with cellulitis than in those with deep vein thrombosis (19.8 g/l [5.0] vs 5.85 g/l [1.6]), and the oncotic pressure of oedema-fluid was also significantly higher in cellulitis (6.3 mm Hg [1.3] vs 2.1 mm Hg [0.6]). In hospitals where phlebography, plethysmography, or doppler ultrasound are not available, measurement of oedema-fluid protein concentrations may be a rapid and inexpensive guide to the cause of a red, swollen leg.

Acute Disease↗

Ratio of Langerhans cells to Thy-1+ dendritic epidermal cells in murine epidermis influences the intensity of contact hypersensitivity.

We have initiated a series of studies in vivo to investigate the physiologic role of Langerhans cells and Thy-1+ dendritic epidermal cells in the development and regulation of contact hypersensitivity. The density of I-A+ Langerhans cells and Thy-1+ dendritic epidermal cells in ammonium thiocyanate-separated epidermal sheets was determined in ten strains of inbred mice using immunofluorescence microscopy with monoclonal anti-I-A and anti-Thy-1 antibodies. Mice of different inbred strains were sensitized by painting the left ear with varying doses of either oxazolone or trinitrochlorobenzene. From five to 20 days after sensitization, groups of mice were challenged with the relevant antigen and the intensity of contact hypersensitivity, as measured by ear swelling, was determined. We then determined whether the intensity and/or duration of contact hypersensitivity in different strains of mice was influenced by the density of Thy-1+ dendritic epidermal cells or the ratio of I-A+ Langerhans cells to Thy-1+ dendritic epidermal cells. We found that there was marked variability in the density of Thy-1+ dendritic epidermal cells and I-A+ Langerhans cells in the ten strains of mice studied. The ratio of I-A+ Langerhans cells to Thy-1+ dendritic epidermal cells ranged from 0.5 in C57BL/10J mice to greater than 22 in A/J and BALB/cByJ mice. When small amounts of contact sensitizers were used to induce contact hypersensitivity (e.g., 20 micrograms of oxazolone or trinitrochlorobenzene), there was consistent strain variability in the intensity of ear swelling. There was a significant correlation between the ratio of I-A+ Langerhans cells to Thy-1+ dendritic epidermal cells and the intensity of contact hypersensitivity (Pearson's correlation coefficient 0.85, p = 0.002). Strains with the highest ratios of I-A+ Langerhans cells to Thy-1+ dendritic epidermal cells had the most ear swelling. There were no consistent differences in the duration of contact hypersensitivity observed among the ten different strains. Our results indicate that Thy-1+ dendritic epidermal cells may play a physiologic role in down-regulating contact hypersensitivity in vivo.

Animals↗

Effects of chlorpromazine and other calmodulin antagonists on phosphatidylcholine-induced vesiculation of platelet plasma membranes.

Dilauroylglycerophosphocholine (C12:0PC)-induced vesiculation of platelet plasma membranes (Kobayashi, T., Okamoto, H., Yamada, J.-I., Setaka, M. and Kwan, T. (1984) Biochim. Biophys. Acta 778, 210-218; Kobayashi, T., Yamada, J.-I., Satoh, N., Setaka, M. and Kwan, T. (1985) Biochim. Biophys. Acta 817, 307-312) was inhibited by chlorpromazine. Preincubation of platelets with chlorpromazine was required for inhibition but incorporation of chlorpromazine into C12:0PC liposomes was not necessary for it, indicating that the observed inhibition of vesiculation was mainly due to the effect of chlorpromazine on platelets and not that on liposomes. The change in platelet membrane fluidity caused by chlorpromazine was not the cause of inhibition of vesiculation. The inhibition of vesiculation by various other calmodulin antagonists was also observed. The inhibitory activities of these calmodulin antagonists and chlorpromazine correspond very well to their abilities to bind to calmodulin. N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) inhibited vesiculation but a structural analogue of it, N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5), had no inhibitory activity. These results suggest the involvement of calmodulin in membrane vesiculation.

Animals↗

Light-induced potential and current across a large bacteriorhodopsin-asolectin planar membrane stabilized on a polyacrylamide gel surface.

A phospholipid bilayer membrane was spread from an organic solvent solution between a polyacrylamide gel surface and an aqueous buffer solution. The membrane was quite similar to the conventional black lipid membrane, but was of a large size and was stable since it was supported on the gel surface. Bacteriorhodopsin, impregnated into the membrane, generated membrane potential and current upon illumination. The induced current was large, and this was attributed to the large area of the present membrane. Remarkable responses of the light-induced potential and current were also observed with a thick layer of organic solvent containing phospholipids. The effects of applied membrane potential, carbonylcyanide-m-chlorophenyl hydrazone (CCCP) and gramicidin were examined on these photoresponses. Steady-state current, which is due to protons flowing through the membrane, was enormously enhanced by applying membrane potential opposite to the photopotential or by adding gramicidin to the membrane-forming solution.

Acrylic Resins↗

Inhibition of platelet aggregation by synthetic phosphatidylcholines: possible involvement of vesiculation of platelet plasma membranes.

Synthetic phosphatidylcholines inhibited thrombin-induced aggregation of rabbit platelets. The inhibitory effect of the phosphatidylcholines increased with an increase in the chain-length of the constituent fatty acids up to 12, and then decreased, and C14:0PC and C16:0PC did not inhibit platelet aggregation. The activity of synthetic phosphatidylcholines as to induction of vesiculation of platelet plasma membranes (Kobayashi, T., Okamoto, H., Yamada, J.-I., Setaka, M. and Kwan, T. (1984) Biochim. Biophys. Acta 778, 210-218) and the inhibitory effect of these phosphatidylcholines on platelet aggregation showed the same dependence on the constituent fatty acids of the phosphatidylcholines. The amounts of phosphatidylcholines required for 50% inhibition of platelet aggregation correspond very well to those required for 15% exfoliation of acetylcholinesterase activity, suggesting that there is a close relationship between platelet aggregation and vesiculation of the platelet plasma membrane. The possible mechanism of inhibition of platelet aggregation by synthetic phosphatidylcholines is discussed.

Acetylcholinesterase↗