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Biomedical subjects

G Lee

Publications and source records attributed to G Lee.

At least 451 records · Page 25Linked to original sources

Antigens displayed on murine B lymphocyte precursors.

The surface antigen phenotype of the immediate precursors of clonable B lymphocytes was investigated with conventional alloantisera and monoclonal antibodies directed by B lineage antigens. Ia was demonstrable on B cells, but not their immediate precursors in adult marrow. Adult, but not fetal, B cell precursors were susceptible to lysis with anti-Lyb-2 or anti-Qa. A panel of monoclonal rat antibodies was prepared and placed into categories on the basis of recognition patterns obtained with established cell lines. Of 2 groups that are described here, 1 (typified by antibodies from clone 14.8) detect an antigen that is preferentially expressed on B cells and their precursors, a proportion of antibody-secreting cells, and a subpopulation of peripheral T lymphocytes. Cells that did not display demonstrable amounts of antigen include brain, granulocytes, macrophages, mastocytoma cells, and erythroleukemia cells. A 2nd category of antibodies revealed an antigen that was more widely distributed on hemopoietic cells. Cells capable of quickly maturing into functional, colony-forming B lymphocytes in culture or after transfer to irradiated recipients specifically adhered to 14.8 antibody-coated, polystyrene petri dishes in the cold. Reductions in numbers of stem cells (CFU-s) and myeloid progenitors (CFU-c) by this treatment were minimal. Of particular importance was the fact that these antibodies recognized cells in embryonic liver as well as in adults that were destined to become B lymphocytes. These observations provide new perspective on B lineage precursor heterogeneity and suggest ways of localizing and dissecting some of the earliest events that are critical to development of the humoral immune system.

Alleles↗

Intra-aortic balloon counterpulsation: rationale, application and results.

Intra-aortic balloon counterpulsation is an effective means of reducing myocardial ischemia and supporting the failing circulation. Its therapeutic benefits are the direct result of distolic augmentation and systolic unloading, the former increasing myocardial perfusion and the latter enhancing cardiac performance. Indirect effect include diminution of ischemia by decrease in the determinants of myocardial oxygen demand and improved ventricular function secondary to the decreased ischemia. Intra-aortic balloon counterpulsation is indicated in clinical syndromes related to intractable cardiac ischemia, including myocardial infarction shock and severe left ventricular failure, refractory ischemic pains, and ventricular arrhythmias unresponsive to medical management. It is also of importance in other situations associated with low cardiac output. This therapeutic modality has recently been considered for early use in extensive myocardial infarction to limit cardiac damage and avert complications. Recent technical advances have facilitated the ease and safety of application of intra-aorta balloon counterpulsation. Complication are of low frequency but can be serious and employment of the method is predicated upon consideration of both potential benefits and risks.

Acute Disease↗

Value and limitations of two dimensional echocardiography in assessment of cardiomyopathy.

Primary myocardial diseases have traditionally been classified into congestive, hypertrophic and restrictive varieties. M mode echocardiography has proved extremely valuable in distinguishing congestive cardiomyopathy with major ventricular dilation and poor contractile performance from hypertrophic cardiomyopathy with predominant left ventricular hypertrophy (septum greater than posterior wall) and normal pump performance, and restrictive disorders with symmetric ventricular wall thickening and normal or diminished contractile function. The contributions of two dimensional echocardiography to the evaluation of patients with congestive or restrictive cardiomyopathy have been limited to certain specific situations, such as the recognition of left ventricular mural thrombi. Twenty-five patients with hypertrophic cardiomyopathy were studied to assess two dimensional echocardiography in the evaluation of patients with this disorder. Two dimensional echocardiography indicated that hypertrophy of the interventricular septum is not uniform from apex to base in all patients but may be greatest in the apical, mid or basal third. In addition, the anterior free wall of the left ventricle was involved in the hypertrophic process in approximately 50 percent of patients. Two dimensional echocardiography documented that the location of systolic anterior motion of the mitral valve in patients with hypertrophic cardiomyopathy is most often at the junction of the mitral valve leaflets and chordae tendineae, although the chordae themselves and even th papillary muscles may be involved in this movement. The heterogeneity of these characteristics may enable patients with hypertrophic cardiomyopathy to be classified into subsets of patients in whom meaningful therapeutic and prognostic implications may be derived. Finally, data derived from two dimensional echocardiography have shown that, although the left ventricle in hypertrophic cardiomyopathy conforms in some degree to the configuration of a catenoid, this geometric conformation is unlikely to account for the genesis of this order.

Cardiomegaly↗

Effects of oral pentaerythritol tetranitrate in cardiac failure and angina pectoris. Assessment by hemodynamic measurement and exercise capacity.

Oral pentaerythritol tetranitrate produces sustained beneficial hemodynamic effects in patients with cardiac failure of varied etiology. The principle action is a reduction of elevated left ventricular filling pressure. In a small group of angina patients, the oral nitrate in high dosage resulted in considerable increase in angina-limited exercise capacity compared to placebo for four hours following drug administration. No side effects were associated with ingestion of pentaerythritol tetranitrate in these investigations.

Administration, Oral↗

Nucleotide sequence of a promoter recognized by Bacillus subtilis RNA polymerase.

We report the nucleotide sequence of a promoter recognized by RNA polymerase from the gram-positive bacterium Bacillus subtilis. This promoter, which was isolated from B. subtilis phage SP01 DNA, is homologous to promoters for Escherichia coli RNA polymerase; the sequences of the "-35 region" and the "Pribnow box" were 5'TTGACT and 5'CATAAT, respectively (T is the thymine analog 5-hydroxymethyluracil in SP01 DNA). These sequences each differed by only a single base pair from the preferred sequences for E. coli promoters. Not surprisingly, the SP01 promoter was actively transcribed in vitro by E. coli RNA Polymerase as well as by B. subtilis RNA polymerase.

Bacillus subtilis↗

Nurse practitioners in a jailhouse clinic.

Six primary nurse practitioners were introduced into a large urban jail health service along with supportive organizational changes. The system's primary care volume capacity doubled. The average cost of each patient visit decreased by about one third. The technical quality of primary care improved continuously during a 3-year period of study while patient outcomes, patient satisfaction levels and overall mortality rates remained unchanged. The inmate suicide rate decreased after the introduction of a psychiatrically directed screening and treatment program, and cardiopulmonary resuscitation (CPR) training for correctional officers. Attribution of the decrease awaits further experience. The nurse practitioners delivered primary care equal in technical quality of care provided by medical subspecialty Fellows. A test of clinical knowledge proved to be a good predictor of the technical quality of care delivered by individual graduate nurse practitioners. One measure of the quality of management of illness episodes in the jail clinic correlated weakly with two measures of patient outcome. The addition of nurse practitioners into a well-organized, well-monitored jail health program was a cost-effective means of expanding the program's patient volume capacity. Screening and referral of inmates with high suicide potential, coupled with CPR training for correctional officers, may have been a factor in reducing the inmate suicide rate.

Evaluation Studies as Topic↗

Evaluation of transluminal angioplasty of chronic coronary artery stenosis. Value and limitations assessed in fresh human cadaver hearts.

The possibility of increasing reduced blood flow in atherosclerotic coronary obstruction by catheter balloon dilatation offers a nonsurgical approach to relieve clinical coronary stenosis. To assess the ability of effectively dilating such diseased vessels by transluminal angioplasty, we used the Grüntzig balloon-tipped catheter in 12 fresh human cadaver hearts in which the intervention was performed in 21 noncalcified stenotic areas, including each of the three major coronary arteries. Quantitative coronary arteriography documented decreased obstruction of each lesion; luminal diameter increased 58% (1.9 +/- 0.2 mm to 2.8 +/- 0.3; p less than 0.001) and luminal diameter relative to the most proximal normal coronary segment diminished 61% (46 +/- 4% to 18 +/- 3%; p less than 0.001). Angioplasty was most successfully applied in proximal, discrete, noncalcified lesions of the right and left anterior descending coronaries; calcified, tortuous, middle and distal lesions and the left circumflex coronary were entered with difficulty or unapproachable. Histologic examination revealed microanatomic changes, most often endothelial disruption and atheroma compression, but no serious vascular tears. Dilatation beyond normal coronary diameter caused vessel rupture. This study extends elucidation of the value and limitations of percutaneous transluminal angioplasty in the clinical use of this technique in selected patients for relieving coronary obstruction without surgery.

Arterial Occlusive Diseases↗

Induction of resistant hepatocytes as a new principle for a possible short-term in vivo test for carcinogens.

The induction of resistant hepatocytes in vivo in the rat has been observed with 21 different chemical carcinogens. The resistance was measured by the ability of the cells to proliferate as focal lesions in the presence of an environment that inhibits the original or surrounding hepatocytes from proliferation. This was created by a dietary 2-acetylaminofluorene plus a stimulus for cell proliferation, a single necrogenic dose of CCl4. The foci were readily visualized by staining for gamma-glutamyl transpeptidase activity. With most of the chemicals, a single administration at an appropriate time after partial hepatectomy is efficacious. However, with safrole and dieldrin, three doses over a 36-hr period were required to induce a significant number of foci of resistant hepatocytes. The presumptive preneoplastic nature of the resistant hepatocytes and the possible usefulness of this approach for the development of a new in vivo short-term test system for carcinogens are discussed.

2-Acetylaminofluorene↗

Possible relationship between glycosphingolipids and the formation of metastasis in certain human experimental tumors.

Two tumors, human sarcoma #1 (HS #1) and human epidermoid carcinoma #3 (HEp #3), were cultured on the chorioallantoic membrane of chick embryos. Under experimental conditions, HS #1 does not metastasize, whereas HEp #3 metastasizes extensively to chick embryo lungs and other organs. The glycosphingolipid profiles of these tumors were studied and HEp #3 wad found to contain about 2.5-fold less lipid-bound sialic acid per 100 mg of total lipid extracted than did HS #1, due mainly to smaller levels of monosialoganglioside (3.7-fold) and disialoganglioside (3.8-fold) in HEp #3. The total amount of neutral glycosphingolipids was approximately the same in both tumors, but their profiles differed. Treatment of these tumors with 6,7,8,9-tetrahydro-1-mercapto-1,2,4-triazolo-[4,3-a]quinazolin-5-ol (2.5 mg/egg/tumor) completely inhibited the formation of metastases in HEp #3 and increased the total content of lipid-bound sialic acid in the tumor by 63% (hematoside, monosialoganglioside, and disialoganglioside by 71, 99, and 67%, respectively). No change was seen in the content of lipid-bound sialic acid in HS #1. Treatment of HEp #3 with a smaller dose of te quinazolinol derivative (1.25 mg/egg) caused an average of 88% inhibition of metastasis, with a 37% increase in lipid-bound sialic acid. Another compound, 2,5-diphenylthiazolo-[5,4-d]thiazole (500 microgram/egg), completely inhibited the formation of metastasis and caused a substantial increase in the amount of lipid-bound sialic acid (77%). The data showed the existence of a correlation between the level of gangliosides in HEp #3 and the ability of these tumors to metastasize.

Animals↗

Plasma high density lipoproteins and coronary artery disease.

Plasma lipid samples and other atherosclerosis risk factors were related to presence of extent of coronary artery disease (CAD) in 102 consecutive patients undergoing coronary angiography. Thirty-six were without CAD and 66 had angiographically documented CAD. In CAD, high density lipoprotein (HDL) cholesterol was lower and total cholesterol and low density lipoprotein cholesterol were higher than in subjects without CAD. Further, HDL was inversely related to extent of CAD (number of major obstructed vessels). Moreover, decreased HDL was the single most important determinant of CAD among all atherosclerosis risk factors (more so in females than in males). In addition, reduced plasma enzymatic activity of lecithin:cholesterol acyltransferase (LCAT) correlated with the presence and extent of angiographically shown CAD. These findings document the protective effect of elevated plasma HDL against coronary obstructive disease and suggest this salutary action may be related to LCAT mobilization of cholesterol from atherosclerotic lesions.

Arteriosclerosis↗

Dansylated thyrotropin as a probe of hormone-receptor interactions.

A strongly fluorescent 5-dimethylamino-1-naphthalene sulfonate (dansyl) derivative of bovine thyrotropin has been prepared. The dye-conjugated hormone is bioactive and shares, essentially unchanged, the membrane binding and adenylate cyclase stimulatory activities of the native hormone. Binding of 125I-labeled dansyl-thyrotropin to thyroid plasma membranes is sensitive to inhibition by gangliosides and, as is the case for the binding of 125I-thyrotropin, galactosyl-N-acetylgalactosaminyl[N-acetylneuraminyl-N-acetylneuraminyl]-galactosylglucosylceramide (GDIb) is the most potent binding inhibitor. Gangliosides interact with dansyl-thyrotropin, causing a large increase of the quantum yield and a 5- to 10-nm blue shift of the emission maximum of the hormone-bound naphthalene chromophore; gangliosides cause no change in the fluorescent properties of the free dye. The fluorescence enhancement caused by gangliosides can be specifically reversed by unlabeled thyrotropin. The effect of gangliosides on dansyl-thyrotropin fluorescence is strongly salt-dependent; salts cannot, however, reverse the formation of the dansyl-thyrotropin.ganglioside complex once it has formed. The salt data suggest that the association of the ganglioside with dansyl-thyrotropin is dominated by electrostatic interactions, but that salt-independent, short range interactions, most likely hydrophobic, dominate the dissociation of the dansyl-thyrotropin-ganglioside adduct. Sucrose gradient centrifugation, ultracentrifugation, and fluorescence polarization data indicate that the gangliosides are micellar in nature under the conditions of these experiments. Acid titration of dansyl-thyrotropin causes a marked quenching of dansyl fluorescence which in part reflects dissociation of the hormone into its constituent alpha and beta subunits. In the presence of GDIb, but not N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (GDIa), pH-dependent quenching and subunit dissociation are essentially eliminated. Circular dichroism results and fluorescence polarization studies support the interpretation that the ganglioside interaction causes a conformational change in the thyrotropin molecule. The acid titration data together with differences in the ability of gangliosides to influence the tyrosine fluorescence of the thyrotropin molecule indicate that different gangliosides induce different conformational perturbations in the thyrotropin molecule.

Animals↗