Search PubMed⌕ Search

Biomedical subjects

G Lee

Publications and source records attributed to G Lee.

At least 325 records · Page 18Linked to original sources
PubMed1988

Corticotropin releasing factor and amphetamine exaggerate partial agonist properties of benzodiazepine antagonist Ro 15-1788 in the conflict test.

The central nervous system stimulants corticotropin releasing factor (CRF) and amphetamine were administered in combination with the benzodiazepine ligands Ro 15-1788 and FG 7142 in order to assess their benzodiazepine agonist and antagonist receptor properties in an operant conflict test in rats. Ro 15-1788, which was without behavioral activity in this test when given alone, reversed the suppression of punished responding produced by CRF and amphetamine in a dose-dependent manner. Chlordiazepoxide, which produced a release of punished responding by itself, also reversed the suppression of punished responding produced by CRF but not that of amphetamine. The benzodiazepine inverse agonist FG 7142, in contrast, enhanced the rate suppressing actions of both CRF and amphetamine. In a locomotor activity test, Ro 15-1788 failed to block the locomotor activation observed with CRF and amphetamine. The results suggest that "anxiety" or stress-enhancing compounds may enhance the partial agonist properties of Ro 15-1788 in certain test situations.

Amphetamine↗
PubMed1988

Hazards of angioscopic examination: documentation of damage to the arterial intima.

The fiberoptic scope is increasingly used in the coronary and peripheral arteries to quantitate the degree and type of arterial obstructive disease and to inspect the results of procedures such as bypass grafting and laser irradiation of obstructive lesions. Since little is known about this instrument's potential complications, we passed a variety of fiberoptic scopes (1.8 to 3.6 mm outer diameter) in fresh postmortem pig coronary arteries and live monkey and canine peripheral arteries, and observed the intraluminal anatomy through the angioscope. No perforations were created, but ridges rising from the vascular luminal surface, avulsion of the endothelial lining, and small flaps attached at one end to the vessel wall were observed. Histologically, subintimal and medial tears were evident. Inserting large diameter scopes or making frequent passes (10 to 100) in coronary arteries increased intravascular injury. The use of small diameter flexible scopes or infrequent passes (less than 10) in the larger iliac and femoral arteries of live monkeys and dogs resulted in a lower frequency of myointimal sloughing or flap formation. Current fiberoptic scopes are not ideal angioscopes; they have a rigid tip, cannot be steered adequately, and are relatively stiff, resulting in a high probability of intraluminal injury, especially when used in small tortuous arteries. To decrease the risk of such injury, we recommend gentle manipulations while passing the scope and use of the smallest diameter scope possible. We further suggest limited use of the fiberscope, or at least limiting the number of passes in small vessels such as coronary arteries.

Animals↗
PubMed1988

Influence of interferon gamma on B cell replication.

Semisolid agar culture techniques, recombinant murine gamma interferon, (Mu IFN gamma) and monoclonal anti-Mu IFN gamma antibodies were used to evaluate the role of interferon in mitogen-dependent B cell proliferation. Subtle, but significant, effects of interferon addition were noted when unseparated spleen cells were cultured. Depending on culture conditions, the cloning efficiency of the B cells was slightly increased by optimal concentrations of interferon. When the spleen cells were cultured over unstimulated peritoneal macrophages separated by an agar spacer, and especially when no other potentiators were added to the cultures, substantial enhancement of B cell proliferation routinely resulted. The mechanism of this effect was then investigated with macrophage depleted spleen cells as well as highly enriched, positively selected, B cell suspensions. Results of these experiments indicated that B cell replication can be modulated by direct interaction with interferon and again, the conditions of culture determined the magnitude and direction of the effect. Addition of anti-interferon antibodies, indomethacin, or interleukin 1 (IL-1) to the cultures did not influence the cloning efficiency of normal splenic B cells. Therefore, we found no evidence that endogenously produced interferon, prostaglandins, and IL-1 influence B cell colony formation. Since interferon stimulated macrophages dramatically improved B cell proliferation without direct cell contact, some other monokine may be involved. Therefore, gamma interferon can participate in humoral immune responses by influencing the expansion of activated B cells directly as well as indirectly via stimulation of macrophages.

Animals↗
PubMed1988

Epitopes that span the tau molecule are shared with paired helical filaments.

Tau protein has been shown to be an integral component of Alzheimer paired helical filaments (PHF). However, the extent to which tau is incorporated into PHF has not been clear because the antibodies used to label PHF generally do not have precisely defined epitopes. Here we define the antigenic sites for five monoclonal antibodies that react with tau and cross-react with SDS-extracted neurofibrillary tangles. The reactive sites were determined by screening a lambda gt11 sublibrary expressing small fragments of the tau sequence. The mapped epitopes were found to span almost the entire length of tau, suggesting that PHF contains tau in its entirety or nearly in its entirety. One antibody was found to cross-react with microtubule-associated protein 2, implying some degree of homology between the two proteins.

Alzheimer Disease↗
PubMed1988

Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues.

Progressive cerebral deposition of extracellular filaments composed of the beta-amyloid protein (beta AP) is a constant feature of Alzheimer disease (AD). Since the gene on chromosome 21 encoding the beta AP precursor (beta APP) is not known to be altered in AD, transcriptional or posttranslational changes may underlie accelerated beta AP deposition. Using two antibodies to the predicted carboxyl terminus of beta APP, we have identified the native beta APP in brain and nonneural human tissues as a 110- to 135-kDa protein complex that is insoluble in buffer and found in various membrane-rich subcellular fractions. These proteins are relatively uniformly distributed in adult brain, abundant in fetal brain, and detected in nonneural tissues that contain beta APP mRNA. Similarly sized proteins occur in rat, cow, and monkey brain and in cultured human HL-60 and HeLa cells; the precise patterns in the 110- to 135-kDa range are heterogeneous among various tissues and cell lines. Confirmation that the immunodetected tissue proteins are forms of beta APP was obtained when mammalian cells transfected with a full-length beta APP cDNA showed selectively augmented expression of 110- to 135-kDa proteins and specific immunocytochemical staining. Unexpectedly, the antibodies to the carboxyl terminus of beta APP labeled amyloid-containing senile plaques in AD brain. We conclude that the highly conserved beta APP molecule occurs in mammalian tissues as a heterogeneous group of membrane-associated proteins of approximately 120 kDa. Detection of the nonamyloidogenic carboxyl terminus within plaques suggests that proteolytic processing of the beta APP into insoluble filaments occurs locally in cortical regions that develop beta-amyloid deposits with age.

Alzheimer Disease↗
PubMed1988

Upstream region of hepatitis B virus S gene responsible for transcriptional stimulation by dexamethasone.

Transcriptional regulation of hepatitis B virus (HBV) surface antigen (HBs Ag) gene was studied in human hepatoma-derived cell lines. Treatment with dexamethasone (Dex; 1 microM) induced an increase in the smaller HBs-mRNA initiated within Pre-S region encoding S and Pre-S2 proteins, but not the larger HBs-mRNA initiated in the further upstream encoding Pre-S1 protein. The Bg1II-MstII fragment (map position 2425-3201) in the upstream of the S gene was used as a transcriptional promoter of chloramphenicol acetyltransferase (CAT) gene. The CAT activity brought about by this construct in the transient assay was elevated by 5-fold in the presence of Dex. Deletion analysis localized the sequence required for the full response to Dex within a 590-base pair fragment in the upstream of the transcriptional initiation site of the smaller HBs-mRNA. And this fragment contained the binding site for the nuclear factor I (NF-I), which might have some role in Dex-dependent transcriptional stimulation.

CCAAT-Enhancer-Binding Proteins↗
PubMed1988

A new specificity, SH7 (Bw75), defined by antisera produced by planned immunization.

SH7 specificity was defined by a group of antisera developed in Shanghai, China by planned immunization. SH7 antibody is cross-reactive with B5 and B15, as demonstrated by the serological reaction patterns obtained during planned immunization. Using 9th and 10th International Histocompatibility Workshop sera, we were able to confirm SH7, TS-1 and B15Kemp as identical specificities. They are equivalent to BW62S and B15Short-Thai. In view of the cross-reaction patterns obtained during planned immunization, SH7 appears to belong to the B5, B15, B35 and Bw70 cross-reactive groups.

Epitopes↗
PubMed1988

The polymorphism of HLA antigens in the Chinese.

Remarkable differences were observed in antigen frequencies (AF), gene frequencies (GF) and haplotype frequencies (HF) when 2441 healthy Chinese individuals representing nine different ethnic groups and living in 14 different geographic locations were examined for the genetic distribution of the various HLA Class I and II markers. A sizable number of individuals of each ethnic group within each of the three major categories of the Chinese population, namely, Hans, Mongols, and Southern minorities, have been studied here, providing useful population statistics for applications such as determination of probabilities of paternity, comparisons for HLA and disease associations, and anthropologic studies.

China↗
PubMed1987

Beta transforming growth factors are potential regulators of B lymphopoiesis.

Members of the transforming growth factor beta (TGF-beta) family of polypeptides were found to be potent in vitro inhibitors of kappa light chain expression on normal bone marrow-derived and transformed cloned pre-B cells, and of the maturation of these cells to mitogen responsiveness. The inhibition by TGF-beta was selective in that Ia expression was not blocked. Together with the observations that LPS, IL-1, NZB serum factors, IL-4, and IFN-gamma preferentially induced either kappa or Ia, or both, on a pre-B cell line, these results further suggest that acquisition of Ig and class II molecules is independently controlled by different antagonists as well as agonists. In addition, kappa chain induction by IFN-gamma does not appear to be as sensitive to TGF-beta downregulation as that stimulated by other factors tested, and this raises the possibility that activation of the same gene may result from different transmembrane signaling pathways. In contrast to the inhibitory effects of TGF-beta on kappa acquisition by pre-B cells and on kappa increase after exposure of mature B cells to LPS, as measured by kappa RNA levels and/or surface fluorescence, no inhibition was observed on unstimulated spleen B cells or on two cloned B cell lines that constitutively produce kappa. Thus, TGF-beta may function during specific stages of B cell differentiation by inhibiting initiation of, or increased transcription of Ig genes, and therefore, may be an important negative regulator of B lymphopoiesis. It is the first natural substance found to have this effect.

Animals↗
PubMed1987

Inability of mitogen-induced liver hyperplasia to support the induction of enzyme-altered islands induced by liver carcinogens.

Experiments were designed to determine whether liver cell proliferation induced by direct mitogens is as effective as compensatory cell proliferation consequent to previous cell loss, in supporting the growth of enzyme-altered islands in the liver induced by chemical carcinogens. Male Wistar rats were given injections of a single nonnecrogenic dose of N-methyl-N-nitrosourea or benzo(a)pyrene during the S phase following the administration of four different liver mitogens, namely, lead nitrate, ethylene dibromide, nafenopin, and cyproterone acetate, or during compensatory cell proliferation following partial hepatectomy or a necrogenic dose of CCl4. The carcinogen-altered hepatocytes were monitored as gamma-glutamyltransferase- or placental glutathione S-transferase-positive foci using a 2-wk promoting regimen consisting of 0.03% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results indicate that, unlike compensatory cell proliferation induced by partial hepatectomy or CCl4, the mitogen-induced cell proliferation did not result in a significant number of enzyme-altered islands, despite the fact that the extent of cell proliferation at the time of carcinogen administration, as monitored by the examination of labeled cells, is similar with both types of proliferative stimuli.

Animals↗
PubMed1987

Gene dosage of the amyloid beta precursor protein in Alzheimer's disease.

The progressive deposition in the human brain of amyloid filaments composed of the amyloid beta protein is a principal feature of Alzheimer's disease (AD). Densitometric analysis of Southern blots probed with a complementary DNA for the amyloid protein has been carried out to determine the relative dosage of this gene in genomic DNA of 14 patients with AD, 12 aged normal subjects, and 10 patients with trisomy 21 (Down syndrome). Whereas patients in the last group showed the expected 1.5-fold increase in dosage of this gene, none of the patients with AD had a gene dosage higher than that of the normal controls. These results do not support the hypothesis that the genetic defect in AD involves duplication of a segment of chromosome 21 containing the amyloid gene. Alternative mechanisms for the brain-specific increase in amyloid protein deposition in AD should be considered.

Adult↗
PubMed1987

Antihypertensive therapy and the concept of total cardiovascular protection.

Drug-induced reduction of elevated blood pressure decreases cardiovascular mortality and morbidity in patients with moderate and severe hypertension. Furthermore, antihypertensive drug studies in mild hypertensive subjects (diastolic blood pressure 90 to 104 mm Hg) have shown protection against stroke, left ventricular hypertrophy, congestive heart failure and progression of renal damage, as well as improved patient longevity. The Hypertension Detection and Follow-up Program trial, recently carried out in the U.S., documented reduced coronary artery disease events (fatal and nonfatal) in special drug-treated patients with mild hypertension. From the standpoint of practical management and considering the ubiquity of essential hypertension, a modified stepped-care regimen advocating initial drug therapy with a beta blocker and addition of low-dose thiazide diuretic when necessary constitutes a judicious approach for widespread application. Although there are 8 orally active beta blockers currently approved in the U.S. for clinical use in systemic hypertension, only acebutolol possesses all of the salutary pharmacologic properties of cardioselectivity, intrinsic sympathomimetic activity and hydrophilicity, thereby making this compound an effective and safe beta-blocking agent for first-order management of a broad segment of the hypertensive population.

Acebutolol↗