Showing papers by "Baylor College of Medicine published in 1974"

Female steroid hormones and target cell nuclei.

Abstract: The data discussed herein demonstrate the great variation in target-tissue response that can occur after administration of steroid hormones. The female sex steroids can exert regulatory effects on the synthesis, activity, and possibly even the degradation of tissue enzymes and structural proteins. Each response, nevertheless, appears to be dependent on the synthesis of nuclear RNA. In many instances, the steroid actually promotes a qualitative change in the base composition and sequence of the RNA synthesized by the target cell, implying a specific effect on gene transcription. Most important is our direct quantitative evidence that sex steroids cause a net increase in the intracellular amounts of specific mRNA molecules in target tissues. It thus appears that we are discovering a pattern of steroid hormone action which includes (Fig. 1): (i) uptake of the hormone by the target cell and binding to a specific cytoplasmic receptor protein; (ii) transport of the steroid-receptor complex to the nucleus; (iii) binding of this "active" complex to specific "acceptor" sites on the genome (chromatin DNA and acidic protein); (iv) activation of the transcriptional apparatus resulting in the appearance of new RNA species which includes specific mRNA's; (v) transport of the hormone-induced RNA to the cytoplasm resulting in synthesis of new proteins on cytoplasmic ribosomes; and (vi) the occurrence of the specific steroid-mediated "functional response" characteristic of that particular target tissue. To elucidate fully the mechanism of steroid hormone action we must study the biochemistry of the process by which information held by the steroid hormone-receptor complex is transferred to the nuclear transcription apparatus. If our assumptions are correct, we should ultimately be able to discover how this hormone-receptor complex exerts a specific regulatory effect on nuclear RNA metabolism. Such regulation might be achieved (i) by direct effects on chromatin template leading to increased gene transcription and thus RNA synthesis; (ii) by activation of the polymerase complex itself; (iii) by inhibition of RNA breakdown; or (iv) by intranuclear processing of large precursor molecules so that smaller biologically active sequences are produced, and (v) by transport of RNA from the nucleus to the cytoplasmic sites of cellular protein synthesis.

Oestrogen receptors and antagonism of steroid hormone action.

Abstract: NON-STEROIDAL anti-oestrogens antagonise the effects of oestrogen on uterine growth, vaginal cornification and ovulation1, and their mechanism of action has been suggested to reside in their ability to compete for cytoplasmic oestrogen binding sites, or receptors, thereby reducing the formation of receptor oestrogen complexes2–4. Since the formation of these complexes in oestrogen target tissues, with subsequent translocation to nuclear sites, is considered the primary event in oestrogen action5,6, the reduction in their number would lead to decreased physiological responses to oestrogen. This implies that the receptor antagonist complex should have a lower intrinsic biological activity than that of the receptor oestradiol complex; that is, the ability of the receptor antagonist complex to stimulate oestrogenic responses would be less than that of the receptor oestradiol complex. Based on these assumptions, oestrogen antagonism should be observed after a single injection of oestrogen and antagonists; we have now found that this is not the case. Thus, non-steroidal anti-oestrogens could not be acting as antagonists by competing initially for oestrogen receptors.

Echocardiographic assessment of left ventricular function. With special reference to normalized velocities

Abstract: The concept of "normalized velocity" has been applied in this study to the echocardiographic (echo) assessment of left ventricular (LV) function in 87 patients. The following normalized velocities were calculated from the ultrasound recording of LV wall motion: 1) the mean circumferential fiber shortening rate (mean VCF), 2) the mean normalized posterior wall velocity (VPW), and 3) the mean normalized interventricular septal velocity (VIVS). Systolic ejection fraction (SEF), and mean (non-normalized) posterior wall velocity (PWV) were also determined. There were 19 patients with normal LV function, 5 with atrial septal defect (mean VCF, VIVS and SEF were not calculated in these patients), 16 with LV volume overload, 29 with myocardial disease, 6 with hypertrophic cardiomyopathy and 12 with coronary artery disease (CAD). Single plane cineangiographic (angio) determinations of mean VCF and SEF were obtained in 50 of the 87 patients (including all 12 patients with CAD). Mean VCF and SEF done by echo correlated very well with mean VCF and SEF done by angio in the patients without CAD ( r = 0.94 and 0.91, respectively). Mean VCF (by echo or by angio) adequately separated normal from abnormal LV function. Although correlation between mean VCF and SEF was good, mean VCF was reduced while SEF was well preserved in several patients. In spite of LV asynergy, most of the patients with CAD had good correlation between echo and angio measurements of mean VCF and SEF. Although PWV correlated with echo and angio mean VCF in the patients without CAD, the overlap of normal and abnormal values made PWV an unreliable index of LV function. In contrast, VPW proved to be a reliable indicator of LV performance in patients without LV asynergy. Agreement between VPW and mean VCF (by echo or angio) was seen in 94% of the patients; in the presence of CAD, however, greater discrepancy was seen between these two measurements. Agreement between VIVS and VPW was present in 90% of the patients without CAD, but in only 58% of the patients with CAD. The analysis of LV wall motion by echocardiography utilizing the "normalized velocity" concept appears to be a rational and practical method for evaluation of LV performance. In the absence of asynergy, VPW provides a reliable index of LV performance which may be of particular value when abnormal septal motion precludes the determination of SEF and mean VCF. In the presence of asynergy, however, mean VCF, VPW and VIVS may reflect only the performance of the visualized segment of myocardium.

Regulatory mechanisms in cell-mediated immune responses. I. Regulation of mixed lymphocyte reactions by alloantigen-activated thymus-derived lymphocytes.

Abstract: Regulatory effects of alloantigen-activated thymus-derived lymphocytes in mixed lymphocyte reactions have been demonstrated. Mice were injected into foot pads with allogeneic spleen cells; 4 days following sensitization spleen or regional lymph node cells from these animals were treated with mitomycin C and incorporated into MLR as regulator populations syngeneic to the responder cell type. Activated spleen cells suppressed MLR responses 60–90% whereas activated lymph node cells from the same animals enhanced MLR responses. Suppression by activated spleen cells was not due to cytotoxic effects nor to altered kinetics of the proliferative response. Studies of splenic suppressor cell generation in vivo revealed peak activity four days after alloantigen stimulation with no activity demonstrable at 7 days or at later times. Suppressor cell activity was abrogated by treatment with anti-θC3H serum and complement, and was not alloantigen specific.

Effects of Tetracycline on Leukotaxis

Abstract: Tetracycline, in concentrations common during therapy, markedly depressed migration of human leukocytes in vitro. Sera from 12 of 13 volunteers who received oral tetracycline after infection with Mycoplasina pneuimoniae inhibited leukotaxis of normal leukocytes. Random migration and chemotaxis of leukocytes from two additional subjects were depressed for up to 24 hr after a single 1-g dose of tetracycline. When tetracycline was tested over a wide range of concentrations, leukotaxis was depressed by lower concentrations (0.01-10 [tg/ml) but was stimulated by higher concentrations (30-300 [ig/ml) of the antibiotic. Metabolic studies revealed that production of leukocyte lactate was elevated significantly in the presence of a high level of tetracycline. The mechanisms by which tetracycline affects leukotaxis are not known.

Pathogenesis and Natural History of Transient Global Amnesia

Abstract: Fourteen patients aged between 49 and 92 years who had suffered from one or more attacks of transient global amnesia (TGA) have been followed for a mean interval of 30 months. Thirteen patients had one or more risk factors for cerebrovascular disease, such as hypertension, cardiac abnormalities, diabetes and hyperlipidemia. Clinical evidence for vertebrobasilar arterial insufficiency was demonstrated in 11 cases. EEG examination revealed bitemporal or bioccipital slow wave activity. Four-vessel arteriography showed atherosclerotic, stenotic, or occlusive lesions predominantly in the vertebrobasilar and posterior cerebral arterial systems. Five patients without recurrence of TGA showed no permanent impairment of memory, whereas eight who had recurrent attacks of TGA showed permanent memory impairment as well as mild visual-spatial or visual-motor dyspraxia as judged by neuropsychological tests on follow-up visits. "Amnesic stroke" with permanent and gross memory defect and dyspraxia occurred in two patient...

Evaluation of reinforcing capability of delta-9-tetrahydrocannabinol in rhesus monkeys

Abstract: Harnessed rhesus monkeys, surgically prepared with indwelling jugular catheters, were given access by means of remotely controlled infusion pumps to unlimited quantities of delta-9-trans-tetrahydrocannabinol. Naive monkeys as well as monkeys which were automatically infused with THC for over 28 days did not self-administer THC. Monkeys which had a history of multiple drug self-administration also did not self-infuse THC.

Blue-green bacteria synthesise L-tyrosine by the pretyrosine pathway.

Abstract: THE similarity of major biochemical pathways throughout the animal and plant kingdoms1 presumably reflects the ancient formation of the pathways in a common ancestral counterpart of modern cell types. The pathway previously known for L-tyrosine biosynthesis in both prokaryotie and eukaryotic microorganisms (Fig. 1a) involves a dehydrogenation-decarboxylation conversion of prephenate to 4-hydroxyphenylpyruvate followed by transamination in the presence of a suitable amino donor. Our data (Fig. 1b) demonstrate a reversed order of these two reactions in several species of blue–green algae (more appropriately designated bacteria (order Chrooeocales2)).

Conservative management of malignant pericardial effusion

Abstract: The traditional approach to treatment of malignant pericardial effusion has been surgical, with establishment of a pericardial window. Conservative management with local instillation of chemotherapeutic agents and/or focal radiotherapy has received less attention, particularly when solid tumors have been causative. This series of 5 patients with antemortem diagnoses of malignant pericardial disease had predominant pericardial effusion rather than tumor encasement as the basis for tamponade. These 5 patients received initial therapy with local instillation of a chemotherapeutic agent ± radiotherapy. Four of the 5 made complete responses with total disappearance of cardiac symptoms and signs. Two of the responders are dead, 4 and 12 months, respectively, after initial treatment, neither showing significant pericardial fluid at postmortem examination. Two patients are alive and asymptomatic, 40 months and 8 months, respectively, after initial therapy. A literature review of treatment of malignant pericardial effusions discloses longer symptom-free intervals in patients treated by conservative measures compared to surgical programs utilizing pericardial window accompanied by any combination of other treatment modalities.

Endometrial adenocarcinoma in Stein-Leventhal syndrome.

Abstract: Descriptions are given of 4 cases of sclerocystic ovaries in patients 21-34 years of age in whom the endometrium was morphologically indistinguishable from well-differentiated adenocarcinoma. In 2 cases immediate hysterectomy revealed lesions confined to the endometrium. Another patient underwent wedge resection of the ovaries with resulting resumption of menses. The 4th patient was treated by wedge resection which led to successful resumption of menses for several months but abnormal bleeding resumed and was controlled with clomiphene therapy. When abnormal bleeding again recurred the patient underwent hysterectomy (26 months after the original diagnosis) which revealed adenocarcinoma superficially invading the myometrium. As a result of this experience and an analysis of previously reported cases a conservative management approach based on clinical factors the patients desire to have children and followup endometrial biopses is suggested for patients with Stein-Leventhal syndrone. The delay in removing what may prove to be an invasive lesion has not been shown to be harmful as no cases of extrauterine metastases have been reported.

Reduction in the rate of diastolic descent of the mitral valve echogram in patients with altered left ventricular diastolic pressure volume relations

Abstract: Echocardiographic measurements of the rate of descent of the E wave of the anterior leaflet of the mitral valve during diastole (the mitral valve slope) have been said to correlate with the rate of early left ventricular (LV) filling. Thus, a reduced mitral valve slope in the absence of mitral valve obstruction might be related to impaired LV filling secondary to decreased diastolic compliance. In this study mitral valve slope was compared to several estimates of LV compliance and to the LV end diastolic pressure (EDP) in 32 patients undergoing diagnostic cardiac catheterization: nine normal, 11 coronary artery disease (CAD), seven congestive cardiomyopathy (CC), five left ventricular hypertrophy (LVH). Assuming an exponential relation between pressure (P) and volume (V) at end diastole, and a fixed P intercept at zero V, the following estimates of LV compliance were calculated: (1) the slope of the ln P-V relation (k), which indicates whether a P-V curve is shifted to the left or to the right of normal, ...

Energy dosage for human trans-chest electrical ventricular defibrillation.

Abstract: NO published data have defined the electrical dose for countershock in human subjects, pediatric or adult. Animal studies completed in our laboratories have demonstrated an electrical energy-to-bod...

The Primary Structure of High Density Apolipoprotein-Glutamine-I

Abstract: The major protein constituent of human plasma high density lipoproteins has been isolated and its complete amino-acid sequence determined. The protein, designated apolipoprotein-glutamine-I by the presence of carboxyl-terminal glutamine, is a single polypeptide chain of 245 amino-acid residues, including three residues of methionine. The protein is devoid of cysteine, cystine, and isoleucine. Cleavage of apolipoprotein-glutamine-I with cyanogen bromide yields four fragments with 94, 90, 36, and 25 amino acids. The amino-acid sequence of each fragment was determined by conventional methods, with proteolytic digestion with trypsin, chymotrypsin, and thermolysin. The alignment of the cyanogen bromide fragments was determined by the isolation of the methionine-containing tryptic peptides from apolipoprotein-glutamine-I. Inspection of the sequence of apolipoprotein-glutamine-I suggests an interesting distribution of amino acids that may account for its helical structure and its ability to bind and transport lipid.