Showing papers by "Baylor College of Medicine published in 1984"

Efficacy of Methylprednisolone in Acute Spinal Cord Injury

Abstract: A multicenter double-blind randomized trial was conducted to examine the efficacy of a high dose of methylprednisolone (1,000-mg bolus and daily thereafter for ten days) compared with a standard dose (100-mg bolus and daily thereafter for ten days) in 330 patients with acute spinal cord injury. No difference in neurological recovery of motor function or pinprick and light touch sensation was observed between the two treatment groups six weeks and six months after injury. The lack of a treatment effect was independent of the severity of the initial lesion or the time from injury to starting treatment. Although not statistically significant, early case fatality was greater in the high-dose protocol (relative risk of 3.1 and 1.9, ≤ 14 and 15 to 28 days after injury, respectively) but not from 29 to 210 days after injury. Wound infections of both trauma and operative sites were more prevalent in the high-dose regimen (relative risk of 3.6). (JAMA1984;251:45-52)

Replication timing of genes and middle repetitive sequences

Abstract: DNA replication in mammals is temporally bimodal. "Housekeeping" genes, which are active in all cells, replicate during the first half of the S phase of cell growth. Tissue-specific genes replicate early in those cells in which they are potentially expressed, and they usually replicate late in tissues in which they are not expressed. Replication during the first half of the S phase is, therefore, a necessary but not sufficient condition for gene transcription. A change in the replication timing of a tissue-specific gene appears to reflect the commitment of that gene to transcriptional competence or to quiescence during ontogeny. Most families of middle repetitive sequences replicate either early or late. These data are consistent with a model in which two functionally distinct genomes coexist in the nucleus.

myo-Inositol polyphosphate may be a messenger for visual excitation in Limulus photoreceptors.

Abstract: Photoreceptor excitation begins with the absorption of a photon by rhodopsin and proceeds through an unknown sequence of steps that leads to changes in specific ionic conductances. These conductance changes produce the receptor potential. It has been proposed that hydrolysis of phosphoinositides is involved in the control of a variety of physiological processes. Recent studies have implicated inositol 1,4,5-trisphosphate as an intracellular messenger in the cascade mediating hormone-stimulated secretion. We propose that one of the steps in the excitatory cascade in Limulus ventral photoreceptors may be an increase in intracellular concentration of myo-inositol polyphosphates, derived from hydrolysis of the membrane component phosphatidylinositol bisphosphate by a phospholipase. Here we present biochemical and electrophysiological evidence that an inositol polyphosphate may be an intracellular messenger in the cascade mediating excitation, based on the following criteria: the cells possess the synthetic and degradative metabolism for the messenger; the natural stimulus leads to a change in the concentration of the messenger within the cells; and intracellular injection of exogenous messenger mimics naturally occurring electrophysiological events.

Silver staining, immunofluorescence, and immunoelectron microscopic localization of nucleolar phosphoproteins B23 and C23

Abstract: Nucleolar organizer region (NOR)-specific silver staining and immunolocalization of nucleolar phosphoproteins B23 and C23 were compared in Novikoff hepatoma ascites cells. Silver staining and protein C23 immunostaining were both localized in the fibrillar shell surrounding the fibrillar center and in the fibrillar center. During mitosis, silver staining and protein C23 were localized at the NORs. Therefore, protein C23 and the silver-staining protein both seem to be associated with rDNA-containing structures (Mirre and Stahl 1981). A comparison of toluidine blue staining specific for RNA and B23 immunostaining demonstrated that protein B23 was associated with RNA-containing regions of the nucleolus and was absent from the fibrillar centers. Localization of these proteins and their functions are discussed in relation to the organization of the nucleolus.

Postprandial lipemia. A key for the conversion of high density lipoprotein2 into high density lipoprotein3 by hepatic lipase

Abstract: In this study, we have investigated the effects of alimentary lipemia in 15 normotriglyceridemic individuals on high density lipoproteins2 (HDL2) with respect to structure, composition, and substrate efficacy for hepatic lipase in vitro. In the study subjects, HDL2 levels ranged widely from 4.7 to 151.7 mg/dl plasma. HDL2 were isolated in the postabsorptive (pa) state and in the postprandial (pp) state, i.e., 7 h after ingestion of a standard fatty meal. In going from the pa state to the pp state, HDL2 exhibited higher flotation rates and lower densities due to a decreased proportion of protein (38.7----36.2%) and a higher abundance in phospholipid (32.5----34.9%). There was a variable increase in triglyceride at the expense of cholesteryl esters; this increase was correlated positively with the magnitude of pp lipemia (r = 0.69, P less than 0.01) and inversely with HDL2 levels (r = -0.72, P less than 0.01). Hdl2 fractions were incubated with human hepatic lipase in vitro. Product lipoproteins formed from lipolysis of pa-HDL2 and triglyceride-poorer pp-HDL2 were reduced in phospholipid content (by 25 and 50%, respectively) but remained in the size and density range of native HDL2. By contrast, a major fraction of triglyceride-richer pp-HDL2 was converted to particles with density, size, and apoprotein composition of native HDL3. Changes consistent with these findings in vitro were observed in vivo also, where 15 h postprandially, individuals with high-level lipemia showed a decrease in HDL2 and rise in HDL3, while those with lower-level lipemia did not. This study indicates that the magnitude of postprandial lipemia determines the proportion of triglyceride in pp-HDL2, which in turn determines whether or not HDL2 are converted to HDL3 by hepatic lipase action.

Frequency-dependent noradrenergic modulation of long-term potentiation in the hippocampus.

Abstract: Norepinephrine, briefly superfused during high-frequency stimulation of the mossy fibers in the rat hippocampal slice in vitro, produced a reversible increase in the magnitude, duration, and probability of induction of long-term synaptic potentiation in the CA3 subfield. Similar results were obtained with isoproterenol, whereas propranolol or timolol reversibly blocked long-term potentiation. Norepinephrine had little apparent effect on responses obtained during low-frequency stimulation of the mossy fibers. These data suggest that norepinephrine can mediate long-lasting, frequency-dependent modulation of synaptic transmission in the mammalian brain. Furthermore, the results suggest a plausible mechanism for some of the known associative interactions between synaptic inputs to hippocampal neurons.

Hypsarrhythmia: variations on the theme.

Abstract: Prolonged monitoring studies of patients with infantile spasms have shown that hypsarrhythmia is a highly variable and dynamic electroencephalographic pattern. Variations of the prototypic pattern (modified hypsarrhythmia) include hypsarrhythmia with increased interhemispheric synchronization, asymmetrical hypsarrhythmia, hypsarrhythmia with a consistent focus of abnormal discharge, hypsarrhythmia with episodes of attenuation, and hypsarrhythmia comprising primarily high-voltage slow activity with little sharp-wave or spike activity. Marked changes in the hypsarrhythmic pattern usually occur during sleep, chiefly during rapid eye movement sleep, when there is a marked reduction in, or total disappearance of, the hypsarrhythmic pattern. Relative normalization of the hypsarrhythmic pattern can also be seen immediately on arousal and during clusters of infantile spasms. Thus, the specific EEG features seen in a given patient depend on multiple factors, including the duration of the EEG recording, the clinical state of the patient, and the presence of various structural abnormalities of the brain.

Non-asbestos-related malignant mesothelioma. A review

Abstract: Malignant mesothelioma is an uncommon, but increasingly important, neoplasm. The existing English-language medical literature concerning non-asbestos-related malignant mesotheliomas was reviewed for evidence of other agents associated with the induction of malignant mesothelioma. Both animal and human data were reviewed. In most reviews of malignant mesothelioma, there are a significant proportion of cases without documented asbestos exposure (range, 0% to 87%). Furthermore, there are several fairly well-documented agents other than asbestos that induce malignant mesothelioma in animals, and strong evidence exists that such is the case in man. In reviews of malignant mesothelioma, the percentage of cases with asbestos exposure varies, but a significant number are apparently not asbestos related. It is believed that sufficient evidence exists to suggest that non-asbestos agents can induce malignant mesotheliomas in man, and additional epidemiologic studies in this area are needed.

The metabolic response to severe head injury

Abstract: Caloric expenditure and nitrogen balance were measured in 14 steroid-treated comatose head-injured patients acutely and up to 28 days after injury. During this period patients were fed with a continuous enteral infusion of a formula containing 2 Kcal/cc and 10 gm nitrogen/liter. Indirect calorimetry was carried out for 102 patient-days. The mean resting metabolic expenditure (RME) for nonsedated nonparalyzed patients was 138% +/- 37% of that expected for an uninjured resting person of equivalent age, sex, and body surface area. Nitrogen excretion was measured for 135 patient-days. The mean excretion was 20.2 +/- 6.4 gm/day. The mean protein caloric contribution was 23.9% +/- 6.7% and was greater than 25% for six patients, compared to normal values of 10% to 15%. Despite hyperalimentation, positive nitrogen balance for any 3-day period was achieved in only seven patients, and required replacement of 161% to 240% of RME with enterally administered formula. Head-injured patients had a metabolic response similar to that reported for patients with burns of 20% to 40% of the body surface.

Central Gating Mechanisms That Regulate Event-Related Potentials and Behavior

Abstract: Previous work in our laboratory showed that the mesencephalic reticular formation (MRF) and frontal granular cortex (FC) jointly regulate the activity in the thalamic reticular nucleus (R). The R neurons project specifically into relay nuclei and, when activated, inhibit the specific transmission of sensory information through the thalamus to primary receptive cortex. The MRF has a generalized inhibitory effect on the R cells and can produce generalized disinhibition of sensory channels, as is known to occur during orienting responses. The frontal cortex, on the other hand, provides specific and tonic excitation of individual R cells and can selectively turn off specific sensory channels, as is known to occur during selective attention. Our more recent work has focused on the cellular mechanisms in the frontal cortex that result in the specific sensory gating that occurs during operationally defined states of behavioral attention. The occurrence of the event-related potential (ERSP) in the FC seems to be the harbinger of both EEG desynchronization and sensory channel selection. Both of these latter event-related activities are explainable by FC effects on R cells. We have found that during an ERSP in the FC, in the underlying tissue: (a) norepinephrine (NE) is released, (b) cAMP is activated, (c) extracellular potassium ion activity is reduced, and (d) slow membrane potential shifts occur in some of the neurons. These results suggest that the same neuromodulatory mechanism exists in the cortex as is known to operate in a model preparation, the sympathetic ganglion.

Retinoids in Photosensitive Systems

Abstract: Publisher Summary This chapter discusses retinoids in photosensitive systems. The biosynthesis and regeneration of the photosensitive pigments requires the retinaldehyde to be provided to the membranes in which they are sequestered. The chapter describes the critical role of retinoid-binding proteins in the normal functioning of the vertebrate visual system. Vision is initiated by the capture of quanta of radiation by integral transmembrane proteins called visual pigments. In all known visual pigments, the protein is conjugated to a retinaldehyde prosthetic group. The visual pigments of invertebrates, like those of their vertebrate counterparts, are based on 11- cis -retinaldehyde. Squid and octopus rhodopsins are glycoproteins that bind concanavalin A. Bacteriorhodopsin is an integral transmembrane protein, which is the only protein found in the purple membrane of Halobacterium haiobium and other extremely halophilic bacteria. Bacteriorhodopsin is a light-activated vectorial ion pump that translocates protons across the bacterial plasma membrane. In addition to their occurrence as covalently linked prosthetic groups in the light-sensitive pigments, retinoids are also found non-covalently associated with a number of soluble retinoid-binding proteins.

Heterogeneity of human colon carcinoma

Abstract: In order to better understand colon cancer, a model system reflecting the heterogenous nature of this disease was developed and used in the development of new cytotoxic and non-cytotoxic therapeutic approaches. A large bank of colon carcinoma cell lines was established from primary human colon carcinomas and grouped based on their tumorigenicity in athymic mice, their growth rates in soft agarose and in tissue culture, and their secreted levels of carcinoembryonic antigen. These cell lines were later characterized based on cell surface proteins and antigens detected with antisera raised against a differentiated colon carcinoma cell line. Although these biochemical markers correlated with the biological classification of these cell lines, there was still extensive heterogeneity within each group in all properties examined. This colon carcinoma cell system was used to study natural vs. selected resistance to the anticancer drug mitomycin C (MMC). The differing IC50 values in vitro were reflected in the inhibition by MMC of xenograft growth in athymic mice. A new, more readily bioactivatable analogue of MMC was tried and shown to be more active in vitro and in vivo, suggesting that rapid efflux of the drug before activation may be important in examining causes of resistance to MMC. Another approach to the treatment of colon cancer is the use of non-cytotoxic agents such as growth factors and differentiation agents to restore normal growth to the malignant cells. We have isolated and characterized two types of polypeptides from colon carcinoma cells and conditioned medium from these cells. The first, transforming growth factors (TGF's) confer a transformed phenotype on non-transformed fibroblasts while the second, tumor inhibitory factors (TIF's), inhibits the anchorage independent growth of transformed cells. The fact that extracts of colon carcinoma cells contain both activities suggests that the heterogeneity of the cell lines could be due to different levels of TGF's and TIF's produced. The effectiveness of differentiation agents to restore normal growth control using a transformed mouse embryo cell line was examined. Treatment of these cells with differentiation agents restored normal growth control to these cells. An increased synthesis of TGF's resulted from these treatments. Therefore, differentiation agents may be useful in non-cytotoxic treatment. The use of this model system for human colon carcinoma will hopefully lead to more effective drugs for the treatment of colon cancer in man.

Immunization with zona pellucida proteins results in abnormal ovarian follicular differentiation and inhibition of gonadotropin-induced steroid secretion.

Abstract: Changes in rabbit ovarian hormonal responses and cellular differentiation of ovarian follicles after immunization with porcine zona pellucida (ZP) have been examined. Steroid and peptide hormone levels were monitored after immunization to evaluate ovulation and pseudopregnancy cycles in immunized and control animals. All immunized rabbits developed serum antibodies to specific ZP antigens and failed to form functional corpora lutea in response to hCG administration, as evidenced by the absence of elevated serum progesterone concentrations. This is in contrast to control rabbits, which had elevated progesterone levels 8–9 days after hCG administration. Furthermore, all immunized animals showed greatly increased serum levels of FSH and LH compared to those of control animals. These effects on ovarian function were apparent within 20 weeks of the primary immunization. Follicular development was analyzed by light and electron microscopies. The numbers of primary, secondary, and tertiary follicles in ovaries o...

Comparison of cytotoxicity and DNA breakage activity of congeners of podophyllotoxin including VP16-213 and VM26: a quantitative structure-activity relationship.

Abstract: Fourteen congeners of podophyllotoxin were evaluated for their abilities to induce DNA breakage and inhibit growth of A549 human lung adenocarcinoma cells. Among the congeners studied were VP16-213, VM26, alpha-peltatin, beta-peltatin, and picropodophyllotoxin. Alkaline elution methods were used to assess DNA break frequencies following 1-h exposure to different concentrations of the congeners. DNA breakage was dependent upon drug concentration and was detectable when cells were exposed for 1 h to concentrations of VM26 as low as 0.05 microM. DNA breaks formed rapidly in cells after addition of drug but increased little after 30 min of continuous exposure. Repair of drug-induced DNA breaks was equally rapid with repair of 90% of the breaks occurring within 1 h following removal of the drug. Relationships between the structures of the congeners and the resulting DNA breakage activities were obtained, which correlated well with the cytotoxicity. The data suggest that a free hydroxyl group at the 4'-position is essential for DNA breakage activity, epimerization at the 4-position of the podophyllotoxin rings enhances activity, glucosylation of the hydroxyl group at the 4-position diminishes activity, aldehyde condensation with the glucose moiety greatly enhances activity, and the structure of the group associated with the resulting acetal linkage influences DNA breakage activity. These studies present quantitative data supporting and expanding upon the structure-activity relationship first proposed by Loike and Horwitz [Loike, J. D., & Horwitz, S. B. (1976) Biochemistry 15, 5443-5448].

Lipid peroxidation and retinal degeneration

Abstract: Retinal degenerations were produced in albino rats by exposure to constant illumination or in frogs and albino rats by intravitreal injections of ferrous sulfate. Both treatments resulted in the loss of long-chain polyunsaturated fatty acids and the accumulation of lipid hydroperoxides in isolated rod outer segments. We suggest that lipid peroxidation is a factor in certain types of retinal degenerations.

Molecular evidence for new mutation at the hprt locus in Lesch-Nyhan patients.

Abstract: Hypoxanthine-guanine phosphoribosyltransferase (HPRT; EC2.4.2.8), which functions in the metabolic salvage of purines, is encoded by an X-linked gene in man. Partial HPRT deficiencies are associated with gouty arthritis, while absence of activity results in Lesch-Nyhan syndrome (L-N). L-N patients fail to reproduce and the heterozygous state appears to confer no selective advantage. Thus, Haldane's principle predicts that new mutations at the hprt locus must occur frequently in order for L-N syndrome to be maintained in the population. This constant introduction of new mutations would be expected to result in a heterogeneous collection of genetic lesions, some of which may be novel. As we report here, the mutations in the hprt gene of seven L-N patients, selected from an initial survey of 28 patients, have been characterized and all were found to be distinctly different, as predicted. The origin of one unusual mutation has been identified by analysis of DNA from four generations of family members. Further molecular analysis of the origin of new mutations at the hprt locus should aid in resolving the issue of an apparent difference in the frequency of hprt mutations in males and females.

Reliability and Validity of Self Report of Aerobic Activity: Family Health Project

Abstract: Two studies are presented which deal with the reliability and validity of self-reports of aerobic activity. The first study compared two forms of self-report data obtained as part of a study of intervention strategy. The two forms were daily self-report and weekly retrospective report. Analyses covering the overlapping time period revealed differences in mean minutes engaged in activity, but modest and statistically significant correlations between the two forms among adults participating in the intervention group. No meaningful results were obtained among adults in the control group, nor among children in either group. The need for the development and testing of self-report forms among children was noted, and was the subject of the second study. In Study II, six different forms on which third to sixth grade children recorded their aerobic activity were compared against two days of continuous observations of their behavior. The six forms varied along two dimensions. The first dimension varied the...

Enterovirus Type 71 Infections: A Varied Clinical Pattern Sometimes Mimicking Paralytic Poliomyelitis

Abstract: Not all poliomyelitis-like paralytic illnesses can be attributed to polioviruses. Among the most recently recognized agents able to cause severe central nervous system disease with persistent flaccid paralysis is enterovirus type 71. In the 1969-1973 California outbreaks during which strains of this type were first reported, meningitis predominated, but cases of encephalitis were also seen. Outbreaks in different regions of the world followed. In some, hand-foot-and-mouth syndrome predominated; in others, meningitis; and in some, the clinical patterns were mixed. In the 1975 Bulgarian outbreak of greater than 705 cases, 149 patients developed paralysis and 44 others died. Enterovirus 71 was incriminated as the cause of the epidemic, in which infants and young children were the chief victims. The 1978 Hungarian epidemic of central nervous system disease was mixed, involving a tick-borne encephalitis virus among adults and enterovirus 71 among children. This newly recognized enterovirus is also significant in relation to polio vaccines. At some time, vaccine inevitably will be given to persons already incubating enterovirus 71 infection, who then may present with the paralytic syndrome due to the wild enterovirus. Such cases could be mistakenly designated as related to polio vaccine, particularly since many enterovirus 71 strains are difficult to isolate under conditions that would readily yield poliovirus isolates from the vaccine.

Coronary artery disease in patients with cerebrovascular disease: a prospective study.

Abstract: Coronary artery disease is the cause of death in most patients who have transient ischemic attacks or stroke. Evaluation for this condition is not routinely performed in such patients, and no prospective studies have been reported. We prospectively examined 50 consecutive patients with transient ischemic attacks or mild stroke to determine the prevalence and importance of coronary artery disease. All patients were examined by a cardiologist and underwent both exercise thallium-201 scintigraphy and exercise radionuclide ventriculography. Sixteen patients were suspected to have coronary artery disease on the basis of clinical evaluation. In 15 of these the was confirmed by the nuclear scans. The remaining 34 patients had no clinical evidence of heart disease, yet 14 had abnormal cardiac scans. Twenty of 22 patients with abnormal scans who underwent cardiac catheterization had significant coronary artery disease or a cardiomyopathy. The discovery of heart disease altered clinical management in 13 patients. Overall, 29 of 50 patients had significant coronary artery disease, compared with a 7% prevalence of the condition in other patients of similar age at the same institution.

Civilian trauma in the 1980s. A 1-year experience with 456 vascular and cardiac injuries

Abstract: During 1982, 312 patients with 408 vascular injuries and 48 cardiac injuries were seen. Two or more vascular or cardiac injuries were present in 34% of patients. Over 87% of injuries were secondary to gunshot wounds, stab wounds, or shotgun wounds. Vascular injuries were most commonly seen in the extremities (39.9%) or abdomen (31.9%). The most common arterial injuries occurred in the brachial artery (39 patients), while the most common venous injuries occurred in the internal jugular vein (26 patients). Arterial injuries were treated by the insertion of substitute vascular conduits (33.9%), ligation (22.6%), lateral arteriorrhaphy (18.6%), or end-to-end anastomosis (15.4%). Venous injuries were treated by lateral venorrhaphy (63.7%) or ligation (25.1%). In the 272 patients admitted with only vascular injuries, survival was 84.2%. Cardiac injuries in 38 patients most commonly occurred in the right ventricle (50%) and right atrium (25%). In the 34 patients who had only cardiac injuries and less than 4 minutes of prehospital cardiopulmonary arrest prior to arrival in the emergency center, survival was 64.7%.