Showing papers by "University of Texas Health Science Center at Houston published in 1984"
TL;DR: A mathematical formula for estimating the average number of nucleotide substitutions per site (6) between two homologous DNA sequences is developed by taking into account unequal rates of substitution among different nucleotide pairs as discussed by the authors.
Abstract: A mathematical formula for estimating the average number of nucleotide substitutions per site (6) between two homologous DNA sequences is developed by taking into account unequal rates of substitution among different nucleotide pairs. Although this formula is obtained for the equal-input model of nucleotide substitution, computer simulations have shown that it gives a reasonably good estimate for a wide range of nucleotide substitution patterns as long as 6 is equal to or smaller than 1. Furthermore, the frequency of cases to which the formula is inapplicable is much lower than that for other similar methods recently proposed. This point is illustrated using insulin genes. A statistical method for estimating the number of nucleotide changes due to deletion and insertion is also developed. Application of this method to globin gene data indicates that the number of nucleotide changes per site increases with evolutionary time but the pattern of the increase is quite irregular.
933 citations
TL;DR: Normal systolic function is common among patients with CHF, and diastolic dysfunction, consistent with a noncompliant left ventricle, was found in both CHF groups.
Abstract: Although there have been isolated reports of congestive heart failure (CHF) with normal systolic function, the prevalence and characteristics of this condition have not previously been described. Accordingly, 188 patients with CHF undergoing radionuclide ventriculography were prospectively evaluated. Sixty-seven (36%) had a normal ejection fraction (EF) of 0.45 or greater, and 121, an abnormal EF of less than 0.45. Of these, 72 (55 with an abnormal EF [group I] and 17 with a normal EF [group II]) were also reviewed for clinical characteristics. There was no demographic difference between groups, except that systemic hypertension appeared to be a contributing factor in 65% of the patients in group II, compared with 23% of the patients in group I (p
608 citations
TL;DR: A revised estimate of the pattern of point mutation is obtained by considering more pseudogene sequences and indicates that mutation occurs nonrandomly among the four nucleotides, with a high proportion of transitional mutations.
Abstract: We have obtained a revised estimate of the pattern of point mutation by considering more pseudogene sequences. Compared with our previous estimate, it agrees better with expectations based on the double-strand structure of DNA. The revised pattern, like the previous one, indicates that mutation occurs nonrandomly among the four nucleotides. In particular, the proportion of transitional mutations (59%) is almost twice as high as the value (33%) expected under random mutation. The same high proportion of transitions is observed in synonymous substitutions in genes. The proportion of transitional changes observed among electrophoretic variants of human hemoglobin is about the same as that predicted by the revised pattern of mutation. We also show that nonrandom mutation increases, by about 15%, the proportion of synonymous mutations due to single-nucleotide changes in the codon table, and increases, from 10% to 50%, the rate of synonymous mutation in the seven genes studied. However, nonrandom mutation reduces (by about 10%) the proportion of polar changes among nonsynonymous mutations in a gene. As far as single-nucleotide changes (in the codon table) are concerned, nonrandom mutation only slightly favors relatively conservative amino acid interchanges, and has virtually no effect on the proportions of radical changes and nonsense mutations.
363 citations
01 Jan 1984
212 citations
TL;DR: The results suggest that the markedly improved therapeutic index of liposomal Amphotericin B is largely due to a fundamental alteration in the ability of the drug to interact with mammalian cell membranes rather than to alterations in pharmacokinetics or drug distribution.
196 citations
TL;DR: Analysis of data from the National Survey of Personal Health Practices and Consequences indicated that age, income, education, and life events affected health directly, while the effects of church attendance and marriage were likely mediated through smoking and alcohol behaviors.
Abstract: The relationships among social structure, stress, social support, life-style health behavior, and health status are explored in this multivariate analysis of data from the National Survey of Personal Health Practices and Consequences. Path analyses showed social structural factors to influence life-style practices both directly and indirectly through social network and negative life events. For women, social network and life events had direct relationships to health related life-style practices, while age and income acted both directly and indirectly through social network and, for income, through life events. Education was also directly related to life-style. For men, social network and education had the only direct effects on health practices, and age and income had indirect effects through network. We then examined the relative contributions of the social network index elements, life events, and demographic variables to each of the life-style practices. These analyses confirmed the importance of gender, education, age, and income to predicting life-style behaviors. Negative life events were associated with smoking for both men and women, sleep for women only, and physical activity and alcohol use for men, which suggests sex-specific norms for coping with stress. For both sexes, church attendance and marriage were associated with favorable smoking and alcoholic use, implicating cognitive social support or social control as a mediator of health promotion. Finally, analyses for each gender using health status as the outcome variable indicated that age, income, education, and life events affected health directly, while the effects of church attendance and marriage were likely mediated through smoking and alcohol behaviors.
182 citations
TL;DR: Data suggest that stocks either diverged rather recently or that the amount of gene flow between groups of fish classified as stocks has been large enough to prevent substantial differentiation, and that morphologic and ecologic divergence may to a large extent be environmentally induced.
Abstract: The Atlantic herring (Clupea harengus) stock complex is confusing from the perspectives of both evolutionary biology and systematics. There are numerous ecologically and morphologically divergent stocks classified as species, subspecies, races, tribes, etc. with an unknown degree of genetic differentiation and reproductive isolation between them. The genetic population structure of herring from the Scandinavian waters was analysed electrophoretically. The pattern for distribution of genetic variation was compared to that of the morphological characters most frequently used for stock classification, i.e., the number of vertebrae and keeled scales. Fish were collected from 17 locations distributed from the northern Gulf of Bothnia to the north-east Atlantic off the west coast of Norway. The genetic analysis was based on 17 electrophoretic loci, 13 of which were variable. There are statistically significant allele frequency heterogeneities, but there is a conspicuously small amount of genetic differentiation, even between stocks classified as representing different subspecies. More than 99 per cent of the total gene diversity was found within populations, and genetic distances are typically of the order of 0·001. The genotypic distribution of the total material is very similar to the one expected if all the samples had been drawn from a single panmictic population. There appears to be no association between the variation of morphological characters and that at electrophoretic loci, and this is true for the variation between as well as within samples. Data suggest that stocks either diverged rather recently or that the amount of gene flow between groups of fish classified as stocks has been large enough to prevent substantial differentiation, and that morphologic and ecologic divergence may to a large extent be environmentally induced.
156 citations
TL;DR: Attempts to prevent disuse osteoporosis with both mechanical and biochemical means, including exercise, skeletal compression, increased hydrostatic pressure to the lower body, supplemental calcium and/or phosphorus, calcitonin, or etidronate were not successful.
Abstract: Maintenance of a skeleton capable of resisting the stresses of everyday life is dependent on the mechanical forces applied to the skeleton during normal activity in a 1-G environment. When the effects of 1-G on the longitudinal skeleton are removed, as with space travel or inactivity, bone and bone mineral are lost because bone resorption is greater than bone formation. Ninety healthy young men were studied during 5-36 weeks of continuous bed rest. During inactivity, urinary calcium increases rapidly and by the sixth week of bed rest, output has risen by 100 mg/day, plateaus for several weeks, and then decreases but remains above ambulatory baseline thereafter. This occurred even though they received vitamin D supplements throughout the study. Calcium balance becomes negative after 2 weeks and by the end of the first month, 200 mg/day is lost. The loss continues at this rate for at least 36 weeks. Calcaneal mineral loses 5% of its mass each month. Attempts to prevent disuse osteoporosis with both mechanical and biochemical means, including exercise, skeletal compression, increased hydrostatic pressure to the lower body, supplemental calcium and/or phosphorus, calcitonin, or etidronate were not successful.
139 citations
TL;DR: The data suggest that the development of both neural and nonneural elements are significantly affected by undernutrition, including processes and substances important for neurotransmission such as transmitter synthesis, degradation and receptor sites.
131 citations
TL;DR: Although the CT appearance of leiomyosarcoma is not specific, these findings, when present, suggest consideration of this diagnosis.
Abstract: The computed tomographic (CT) findings in 118 patients with the diagnosis of leiomyosarcoma were reviewed. The tumor masses visualized in these patients were often quite large; extensive necrotic or cystic change was a frequent finding. Calcification was not observed in these tumors. The liver was the most common site of metastasis in these patients, with marked necrosis of the liver lesions a common finding. Other manifestations of tumor spread included pulmonary metastases, mesenteric or omental metastases, retroperitoneal lymphadenopathy, soft-tissue metastases, bone metastases, splenic metastases, and ascites. The metastatic lesions were often centrally necrotic. Although the CT appearance of leiomyosarcoma is not specific, these findings, when present, suggest consideration of this diagnosis.
130 citations
TL;DR: Thirty‐five patients with malignant brain tumors progressing after cranial irradiation chemotherapy received cisplatin, 60 to 120 mg/m2, into the internal carotid artery by a transfemoral approach, and five of 10 evaluable patients with brain metastases responded to intracarotid cisPlatin, and 2 patients had stable disease.
Abstract: Thirty-five patients with malignant brain tumors (23 with primary brain tumors and 12 with brain metastases) progressing after cranial irradiation +/- chemotherapy received cisplatin, 60 to 120 mg/m2, into the internal carotid artery by a transfemoral approach. Courses of therapy were repeated every 4 weeks. Therapeutic evaluation was performed monthly using the CT scan of the brain and clinical neurologic examination. Thirty patients were evaluable for response. Of 20 evaluable patients with primary malignant brain tumors, 6 responded to therapy and 5 had stable disease. The median time to tumor progression for responding patients was 33 weeks, for stable patients 16 weeks, and 13 weeks for all patients. Five of 10 evaluable patients with brain metastases responded to intracarotid cisplatin, and 2 patients had stable disease. The estimated median time to progression for responding patients was 30+ weeks and 12+ weeks for patients with stable disease. Side effects included seizures in 5 courses, mental agitation and motor restlessness in 1, and transient hemiparesis in 7. One patient may have had a drug-related death, and one patient appeared to develop encephalopathy after treatment. Five patients had clinical deterioration in vision; in two patients it was bilateral. Intracarotid cisplatin has definite activity in patients with malignant primary brain tumors and in patients with brain metastases. The recommended starting dose for intracarotid cisplatin is 60 to 75 mg/m2. At this dose level side effects are uncommon, but includes the risk of neurologic and retinal toxicity.
TL;DR: The occurrence of viruses in conventionally treated drinking water derived from a heavily polluted source was evaluated by collecting and analyzing 38 large-volume samples of water from a water treatment plant.
Abstract: The occurrence of viruses in conventionally treated drinking water derived from a heavily polluted source was evaluated by collecting and analyzing 38 large-volume (65- to 756-liter) samples of water from a 9 m3/s (205 X 10(6) gallons [776 X 10(6) liters] per day) water treatment plant. Samples of raw, clarified, filtered, and chlorinated finished water were concentrated by using the filter adsorption-elution technique. Of 23 samples of finished water, 19 (83%) contained viruses. None of the nine finished water samples collected during the dry season contained detectable total coliform bacteria. Seven of nine finished water samples collected during the dry season met turbidity, total coliform bacteria, and total residual chlorine standards. Of these, four contained virus. During the dry season the percent removals were 25 to 93% for enteric viruses, 89 to 100% for bacteria, and 81% for turbidity. During the rainy season the percent removals were 0 to 43% for enteric viruses, 80 to 96% for bacteria, and 63% for turbidity. None of the 14 finished water samples collected during the rainy season met turbidity standards, and all contained rotaviruses or enteroviruses.
TL;DR: The relative efficacies of free amphotericin B and liposome-encapsulated Amp B in the treatment of established Candida albicans infection in mice rendered neutropenic with cyclophosphamide were studied and provided a rational basis for using high-dose L-AmpB to treat fungal diseases in humans.
Abstract: The relative efficacies of free amphotericin B (Amp B) and liposome-encapsulated Amp B (L-AmpB) in the treatment of established Candida albicans infection in mice rendered neutropenic with cyclophosphamide were studied. AmpB was entrapped in multilamellar liposomes composed of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol in a molar ratio of 7:3. Infected mice treated with single doses of 3 mg L-AmpB/kg of body weight had an increased survival time compared with those injected with either single (dose, 0.8 mg/kg) or multiple doses (dose, 0.8 mg/kg daily for five days) of free AmpB. When treatment was delayed beyond three days postinfection, neither single nor multiple doses of free AmpB resulted in increased survival, whereas treatment with single-dose L-AmpB (dose, 4 mg/kg) showed efficacy when delayed as much as four days postinfection. Five days postinfection only higher doses (dose, 5.6 mg-11.2 mg/kg) of L-AmpB improved survival time and the renal impairment present in the infected animals. These data provided a rational basis for using high-dose L-AmpB to treat fungal diseases in humans, particularly in neutropenic patients.
TL;DR: Previous hemodynamic studies in patients with severe pregnancy-induced hypertension indicating a hyperdynamic state with large fluctuations in systemic and pulmonary vascular resistances are confirmed, and magnesium sulfate has been shown to have a transient hypotensive effect on mean arterial pressure that is not present with continuous infusion.
Journal Article•
TL;DR: The pharmacokinetics, organ distribution, and 24-hr urinary excretion of negatively charged 99mTc-labeled multilamellar liposomes provide a basis for the use ofliposomes as potential target-specific and safe drug carriers in the treatment of pathological conditions that involve organs rich in reticuloendothelial cells.
Abstract: The pharmacokinetics, organ distribution, and 24-hr urinary excretion of negatively charged 99mTc-labeled multilamellar liposomes, composed of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol in a 7:3 molar ratio, were studied in seven patients with cancer. The radiolabeled liposomes were administered i.v. in three doses: 150 mg/sq m of body surface area; 300 mg/sq m; and 450 mg/sq m of lipid. The dose of 99mTc was 4.8 to 7.6 mCi per patient. The plasma disappearance curve was biphasic (half-life α = 5.53 min, half-life β = 289 min), suggesting a two-compartmental model of distribution. The calculated volume of distribution indicated considerable tissue retention of liposomes. This was confirmed by body imaging. Twenty-four hr after injection, liposomes were localized in organs rich in reticuloendothelial cells, i.e., liver [44.5 ± 9.1% (S.E.)], spleen [25.5 ± 7.7%], lung [14.5 ± 4.9%], and bone marrow. Although the hepatic uptake accounted for more than 40% of the total uptake, the spleen retained liposomes at a higher density. Cumulative urinary excretion of radioactivity was 13.4 ± 1.5% over 24 hr. Liposome administration was safe and devoid of any adverse side effects. The results provide a basis for the use of liposomes as potential target-specific and safe drug carriers in the treatment of pathological conditions that involve organs rich in reticuloendothelial cells.
TL;DR: While medical students evidenced levels of symptomatology that were considerably lower than those previous reported in outpatient psychiatric samples, they evidenced considerably higher symptom levels than those previously reported in a general population survey.
TL;DR: Fertilization success was independent of the follicular recruitment protocol used, and with preovulatory eggs, was inversely related to sperm concentration over the range of 2.5 - 50 X 10(4) motile sperm/ml, while that of immature eggs cultured in vitro, then inseminated demonstrated an inverse relationship between fertilization and sperm concentration.
Abstract: The effect of sperm concentration on the fertilization of preovulatory and immature human eggs was studied in the context of an ongoing in vitro fertilization-embryo transfer (IVF-ET) program. Fertilization success was independent of the follicular recruitment protocol used, and with preovulatory eggs, was inversely related to sperm concentration over the range of 2.5 - 50 X 10(4) motile sperm/ml. Maximum fertilization (80.8%) occurred at a concentration of 2.5 X 10(4) motile sperm/ml. The incidence of polyspermic fertilization was directly related to the sperm concentration, decreasing from 5.5% at 10 X 10(4) to 0% at 1-2.5 X 10(4) motile sperm/ml. Immature eggs cultured in vitro, then inseminated, also demonstrated an inverse relationship between fertilization and sperm concentration with a maximum fertilization rate of 66.6% at 5 X 10(4) motile sperm/ml. The percentage of motile sperm in the inseminating population had no influence on fertilization rates unless the value dropped below 40%. Fertilization success using sperm from oligospermic and polyzoospermic males was also examined. In contrast to males with normal semen parameters, oligospermic males demonstrated highest fertilization success at 50 X 10(4) motile sperm/ml. The IVF of preovulatory eggs using sperm from polyzoospermic males was comparable to that for males with normal semen parameters at equivalent sperm concentrations. The implications of these findings to the application of IVF-ET technology to the infertile couple is discussed.
TL;DR: Large microthrombi were more common in patients who had died within less than 24 hours, suggesting a relationship to death or to less time for lysis, and the liver, pituitary gland, pancreas, thymus, brain/spinal cord, large intestine, kidneys, and lungs had the greatest density of microthROMbi.
Abstract: To try to define the significance of disseminated intravascular coagulation (DIC) in head-injured patients, we correlated clinical, laboratory, and pathological findings in 16 patients with head injury as their main problem who had DIC, who died within 4 days of injury, and who were examined postmortem. Patients were ranked according to the number of abnormal laboratory screening tests for DIC and the severity of these abnormalities. The most frequently abnormal laboratory tests were the fibrinogen degradation products and fibrinogen, followed in order by the activated partial thromboplastin time, prothrombin time, and thrombin time. The platelet count was the least abnormal value. The patients with the fewest abnormalities had the least abnormal computed tomographic scans. Autopsy reports revealed necrosis and bleeding in the brain and in a number of other organs, particularly the lungs. Microthrombi were not reported in the original autopsy reports. However, when these cases were reevaluated and their slides were stained with an immunoperoxidase technique using rabbit anti-human fibrinogen antiserum, microthrombi were seen frequently. Large microthrombi were more common in patients who had died within less than 24 hours, suggesting a relationship to death or to less time for lysis. In order of frequency, the brain/spinal cord, liver, lungs, kidneys, and pancreas were most commonly affected, and the liver, pituitary gland, pancreas, thymus, brain/spinal cord, large intestine, kidneys, and lungs had the greatest density of microthrombi. Pulmonary dysfunction had been a frequent problem in these patients, which may have been related to the high incidence of microthrombi and bleeding found in the lungs.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: The results suggest that capillary endothelial damage and phagocytic cell uptake may contribute to an enhanced liposome delivery of Amp-B to those organs most frequently infected with fungi.
Abstract: Recently, it has been observed that encapsulation of Amphotericin B (Amp-B) into multilamellar vesicles (liposomes) decreases the toxicity associated with the administration of Amp-B, while maintaining its antifunga efficacy. In this study, the tissue concentrations of Amp-B in normal mice and in mice infected with Candida albicans were examined. Amp-B concentrations in various tissues were quantitated by high-performance liquid chromatography. Liposomal encapsulation improved the delivery of Amp-B to the liver, spleen, lung, and kidney in both normal and infected mice. Furthermore, after injection of the encapsulated drug, Amp-B was demonstrable in brain tissue of infected animals at potentially therapeutic concentrations. None was demonstrable in the brains of normal animals or animals injected with free Amp-B. The results suggest that capillary endothelial damage and phagocytic cell uptake may contribute to an enhanced liposome delivery of Amp-B to those organs most frequently infected with fungi.
TL;DR: This review of theory, research and the experience of national and community-based studies in mass media and community development for health, family planning and cardiovascular risk reduction identifies some distinctions between micro- and macrointerventions, as well as between the uses of mass media in commercial marketing and those in health promotion.
Abstract: Large-scale, integrated programs--as distinct from multiple and widespread replications of small-scale programs--require for their planning, implementation and evaluation a qualitatively different set of concepts, methods, and procedures. They are not merely the sum of the parts making up numerous applications of the same health education messages and objectives in various organizations or communities. This review of theory, research and the experience of national and community-based studies in mass media and community development for health, family planning and cardiovascular risk reduction identifies some distinctions between micro- and macrointerventions, as well as between the uses of mass media in commercial marketing and those in health promotion.
TL;DR: The Percoll purification method has been applied successfully to physiology, recombinant DNA, and antigenic structure studies, and to the preparation of antigen for the fluorescent treponemal antibody-absorbed (FTA-Abs) test for syphilis.
Abstract: The purification of motile and virulent Treponema pallidum, Nichols strain, from rabbit testicular tissue is reported. Suspensions of T. pallidum were overlayed onto 20-ml cushions of 43% Percoll and in-situ density gradients were formed by centrifugation at 34,800 g for 30 min. Gradient fractionation indicated that T. pallidum banded at a density of 1.051 g/cc3 and that soluble proteineous testicular components remained in the upper portion of the gradient. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) confirmed the removal of host testicular and serum components. Purified suspensions of T. pallidum were greater than 95% actively motile and fully virulent, and greater than 50% motility could be maintained in vitro for up to five days. As determined by electron microscopy, Percoll-purified T. pallidum was structurally unaltered and contained much less tissue debris than did crude extracts or T. pallidum prepared by differential centrifugation. The Percoll purification method has been applied successfully to physiology, recombinant DNA, and antigenic structure studies, and to the preparation of antigen for the fluorescent treponemal antibody-absorbed (FTA-Abs) test for syphilis.
TL;DR: Site-specific recombination of the bacteriophage λ genome into and out of the host bacterial genome is postulated to involve the formation of Holliday structure intermediates by reciprocal single-strand exchanges.
Abstract: Site-specific recombination of the bacteriophage λ genome into and out of the host bacterial genome is postulated to involve the formation of Holliday structure intermediates by reciprocal single-strand exchanges. Synthetic analogues of the predicted recombination intermediates are resolved in vitro by the protein product of the λ int gene. Some of the structural features and reaction conditions for this genetic recombination can now be defined.
TL;DR: Results indicated that the induction of gene transcription and protein synthesis was responsible for the increased transglutaminase levels and activity observed with cultured human monocytes, and may be a component in the in vivo differentiation of human monocyte into macrophages.
Abstract: The levels and activity of tissue transglutaminase were studied in human peripheral blood monocytes during differentiation into macrophages in vitro. The enzyme was present at low levels in freshly isolated monocytes (less than 20 ng/mg cell protein) but increased 50-fold during 10 d of adherent culture in autologous serum, reaching levels of 0.1% of total cellular protein. The rate of appearance of tissue transglutaminase in monocytes was accelerated by low levels of lipopolysaccharide. The half-life of disappearance of transglutaminase from human monocytes was 11 and 7 h in 2-d-old and 10-d-old cells, respectively. Treatment of 1-day-old monocytes with actinomycin D for 24 h blocked the increase in transglutaminase levels. These results indicated that the induction of gene transcription and protein synthesis was responsible for the increased transglutaminase levels and activity observed with cultured human monocytes. The induction of tissue transglutaminase may be a component in the in vivo differentiation of human monocytes into macrophages.
TL;DR: Characteristics of DCC associated with higher rates of disease among children were the presence of young, non-bowel trained children, staff who both diapered infants and prepared food on a regular basis, DCC for profit management, and DCC whose only guidelines were provided by the State.
Abstract: Sixty day care centers (DCC) randomly selected from 736 licensed child care facilities in Harris County (Houston), Texas were surveyed for the incidence of diarrhea by periodic visits and weekly telephone calls over two years. A total of 2,708 episodes of diarrhea were reported in 3,800 children under 6 years of age, and 84 cases occurred in center staff. Overall incidence was 0.44 episodes/person/year among children and 0.14 among staff. Attack rates among the 60 DCC ranged from none to 3.64 cases/year in each child. The incidence for children under 36 months of age was 17 times higher than for the older group. Characteristics of DCC associated with higher rates of disease among children were the presence of young, non-bowel trained children, staff who both diapered infants and prepared food on a regular basis, DCC for profit management, and DCC whose only guidelines were provided by the State. The socioeconomic burden associated with DCC disease, its transmission, and control is considerable and needs t...
TL;DR: These studies suggest that retinoic acid and serum retinol-binding protein can directly regulate macrophage gene expression and specifically induce the synthesis of tissue transglutaminase.
TL;DR: It is concluded that the paracellular pathway provides a major route for transepithelial C1- transport and a significant transcellular flux of C2- must exist, implicating a neutral exchange mechanism at the apical cell membrane in series with the high basolateral membrane C 1- conductance.
Abstract: The chloride-conductive properties of the isolated rabbit cortical collecting duct were assessed with microelectrode techniques. The transepithelial, apical, and basolateral membrane potential diff...
TL;DR: Immunocytochemical methods were used to search for virus antigen in formalin‐fixed, paraffin‐embedded central nervous system tissues from 10 patients with measles encephalomyelitis and 12 patients who had died of measles without CNS involvement, and all the CNS tissues studied were viral antigen negative.
Abstract: Measles encephalomyelitis appears to be an immune-mediated parainfectious disorder, but it is unclear whether viral invasion of brain is an obligate step in its development. Immunocytochemical methods were used to search for virus antigen in formalin-fixed, paraffin-embedded central nervous system (CNS) tissues from 10 patients with measles encephalomyelitis and 12 patients who had died of measles without CNS involvement. All the CNS tissues studied were viral antigen negative. Similarly fixed CNS tissues from all of 6 patients with subacute sclerosing panencephalitis were viral antigen positive and served as controls. The pattern of perivenular demyelination was also determined in 4 cases of measles encephalomyelitis using antibodies to myelin associated glycoprotein and myelin basic protein and a Luxol fast blue stain. Areas of demyelination in serial sections were quantitated, and no morphometrical differences were found among tissues stained with the three stains.
The data suggest the lack of virus replication in the CNS during encephalomyelitis or fatal measles without CNS symptoms. The pattern of loss of myelin associated glycoprotein and myelin basic protein in regions of perivenular demyelination resembles that reported in experimental allergic encephalomyelitis. This pattern of demyelination has been proposed to result from a primary attack on the myelin sheath rather than from direct involvement of the oligodendroglial cell.
TL;DR: The apparent discrepancy between weak familial aggregation and the known strong HLA-DR4 association with rheumatoid arthritis was resolved by examining the mathematical relationship between the measures of association in the two different types of studies.
Abstract: This investigation of the familial aggregation of rheumatoid arthritis in Rochester, Minnesota, was prompted by the considerable variability in previous reports and the need to interpret findings in light of the recently established human lymphocyte antigen (HLA)-DR4 association. The historical cohort methodology was applied to determine the incidence of adult-onset rheumatoid arthritis in 1631 biologic relatives of 78 probands compared with the Rochester population incidence. The ratio of the age- and sex-adjusted rates in first-degree relatives compared with the general population was 1.7 (95% confidence interval 1.0-2.9). The increase was concentrated in the 16- to 40-year-old age group, suggesting some disease heterogeneity. However, the level of familial risk was not significantly affected by the proband's sex, seropositivity, age, or parental disease status. Integrating these findings with prior research in which case ascertainment was complete led to the conclusion that familial aggregation of rheumatoid arthritis is weak. The apparent discrepancy between weak familial aggregation and the known strong HLA-DR4 association with rheumatoid arthritis was resolved by examining the mathematical relationship between the measures of association in the two different types of studies. Results show that to be consistent with weak familial clustering, any putative susceptibility gene must have very low penetrance, and/or there must be a large residual of sporadic cases.
TL;DR: Current mental disorder DRGs and alternate DRGs examined here explain less than 3-12% of the variation in psychiatric length of stay, in contrast to 30-50% explained variation for other disorders.
Abstract: On October 1, 1983, Medicare began paying general hospitals by a prospective payment system based on DRGs. Psychiatric settings are exempted automatically or by request. By January 1985, however, a decision is required on how to integrate psychiatric settings into this system. This article provides an empirical analysis of the current DHHS DRGs categories for mental disorders. Current mental disorder DRGs and alternate DRGs examined here explain less than 3-12% of the variation in psychiatric length of stay. This is in contrast to 30-50% explained variation for other disorders. Alternatives and policy implications are discussed.
TL;DR: It is concluded that microelectrode techniques can be applied successfully to the cortical collecting duct and that the apical cell membrane possesses an amiloride-sensitive Na+ conductance and a Ba2+- and H+-sensitive K+ Conductance.
Abstract: The apical cell membrane ionic conductive properties of the isolated perfused rabbit cortical collecting duct (tubule) were assessed at 37 degrees C using microelectrode techniques. In the initial evaluation of the methodology, it was observed that stable cell membrane voltage recordings could be obtained by impaling cells either from the luminal side across the apical cell membrane or from the bath side across the basolateral cell membrane, providing initial evidence supporting the application of these techniques to this tissue. With the latter method of impalement, it was observed that addition of amiloride (50 microM) to the luminal perfusate caused a hyperpolarization of the apical cell membrane voltage, a decrease in the transepithelial conductance, and an increase in the fractional resistance (estimated as the ratio of the resistance of the apical cell membrane to the sum of apical and basolateral cell membrane resistances). These results are consistent with an amiloride-sensitive Na+ conductance at the apical cell border. In a similar manner it was deduced from the effects of elevating K+ in the luminal perfusate from 5 to either 25 or 50 mM that there was a high K+ conductance at the apical border. This conductive pathway was blocked by the luminal addition of 5 mM Ba2+ or reduction of the luminal pH to 4.0. Furthermore, since addition of both amiloride and Ba2+ to the perfusate caused the fractional resistance to increase from 0.52 +/- 0.04 to 0.91 +/- 0.03, the Na+ and K+ conductances are the apparent dominant conductive pathways at that border. It is concluded that microelectrode techniques can be applied successfully to the cortical collecting duct and that the apical cell membrane possesses an amiloride-sensitive Na+ conductance and a Ba2+- and H+-sensitive K+ conductance.