Showing papers by "University of Texas Health Science Center at Houston published in 1978"

Estimation of average heterozygosity and genetic distance from a small number of individuals

Abstract: The magnitudes of the systematic biases involved in sample heterozygosity and sample genetic distances are evaluated, and formulae for obtaining unbiased estimates of average heterozygosity and genetic distance are developed. It is also shown that the number of individuals to be used for estimating average heterozygosity can be very small if a large number of loci are studied and the average heterozygosity is low. The number of individuals to be used for estimating genetic distance can also be very small if the genetic distance is large and the average heterozygosity of the two species compared is low.

Physical Illness Presenting as Psychiatric Disease

Abstract: • A study of 658 consecutive psychiatric outpatients receiving careful medical and biochemical evaluation, defined an incidence of medical disorders productive of psychiatric symptoms in 9.1% of cases. The most frequent presentations were of depression, confusion, anxiety, and speech or memory disorders. The presence of visual hallucinations was believed to indicate medical etiology until proved otherwise. Major illnesses presenting with psychiatric symptoms in order of frequency were infectious, pulmonary, thyroid, diabetic, hematopoietic, hepatic and CNS diseases. Forty-six percent of these patients suffered from medical illnesses previously unknown to either them or their physician. A plea is made for careful medical evaluation of psychiatric patients.

On the role of organized multienzyme systems in cellular metabolism: a general synthesis.

Abstract: Throughout this article, vector quantities are denoted by use of bold type face (e.g. Ai, ri). The symbol ▿ denotes the “gradient” operator and δ(r−r′) the three-dimensional Dirac delta function (see Appendix 1). All other terms and symbols are defined as they occur.

Schizophrenic symptoms improve with apomorphine

Abstract: Eighteen chronic schizophrenic patients received subcutaneous doses of apomorphine, a dopamine receptor agonist, and of placebo in separate trials. A significant improvement in psychotic symptoms occurred after apomorphine compared to placebo. The results are interpreted as a consequence of presynaptic dopamine receptor activation by apomorphine with a subsequent decrease in dopamine-mediated neural transmission.

Detection and characterization of colonization factor of enterotoxigenic Escherichia coli isolated from adults with diarrhea.

Abstract: The fimbriate colonization factor antigen (CEA) of Escherichia coli strain H-1047 was isolated and used to prepare anti-CFA antiserum. Enterotoxigenic E. coli (ETEC) isolated from 29 adults with diarrhea acquired in Mexico were examined for CFA by using this serum. Retrospectively, it was found that ETEC possessing the H-10407-type CFA were isolated from 25 (86%) of these diarrhea cases as compared with 2 of 11 (18%) from asymptomatic controls from whom ETEC had been isolated. CFA was found onE. coli of various serotypes, as demonstrated by bacterial agglutination by the anti-CFA serum. Heat treating the cells at 65 degress C for 1 h prevented the agglutination. CFA-positive strains did not react with anti-CFA serum when the cultures were grown at a low incubation temperature (18 degrees C). E. coli isolates identified serologically as CFA positive were shown to adhere to the intestinal villous surfaces of infant rabbits. By the indirect immunofluorescence technique, it was found that adhesion occurred preferentially in the upper 20 cm of the small intestine. Also, the ability or inability of various isolates to adhere to intestinal mucosa in vivo correlated with the presence or absence of fimbriae on the cells when grown in vitro. Agglutinability with anti-CFA serum, fimbriae, and adhesiveness were spontaneously lost by many isolates after laboratory passage in a manner previously described with E. coli H-10407. These observations suggest that the H-10407-type CFA plays a role in the virulence of ETEC possessing this antigen.

The theory of genetic distance and evolution of human races

Abstract: 1. Theoretical works on Nei's genetic distance and its extensions are discussed. New formulae for the sampling variances of genetic distance estimates are presented. Formulae for the genetic identity of genes at the electrophoretic level when the mutation rate varies from locus to locus are also presented. 2. Empirical data suggests that the rate of gene substitution or mutation rate per locus varies considerably among protein loci, and if this factor is taken into account, the rate of decline of genetic identity (I) is no longer constant but decreases with evolutionary time. Using both the infiniteallele model and the stepwise mutation model, the numerical relationship betweenI and evolutionary time is presented. This relationship may be used for estimating the time after divergence between populations. The value of genetic distance or genetic identity is also affected considerably by the bottleneck effect. The bottleneck effect generally accelerates the increase of genetic distance with time, and the effect remains for a long time after the population size returns to the original level. A method for correcting for this effect is presented. 3. Application of the theory of genetic distance to data on protein polymorphism in man indicates that the genetic variation between the three major races, Caucasoid, Negroid, and Mongoloid, is much smaller than the variation within them, despite the fact that there is a conspicuous difference in some morphological characters such as pigmentation, facial structure, and hair texture. It is proposed that the differentiation of these morphological characters was brought about by relatively strong natural selection through a small number of gene substitutions, whereas general protein loci are subject to little or very weak selection. Analysis of blood group gene frequency data gives essentially the same result as those from protein loci, though they are likely to have been affected by nonrandom sampling of the loci. It is also shown that at the protein level the racial differences in man correspond to those between local races in other organisms. 4. Rough estimates of the number of codon differences between an individual of man and his various relatives are presented. It seems that the mean number of codon differences between man and chimpanzee is about 10 times larger than that between second degree relatives in Caucasians or Japanese, but about 1/19 of that between man and horse. 5. Genetic distance estimates suggest that among the three major races of man the first divergence occurred about 120,000 years ago between Negroid and a group of Caucasoid and Mongoloid and then the latter group split into Caucasoid and Mongoloid around 60,000 years ago. It is also shown that the genetic identity between man and chimpanzee corresponds to a divergence time of 4–6 million years if the assumption of constant rate of amino acid substitution is correct. 6. Methods of constructing a phylogenetic tree from genetic distance estimates are discussed. For constructing the topology of a tree, Fitch and Margoliash's method is quite efficient. For estimating branch lengths, however, Nei's method of averaging distances seems to be better. 7. A phylogenetic tree for twelve races of man is constructed by using gene frequency data for 11 protein and 11 blood group loci. This tree roughly agrees with what we expect intuitively from the morphological characters and the historical record of these races.

IgG subclasses in human periodontal disease. I. Distribution and incidence of IgG subclass bearing lymphocytes and plasma cells.

Abstract: Lymphocyte membrane-associated IgG subclass antibodies in human periodontal disease were studied to ascertain the elative presence of cytophilic IgG antibodies and the membrane Fc receptors which bind them. The experimental approach correlated the efect of incubating gingiva in tissue culture medium to remove cytophilic antibodies with the changes in the number of Fc receptors detectable after washing. The evidence indicated that the majority of lymphocytes in mild gingivitis lesions lacked cytophilic IgG antibodies as well as Fc receptors. IN severe gingivitis, the number of IgG subclass bearing lymphocytes increased to about half of the total lymphoid population, while the perentage of Fc receptor bearing cells remained qite low (12.3%± 3.2, S.E.). The majority of IgG subclass bearing lymphocytes had membrane IgG which serve as receptors for antigen; such cells are classically defined as bone marrow (B) derived lymphocytes and serve as the progenitor for plasma cells. Gingival specimens for patients with periodontitis were found to contain the highest percentage of Fc receptor bearing lymphocytes (38.3%± 12.6 S.E.) and cytophilic IgG antibodies. The findings indicae tha the clinical stages of human perodontal disease are characterized by different populations of infiltrating lymphocytes.

The effect of a reduction in leading causes of death: potential gains in life expectancy.

Abstract: The potential gains in total expectation of life and in the working life ages among the United States population are examined when the three leading causes of death are totally or partially eliminated. The impressive gains theoretically achieved by total elimination do not hold up under the more realistic assumption of partial elimination or reduction. The number of years gained by a new-born child, with a 30 per cent reduction in major cardiovascular diseases would be 1.98 years, for malignant neoplasms 0.71 years, and for motor vehicle accidents 0.21 years. Application of the same reduction to the working ages, 15 to 70 years, results in a gain of 0.43, 0.26, and 0.14 years, respectively for the three leading causes of death. Even with a scientific break-through in combating these causes of death, it appears that future gains in life expectancies for the working ages will not be spectacular. The implication of the results in relation to the current debate on the national health care policy is noted.

Maintenance of Genetic Variability under the Joint Effect of Mutation, Selection and Random Drift.

Abstract: Formulae are developed for the distribution of allele frequencies (the frequency spectrum), the mean number of alleles in a sample, and the mean and variance of heterozygosity under mutation pressure and under either genic or recessive selection. Numerical computations are carried out by using these formulae and Watterson9s (1977) formula for the distribution of allele frequencies under overdominant selection. The following properties are observed: (1) The effect of selection on the distribution of allele frequencies is slight when 4 Ns ≤ 4, but becomes strong when 4 Ns becomes larger than 10, where N denotes the effective size and s the selective difference between alleles. Genic selection and recessive selection tend to force the distribution to be U-shaped, whereas overdominant selection has the opposite tendency. (2) The mean total number of alleles in a sample is much more strongly affected by selection than the mean number of rare alleles in a sample. (3) Even slight heterozygote advantage, as small as 10 -5 , increases considerably the mean heterozygosity of a population, as compared to the case of neutral mutations. On the other hand, even slight genic or recessive selection causes a great reduction in heterozygosity when population size is large. (4) As a test statistic, the variance of heterozygosity can be used to detect the presence of selection, though it is not efficient when the selection intensity is very weak, say when 4 Ns is around 4 or less. A model, which is somewhat similar to Ohta9s (1976) model of slightly deleterious mutations, has been proposed to explain the following general patterns of genic variation: (i) There seems to be an upper limit for the observed average heterozygosities. (ii) The distribution of allele frequencies is U-shaped for every species surveyed. (iii) Most of the species surveyed tend to have an excess of rare alleles as compared with that expected under the neutral mutation hypothesis.

Early postnatal starvation causes lasting brain hypomyelination.

Abstract: — Rats were starved during various intervals of postnatal development, and subsequently, they were rehabilitated by feeding ad lib. through 60 days of age. Starvation was induced by an increasingly severe regime of maternal deprivation that results in a 50% deficit in body weight at 20 days. Relatively mild and brief starvation, from birth through 8 days, as well as more severe starvation occurring late, from 14 to 30 days, produced no lasting deficit in myelin accumulation. Starvation from birth through 14 days or from birth through 20 days produced lasting, significant myelin deficits in all regions (cerebrum, cerebellum, medulla, midbrain, hippocampus, hypothalamus, and striatum) of the brain. These data, in combination with our previous metabolic studies of myelin synthesis of starved and control rats, show that starvation early in development, during the period of oligodendroglial cell multiplication, accounts for an immediate reduction in myelin synthesis, and that the consequent myelin deficit proves irreversible in subsequent nutritional rehabilitation. In contrast, brain weight is subject to substantial growth catch-up upon rehabilitation. Where the onset of starvation was late, during the period of rapid myelin synthesis, but after completion of the major period of oligodendroglial cell proliferation, no lasting myelin deficit was observed upon rehabilitation.

A multinational Andean Genetic and Health Program: Growth and development in an hypoxic environment

Abstract: In 1972 a multidisciplinary study sought to assess the health status of the indigenous peoples of the Department of Arica in northern Chile, the Aymara, and to relate disease, morphological, physiological and biochemical variation, to the wide changes in altitude of the region. Presented here are the morphological changes which accompany age, altitude and ethnicity amoung 1047 children and adults, permanent residents of the coast, sierra and altiplano. At comparable ages, high-altitude residents were shorter, lighter and leaner but with more expansive and rounder chests than sea-level controls. None of these effects was systematically related to ethnicity (Spanish-Aymara surname), although when stature was held constant, children with greater Aymara ancestry had largest chest circumferences and longer bones. These results suggest that (1) altitude confers allometric growth changes (expensive growth of the chest and diminished growth of the structures less related to oxygen transport); and (2) size changes associated with altitude are acquired during development while shape changes may be under genetic control. Altitude appears to account for less of the variation in growth in this relatively homogeneous Chilean sample than has been reported for other Andean samples, suggesting other concomitants confounding the effects of hypoxia in Andean South America.

The response of single human cells to zero-gravity

Abstract: The 59-day Skylab III earth-orbital mission carried an experiment designed to observe the effects of zero-gravity on a strain of diploid human embryonic lung cells, WI-38. The experiment (NASA Exp. No. S015) was performed in a miniaturized, fully automated tissue-culture laboratory package called the Woodlawn Wanderer Nine. The package, which weighed less than 10 kg, photographed two perfused cultures for 28 days using phase-contrast microscopes and 16-mm time-lapse cameras; fixed 10 perfused cultures in gluteraldehyde one at a time over a 12-day period; and returned to earth eight perfused cultures in a viable state for subsequent subculture and study. Two ground control experiments using specimens from the same clone were run simultaneously with the flight experiment in identical packages. The controls were subjected to simulated flight vibration profile within an hour after spacecraft liftoff. All packages were sealed at 1-atmosphere pressure. Analysis of the flight and control films showed no differences in mitotic index, cell cycle or migration rates. Growth curve, DNA microspectrophotometry, phase microscopy and ultrastructural studies on the fixed cultures revealed no effects of zero-gravity. Karyotyping and chromosome-banding studies were performed on subcultures of the returned viable cells and these showed no significant differences from the controls. Minor unexplained differences were found in the biochemical constituents of the spent media of the flight and control experiments. Within the limits of this, experimental design it was found that the zerogravity environment produced no detectable effects on WI-38.

Statistical Studies on Protein Polymorphism in Natural Populations II. Gene Differentiation between Populations.

Abstract: With the aim of testing the validity of the mutation-drift hypothesis, we examined the pattern of genetic differentiation between populations by using data from Drosophila, fishes, reptiles, and mammals. The observed relationship between genetic identity and correlation of heterozygosities of different populations or species was generally in good agreement with the theoretical expectations from the mutation-drift theory, when the variation in mutation rate among loci was taken into account. In some species of Drosophila, however, the correlation was unduly high. The relationship between the mean and variance of genetic distance was also in good agreement with the theoretical prediction in almost all organisms. We noted that both the distribution of heterozygosity within species and the pattern of genetic differentiation between species can be explained by the same set of genetic parameters in each group of organisms. Alternative hypotheses for explaining these observations are discussed.

Bleomycin pharmacokinetics in man. I. Intravenous administration.

Abstract: SummaryDisposition of bleomycin was studied in plasma and urine (14 patients) and ascites fluid (2 patients) after intraperitoneal (IP) and intrapleural (IPl) administration, by radioimmunoassay. Peak plasma bleomycin concentrations after 60 U/m2 in 12 patients ranged between 0.4 and 5.0 mU/ml. For those patients with creatinine clearances greater than 50 ml/min the composite terminal phase bleomycin plasma half-lives (±SD) for three ‘IPl’ and six ‘IP’ patients were 3.4±0.3 and 5.3±0.4 h, respectively. The composite IP plasma half-life was significantly longer than the IPl hal-life (P<0.001) and previously reported IV half-life (t1/2=4.0 ±0.6 h) (P<0.01). In patients with normal renal function, bleomycin excretion during the first 24 h was in most cases lower following intracavitary (IC) than following IV administration (21.7%±8.6% vs. 44.8%±12.6%, respectively) (P<0.005). Comparison of bleomycin plasma concentration time products normalized for dose and half-life for IV and IC administration allowed an estimate that about 45% of the IC bleomycin dosage is absorbed into the systemic circulation. When calculating the total systemic exposure to bleomycin for a patient we suggest using the sum of the IV dose and one-half of the IC dose.

BRIEF COMMUNICATION: Tricyclic Exacerbation Of Steroid Psychosis

Abstract: Four patients in a series of 14 cases of steroid psychosis where steroids were used to treat disease not effecting the central nervous system, are reported. All demonstrated a predominantly affective mood change prior to initiation of treatment with tricyclic antidepressants by the primary physician. In each case, the patient's mental state deteriorated rapidly following initiation of tricyclics in mid-dose range (i.e., 100 to 150 mg q.d.). These agents produced a qualitative change in the nature of the patient's psychosis rather than simply aggravating pre-existent features. All patients experienced visual hallucinations within 4 days of tricyclic administration. Persistent auditory hallucinations (two cases) became threatening, accusatory, and constant. The exacerbated psychosis cleared rapidly with the discontinuation of the antidepressant and the addition of a phenothiazine. Phenothiazines, in doses of 400 to 800 mg q.d., were necessary to reverse the symptoms of these patients. Phenothiazines were also required to produce a salutary effect in the 10 patients who did not receive tricyclics, but at an average dose of only 200 mg. Steroids raise the effective blood level of tricyclics and alter central catecholamine movement across membranes. These changes may represent the mechanism for exacerbation of steroid psychoses.

Prazosin and clonidine for moderately severe hypertension.

Abstract: In a single-blind comparative study of the cases of 30 moderately hypertensive patients, clonidine hydrochloride and prazosin hydrochloride had similar effectiveness in lowering blood pressure. Neither agent had significant effects on the renin-aldosterone axis. Addition of polythiazide to prazosin and chlorthalidone to clonidine notably increased the antihypertensive effect of both drugs. Serum cholesterol levels were observed to decrease when prazosin and clonidine were given and to rise when the diuretics were added to the regimen. The patients treated with clonidine were troubled by side effects, particularly drowsiness and dry mouth. Prazosin was better tolerated, with side effects tending to diminish with time. The "first-dose" effect was seen in two patients given prazosin, but it did not limit treatment. Both diuretics induced notable hypokalemia. ( JAMA 240:2553-2556, 1978)

Comparison between adsorption of poliovirus and rotavirus by aluminum hydroxide and activated sludge flocs.

Abstract: Adsorption of poliovirus and rotavirus by aluminum hydroxide and activated sludge flocs was studied. Both aluminum hydroxide and activated sludge flocs adsorbed greater amounts of poliovirus than rotavirus. Aluminum hydroxide flocs reduced the titer of poliovirus in tap water by 3 log10, but they only reduced the titer of a simian rotovirus (SA-11) in tap water by 1 log10 or less and did not noticeably reduce the number of human rotavirus particles present in a dilute stool suspension. Activated sludge flocs reduced the titer of added poliovirus by 0.7 to 1.8 log10 and reduced the titer of SA-11 by 0.5 log10 or less. These studies indicate that a basic difference in the adsorptive behavior of enteroviruses and rotaviruses exists and that water and wastewater treatment processes that are highly effective in removal of enteroviruses may not be as effective in removing other viral groups such as rotaviruses.

Elevated frequency of Tay-Sachs disease among Ashkenazic Jews unlikely by genetic drift alone.

Abstract: Using the steady-state distribution of recessive lethal gene the probability of finding the elevated frequency of Tay-Sachs (TSD) gene among Ashkenazic Jews is computed. For various estimated values of mutation rate and population size, this probability is found to be statistically significant. This probabiltiy, in fact, becomes even smaller if a steady influx of foreign genes into the Ashkenazic Jewish populations is considered. It is suggested that heterozygote advantage together with random genetic drift should be considered as the most probable mechansim for the elevation of TSD gene frequency among the Ashkenazic Jews.

Single-Dose Tetracycline Therapy for Shigellosis in Adults

Abstract: Forty-two adults who had Shigella isolated from stool (26 symptomatic, 16 asymptomatic) received a single oral dose of tetracycline hydrochloride (2.5 g). Minimal inhibitory concentrations of the 42 isolates demonstrated that 41% were sensitive to tetracycline. Sixteen of 18 patients with diarrhea who had tetracycline-resistant Shigella and all eight patients with diarrhea who had tetracycline-sensitive Shigella were clinically well and had Shigella -negative stools 48 hours after therapy. Fifteen of 16 asymptomatic patients demonstrated clearing of Shigella from stool within 48 hours of therapy. Single-dose tetracycline therapy is effective in the treatment of Shigella regardless of clinical expression of illness or in vitro sensitive of the organism. ( JAMA 239:853-854, 1978)

Intra‐Aortic Balloon Pumping: Theory and Practice Experience with 325 Patients

Abstract: Intra-aortic balloon pumping to support the failing circulation is now an accepted therapeutic modality. The device is simple. Insertion can be accomplished rapidly and efficiently in emergency rooms, coronary care units, cardiac catheterization suites and operating rooms, preoperatively, intraoperatively and postoperatively. The hemodynamic effects are immediate and predictable, and the accruing clinical results show increasing survival and hospital discharge rates. In these institutions, mechanical support of the circulation by this and more advanced methods has been formalized within the responsibility of a Circulatory Support Service. The purpose of this Report is to summarize some observations and analyses which have been made during care of 325 consecutive postcardiotomy and/or postinfarction cardiogenic shock patients. Historical, theoretical, basic, and applied aspects and current results are included. Foremost are the straightforward concepts of considering the heart as a pump, the failing heart as a failing pump and intra-aortic balloon pumping as a temporary intravascular, auxiliary pump, capable of stabilizing or reversing that failure if utilized early in its evolution.

A client satisfaction survey as one element in evaluation.

Abstract: Surveys and interviews were conducted with clients and former clients of units of a large mental health and mental retardation authority as part of an evaluation of the agency. Both clients and former clients reported overall satisfaction with services. Highest percent of dissatisfaction was reported toward operating hours of the agency. Results of the survey were compared with those from similar investigations and conclusions drawn as to why clients are inclined to give favorable ratings to services.

Telangiectasia and von Willebrand's disease in two families

Abstract: Two families are described with members who have both von Willebrand's disease and telangiectasias. Family A has four members in three consecutive generations that have both von Willebrand...

Gene differentiation among the Dhangar caste-cluster of Maharashtra, India.

Abstract: Genetic differentiation among the 22 Dhangar castes of Maharashtra, India, is studied using data on several polymorphic serological and biochemical loci employing Nei’s distance measures. The intercas

Construction of equal-hue discriminability scales for the pigeon.

Abstract: Equal-hue discriminability steps for the pigeon are shown as tabular entries that can be summed or interpolated to produce sequences of equal discriminability steps of various step size. Equal-hue discriminability sequences can be constructed where the number of stimuli and spectral range are specified, or where an interval in one spectral region is to be equated to an interval in another spectral region.