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PubMed1988

Pigeons' choices in situations of diminishing returns: fixed- versus progressive-ratio schedules.

In two different discrete-trial procedures, pigeons were faced with choices between fixed-ratio and progressive-ratio schedules. The latter schedules entail diminishing returns, a feature analogous to foraging situations in the wild. In the first condition (no reset), subjects chose between a progressive-ratio schedule that increased in increments of 20 throughout a session and a fixed-ratio schedule that was constant across blocks of sessions. The size of the fixed ratio was varied parametrically through an ascending and then a descending series. In the reset condition, the same fixed-ratio values were used, but each selection (and completion) of the fixed ratio reset the progressive-ratio schedule back to its minimal value. In the no-reset procedure, the pigeons tended to cease selecting the progressive ratio when it equaled or slightly exceeded the fixed-ratio value, whereas in reset, they chose the fixed ratio well in advance of that equality point. These results indicate sensitivity to molar as well as to molecular reinforcement rates, and those molar relationships are similar to predictions based on the marginal value theorem of optimal foraging theory (e.g., Charnov, 1976). However, although previous results with monkeys (Hineline & Sodetz, 1987) appeared to minimize responses per reinforcement, the present results corresponded more closely to predictions based on sums-of-reciprocals of distance from point of choice to each of the next four reinforcers. Results obtained by Hodos and Trumbule (1967) with chimpanzees in a similar procedure were intermediate between these two relationships. Variability of choices, as well as median choice points, differed between the reset and no-reset conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1978

Hemoglobin H disease in Sardinia: phenotypic and genetic observations.

In this study the clinical and hematological characteristics, the transmission pattern and the relative rates of globin chain synthesis were determined in the members of four Sardinian families with 14 patients affected by hemoglobin H disease. The severity of hemoglobin H disease in Sardinian subjects shows a high degree of variability. Clinically it usually appears intermediate between the hemoglobin H disease found in Oriental and Negro populations. The alpha/beta specific activity ratio was 0.42 +/- 0.10 indicating an analogous biochemical defect like that described in the Chinese. On the basis of hematological data and alpha/beta ratio, the genetics of hemoglobin H disease in Sardinians seem to follow a pattern similar to that observed in Orientals: one parent showing alpha-thalassemia-1 trait and the other alpha-thalassemia-2 trait. Parent offspring transmission of hemoglobin H disease did occur in 2 out of 6 hemoglobin H matings with spouses carrying the alpha-thalassemia-1 gene. This observation indicates either a high frequency of alpha-thalassemia trait in Sardinians or a high incidence of inbreeding. In one family the mating of a patient with hemoglobin H disease and a normal person produces 6/6 offspring with alpha-thalassemia-1. The genetic implications of this transmission pattern are discussed.

Adult↗

PubMed1992

Protein and energy metabolism in patients with progressive muscular dystrophy.

Studies were made on whether body weight loss in patients with muscular dystrophy is due to reduced intake and/or abnormal expenditure of energy. For this, food intakes and various physiological variables were surveyed in totals of 310 patients with Duchenne muscular dystrophy (DMD) of 11 to 29 years old and 28 patients with limb-girdle muscular dystrophy (LGMD) of 30 to 47 years old. Energy and protein intakes, expressed on a unit body weight basis, in DMD patients were comparable to, or higher than the allowances for age-matched healthy controls, whereas those in LGMD patients were 92 and 94% respectively of these allowances. The basal metabolic rate (BMR), expressed as kcal/kg/day, of DMD patients of all ages was higher than that of controls, the difference increasing with age, and being about 20 to 30% higher than that of controls in older patients with DMD. The BMR of LGMD patients was nearly normal. The maintenance requirements of conventional dietary protein in DMD and LGMD patients were 1.26 and 0.84 g/kg/day, respectively. These values were about 68 and 12% higher than the normal adult value (0.75 g/kg/day), indicating decreased protein utilization and increased protein catabolism. Daily excretion of urinary 3-methylhistidine (3MH) per unit muscle mass (micrograms/mg creatinine) by MD patients was significantly higher than that by controls, indicating increased degradation of muscle protein. The BMR, maintenance protein requirement and 3MH excretion of DMD patients suggest that DMD is a hypercatabolic disease. Comparison of the energy and protein intakes with the allowances estimated in consideration of increased requirements showed deficiencies of energy and protein in DMD patients. Thus, we conclude that the underweight of the DMD patients resulted from nutrient deficiencies due to hypercatabolism, despite their considerably high intakes of energy and protein, expressed as per kg body weight. These deficiencies were confirmed by demonstrating decreased concentrations of free essential amino acids, particularly branched chain amino acids, in their serum. The values of variables of LGMD patients were intermediate between those of DMD patients and control subjects.

Adolescent↗

PubMed1999

Primary hepatic epithelioid hemangioendothelioma: case report.

Hepatic epithelioid hemangioendothelioma (HEH) is a very rare vascular tumor of the liver. It usually affects adult women and presents as multiple hepatic nodules with mainly peripheral distribution. It poses special difficulties for clinicians in its diagnosis and treatment because of its non-specific clinical manifestations and findings on imaging, and it is easy to be misdiagnosed pathologically. Its clinical course and prognosis are variable but supposed to be intermediate between hemangioma and angiosarcoma. The primary treatments of choice are radical resection or liver transplantation. We report a 62-year-old man with right upper quadrant abdominal pain of several days' duration, who was initially misdiagnosed as having a liver abscess. Finally, HEH was diagnosed on the basis of positive immunohistochemical staining for factor VIII-related antigen in tumor cells. This case could serve to highlight the pitfalls in diagnosing this rare tumor. Increasing the index of suspicion and familiarity with the radiological and histological characteristics of this tumor would facilitate the accurate diagnosis and thus avoid unnecessary interventions.

Biopsy↗

PubMed1994

[Maternal mortality in Latin America and the Caribbean].

"The underlying analytical scheme in this study [focuses] on the phenomena of maternal mortality in relation to fertility rates [in Latin America and the Caribbean].... The countries of the region are classified under a typology, formulated in function of the association between maternal mortality and fertility rates. Using that typology, the causes of maternal death are then presented, stressing...recent trends. Finally, the intermediate factors and the contextual variables related to fertility are discussed...." (SUMMARY IN ENG)

Americas↗

PubMed1992

[The problem of breeding for spots in rabbits. 2. Further results on the variation of characteristics in fattening and breeding animals].

The mode of inheritance of spotting in both breeds (ES and DRS) is compatible with incompletely dominant resp. intermediate segregation, though a broad variability of spotted areas exists, indicating the influence of minor genes or other ontogenetic factors. Additional findings support the conclusion, that there is a very distinct predisposition of homozygous KK animals to develop megacolon with growing age. This also has consequences for the relative organ weight of the heart and of the adrenals in this genotype. Sporadically encountered accessory adrenal cortical tissue however did not exhibit genotypic preferences.

Adrenal Glands↗

PubMed1981

Assessment of vitamin A status by an isotope dilution method.

The body pool of Vitamin A was estimated by an isotope dilution method and the values obtained were compared with values for total liver Vitamin A obtained by chemical analysis. Rats with varying hepatic levels of Vitamin A were administered a single oral dose of [11,12-3H] retinol at two dose levels (10 micrograms and 20 micrograms) and sacrificed on the seventh day after dosing. The vitamin A body pool was calculated by dividing total liver radioactivity by the specific activity of plasma Vitamin A. At both dose levels significant correlations between analysed and calculated values were obtained at low and high levels of liver Vitamin A, but not at intermediate levels. There was considerable variability in the proportion of the administered dose stored in the liver.

Animals↗

PubMed1998

Simultaneous analysis of plasma free fatty acids and their 3-hydroxy analogs in fatty acid beta-oxidation disorders.

We present a new derivatization procedure for the simultaneous gas chromatographic-mass spectrometric analysis of free fatty acids and 3-hydroxyfatty acids in plasma. Derivatization of target compounds involved trifluoroacetylation of hydroxyl groups and tert-butyldimethylsilylation of the carboxyl groups. This new derivatization procedure had the advantage of allowing the complete baseline separation of free fatty acids and 3-hydroxyfatty acids while the superior gas chromatographic and mass spectrometric properties of tert-butyldimethylsilyl derivatives remained unchanged, permitting a sensitive analysis of the target compounds. Thirty-nine plasma samples from control subjects and patients with known defects of mitochondrial fatty acid beta-oxidation were analyzed. A characteristic increase of long-chain 3-hydroxyfatty acids was observed for all of the long-chain 3-hydroxyacyl-CoA dehydrogenase-deficient and mitochondrial trifunctional protein-deficient plasma samples. For medium-chain acyl-CoA dehydrogenase deficiency and very-long-chain acyl-CoA dehydrogenase deficiency, decenoic and tetradecenoic acids, respectively, were the main abnormal fatty acids, whereas the multiple acyl-CoA dehydrogenase-deficient patients showed variable increases of these unusual intermediates. The results showed that this selective and sensitive method is a powerful tool in the diagnosis and monitoring of mitochondrial fatty acid beta-oxidation disorders.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed1986

Homology and diversity between intermediate filament proteins of neuronal and nonneuronal origin in goldfish optic nerve.

The predominant intermediate filament proteins of the goldfish optic nerve have molecular weights of 58K. They can be separated into a series of four major isoelectric variants of neuronal (ON1 and ON2) and nonneuronal (ON3 and ON4) origin. The extent of homology between the goldfish 58K intermediate filament proteins themselves and to rat optic nerve vimentin and glial fibrillary acidic protein (GFAP) was investigated. Unlabeled and [32P]orthophosphate-labeled proteins were subjected to partial hydrolysis by V8 protease, chymotrypsin, and CNBr. The results show that the goldfish intermediate filament proteins share with vimentin and GFAP a 40K chymotrypsin-resistant core fragment. Phosphorylated moieties appear to be located outside the core region since they are preferentially cleaved off by chymotrypsin and not found associated with the 40K core. In addition, the goldfish ON proteins contain the antigenic site within the core that is common to most intermediate filaments. V8 or CNBr digestion indicates that many fragments that are common to ON1 and ON2 are clearly distinct from fragments that are common to ON3 and ON4. In addition, structural variability is observed between the goldfish intermediate filament proteins and vimentin and GFAP. The results are discussed in terms of intermediate filament structure and their possible role in nerve growth.

Animals↗

PubMed1994

The problem of missing clinical data for research in psychopathology: some solution guidelines.

There are no guidelines to help psychiatric researchers statistically adjust for missing data. We discuss the problems resulting from missing values, and illustrate some of them with examples from our work. Using structured instruments, we obtained clinical information from 241 patients. Some instrument items were not rated, and these did not occur randomly: hallucinations and delusions were most frequently unrated, especially in chronic schizophrenics, and patients with high scores for other psychopathology. Systematically assigning an intermediate value between present and absent to nonrated items was a satisfactory solution, unaffected by nonrandom missing values. This simple solution was equivalent to a complicated one (vectoring) in discriminating patients. When relationships between variables are linear, we recommend the intermediate value method as a practical solution to missing values. We stress that missing values do not mean missing information, and the most common response to missing values (dropping subjects) is least informative.

Data Collection↗

PubMed2002

Prognostic variables for response and outcome in patients with extragonadal germ-cell tumors.

BACKGROUND: This investigation evaluates prognostic variables in patients with seminomatous and non-seminomatous extragonadal germ-cell tumors (EGCT) in order to identify relevant factors for long-term outcome following cisplatin-based chemotherapy. PATIENTS AND METHODS: Patients from six countries treated at 11 centers in Europe and the USA from 1975 to 1996 were evaluated retrospectively. Uni- and multivariate analyses of prognostic variables for survival and for response to chemotherapy were performed. RESULTS: Data were available for 635 EGCT patients, 104 with seminomatous and 524 with non-seminomatous EGCT (n = 7 not specified). For non-seminomatous EGCT the following independent adverse factors were identified: presence of either liver, lung or central nervous system metastases, primary mediastinal tumor or elevation of pretreatment beta-human gonadotropin; for extragonadal seminoma (only univariate) adverse factors were: presence of liver metastases, two or greater metastatic sites or International Germ Cell Cancer Collaborative Group (IGCCCG) grouping (intermediate versus good). Integration of these variables produced the following prognostic risk groupings: 'excellent prognosis', all seminomatous EGCT (89% 5-year survival rate); 'intermediate low', 'intermediate high' and 'poor', all non-seminomatous EGCT with a 69, 55 and 17% 5-year survival rate, respectively. The decreased survival among the different groups was due to a lower rate of favorable objective remissions and a higher rate of relapses. Classification and regression tree (CART) modeling confirmed histology and location of primary tumor as the major prognosticators. For the subgroup of patients with mediastinal non-seminoma, the 2-year survival rate ranged from 34 to 84%. Multivariate testing for the probability to respond to chemotherapy revealed non-seminomatous histology, primary mediastinal tumor site, and the presence of liver, lung or CNS metastases as independent adverse factors. CONCLUSIONS: In EGCT, prognostic variables for the outcome and for the response to chemotherapy could be identified, which in part differ from gonadal GCT. The proposed model might help to better understand the specific prognosis of EGCT and to tailor risk-adapted treatment strategies. In addition, CART analysis demonstrated the heterogenous prognosis of patients with mediastinal non-seminoma.

Abdominal Neoplasms↗

PubMed2002

The effects of type of female circumcision on infertility and fertility in Sudan.

This study explores the association between type of female circumcision and infertility and fertility in Sudan using the 1989-90 Demographic and Health Survey. It is hypothesized that women with either Pharaonic or Intermediate circumcision would have higher infertility and lower fertility compared with women with Sunna circumcision, and that uncircumcised women would have the lowest infertility and highest fertility of the three groups. This hypothesis, a widely held assumption, proved to be largely incorrect. Though women with Pharaonic or Intermediate circumcision did have a higher prevalence of primary infertility than uncircumcised women, women with Sunna circumcision had even lower rates of primary infertility compared with uncircumcised women. This pattern prevailed in multivariate models controlling for confounding variables, where women with Pharaonic or Intermediate circumcision had significantly higher primary infertility. Moreover, though women with Pharaonic or Intermediate circumcision also had the highest prevalence of secondary infertility, once confounding covariates were controlled in multivariate models, there was no significant difference among the three groups of women. With respect to fertility, the total fertility rate was 7.6 for women with Pharaonic or Intermediate circumcision, 8.1 for women with Sunna circumcision and 8.3 for uncircumcised women. Differences in fertility were found to be insignificant when covariates were controlled. The multivariate models were estimated using logistic regression. In conclusion, Pharaonic or Intermediate circumcision may be associated with higher primary infertility while there was no evidence suggesting that either secondary infertility or fertility was associated with a woman's circumcision status.

Circumcision, Female↗

PubMed1978

Template-determined, variable rate of RNA chain elongation.

Q beta replicase polymerizes MDV-1 RNA at a markedly variable rate. Electrophoretic analyses of partially synthesized strands showed that a few of the elongation intermediates are much more abundant than others, reflecting a variable rate of chain elongation. Our data suggest that at a relatively small number of specific sites in the sequence of this RNA, the progress of the replicase is temporarily interrupted, and then resumes spontaneously, with a finite probability. Since the time spent between these pause sites is negligible compared with the time spent at pause sites, the mean time of chain elongation is well approximated by the sum of the mean times spent at each pause site. Nucleotide sequence analysis of the most prominent elongation intermediates indicated that they all have the potential to form a 3' terminal hairpin structure. This suggests that the marked variability in the rate of chain elongation is due to the formation of terminal hairpins in the product strand, or the reformation of hairpins in the template strand. A survey of the literature shows that this phenomenon occurs with most, if not all, nucleic acid polymerases. Structure-induced pauses may play a role in the regulation of nucleic acid synthesis.

Base Sequence↗

PubMed1981

Anthropometric determinants of birth weight.

The correlation of maternal and paternal physical characteristics to the weight of the newborn infant was investigated. It was found that a different anthropomorphic variable best explained the outcome in each group when mothers were divided by weight for height. In women of low weight for height, weight gain was most significantly associated with birth weight (P less than .01); and in women of intermediate weight for height, the significant variable was maternal prepregnancy weight (P less than .01); in women of high weight for height the outcome was best explained by maternal height (P less than .05). The model accounted for 17, 21, and 32% of the variance in birth weight in the 3 weight-for-height groups, respectively. It appears that the relative value of genetic and environmental factors may be different depending on the body type of the mother. It is postulated that other genetic and environmental factors, including smoking, alcohol ingestion, and exact gestation age, may be of significance. The conclusions of this study differ from those of previously reported studies. Possible explanations include variable population homogeneity and different socioeconomic groups studied as well as the obscuring of biologically significant variables if outcomes in subjects with different body types are not analyzed separately.

Adult↗

PubMed1993

Comparative analysis of DNA ploidy and proliferative index in fine needle aspirates of non-Hodgkin's lymphomas by image analysis and flow cytometry.

To determine the application of image analysis (IA) to fine needle aspiration (FNA) of non-Hodgkin's lymphomas, 78 cases, categorized according to the Working Formulation, were analyzed and compared with those analyzed by flow cytometry (FCM). Aspirated material was immediately fixed in either IA fixative (31 cases) or acetone, stored at -70 degrees C (47 cases) for periods up to 48 months and postfixed in IA fixative. IA assessed DNA index (DI), ploidy balance, degree of hyperdiploidy and proliferation index (PI). DNA index, % S + G2M and RNA index were obtained by acridine orange FCM. There were no significant differences in measured variables between fresh and stored cases. Statistically significant differences between low, intermediate and high grade lymphomas were present in all evaluated variables except DNA ploidy (DI) (P = .074) measured by IA. DI, however, showed a very high correlation with the DI obtained by FCM (r = .94). PIs, although generally lower, also had a high correlation with S + G2M (r = .85). We conclude that results obtained by IA were comparable to results by FCM and that frozen material can be used to retrospectively evaluate ploidy and proliferation. IA is especially suitable for the evaluation of low-volume specimens obtained by FNA.

Biopsy, Needle↗

PubMed2003

Olfactory learning and memory impairments following lesions to the hippocampus and perirhinal-entorhinal cortex.

The role of the hippocampus and perirhinal-entorhinal cortex was examined in an olfactory discrimination paradigm. Small neurotoxic lesions of the hippocampus (21% tissue damage) yielded relatively unimpaired olfactory retention across brief (30 s), intermediate (approximately 5 min), and 24-hr delays, whereas impairments were noted at 5-day retention intervals. Larger hippocampal lesions (63% tissue damage) spared memory at intermediate delays, with no impact at 8-day retention intervals. Aspiration lesions directed at the perirhinal-entorhinal cortex produced a variable performance pattern, with impairments noted at intermediate, 24-hr, and 5-day delays. Results suggest the hippocampus is not specifically involved in retaining olfactory information, with additional consideration given to the relationship between lesion size and memory impairment.

Animals↗

PubMed1997

Acylation of human insulin with palmitic acid extends the time action of human insulin in diabetic dogs.

To test whether the binding of insulin to an endogenous serum protein can be used to extend the time action of insulin, human insulin was acylated at the epsilon-amino group of Lys(B29) with palmitic acid to promote binding to serum albumin. Size-exclusion chromatography was used to demonstrate specific binding of the resulting analog, [N(epsilon)-palmitoyl Lys(B29)] human insulin, to serum albumin in vitro, and the time action and activity of the analog were determined in vivo using overnight-fasted, insulin-withdrawn diabetic dogs. In the diabetic animal model, the duration of action of [N(epsilon)-palmitoyl Lys(B29)] human insulin administered intravenously was nearly twice that of unmodified human insulin, and the plasma half-life was nearly sevenfold that of the unmodified protein. Administered subcutaneously, [N(epsilon)-palmitoyl Lys(B29)] human insulin had a longer duration of action; a flatter more basal plasma insulin profile; and a lower intersubject variability of response than the intermediate-acting insulin suspension Humulin L (Lilly, Indianapolis, IN). These studies support the concept that modification of insulin to promote binding to an existing serum protein can be used to extend the time action of human insulin. In addition, the time action, pattern, and decreased variability of response to [N(epsilon)-palmitoyl Lys(B29)] human insulin support the development and further testing of this soluble insulin analog as a basal insulin to increase the safety of intensive insulin therapy.

Acylation↗

PubMed1994

Graded action potentials generated by differentiated human neuroblastoma cells.

Stimulus-dependent impulses and resting membrane parameters of human SH-SY5Y neuroblastoma cells, induced to differentiate by retinoic acid, were investigated with tight-seal recording techniques. Mean resting potential was -53 mV, mean input resistance 2.1 G omega, mean capacitance 14 pF, and mean time constant 30 ms. Rectangular current steps induced clearly stimulus-dependent impulses, with stronger current steps causing impulses of larger amplitude. The degree of impulse variability differed significantly among different cells. The current thresholds for impulse generation ranged from 35 to 100 pA for 10 ms current steps. With longer current steps, thresholds below 10 pA were recorded. In response to 0.5-1 s long current steps, most cells generated only a single impulse, but a few cells generated two impulses. When two impulses were generated, the interval between the impulses decreased with increasing stimulus strength. Whole-cell currents were recorded under voltage-clamp conditions. Voltage-activated, tetrodotoxin-sensitive Na+ currents and 'delayed rectifier' K+ currents were recorded. The degree of impulse variability was correlated to the maximum Na+ current density. Cells with large Na+ currents showed little impulse variability, while a marked variability was recorded in cells with intermediate or small Na+ currents. Cells which generated more than one impulse in response to prolonged stimuli belonged to the group with large Na+ currents. Spontaneous impulse-currents were recorded from cell-attached membrane patches on intact cells. Also these impulses showed a large variability in amplitude: In each of five cells analysed, the peak-to-peak amplitude varied by a factor larger than 1.7.

Action Potentials↗