Genealogy of the 129 inbred strains: 129/SvJ is a contaminated inbred strain

The 129 mouse is the most widely used strain in gene targeting experiments. However, numerous substrains exist with demonstrable physiological differences. In this study a set of simple sequence length polymorphisms (SSLPs) was used to determine the relatedness of selected 129 substrains. 129/SvJ was significantly different from the other 129 substrains and is more accurately classified as a recombinant congenic strain (129cX/Sv), being derived from 129/Sv and an unknown strain. This mixed genetic background could complicate gene targeting experiments by reducing homologous recombination efficiency when constructs and ES cells are not derived from the same 129 substrain. Additionally, discrepancies due to different genetic backgrounds may arise when comparing phenotypes of genes targeted in different 129-derived ES cell lines.     

Voluntary alcohol consumption in BXD recombinant inbred mice: relationship to alcohol metabolism

Studies were initiated to characterize behaviorally and biochemically C57BL/6J and DBA/2J inbred mice, as well as BXD Recombinant Inbred (RI) strains derived from them. The C57BL/6J, DBA/2J, and 7 BXD RI strains were tested for voluntary alcohol consumption (VAC) by receiving 4 days of forced exposure to a 10% (w/v) solution of alcohol, followed by 3 weeks of free choice between water and 10% alcohol. Measures of VAC included the absolute intake of alcohol (g/kg), as well as alcohol preference. A wide range of VAC was displayed by the various BXD RI strains with a continuous (rather than bimodal) distribution, indicating that there is likely to be additive effects of several genes involved in regulating alcohol-related behaviors. Kinetic characteristics of aldehyde dehydrogenase and catalase in liver and brain of the C57BL/6J, DBA/2J, and BXD strains of mice were determined to test the hypothesis that the genetic regulation of the levels of alcohol-metabolizing enzymes mediate differences in VAC. Aldehyde dehydrogenase activity was determined spectrophotometrically by observing the change in absorption at 340 nm. Catalase activity was determined by measuring oxygen production with a Yellow Springs Biological Oxygen monitor and oxygen electrode. There was a strong negative relationship between VAC and brain catalase activity in the BXD RI and parental strains. These data suggest that RI strains are likely to be useful genetic models in the examination of quantitative trait loci controlling VAC and other responses to alcohol.     

An edited linkage map for the AXB and BXA recombinant inbred mouse strains

We have updated the history of the AXB and BXA recombinant inbred (RI) strains, typed additional loci, and edited the AXB, BXA RI database. Thirteen of the original 51 AXB and BXA RI strains are either extinct or genetically contaminated, leaving 33 living strains available from The Jackson Laboratory. However, we found a high degree of similarity among three sets of strains, indicating that these strains are not independent, which leaves 27 independent RI strains in the set. Accordingly, we modified the database by combining the AXB and BXA RI sets and eliminating strains that were genetically contaminated or extinct with no available DNA. We added 92 newly typed loci, retyped some questionable genotypings, and removed loci with excessive double crossovers or an insufficient number of typed strains. The edited strain distribution pattern (SDP) is available on the World Wide Web (WWW) (http://www. informatics.jax.org/riset.html) and now includes over 700 loci. Each locus is linked to adjacent loci with a LOD score of at least 3.0 with a few described exceptions. We also carried out a second editing designed for the analysis of quantitative trait loci by deleting extinct strains and loci with identical SDPs; this edited database is also available on the WWW.     

Iowa wrestling study: weight classification systems

Serum vitamin E and cholesterol levels were determined for the residents in rural regions of Yamagata Prefecture, Japan. The average serum vitamin E were 0.99 +/- 0.25 mg/100ml in 166 men, and 1.06 +/- 0.26 mg/100ml in 178 women. Only 0.6% of the subjects were below 0.5 mg/100 ml. There was a significant difference between the serum vitamin E levels of men and women. However there were no statistically significant differences among serum vitamin E of various age groups. The best correlation for serum vitamin E was found with serum cholesterol.     

Multiple system organ failure: a study of outcome

One hundred patients with Multiple System Organ Failure (MSOF) were studied. The precipitating factors were infections, poisoning, metabolic disorders, surgical disorders and cardiac arrest resulting in an overall mortality of 65%. Mean inpatient stay was 3.86 days, being significantly longer in patients who survived (6.25 days). Age, sex, addictions and premorbid health did not affect outcome. GIT (89%), CNS (81%) and Liver failure (62%) were seen most commonly. Highest mortalities were observed with RS (81.2%), CVS (80.37%) and CNS (76.5%). The mortality with 2,3,4,5,6 and 7 OSF was 8.3%, 18.7%, 70%, 92%, 100% and 100% respectively. The mortality was highest (50.76%) on the first day of MSOF and during the initial 48 hours of the total duration of disease. The method proposes an easily reproducible way to evaluate severity of illness and predicting outcome in acute MSOF.     

Propranolol in hypertension: a dose-response study

The effect of propranolol was studied in a double-blind crossover trial in 24 carefully selected hypertensive outpatients. Each patient received propranolol 60 mg/day, 120 mg/day, 240 mg/day, and placebo for four weeks each according to a randomised sequence. Propranolol 60 mg/day was no better than placebo in reducing blood pressure. The effects of propranolol 120 mg/day and 240 mg/day were not significantly different. Both doses reduced lying blood pressure by about 20/10 mm Hg from an initial level of 173/104 mm Hg. No difference was detected between the effects of the different doses of propranolol and placebo on weight or on the occurrence of adverse reactions.     

Angiotensinogen genotype, sodium reduction, weight loss, and prevention of hypertension: trials of hypertension prevention, phase II

Hox genes are segmentally expressed in the developing vertebrate hindbrain, neural crest cells and pharyngeal arches suggesting an important role in patterning these structures. Here we discuss the cellular and molecular mechanisms controlling segmentation and specification in the branchial region of the head. In addition, based on the recent phenotypical and molecular analysis of loss-of-function mutants in the mouse, we speculate that Hox genes may act like Drosophila selector genes in this system.     

Necrosis of a phaeochromocytoma associated with spontaneous remission of diabetes and hypertension

The diagnosis of phaeochromocytoma is sometimes difficult since its clinical presentation is quite variable. We report a 52-year-old woman who presented with acute diabetes mellitus and severe hypertension, which spontaneously disappeared. MIBG-scintigraphy and urine and plasma catecholamines were normal. At surgery, a largely necrotic phaeochromocytoma was found. Pathological examination demonstrated extensive avascular necrosis, which had occurred spontaneously without any major symptoms.     

Endometriosis and spontaneous abortion rate: a cohort study in infertile women

Oxidative stress is believed to play an important role in the development of vascular complications associated with diabetes mellitus. In this study, we examined the efficacy of long-term treatment with the antioxidant, N-acetylcysteine, in preventing the development of defective endothelium-dependent relaxation in streptozotocin-induced, Sprague-Dawley diabetic rats. At 48 h after injection of streptozotocin, a portion of diabetic rats received 250 mg/L N-acetylcysteine in drinking water for a total duration of 8 weeks. Oral administration did not alter the increase in blood glucose or the reduction in serum insulin but did modestly reduce total glycosylated hemoglobin. In precontracted thoracic aortic rings suspended in isolated tissue baths, endothelium-dependent relaxation to acetylcholine was impaired in diabetic rings compared with control rings. Endothelium-independent relaxation to nitroglycerin was unaltered. Long-term oral administration of N-acetylcysteine did not alter responses to nitroglycerin but completely prevented the defective relaxation to acetylcholine. These studies indicate a dissociation between glycemic control and correction of endothelial dysfunction and suggest that long-term exposure to reactive oxygen subsequent to diabetes rather than hyperglycemia per se is responsible for the development of endothelial dysfunction in diabetes mellitus.     

Unilateral spontaneous abdominal cryptorchidism: structural and ultrastructural study of sperm morphology

Sperm morphology of three healthy boars and three boars with spontaneous abdominal cryptorchidism in the right testis has been evaluated by light microscopy. For each boar, two ejaculates have been analysed, corresponding to semen collections at the ages of 6.5 months (first collection) and 8 months (seventh collection). A comparative study of the sperm malformations present in the seventh semen collection between the healthy boars and the unilateral abdominal cryptorchid boars has also been performed by light microscopy. Sperm malformations of the seventh semen collection from the unilateral abdominal cryptorchid boars have been examined by scanning and transmission electron microscopy. The frequency of mature spermatozoa, immature spermatozoa, aberrant spermatozoa and detached heads maintained normals values in the first and the seventh semen collection from the unilateral abdominal cryptorchid boars. The comparative study of sperm abnormalities in the seventh semen collection between the cryptorchid boars and the healthy boars indicated that the unilateral abdominal cryptorchid boars had a significantly higher frequency of primary abnormalities, and a significantly lower frequency of secondary abnormalities. Some primary abnormalities, such as crater defect, knobbed acrosome defect, nuclear crests and abaxial tails were only observed in the unilateral abdominal cryptorchid boars. It was concluded that unilateral abdominal cryptorchidism provokes disturbances in the late stages of spermiogenesis, at testicular level. Alterations in the sperm maturation process at epididymal level were not found.     

Identification of quantitative trait loci involved in contextual and auditory-cued fear conditioning in BXD recombinant inbred strains.

Fear conditioning shows associations formed between contextual or auditory stimuli with an unconditioned stimulus. Inbred mouse strains differ in their ability to demonstrate fear conditioning, suggesting at least a partial genetic influence. The present study identified the possible chromosomal loci regulating fear conditioning in BXD recombinant inbred strains using quantitative trait loci (QTL) analysis. Estimates of heritability for all 3 measures of conditioning were about .28. Correlational analyses between genetic markers and strain means identified multiple putative QTLs. The strongest associations were on Chromosomes 1 and 17 for freezing to the context, Chromosome 12 for freezing to an altered context, and Chromosome 1 for freezing to the auditory stimulus. Overlapping QTLs may indicate some common genes that underlie aspects of this learning task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Caffeine intake and low birth weight: a population-based case-control study

The authors conducted a matched case-control study to investigate the effects of caffeine intake during pregnancy on birth weight. From January to November 1992, in the first 24 hours after delivery, 1,205 mothers (401 cases and 804 controls) were interviewed and their newborns were examined to assess birth weight and gestational age by means of the method of Capurro et al. (J Pediatr 1978;93:120-2). The cases were children with birth weight < 2,500 g and gestational age > or = 28 weeks. Cases and controls were matched for time of birth and hospital of delivery and were recruited from the four maternity hospitals in Pelotas, southern Brazil. Daily maternal caffeine intake during pregnancy for each trimester was estimated. To assess caffeine intake, 10% of the mothers were reinterviewed at their households and samples of reported information on drip coffee and maté (a caffeine-containing drink widely used in South America) were collected and sent to the laboratory for caffeine determination through liquid chromatography. When instant coffee was reported, the weight of powder was measured using a portable scale, and caffeine intake was estimated from a reference table. Caffeine intake from tea, chocolate, soft drinks, and medicines was estimated from a reference table. Analyses were performed by conditional logistic regression. Crude analyses showed no effect of caffeine on low birth weight, preterm births or intrauterine growth retardation. The results did not change after allowing for confounders.     

Epidemiology of idiopathic intracranial hypertension: a prospective and case-control study

Congenital deformities frequently produce problems not always discernible at birth. Often, a period of time is required for the development of signs and symptoms. The present discussion presents the intrauterine anatomy of a midterm fetus relative to conditions of the hip and thigh. Cryomicrotomy is used in this study to present the best anatomical evidence of the morphology involved.     

CD16+ monocytes in patients with cancer: spontaneous elevation and pharmacologic induction by recombinant human macrophage colony-stimulating factor

The small subset of circulating monocytes that express the maturation-associated CD16 antigen has recently been reported to be elevated in patients with bacterial sepsis. We now show that this novel CD16+ monocyte population is also spontaneously expanded in patients with cancer. We studied 14 patients with metastatic gastrointestinal carcinoma enrolled ina clinical trial of recombinant human macrophage colony-stimulating factor (rhMCSF) plus monoclonal antibody D612. We found that before any cytokine treatment, 12 of 14 patients constitutively displayed significant elevations in both the percentage and the absolute number of CD16+ monocytes, as compared with both normal subjects and ill patients with elevated monocyte counts but without malignancy. CD16+ monocytes accounted for 46% +/- 22% of total monocytes in the patients with cancer versus 5% +/- 3% for controls (P < .01). The increase was not attributable to infection or intercurrent illness and appeared to be associated with the underlying malignancy itself. A similar spontaneous elevation of CD16+ monocytes was observed in 35 of 44 additional patients diagnosed with a variety of other solid tumors. When patients with gastrointestinal carcinoma were treated with rhMCSF, there was a marked further increase in the percentage of CD16+ monocytes (to 83% +/- 11%), as well as in the absolute number of CD16+ cells and the level of CD16 antigen expression. In every case, the patients with cancer showed a greater CD16+ monocyte response than the maximal response obtained in normal volunteer subjects treated witha similar regimen of rhMCSF (n = 5, P < .001), suggesting that the presence of malignancy primed patients for enhanced responsiveness to rhMCSF. We hypothesize that spontaneous expansion of the CD16+ monocyte population may represent a novel biologic marker for a widespread and previously unsuspected host immune response to malignancy.     

Stress-management training for essential hypertension: a controlled study

Forty three patients with essential hypertension participated in a study on the effectiveness of stress-management training for essential hypertension. After 6-9 clinic and 48 self-measured readings of systolic and diastolic blood pressures (SBP and DBP), 22 patients were treated with a program based on education, relaxation, and problem-solving training; and another 21 patients were assigned to a waiting list control group. At post-treatment, mean reductions of clinic BP (17/13 mm Hg vs. 6.9/4.7 mm Hg for SBP/DBP), percentages of subjects who achieved at least a 5 mm Hg reduction (86/86% vs. 48/48% for SBP/DBP) and percentages of subjects who in addition achieved a normotensive level (59/68% vs. 29/14% for SBP/DBP) were significantly higher in the treated group than in the control group. Concerning self-measured BP, the effectiveness of the stress-management training was not so considerable (mean reductions of 3.6/2.4 mm Hg and percentages of subjects who achieved a 5 mm Hg reduction of 52/38% for SBP/DBP), but it was significant and maintained in a 4-month follow-up assessment (mean reductions of 4/2 mm Hg and percentages of subjects who achieved a 5 mm Hg reduction of 48/33% for SBP/DBP). It is suggested that stress-management training can be beneficial for treatment of essential hypertension.     

Association between air pollution and low birth weight: a community-based study

The relationship between maternal exposure to air pollution during periods of pregnancy (entire and specific periods) and birth weight was investigated in a well-defined cohort. Between 1988 and 1991, all pregnant women living in four residential areas of Beijing were registered and followed from early pregnancy until delivery. Information on individual mothers and infants was collected. Daily air pollution data were obtained independently. The sample for analysis included 74,671 first-parity live births were gestational age 37-44 weeks. Multiple linear regression and logistic regression were used to estimate the effects of air pollution on birth weight and low birth weight (< 2,500 g), adjusting for gestational age, residence, year of birth, maternal age, and infant gender. There was a significant exposure-response relationship between maternal exposures to sulfur dioxide (SO2) and total suspended particles (TSP) during the third trimester of pregnancy and infant birth weight. The adjusted odds ratio for low birth weight was 1.11 (95% CI, 1.06-1.16) for each 100 micrograms/m3 increase in SO2 and 1.10 (95% CI, 1.05-1.14) for each 100 micrograms/m3 increase in TSP. The estimated reduction in birth weight was 7.3 g and 6.9 g for each 100 micrograms/m3 increase in SO2 and in TSP, respectively. The birth weight distribution of the high-exposure group was more skewed toward the left tail (i.e., with higher proportion of births < 2,500 g) than that of the low-exposure group. Although the effects of other unmeasured risk factors cannot be excluded with certainty, our data suggests that TSP and SO2, or a more complex pollution mixture associated with these pollutants, contribute to an excess risk of low birth weight in the Beijing population.     

Mothers' birth weight and survival of their offspring: population based study

OBJECTIVE: To test the hypothesis that a baby's survival is related to the mother's birth weight. DESIGN: Population based dataset for two generations. SETTING: Population registry in Norway. SUBJECTS: All birth records for women born in Norway since 1967 were linked to births during 1981-94, thereby forming 105104 mother-offspring units. MAIN OUTCOME MEASURES: Perinatal mortality specific for weight for offspring in groups of maternal birth weight (with 500 g categories in both). RESULTS: A mother's birth weight was strongly associated with the weight of her baby. Maternal birth weight was associated with perinatal survival of her baby only for mothers with birth weights under 2000 g. These mothers were more likely to lose a baby in the perinatal period (odds ratio 2.3, 95% confidence interval 1.4 to 3.7). Among mothers with a birth weight over 2000 g there was no overall association between mother's weight and infant survival. There was, however, a strong interaction between mother's birth weight, infant birth weight, and infant survival. Mortality among small babies was much higher for those whose mothers had been large at birth. For example, babies weighing 2500-2999 g had a threefold higher mortality if their mother's birth weight had been high (> or = 4000 g) than if the mother had been small (2500-2999 g). CONCLUSION: Mothers who weighed less than 2000 g at birth have a higher risk of losing their own babies. For mothers who weighed > or = 2000 g their birth weight provides a benchmark for judging the growth of their offspring. Babies who are small relative to their mother's birth weight are at increased risk of mortality.     

Meal patterns in obese and normal weight men: the ''Gustaf'' study

OBJECTIVE: To compare the reported meal patterns between obese and normal weight men. DESIGN: A dietary survey, by means of 12 repeated telephone-administered 24-hour dietary recalls, was conducted in obese and normal weight men. The study period was three months with all seven days of the week included. The contribution of intake types to the reported daily energy intake (EI) was studied as well as the circadian distribution of EI and the reported number of intakes. SUBJECTS: 86 obese men (BMI 37.7 +/- 4.4 kg/m2, mean +/- SD) from the waiting list of the outpatient clinic completed the study altogether with 61 normal weight men (BMI 23.0 +/- 1.9 kg/m2), randomly selected from the Stockholm County Census Bureau. All men were 20-60 years old. RESULTS: Results were analyzed for Group A = all men who completed the study and for Group B = the men who exceeded the CUT-OFF 1 limit for energy intake (reasonably true report as defined by Goldberg). The obvious under-reporters amounted to 73% of the obese and to 28% of the normal weight men. The meal patterns were similar for the obese and the normal weight men. The greatest contributors to EI in both groups were cooked meals, sandwich meals, snacks and breakfast-like meals. The circadian eating pattern was mainly the same in both obese and normal weight men. The reported number of intakes was 5.3 (median) per day in all obese men vs 5.6 in all the controls (P = 0.02), and in Group B 5.3 s 5.9 (P = 0.16) intakes. No specific "obese eating style' could be detected in this study.     

Self-directed program for weight control: A pilot study.

Designed a treatment program to enable 16 undergraduates to lose weight through the use of self-monitored techniques for changing their eating behaviors. All Ss achieved a stable loss in weight, and their mean loss was significantly greater than the change shown by a group of similarly motivated controls. No additional effects due to a few sessions of aversive counterconditioning were demonstrated, and no general mood changes accompanied the weight loss. The Ss reported a decreased temptation to overeat. It was suggested that similar programs of gradual habit change through self-control of stimulus conditions and reinforcement contingencies might be applied to the treatment of other addictive behaviors, which are also refractory to change. (26 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mouse strain differences in apomorphine-induced behavior: An empirical and methodological study.

Evaluated the behavioral response to intraperitoneal apomorphine HCl (0.5–32 mg/kg) in BALB/cJ, CBA/J, and C57BL/6J male mice. Dose–response curves for each component of the drug-induced behavioral repertoire were derived, and effective dose-50 (the dose at which 50% of the Ss met or exceeded a given rating) and slope were calculated for each. This method of analysis allows for a more quantitative estimate of drug sensitivity. Behaviors assessed included grooming, sniffing, climbing, and gnawing. Although some strain differences were observed in the qualitative characteristics of the response, differences in actual drug sensitivity were significant only at the higher ratings. Findings are discussed in relation to methodological and analytical problems in previous strain-comparison experiments. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)