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J R Hofstetter

Publications and source records attributed to J R Hofstetter.

At least 19 recordsLinked to original sources
PubMed2003

New quantitative trait loci for the genetic variance in circadian period of locomotor activity between inbred strains of mice.

Provisional quantitative trait loci (QTL) for circadian locomotor period and wheel-running period have been identified in recombinant inbred (RI) mouse strains. To confirm those QTL and identify new ones, the genetic component of variance of the circadian period was partitioned among an F2 intercross of RI mouse strains (BXD19 and CXB07). First, a genomic survey using 108 SSLP markers with an average spacing of 15 cM was carried out in a population of 259 (BXD19 x CXB07)F2 animals. The genome-wide survey identified two significant QTL for period of locomotor activity measured by infrared photobeam crossings on mouse chromosomes 1 (lod score 5.66) and 14 (lod score 4.33). The QTL on distal chromosome 1 confirmed a previous report based on congenic B6.D2-Mtv7a/Ty mice. Lod scores greater than 2.0 were found on chromosomes 1, 2, 6, 12, 13, and 14. In a targeted extension study, additional genotyping was performed on these chromosomes in the full sample of 341 F2 progeny. The 6 chromosome-wide surveys identified 3 additional QTL on mouse chromosomes 6, 12, and 13. The QTL on chromosome 12 overlaps with circadian period QTL identified in several prior studies. For wheel-running period, the chromosome-wide surveys identified QTL on chromosomes 2 and 13 and one highly suggestive QTL on proximal chromosome 1. The results are compared to other published studies of QTL of circadian period.

Animals↗
PubMed1999

A QTL for the genetic variance in free-running period and level of locomotor activity between inbred strains of mice.

Many genes support the manifestation of the circadian period in mice. In a multiple-gene trait all genes contributing in a minor way to this characteristic are quantitative trait loci (QTL). Screens of both the BXD and the CXB panels of recombinant inbred mice suggested that distal chromosome 1, between 90 and 100 cM, contained a QTL, Cplaq3, for a difference in the circadian period of locomotor activity between the C57BL/6J and the DBA/2J and between the BALB/cBy and the C57BL/6By progenitor strains. The mice studied were a commercially available congenic strain, B6.D2-Mtv7a/Ty, from 50 to 100 days old. This congenic strain contains a small DBA/2J genomic insert that covers the region of the provisional QTL in a 99.9% C57BL/6J background. The congenic mice had a shorter period than C57BL/6J mice, confirming that this region has a QTL for the difference in period between the C57BL/6J and the DBA/2J strains. In addition, these data suggest that this region has a QTL for the mean amount of daily activity and for the pattern of locomotor activity.

Alleles↗
PubMed1999

Provisional QTL for circadian period of wheel running in laboratory mice: quantitative genetics of period in RI mice.

Wheel running was monitored in B x D recombinant inbred (RI) mice under dark-dark (DD) conditions, and the mean circadian period was calculated for each strain. There were significant differences for this trait among B x D recombinant inbred strains (p < .0001) and a narrow-sense heritability of 21%. Analysis of strain means and variances indicates that at least four segregating loci contribute to the genetic variance for the free-running circadian period in this population. Correlation of the strain means for the circadian period of wheel running for each RI strain against the distribution of markers at over 1500 loci along the mouse genome identified a number of provisional quantitative trait loci (QTL). There were provisional QTL for wheel running at p < .001 on chromosome 11 and at p < .01 on chromosomes 1, 6, 9, 17, and 19. Most were in agreement with a second analysis done under similar conditions.

Animals↗
PubMed1998

Provisional quantitative trait loci (QTL) for the Aschoff effect in RI mice.

Mice of the CXB recombinant inbred (RI) panel were phenotyped for period of locomotor activity in continuous dark (tau) and in continuous 10-lux light (tauLL). There were significant differences in the effect of light on period, delta tau (tauLL-tau), among CXB RI strains and their progenitors. By comparing strain means for delta tau in the CXB RI strains with typed genetic loci using a product moment correlation, it was possible to hypothesize quantitative trait loci (QTL) important to the genetic variance in the effect of constant low-level light on circadian period. Some of the candidate genes linked to statistically associated markers are neuropharmacologically interesting. Provisional QTL for delta tau were found on proximal Chromosome 8 and mid Chromosome 11 in regions near QTL identified in a similar analysis of the BXD RI panel. This provides additional evidence for the importance of loci on Chromosomes 8 and 11.

Animals↗
PubMed1997

Genomic DNA from mice: a comparison of recovery methods and tissue sources.

Our aim is to identify an extraction method and the source of mouse tissue(s) that could allow a high-resolution genomic scan from a living mouse. We compared and optimized two methods for yield, purity of DNA, and their use in the polymerase chain reaction (PCR) of DNA extracted from different mouse tissues. In addition to whole blood, tissue samples from the brain, liver, testis, and tail were included in this study. The Rapid Method (RM) is preferable for the whole blood samples and testis and brain tissue samples because it is quicker, less toxic, and more cost-effective than the proteinase K method (PM). For liver the PM produced higher yields of DNA with less degradation than the RM. For tail tip, the PM produced a higher yield of DNA, but the RM resulted in a higher yield of PCR product. From a living mouse, a tail snip generated a sufficient amount of DNA for several hundred PCRs but not a complete genomic scan. We suggest that the RM can be used to extract genomic DNA for a complete genomic scan which requires either testicular tissues or repeated blood samples from the suborbital sinus over several months without sacrificing the animal.

Animals↗
PubMed1997

Aging lengthens TauDD in C57BL/6J, DBA/2J, and outbred SWR male mice (Mus musculus).

The effect of aging on the free-running period (TauDD) of a circadian rhythm for wheel-running activity was observed in two inbred strains (DBA/ 2J and C57BL/6J) and one outbred strain (Tac: (SW)fBR) of laboratory mice (Mus musculus). TauDD in the DBA and C57 mice was monitored at approximately age 100 days and age 300 days. TauDD in the outbred strain was monitored at approximately age 100 days and age 600 days. TauDD increased with age in all three strains. Most studies of age effects in rodent species have shown a shortening of TauDD with age, with th exception of the C57BL inbred mice. These results show that the lengthening of TauDD with age in laboratory mice is not limited to the C57BL strain and may be a general characteristic of this species, in contrast to other rodent species examined.

Aging↗
PubMed1996

Hypothetical quantitative trait loci (QTL) for circadian period of locomotor activity in CXB recombinant inbred strains of mice.

The locomotor activity of male mice (Mus musculus) of 13 CXB (BALB/cBy x C57BL/6J) recombinant inbred (RI) strains and their progenitor strains was monitored for 4 to 6 weeks by infrared photoelectric beams under constant dark. The circadian period (tau) of locomotor activity was calculated and used in quantitative trait locus (QTL) analysis of strains' means. Results were compared with potential QTL found in a previous study of the BXD RI series. The mean tau of 13 CXB RI mouse strains (three to six animals per strain) in constant dark had a unimodal distribution suggesting polygenic inheritance. A number of potential QTL were found for this trait. There were two associations at p < .001. H23 on chromosome 3 and Pmv16 on chromosome 16. A region of chromosome 1 was associated with tau in both CXB and BXD RI series. There was also a conjunction with a locus determined from QTL analysis of the previously reported tau of wheel running activity in seven CXB RI strains (Schwartz and Zimmerman, 1990).

Animals↗
PubMed1995

Quantitative trait loci (QTL) for circadian rhythms of locomotor activity in mice.

The locomotor activity of male mice (Mus musculus) was monitored by infrared photo-electric beams under three lighting regimens: LD (12 h of light and 12 h of dark), DD (constant dark), and LL (constant broad-spectrum light, 10 lux). Circadian period of locomotor activity (tau) was compared among 3 inbred strains of mice, C57BL/6J (B6), BALB/c (C), and DBA/2J (D2), and 26 recombinant inbred strains B x D (B6 x D2). The tau under both continuous low-intensity light and continuous darkness varied significantly among strains. Under DD the mean tau was 23.8 h for B6, 23.7 h for D2, and 23.6 h for C. Under LL the mean tau was 25.1 h for B6, 23.9 h for D2, and 25.5 h for C. Frequency histograms of the mean tau of 26 B x D RI mouse strains (three to seven animals per strain) in either DD or LL and the difference between them, delta tau, had distributions which appeared unimodal, suggesting polygenic inheritances. The narrow-sense heritability determined using 26 strains of B x D RI mice was about 55% for tau and about 38% for both tau in LL and delta tau. An estimated four loci contribute to the variance of tau in constant darkness and five to the variance of tau in constant low-intensity light among the strains studied. Quantitative trait locus (QTL) analysis identified several potential genetic loci associated with tau in constant darkness, tau in constant low-intensity light, and delta tau. The associations of highest probability for each of these traits were the D1Nds4 locus (p < .001) on mouse chromosome 1, the D5Ncvs52 locus (p < .05) on mouse chromosome 5, and the Pmv12 locus (p < .01) at 70 cM on mouse chromosome 5, respectively. A QTL identified for tau was associated (p < .05) with the D2NDS1 marker at 45 cM on chromosome 2 near the Ea 6 marker at 46 cM associated (p < .05) with that reported for the period of wheel running activity in seven C x B RI strains (Schwartz, W.J., and Zimmerman, P., J. Neurosci. 10:3685 1990).

Animals↗
PubMed1994

[Are food preferences affected by body mass index, age, sex or tobacco?].

In recent decades the percentage of energy derived from dietary fat has increased. The aim of this study was to explore the relationship between food taste preferences, BMI, age, gender and smoking habits. A computerized questionnaire using a hedonic scale (range 0 to 8) to quantify the liking for sweet and savoury, lean and fat foods, was filled by 233 adults: 171 normal weight (131 women, 40 men) and 62 overweight subjects (BMI > 25 kg/m2 42 women, 20 men). The majority of the subjects had a general preference for savoury lean food irrespective of their BMI or gender. Similarly, preference for sweet lean food was not influenced by the magnitude of the BMI. In contrast, overweight subjects had a preference for sweet fat food (p = 0.05) as well as for savoury fat food (p < 0.05). At any age or BMI, men preferred sweet fat food (p < 0.01). This was not the case for women. Overweight men over forty preferred savoury fat food, in contrast to overweight women of the same age (p < 0.01). The same difference existed between normal weight smokers and non-smokers. This study demonstrates that fat food preference plays a potential role in the development of obesity.

Adult↗
PubMed1992

Ambulatory blood pressure monitoring as a means to avoid overtreatment of elderly hypertensive patients.

Do elderly similarly to younger hypertensive patients tend to be overtreated if therapeutic decisions are based exclusively on blood pressure measured by the physician in his office? Eighteen hypertensive patients (10 previously treated) aged 70 years or more had repeatedly office systolic blood pressure greater than or equal to 170 mm Hg and/or diastolic blood pressure greater than or equal to 100 mm Hg. The physicians in charge were asked to reduce blood pressure within 4 months to a target of less than or equal to 160/95 mm Hg using any drug regimen. Blood pressure was monitored during daytime using a noninvasive blood pressure recorder, but the results of the recording were not available to the physicians until the end of the study. At the outset, 11 patients had a mean ambulatory recorded blood pressure less than 170/100 mm Hg. Those patients who exhibited high blood pressures only in the doctor's presence did not reduce their ambulatory blood pressure when antihypertensive therapy was initiated or intensified in order to reduce office blood pressure. This contrasted with the significant fall in ambulatory blood pressure observed in the presence of the doctor. Thus ambulatory blood pressure monitoring seems useful to avoid overtreatment not only of younger but also of elderly hypertensive patients.

Aged↗
PubMed1991

[Biliary calculi in a cohort of autopsies (Lausanne 1974-1981)].

In a sample of 5892 consecutive autopsies of adults (3676 men and 2216 women) performed at the pathology department of the university of Lausanne 1469 instances of cholelithiasis and/or cholecystectomy were noted (686 men and 783 women). The total frequency was 24.1% (18.6% for men, 35.3% for women, sex ratio 1:1.9). These figures, constant over the observation period, are actually among the highest ones in Europe. In comparison with other studies they demonstrate that a marked increase in the incidence of cholelithiasis occurred in Switzerland since the beginning of this century.

Adult↗
PubMed1991

Effect of weight reduction in moderately overweight patients on recorded ambulatory blood pressure and free cytosolic platelet calcium.

Although platelet cytosolic calcium has been shown to decrease during pharmacological treatment of hypertension, there is no evidence that cytosolic calcium also falls during a nonpharmacological reduction in blood pressure. To provide such evidence, we examined prospectively the relation between platelet cytosolic calcium and ambulatory blood pressure during weight reduction in moderately overweight (body mass index [BMI] greater than 25), mildly hypertensive individuals. The experimental group (responders: BMI reduction greater than 5%) consisted of 19 patients who lost 8.5 +/- 2.9 kg (mean +/- SD, p less than 0.05) during a 10-week hypocaloric diet, whereas the control group (nonresponders: BMI reduction less than 5%) consisted of 12 patients who showed no relevant change in body weight (-2.0 +/- 1.3 kg) during the same period of time. The moderate weight loss of the responders decreased blood pressure by 14/5 mm Hg (p less than 0.05), as measured by ambulatory monitoring, which renders a placebo effect unlikely. This nonpharmacological reduction in blood pressure was accompanied by a proportional 11% decrease (p less than 0.05) in platelet cytosolic calcium and also by significant (p less than 0.05) decreases in plasma catecholamines and serum cholesterol. These findings establish the concept of a nonpharmacological reduction in free cytosolic platelet calcium in humans and add further evidence suggesting a link between intracellular calcium homeostasis and blood pressure regulation.

Blood Platelets↗
PubMed1989

Plasminogen activators and plasminogen activator inhibitors in liver deficiencies caused by chronic alcoholism or infectious hepatitis.

Plasma concentrations of tissue-type plasminogen activator (t-PA), urokinase (u-PA), plasminogen activator inhibitor 1 (PAI-1) and PAI-2 were studied in 53 patients with liver deficiency caused by chronic alcoholism (n = 40), viral hepatitis (n = 10) or malignant disease of the liver (n = 3) and compared to that of a control group (n = 20) of healthy subjects. u-PA and PAI-1 levels were significantly increased in all patients with chronic alcoholism, whereas high t-PA was only observed in combination with disturbed liver function tests or with liver cirrhosis (two and six-fold above control values, respectively). A good correlation was observed between t-PA and gamma glutamyl transferase (r = 0.615; p less than 0.001). In patients with infectious hepatitis or with malignant disease of the liver t-PA was normal whereas u-PA and PAI-1 were increased. PAI-2 levels were close to or below the detection limit (15 ng/ml) in the control group and in most patients. However, in two patients with alcohol induced cirrhosis PAI-2 levels were approximately 45 ng/ml and in one patient with hepatocarcinoma even 66 ng/ml. Thus, in liver disease, marked elevations of t-PA, u-PA and PAI-1 levels may occur, with increased PAI-1 as an early marker of liver defects and t-PA a marker of severe liver defects.

Female↗
PubMed1989

[Non-ulcer dyspepsia and Campylobacter pylori].

Dyspepsia, defined as chronic vague upper abdominal symptoms, is a common condition. The pathogenesis of this syndrome remains poorly understood. The etiologic role of Campylobacter pylori and associated gastritis remain controversial though this organism colonizes the gastric antrum in one third to one half of patients with non-ulcer dyspepsia. Recent studies raise the prospect that treatment with bismuth improves gastritis and is successful in treating symptoms in the Campylobacter pylori positive and negative patients. To determine if Campylobacter pylori causes dyspepsia requires proof that long term eradication of the organism heals gastritis and abolishes symptoms.

Campylobacter↗
PubMed1989

[Disseminated nocardiosis due to Nocardia brasiliensis in an ambulatory patient].

We report the case of a 76-year-old man with generalized nocardiosis. The microbiologic pattern, the different clinical manifestations and the treatment of nocardiosis are discussed in general. In the particular case of our patient the disease manifested itself primarily as a subcutaneous abscess, a metastasis secondary to pulmonary nocardiosis. The disease was caused by a Nocardia brasiliensis, which is rarely seen in Europe and which does not usually cause a generalized form of nocardiosis.

Abscess↗
PubMed1989

Activity-wheel stress and serotonergic hypersensitivity in rats.

Adult male Wistar rats were subjected to activity wheel stress: unlimited access to an activity wheel for up to twelve days and food for 30 to 60 min each day. Each treated rat was paired with a control, the latter being housed in home cages and given sufficient food to maintain a weight similar to the stressed partner. All rats were previously trained on a variable interval schedule for milk reinforcement. When the activity of the stressed rat increased rapidly then decreased suddenly, the pair was decapitated for biochemical analysis. Levels of the serotonin metabolite, 5-hydroxyindoleacetic acid, decreased by 50%, and the Bmax for ketanserin binding increased by 19% in frontal cortical homogenates from the stressed rats when compared to controls. These data support the concept that stress increases the sensitivity of central serotonin receptors.

Animals↗
PubMed1988

[Current role of biopsy in the diagnosis of hepatic disease].

The criteria for the use of liver biopsy as a diagnostic tool were retrospectively analyzed over a ten-year period in 390 consecutive patients. The four principal conditions in which this procedure was employed were alcoholism (33%), hepatitis (18%), abnormal hepatic tests (16%) and tumors (10%). The development of new, "non-invasive", investigative methods such as echography and tomodensitometry has led to an decrease in the number of liver biopsies performed annually, but no change in the relative frequency of the various indications. In this paper, evidence is presented which demonstrates that hepatic biopsy confirmed the clinical diagnosis in 62.4% of the cases reviewed and fundamentally modified the diagnosis in 20.2%. Based upon these findings, it can be concluded that liver biopsy remains an indispensable diagnostic procedure in the field of hepatology, since it can result in modification of the clinician's diagnosis in one out of five cases.

Adolescent↗