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.

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.

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.

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.

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.

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.

The histological patterns of chronic active hepatitis--excluding cirrhosis--and their prognostic significance.

In a retrospective clinico-pathological analysis of 30 cases of chronic active hepatitis, no significant correlation could be demonstrated between any histological feature and the end result of the evolution. The so-called "bridging" lesion, in particular, has no prognostic value. A possible effect of the therapy (cortico-steroids or not) on the final outcome could not be established. There is however a clearcut difference in the rate of development, be it favorable or not, between the slow progress of chronic aggressive hepatitis, and the rapidly changing subacute hepatitis. We therefore feel that such a distinction should be maintained, and question the nomenclature proposed by the International Association for Study of the Liver.

[Non-ulcer dyspepsia and Campylobacter pylori]. / Dyspepsie non ulcéreuse et 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.

[Biliary calculi in a cohort of autopsies (Lausanne 1974-1981)]. / La lithiase biliaire dans un collectif d'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.

[Disseminated nocardiosis due to Nocardia brasiliensis in an ambulatory patient]. / Nocardiose disséminée à Nocardia brasiliensis chez un patient ambulatoire.

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.

Ambulatory blood pressure monitoring in the elderly hypertensive patient.

In this retrospective analysis, we assessed the usefulness of ambulatory blood pressure monitoring in the evaluation of elderly hypertensive patients. Thirty-eight untreated and 31 treated hypertensives aged 70 years or more had a systolic blood pressure greater than or equal to 160 mmHg and/or a diastolic blood pressure greater than or equal to 95 mmHg in the clinic. All 69 patients underwent blood pressure monitoring during their customary daily activities using a portable semi-automatic blood pressure recorder (Remier M2000). The mean of all blood pressures obtained with this device was taken as the ambulatory recorded blood pressure. Recorded blood pressures were greater than or equal to 160 mmHg systolic and greater than or equal to 90 mmHg diastolic in 17 untreated and 17 treated patients. In these patients, the introduction of antihypertensive therapy, or its modification, markedly reduced blood pressure during a 4-8 month follow-up. A further 21 untreated and 14 treated patients had recorded blood pressures of less than 160/90 mmHg. The treatment status of these patients was left unchanged for 4-8 months of follow-up. Nevertheless, office blood pressure in these groups, with no change in treatment, decreased significantly during the observation period. At the last visit to the outpatient clinic, there was no significant difference in blood pressure between the four subgroups of patients. Thus, ambulatory blood pressure monitoring appears to be useful in the elderly hypertensive patient in detecting those patients whose blood pressure is elevated only in the clinic. Blood pressure profiles obtained outside the clinic may therefore be useful in making therapeutic decisions in the aged hypertensive.