Enhanced sensitivity of postsynaptic serotonin-1A receptors in rats and mice with high trait aggression.

Individual differences in aggressive behaviour have been linked to variability in central serotonergic activity, both in humans and animals. A previous experiment in mice, selectively bred for high or low levels of aggression, showed an up-regulation of postsynaptic serotonin-1A (5-HT(1A)) receptors, both in receptor binding and in mRNA levels, in the aggressive line [Brain Res 736 (1996) 338]. The aim of this experiment was to study whether similar differences in 5-HT(1A) receptors exist in individuals from a random-bred rat strain, varying in aggressiveness. In addition, because little is known about the functional consequences of these receptor differences, a response mediated via postsynaptic 5-HT(1A) receptors (i.e., hypothermia) was studied both in the selection lines of mice and in the randomly bred rats. The difference in receptor binding, as demonstrated in mice previously, could not be shown in rats. However, both in rats and mice, the hypothermic response to the 5-HT(1A) agonist alnespirone was larger in aggressive individuals. So, in the rat strain as well as in the mouse lines, there is, to a greater or lesser extent, an enhanced sensitivity of postsynaptic 5-HT(1A) receptors in aggressive individuals. This could be a compensatory up-regulation induced by a lower basal 5-HT neurotransmission, which is in agreement with the serotonin deficiency hypothesis of aggression.

Y chromosomal and sex effects on the behavioral stress response in the defensive burying test in wild house mice.

Genetically selected short attack latency (SAL) and long attack latency (LAL) male wild house mice behave differently in the defensive burying test. When challenged, SAL males respond actively with more time spent on defensive burying, whereas LAL males are more passive with more time remaining immobile. The first aim of this study was to find out whether the nonpairing part of the Y chromosome (Y(NPAR)) affects the behavioral stress response in this paradigm. Second, to determine if the differential behavioral profile found in males is also present in females, SAL and LAL females were tested. Third, nonattacking and attacking LAL males were compared. Five behavioral elements were recorded: defensive burying, immobility, rearing, grooming, and exploration. Males were first tested for attack latency. The results show that the Y(NPAR) influences defensive burying. However, the size of this effect is overshadowed by the background of the mice. Furthermore, although females differed from males, they tended to demonstrate the same behavioral profile as males. Nongenetic factors may also play a role, as attacking LAL males showed more defensive burying than nonattacking LAL males.

Coping with stress in rats and mice: differential peptidergic modulation of the amygdala-lateral septum complex.

This chapter focuses on the parvicellular vasopressin (VP) system originating from the medial nucleus of the amygdala (MeA) and bed nucleus of the stria terminalis (BNST). The vasopressinergic fibers of these nuclei innervate a number of limbic brain areas including the septum-hippocampal complex. Interestingly, this VP system is sexually dimorphic and the VP synthesis in this system depends on circulating gonadal steroids. Studies in rats and mice show that the variation in the lateral septal VP network within the male gender is as large as the variation between the sexes as reported in the literature. Non-aggressive males are characterized by a far more extensive VP network and a higher VP content in the lateral septal area than aggressive males. A review of the literature on the function of lateral septal VP in the organization of behavior reveals not only a modulatory role of behavior in a social context, but also of fear- and anxiety-related behaviors. It is argued that these seemingly diverse functions might be explained by the concept of coping style. Extensive behavioral and physiological analyses in a variety of animal species show that males may be characterized by the way in which they cope with environmental challenges in general. Aggressive males tend to cope actively with their environment whereas non-aggressive males seem to accept the situation as it is more easily. In several tests, we determined the effects of chronic infusion of the V1 receptor antagonist locally into the lateral septal area in male rats. The main conclusion from these experiments is that LS VP does not modulate coping style in general. However, the experiments confirm the idea that LS VP has a certain degree of functional specificity in social behavior and social learning tasks. Together with the observation that the size and distribution of the vasopressinergic system may be highly variable between individual males in relation to their coping style, this suggests that the lateral septal vasopressinergic system is involved in the differential capacity of individuals to cope behaviorally with challenges of a social nature.

Differential lateral septal vasopressin in wild-type rats: correlation with aggression.

The vasopressin (VP)-containing projections from the cells of the bed nucleus of the stria terminalis to the lateral septum (LS) are sexually dimorphic and dependent on gonadal steroids. Recently, the difference in VP distribution found among both sexes was also demonstrated in male mice genetically selected for different levels of intermale aggression. In the present study we examined whether this differential VP distribution in males also exists in an outbred strain of wild-type rats. After the animals were tested for their level of aggression, the VP content and the fiber density of the LS were measured using radioimmunoassay and immunocytochemistry, respectively. In addition, basal levels of plasma testosterone (T) were measured. Both biochemical data and immunocytochemical data revealed a negative correlation between VP and intermale aggression. Aggressive rats exhibited low levels of VP whereas intermediate and nonaggressive animals showed higher levels. Differences in adult levels of T were not found. The results are in accordance with the observations previously found in male mice, reconfirming the correlation between lateral septal VP and aggression.

The anatomical substrate for a difference in surgical approach to rectal cancer in male and female patients.

This review emphasizes' gender related anatomical differences warranting a difference in surgical approach to the problem of rectal cancer in men and women. Differences in the anatomy of the bony pelvis, the pelvic viscera and the lymphatics of the rectum, inspired the authors to extend the margins of the rectal resection in the anterior plane in female patients. Between 1978 and 1992 a rectal resection was carried out for cancers confined to the pelvis in 158 patients. Of these patients 152 were available for review, 95 male and 57 female. In 24 out of 57 female patients extension of the rectal resection towards the genital tract by en bloc excision of posterior vaginal wall and/or uterus was considered necessary to be confident about obtaining tumour free margins. After a median follow-up of 8 years the risk of local recurrence and cancer related death were significantly lower in female patients.

Aggression in wild house mice: current state of affairs.

This paper reviews our present state of knowledge of genetic variation in (offensive) aggression in wild house mice. The basic tools in this research were lines bidirectionally selected for attack latency (fast attacking SAL and slow attacking LAL males), descended from a feral population. Using congenic lines for the nonpseudoautosomal region of the Y chromosome (YNPAR), reciprocal crosses between (parental) SAL and LAL, and crosses between parentals and congenics, an autosomally dependent Y chromosomal effect on aggression has been found. Both the pseudoautosomal (YPAK) region and the YNPAR play a role. As for environmental sources of variation, prenatal and postnatal maternal effects are of minor importance for the development of aggression differences. One of the physiological factors by which genetic effects may be mediated is testosterone (T). Besides quantitative aspects, the timing of T release seems crucial. Two important time frames are discussed: the perinatal and pubertal time periods. Finally, neurochemical and neuroanatomical correlates are considered. Differences in neostriatal dopaminergic activity, and sizes of the intra- and infrapyramidal mossy fiber terminal fields, as well as Y chromosomal effects on the latter two, are discussed.

Endourological management of ureteral obstruction after renal transplantation.

PURPOSE: We evaluated endourological treatment of ureteral obstruction after renal transplantation. MATERIALS AND METHODS: Between January 1986 and December 1993, 582 kidney transplantations were performed at our center, and ureteral obstruction was suspected in 31 cases (5.3%). RESULTS: Initial treatment consisted of retrograde placement of an internal stent in 6 patients and percutaneous nephrostomy in 25. Due to upper tract dilatation obstruction could not be diagnosed in 3 patients, and rejection was the cause of decreasing renal function. Obstruction was temporary in 8 of the remaining 28 patients, including 6 in whom a Double-J stent was introduced in a retrograde manner without anesthesia. In the other 2 patients was well as the 20 with definitive obstruction, cannulation of the transplant orifice without anesthesia was unsuccessful and percutaneous nephrostomy drainage was necessary. Even with general anesthesia a guide wire could not be passed along the stricture in a retrograde or antegrade fashion in 7 of the 20 patients with definitive obstruction and open surgery was performed. The remaining 13 patients underwent dilation with (9) or without (4) diathermic incision. All 4 patients treated with dilation only had recurrent obstruction, while 9 treated with dilation and incision had no recurrence after a minimum followup of 27 months (mean 58). CONCLUSIONS: Modern endourological procedures have replaced open reconstructive surgery in the majority of patients with ureteral obstruction after renal transplantation.

Cytogenetic support for primary prostatic cancer in a patient presenting with a soft tissue mass in the leg.

A 65-year old man presented with a soft tissue mass in the leg, clinically suspect of a sarcoma. Histologic examination suggested a metastatic adenocarcinoma of the prostate, which could not be confirmed by immunohistologic studies. However, cytogenetic analysis strongly supported this diagnosis. A primary prostatic carcinoma was indeed found and the patient died of widely disseminated disease. These findings illustrate the significance of chromosomal analysis in the search for a primary tumor in patients with an unknown primary.

Brain aromatase activity and plasma testosterone levels are elevated in aggressive male mice during early ontogeny.

Testosterone (T) and estradiol (E2) are involved in intraspecific aggressive behavior. Both steroids exert their effects on behaviour via the hypothalamus and the amygdala (Am) of the central nervous system (CNS). In these brain areas T is converted to E2, by the enzyme aromatase. Both the levels of brain aromatase activity (AA) and the effects of T and E2 on aggressive behavior in adulthood depend on steroidal organization of the CNS during ontogeny. In this study we measured plasma T and in vitro brain AA of males fetuses and neonates derived from two strains of wild house mice, which had been genetically selected for aggression, based upon attack latency. There were no differences in preoptic area (POA) AA levels between selection lines on either embryonic day (E) 17 or 18, or the day after birth (day 1). In the non-aggressive long attack latency (LAL) males the POA AA increases with age, i.e. was higher on E18 than on E17, which is correlated with brain weight (BrW). This was in contrast to aggressive short attack latency (SAL) fetuses, which only showed a slight, but not significant differences between embryonic days or a correlation with BrW. Neonatally, the POA AA of LAL males tended to decrease in contrast to SAL males. However, SAL neonates had a higher AA in the amygdala (Am) than LAL neonates, whereas no differences exist in the anterior hypothalamus. Thus, a differential brain AA distribution exists in SAL and LAL pups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of extent of anterior resection and sex on disease-free survival and local recurrence in patients with rectal cancer.

Results are presented following 119 curative resections for rectal cancer performed on 47 women and 72 men. Throughout the study it was policy to remove part of the female genital tract when the rectal tumour impinged on the uterus and/or the posterior vaginal wall. After a median follow-up of 7.5 years, local recurrence occurred in three of 46 women and 15 of 71 men (P = 0.03). The survival rates at 5 years were 71 per cent for women (95 per cent confidence interval 56-83 per cent) and 60 per cent for men (95 per cent confidence interval 50-71 per cent) (P < 0.05). The risk for distant metastasis was comparable, suggesting an influence of local recurrence on survival. Reduction of the local recurrence rate coincides with the higher proportion of anterior extensions of surgery in women (19 of 47) than in men (two of 72).

[Endo-urological drainage in urinary outflow obstruction caused by cancer]. / Endo-urologische drainage bij urineafvloedbelemmering door kanker.

OBJECTIVE: To determine indications and results of endourological upper urinary tract drainage in patients with obstruction due to malignancy. DESIGN: Retrospective. SETTING: University Hospital Groningen. METHOD: In the period 1987-1992, 57 patients with upper urinary tract obstruction due to cancer were treated primarily with a double-J stent (n = 21) or a percutaneous nephrostomy (n = 36, later replaced by a double-J stent in 13). RESULTS: Indications were: severe renal failure following bilateral ureteral obstruction due to malignancy (n = 17), or unknown cause (n = 19), to optimise a compromised kidney function before chemotherapy (n = 7), to resolve pain caused by unilateral obstruction (n = 10), or other (n = 4). The tumours originated most often in the cervix uteri, followed by the urinary bladder, the prostate and the corpus uteri. Minor complications occurred in 34 of the 57 patients (60%): transient haematuria (22 x), urgency caused by the distal tip of the double-J catheter (8 x), dislocation (17 x) or obstruction (6 x) of the nephrostomy catheter. Major complications were observed in 5 patients with a double-J stent: sepsis (1 x), catheter break (1 x), ureteral perforation (2 x) and fistulization between the ureter and iliac artery (1 x). Survival after drainage varied from several days to 8 years (mean 23 months). In 5 patients treated with drainage only to prolong survival, survival was 0.5-16 months (mean 7.3). CONCLUSION: Endourological drainage may be applied to patients with localised disease, in whom further therapy holds the promise of prolonged survival. However, in view of the low complication rate, selected patients who are on a palliative course and still have rapidly progressive disease can also benefit from extended life-time after endourological drainage.

Aromatase activity in the preoptic area differs between aggressive and nonaggressive male house mice.

Treatment with testosterone (T) or estradiol (E2) facilitates intraspecific aggressive behavior in adult rodents. Brain aromatization of T to E2 appears to be involved in facilitation of fighting behavior. In the present study we measure the in vitro brain aromatase activity (AA) in the preoptic area (POA), amygdaloid nuclei (Am), ventromedial hypothalamus (VMH), and parietal cortex (CTX) from two strains of adult male house mice, which were genetically selected for territorial aggression, based upon their attack latencies (short attack latency: SAL; long attack latency: LAL). The results reveal a higher AA in the POA of nonaggressive LAL males, as compared to aggressive SAL animals. The POA AA is, thus, inversely correlated with aggressiveness. The AA levels in both the VMH and Am do not differ significantly between strains. Furthermore, a differential brain area-specific AA distribution exists: POA > VMH AA in LAL, whereas POA < VMH in SAL. In both selection lines, the Am exhibits the highest levels of AA, as compared to the other investigated areas. Kinetic studies revealed that the aromatase Km is similar in both strains. The results indicate that the strain difference in AA is specific to the POA, but is not necessarily positively correlated with circulating plasma T levels. Other factors, in addition to androgen, are probably involved in the regulation of POA aromatase. We suggest that a higher neural androgen receptor sensitivity exists in the POA of nonaggressive LAL males, resulting in higher adult POA AA, despite lower concentrations of circulating T.

Genetic differences in female house mice in aggressive response to sex steroid hormone treatment.

Male mice, genetically selected for aggression, characterized by short attack latency (SAL) or long attack latency (LAL), differ on several testosterone (T)-related parameters during ontogeny and adult age. The variation in aggressive behavior at adult age may be due to differences in degree of androgenization prenatally. When exposed to T at prenatal, neonatal, and/or adult age, nonlactating females also display intraspecific fighting behavior. In the present study, we investigated in females of the SAL and LAL selection lines, whether the differentiation of aggression involves processes similar to ones seen in males. Therefore, we injected females with testosterone propionate (TP) or vehicle on the day of birth, treated them after ovariectomy at adult age with T, estradiol (E), or vehicle, and tested their aggressive response. We found that neonatally vehicle-treated SAL females show a higher aggressive response to chronic T treatment at adult age than LAL females receiving the same treatment. Females of both selection lines treated with vehicle or E as adults were not aggressive. Neonatal TP treatment did not influence the adult T sensitivity and difference between selection lines in response to T at adult age. However, neonatally TP-treated SAL females showed aggressive behavior when treated with E at adult age, whereas LAL females failed to do so. These results suggest a genetic difference in susceptibility to T and E, which plays a major role prenatally, in organizing the development of sex steroid-dependent neural systems.

Long-term increase in protein kinase C-gamma and muscarinic acetylcholine receptor expression in the cerebral cortex of amygdala-kindled rats--a quantitative immunocytochemical study.

Kindling is an animal model for epilepsy in which repeated application of an electrical stimulus to brain pathways results in an epileptic focus. The animal holds a permanent state of hyperexcitability to the stimulus for the rest of its life. Understanding the cellular and molecular processes underlying hyperexcitability could provide insight into epileptogenesis. Furthermore, it could elucidate cellular and molecular bases of synaptic plasticity in the central nervous system. In the present study the long-term effect of a kindled focus in the amygdala on the gamma-isoform of protein kinase C and the muscarinic cholinergic receptor as cellular messengers was evaluated in the cerebral cortex of rats. Following an average of 10 bilaterally generalized seizures kindling stimulation was terminated and rats were left undisturbed for approximately three months. Brains were processed by immunocytochemistry using monoclonal antibodies against protein kinase C-gamma and muscarinic cholinergic receptor protein. Digital image analysis of sections through the entire forebrain revealed an increase in optical density of both protein kinase C-gamma and the muscarinic cholinergic receptor in the piriform and entorhinal cortex of the hemisphere contralateral to the stimulation site in kindled rats. However, on the ipsilateral side no change was observed in comparison with electrode implanted nonkindled control rats. The observed increase in expression of muscarinic cholinergic receptor protein and a component of the phosphoinositide second messenger system (protein kinase C-gamma) located in specific areas of the cerebral cortex in kindled rats could serve as a basis for the permanent state of hyperexcitability in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Partial least-squares regression for routine analysis of urinary calculus composition with Fourier transform infrared analysis.

Quantitative assessment of urinary calculus (renal stone) constituents by infrared analysis (IR) is hampered by the need of expert knowledge for spectrum interpretation. Our laboratory performed a computerized search of several libraries, containing 235 reference spectra from various mixtures with different proportions. Library search was followed by visual interpretation of band intensities for more precise semiquantitative determination of the composition. We tested partial least-squares (PLS) regression for the most frequently occurring compositions of urinary calculi. Using a constrained mixture design, we prepared various samples containing whewellite, weddellite, and carbonate apatite and used these as a calibration set for PLS regression. The value of PLS analysis was investigated by the assay of known artificial mixtures and selected patients' samples for which the semiquantitative compositions were determined by computerized library search followed by visual interpretation. Compared with that method, PLS analysis was superior with respect to accuracy and necessity of expert knowledge. Apart from some practical limitations in data-handling facilities, we believe that PLS regression offers a promising tool for routine quantification, not only for whewellite, weddellite, and carbonate apatite, but also for other compositions of the urinary calculus.

Differential perinatal testosterone secretory capacity of wild house mice testes is related to aggressiveness in adulthood.

Testosterone secretory capacity of testicular Leydig cells was determined in fetal males of an aggressive and a nonaggressive genetic selection line of wild house mice. They were studied at Days 15-18 of gestation and on the first day after birth. A previously described morphometric method was used to quantify 3 beta-hydroxy steroid dehydrogenase (3 beta-HSD)-stained Leydig cells in testicular sections to determine testosterone secretory capacity, which may be considered to reflect circulating plasma testosterone in the fetus. The results of this study show that the testosterone secretory capacity of Leydig cells in the testis changes differentially during intrauterine development in males of the aggressive and nonaggressive selection lines. The peak secretory capacity is reached at Day 17 of gestation for the males of the aggressive selection line, while the peak for the nonaggressive males is reached on the first neonatal day. The larger anogenital distance observed in aggressive males suggests a higher prenatal testosterone level in these males. The importance of the difference in timing of the perinatal 3 beta-HSD peak top individual variation in adult aggressive behavior is discussed.

Differential lateral septal vasopressin innervation in aggressive and nonaggressive male mice.

The vasopressinergic (VP) projection from the bed nucleus of the stria terminalis (BNST) to the lateral septum (LS) is sexually dimorphic and dependent of androgens at adult and neonatal age. We studied the relation between testosterone (T) and VP in male mice, which were genetically selected for their differences in aggression level. Aggressive males, characterized by a short attack latency (SAL), have a higher production capacity of T at adult age compared to males with a long attack latency (LAL). Neonatally, however, a higher T production occurs in the nonaggressive LAL males than in SAL males. In the present study we showed a more dense VP-immunoreactive (VP-ir) innervation in the LS and a higher VP-ir neuron density in the BNST of LAL males as compared to SAL males. The described differences may be the consequence of a differential neonatal androgen effect on the organization of the forebrain vasopressinergic network.

Differential effects of neonatal testosterone treatment on aggression in two selection lines of mice.

Selection lines of mice, artificially selected for aggression based upon the attack latency score (ALS), were used. In order to determine the relative contribution of neonatal testosterone (T) in the development of aggression, we vary the plasma-T level in males of both selection lines on the day of birth. At 14 weeks the ALS was measured. Neonatal T treatment results in a reduction of aggression in the long attack latency (LAL) line, whereas aggressive behaviour of the short attack latency (SAL) line is not affected. Both selection lines show reduction in testicular weight, although the total amount of T-producing Leydig cells was not affected. Neonatal T may cause a permanent reduction in aggressive behaviour in in the LAL line only, probably due to differential appearance of critical periods. It is suggested that the difference in aggressive behaviour between SAL and LAL selection lines is due to a prenatally determined difference in neonatal T sensitivity of the brain.

Stress and differential alterations in immune system functions: conclusions from social stress studies in animals.

Psychosocial factors are implicated in the development, in the course of, and in the recovery from disease. The immune system may be a mediator of the disease. Studies with animal models using social interactions in rodents suggest that short- and long-term social stress does not invariably suppress immune system functions. The magnitude and direction of changes in diverse compartments of the immune system are highly correlated to the social position of the animal. Furthermore, genetic, developmental, and adult experience may predetermine the animal's coping strategy both in terms of behaviour and neuroendocrinology, and hence in immunology as well. It is argued that disease processes should be considered as a function of baseline immunological state.