CSF 5-HIAA and exposure to and expression of interpersonal violence in suicide attempters.

BACKGROUND: Serotonin is implicated in impaired impulse control, aggression and suicidal behaviour. Low cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been found in violent suicide attempters, suicide victims and in violent offenders. CSF 5-HIAA concentrations have both genetic and environmental determinants. Childhood trauma may have an effect on central monoamine function as an adult. AIM: The aim of this study was to assess the relationship of CSF 5-HIAA and the exposure to and the expression of violence in childhood and during adult life measured with the Karolinska Interpersonal Violence Scale (KIVS). METHOD: 42 medication free suicide attempters underwent lumbar puncture and were assessed with the Karolinska Interpersonal Violence Scale (KIVS) to assess history of childhood exposure to violence and lifetime expressed violent behaviour. RESULTS: In women, but not in men, CSF 5-HIAA showed a significant negative correlation to exposure to violence during childhood. Furthermore, suicide attempters with low CSF 5-HIAA were more prone to commit violent acts as an adult if exposed to violence as a child compared to suicide attempters with high CSF 5-HIAA. In the non-traumatized group, CSF 5-HIAA showed a significant negative correlation to expressed violent behaviour in childhood. CONCLUSIONS: Although central serotonergic function has important genetic determinants, exposure to childhood trauma may also affect serotonergic function. Low serotonergic function may facilitate impaired aggression control in traumatized suicide attempters.

An observational study on early-lactation metabolic profiles in Swedish organically and conventionally managed dairy cows.

The aim of this observational study was to compare indicators of energy balance in early lactation in organically managed dairy cows (OMC) and conventionally managed dairy cows (CMC) under field conditions. The diets of OMC and CMC differ as a consequence of the rules and principles of organic dairy farming. The study was based on clinical examinations and blood samples from cows within the range from 2 wk prepartum to 6 wk postpartum, collected from 20 organic and 20 conventional dairy farms with 3 visits at each farm. The farms were located in a southeastern area of Sweden and ranged in size from 45 to 120 cows. The blood parameters selected to reflect energy metabolism were nonesterified fatty acids, beta-hydroxybutyrate, glucose, and insulin. At clinical examination body condition score was registered. The shape of the lactation curve in early lactation was modeled to assess potential differences that could explain the blood parameter profiles. The conventionally managed cows increased their milk yield faster than OMC within the first 2 wk of lactation. Blood nonesterified fatty acid concentrations were similar between the management types, but with a tendency of lesser concentrations in OMC, primarily in early lactation. Postcalving beta-hydroxybutyrate concentrations were constantly lesser in OMC during the first 6 wk of lactation. An interaction between season and insulin concentration necessitated stratification on season. During spring the profiles overlapped, but there was a significant difference in the first 4 d post-calving, when organically managed cows had greater insulin concentrations and in d 30 to 34 when conventionally managed cows had greater insulin concentrations. During fall the profiles overlapped completely and there was no significant difference at any point in time. Glucose concentrations tended to decrease slightly postcalving followed by a gradual elevation to a concentration just under the precalving concentration during the study period. Body condition scores decreased slightly over the study period. No differences were found between the management types with regard to glucose concentrations or registered body condition score. In conclusion, the OMC did not show a greater extent of mobilization of body tissue than CMC as expressed by our study variables. Hence, OMC adjusted the production amount according to feed intake.

Managements' perception of community nurses' decision-making processes when referring older adults to an emergency department.

In Sweden, older adults are living and being cared for under the responsibility of their respective community. Extensive reorganizations in the community led to management having different backgrounds, which may have caused uncertainty among community nurses, especially in decision-making processes. The aim was to understand how 10 nurses, 10 doctors and 10 home care assistants as leaders for the nurses conceptualized the decision-making processes of community nurses, when referring older persons to Emergency Departments, and whether perceptual differences and/or similarities exist. Narrative interviews and content analysis were performed. The managers had differing views, but all felt there was a need to feel secure in order to trust professional decisions as being correct, thus avoiding inappropriate referrals. Management could see nurses' exposed position, but had varying solutions. This might lead to different messages being given regarding what is important and might explain why the nurses reported that the managers did not understand them.

Health of cows, calves and young stock on 26 organic dairy herds in Sweden.

The health and housing of the stock on 26 organic dairy herds in four counties in eastern Sweden were studied for one year. The herds ranged in size from 12 to 64 cows, and their milk production from 3772 to 10,334 kg per cow per year. A large-animal practitioner visited the farms three times during the year, and a random sample of a third of the cows in each herd were examined. The calves and young stock and their housing were also studied. The calves were in good condition in all but four herds; their serum immunoglobulins varied from almost none to high levels. The young stock were in good condition and in good housing in 20 herds. No cows with clinical signs of metabolic disorders were found. Body condition scores were adequate or good except in two herds. Acetone was analysed in milk samples from individual cows three to six weeks postpartum, and only sporadic cases with high levels were found. The incidence of diseases treated by a veterinarian was lower in the organic herds than the average for the conventional herds in the local dairy association. The findings at the farm visits supported these data, and it is evident that a good standard of health and welfare can be achieved in organic dairy herds.

Acrylamide and N-methylolacrylamide poisoning in a herd of Charolais crossbreed cattle.

Seven beef cattle from a herd accidentally exposed to acrylamide and N-methylolacrylamide while grazing were observed for eight months. They showed clinical signs of impaired nerve function, mainly in the hindlegs, with varying degrees of weakness and ataxia. The animals were irritable, nervous and hypersensitive to touch. Both pupils of the most badly affected animal were dilated and it had poor pupillary light responses; it also showed signs of axonal neuropathy. Selected haematological and clinical chemistry variables were normal. The severity of the neurological signs was correlated with the concentrations of haemoglobin adducts of acrylamides. The animals recovered substantially after their exposure. The gestations of four of the animals which were in calf proceeded normally.

No association between a promoter dopamine D(4) receptor gene variant and schizophrenia.

The dopamine D(4) receptor has been implicated in the pathogenesis of schizophrenia. An association between a putative functional promoter polymorphism (-521C/T) in the dopamine D(4) receptor gene (DRD4) and schizophrenia was recently reported. In the present study, patients with schizophrenia (n = 132) and control subjects (n = 388) were analyzed with respect to the DRD4 - 521C/T polymorphism. No significant case control differences emerged. The present results do not support a major role for DRD4 in the etiology of schizophrenia among Caucasians from Sweden.

No association between serotonin 2A receptor gene variants and personality traits.

Among theories of biological underpinnings to personality traits, different mechanisms of the serotonergic system are perhaps the most common factors suggested to influence individual differences in personality traits. We have investigated two frequent variants in the serotonin 2A receptor gene (5-HT2A) and personality traits. Healthy Swedish subjects (n = 304) were assessed with the Karolinska Scales of Personality (KSP) inventory. After correction for multiple testing, no significant differences were found. We conclude that the investigated 5-HT2A gene variants do not significantly influence personality as assessed by the KSP in the present population.

Androgen receptor trinucleotide repeat polymorphism and personality traits.

Human family and twin studies have established considerable heritable components influencing individual differences in personality traits as assessed by self-report questionnaires. We have investigated a trinucleotide repeat polymorphism in the androgen receptor gene and personality traits. Healthy Swedish subjects (n = 335) were assessed with the Karolinska Scales of Personality inventory. There were tendencies (P > or = 0.006) in some scales indicating possible relationships between the androgen receptor allele length and personality traits related to dominance and aggression. However, after correction for multiple testing, no significant differences were found. We conclude that no significant association could be found between the androgen receptor polymorphism investigated and any personality trait, although the tendencies found are worthwhile subjects for replication attempts.

Excess tryptophan hydroxylase 17 779C allele in surviving cotwins of monozygotic twin suicide victims.

OBJECTIVE: To evaluate the relationship of the tryptophan hydroxylase (TPH) genotype to suicidality by the study of surviving monozygotic (MZ) cotwins of twins who committed suicide. METHOD: Twenty-four surviving Swedish MZ twins whose MZ cotwins had committed suicide were compared to 158 demographically sampled Swedish general population controls for TPH alleles. We also examined serotonin transporter alleles. RESULTS: The living MZ cotwins of suicide victims had a significantly higher TPH 17 779C allele frequency than controls. No significant difference was observed for serotonin transporter alleles. CONCLUSION: These results, in a small sample, suggest the possibility that the 17 779C allele of the TPH gene may be associated with an increased risk of suicide. Further studies in larger samples are needed.

Platelet monoamine oxidase activity is related to MAOB intron 13 genotype.

Monoamine oxidases (MAO) play a critical role in the degradation of endogenous and exogenous amines throughout the body. There are two distinct MAO isoforms, MAO-A and MAO-B, which both are encoded in genes on the X chromosome. Alterations in MAO-B activity have previously been connected with several neurological disorders. Platelet MAO (trbc-MAO) is exclusively of the B-type and the catalytic activity of this enzyme is under strong, yet unknown, genetic control. Specific trbc-MAO activity has been reported to be increased in certain neurodegenerative diseases and to correlate with personality traits such as sensation seeking and impulsiveness. In the present study, we investigated if trbc-MAO activity is associated with genotype at a variable region (A/G dimorphism) in intron 13 of the human gene encoding MAO-B. The MAOB intron 13 allele status and levels of trbc-MAO were determined for 55 Caucasian non-smoking males. Individuals with the "A-allele" displayed significantly lower enzyme activity than individuals with the "G-allele", i.e. 11.4 +/- 0.6 nmol/10(10) platelets/min compared with 13.5 +/- 0.6 (mean +/- SEM, p = 0.019). The present results suggest that the MAOB genotype may be involved in determining trbc-MAO activity.

A polymorphic region in the human transcription factor AP-2beta gene is associated with specific personality traits.

Transcription factor AP-2beta is implicated in playing an important role during embryonic development of different parts of the brain, eg, midbrain, hindbrain, spinal cord, dorsal and cranial root ganglia.1,2 The gene encoding AP-2beta contains a polymorphic region which includes a tetranucleotide repeat of [CAAA] four or five times, located in intron 2 between nucleotides 12593 and 12612.3 Since the midbrain contains structures important for variables such as mood and personality, we have investigated if the AP-2beta genotype is associated with personality traits estimated by the Karolinska Scales of Personality (KSP). Identification of transcription factor genes as candidate genes in psychiatric disorders is a novel approach to further elucidate the genetic factors that, together with environmental factors, are involved in the expression of specific psychiatric phenotypes. The AP-2beta genotype and KSP scores were determined for 137 Caucasian volunteers (73 females and 64 males). The personality traits muscular tension, guilt, somatic anxiety, psychastenia and indirect aggression were significantly associated with the specific AP-2beta genotype, albeit with significant difference between genders. Based on this result the human AP-2beta gene seems to be an important candidate gene for personality disorders. Moreover, the present results suggest that the structure of the intron 2 region of the AP-2beta gene is one factor that contributes to development of the constitutional component of specific personality traits.

Carcass quality in certified organic production compared with conventional livestock production.

By studying carcass quality, expressed as affection, pathological findings, slaughter-weight and evaluation, a picture of an animal's health and potential as high quality food is achieved. This study compares the carcass quality in Swedish certified organic meat production with that of conventional meat production slaughtered during 1997. The study involves 3.9 million pigs, about 570,000 cattle and 190,000 sheep, all reared conventionally and 3483 pigs 4949 cattle and 4997 sheep reared according to organic standards. Pathological and additional findings are registered by meat inspectors from the Swedish National Food Administration at the post-mortem inspection. There was a significant difference at the post-mortem inspection of growing-fattening pigs; 28% of conventionally and 17% of the organically reared pigs had one or more registered lesion. The carcass evaluation of swine shows a higher meat percentage in conventional swine production. The total rate of registered abnormalities in cattle was systems around 28% from organic and 27% from conventionally reared herds. Carcass evaluation of cattle from organic herds gave higher classification in the EUROP system, whereas the fat content was lower than that of conventionally reared cattle. Sheep, reared both organically and conventionally, showed a lower rate of registered abnormalities than swine and cattle.

Mage-b4, a novel melanoma antigen (MAGE) gene specifically expressed during germ cell differentiation.

The MAGE genes were initially isolated from different kinds of tumors, and based on their virtually exclusive tumor-specific expression in adult tissues, they have been used as targets for cancer immunotherapy. However, although a large number of MAGE genes have now been identified and extensively studied in tumors of various origin, their functions in normal cells remain unknown. Here we describe the isolation and characterization of a novel murine MAGE homologue, Mage-b4. mRNA expression studies in a wide variety of adult and embryonic tissues revealed that Mage-b4 is specifically expressed in fetal and adult gonads. An antibody specific to Mage-b4 was developed, and using this antibody, we found that the Mage-b4 protein was confined to the cytoplasm of germ cells. Double-labeling experiments using antibodies against the meiosis-specific SCP3 protein and the Mage-b4 protein showed that Mage-b4 is down-regulated as the germ cells enter meiosis in adult testis. In contrast, Mage-b4 was expressed in female germ cells throughout meiosis, and the protein was also found in dormant primary oocytes.

Improved detection of five closely related ruminant alphaherpesviruses by specific amplification of viral genomic sequences.

The detection and discrimination of five closely related ruminant alphaherpesviruses, bovine herpesvirus 1 (BHV-1), bovine herpesvirus 5 (BHV-5), caprine herpesvirus 1 (CapHV-1), cervine herpesvirus 1 (CerHV-1), and rangiferine herpesvirus 1 (RanHV-1), were achieved by the development of specific PCR systems. The highly variable N-terminal of the glycoprotein C was chosen to select the diagnostic primers, except for the CerHV-1 primers, which targeted the glycoprotein D region. All the assays proved specific since no heterologous virus was amplified. BHV-1 and BHV-5 were detected by using the same PCR assay and the different sizes of the amplification products allowed their identification on agarose gels. The practical diagnostic applicability of the novel PCR assays, with special regard to the BHV-1 system, has been evaluated on clinical samples from experimentally infected animals.

Association between a promoter polymorphism in the dopamine D2 receptor gene and schizophrenia.

Genetic factors and dopamine receptor dysfunction have been implicated in the pathophysiology of schizophrenia. Recently, an association between a putative functional promoter polymorphism (-141C Ins/Del) in the dopamine D2 receptor gene and schizophrenia was reported. We investigated unrelated Swedish schizophrenic patients (n = 129) and control subjects (n = 179) for the same polymorphism. Similarly to a previous Japanese report, the - 141C Del allele frequency was significantly lower in patients than controls (chi2=4.4, 1 df, p<0.05; odds ratio 0.49, 95% confidence interval 0.26-0.91). The present and previous results may indicate that the -141C Ins/Del dopamine D2 receptor gene polymorphism affects susceptibility to schizophrenia.

No association between serotonin transporter gene polymorphisms and personality traits.

Human family and twin studies have established considerable heritable components in personality traits as assessed by self-report questionnaires. Recently, an association between a functional polymorphism in the upstream regulatory region of the serotonin transporter gene and neuroticism-related personality traits was reported. Two different serotonin transporter polymorphisms including the previously associated variant were genotyped in two samples of healthy Swedish subjects (n = 127 and n = 178, respectively) assessed with the Karolinska Scales of Personality (KSP) inventory. No statistically significant association between serotonin transporter polymorphisms and any of the eight neuroticism-related KSP scales was found. Thus, the previously reported association between serotonin transporter alleles and neuroticism-related personality traits could not be replicated in the present study.

Lack of association between dopamine D4 receptor gene and personality traits.

BACKGROUND: Personality traits have shown considerable heritable components. Association between alleles of a polymorphism in the third exon of the dopamine D4 receptor gene (DRD4) and the personality trait Novelty Seeking has been reported. Recently, in a sample of Swedish non-psychiatric subjects we could not detect any significant relationships between the same polymorphism and Novelty Seeking related scales in the Karolinska Scales of Personality (KSP). However, there was a tendency in the direction of the proposed association. There were also tentative associations between an exon I 13 bp deletion polymorphism and the personality traits Socialization and Guilt. METHODS: We investigated a new Swedish population-based sample (N = 167) investigated with the KSP for three DRD4 polymorphisms. RESULTS: Neither of the previous results were replicated. Combining the previous and the present samples did not give rise to any significant association between DRD4 polymorphisms and personality scales. CONCLUSIONS: The dopamine D4 receptor gene is probably not of importance to the different personality dimensions as measured by the Karolinska Scales of Personality.

Two novel adenovirus vector systems permitting regulated protein expression in gene transfer experiments.

Two new adenovirus vector systems based on the tetracycline-regulated Tet-ON- (Gossen, M., et al., Science 268:1766-1769, 1995) and the RU 486-regulated progesterone antagonist (Wang, Y., et al., Proc. Natl. Acad. Sci. USA 91:8180-8184, 1994)-induced gene expression systems are described. We show that both systems permit a tight control of chloramphenicol acetyltransferase reporter gene expression in a variety of cell types, with induction levels of approximately 1,800-fold (Tet-ON system) and 600-fold (RU 486-regulated system), respectively. A significant advantage of our vector systems is that reporter protein expression can be adjusted over a wide range by varying the amount of inducer. The Tet-ON system is also shown to permit an efficient control of reporter gene expression in mice.

Efficient transduction of early passage human melanoma to secrete IL-4.

Augmentation of tumor immunogenicity has been increasingly studied as a strategy to develop host immunity against established malignancies. Genetic modification of tumors to secrete immunoregulatory peptides such as IL-4 has been demonstrated to augment tumor immunogenicity and enhance the induction of tumor reactive lymphoid cells in animal models. To explore the ability of IL-4 to augment the immunogenicity of melanoma cells, we constructed a recombinant retrovirus vector encoding for human IL-4 and used it to transduce human melanomas. After optimizing retrovirus transduction conditions using a reporter virus, an IL-4 encoding retrovirus vector was used to transduce early and late passage melanoma cells. IL-4 production rates of up to 2000 pg/ml per 24 h per 10(6) cells were achieved, and provirus could be detected by Southern blot of the transduced cells at 0.1 copies per cell. The IL-4 produced by the melanoma cells was biologically active. Irradiated transduced melanoma cells continued to produce IL-4 for at least two weeks of observation. Thus melanoma cells can be efficiently modified to secrete biologically active IL-4, and may be suitable substrates for autologous tumor cell vaccines.