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.

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.

Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects: a double-blind PET study of schizophrenic patients.

The relationship between central D2-dopamine receptor occupancy and antipsychotic drug effects was examined in a double-blind study. Raclopride was the compound used to induce a selective occupancy of the D2-dopamine receptors. In addition, 11C-labeled raclopride was the radioligand used to measure occupancy by positron emission tomography (PET). Seventeen schizophrenic patients were randomly assigned to one of three parallel groups treated for 4 weeks with daily doses of 2, 6, or 12 mg of raclopride. D2-receptor occupancy was determined by PET at steady-state conditions in 13 patients who completed the study. A statistically significant relationship was demonstrated between antipsychotic effect and degree of D2-receptor occupancy (p < 0.05). Patients with extrapyramidal side effects had significantly higher D2-receptor occupancy than those without (p = 0.02). The finding of a relationship between selective occupancy of the D2-dopamine receptors and clinical effects in schizophrenic patients principally provides new support for the dopamine hypothesis of antipsychotic drug action.

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.

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.

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.

Ribavirin mitigates wart growth in rabbits at early stages of infection with cottontail rabbit papillomavirus.

The challenge to develop antiviral agents effective against DNA viruses such as human papillomavirus (HPV) has been dependent on finding an animal model which mimics the human forms of the disease. We have used an existing model system for the purpose of measuring the effect of antiviral drugs on the inhibition of growth of these lesions. This was based upon domestic rabbits which efficiently grow cutaneous papillomas (warts) when infected with cottontail rabbit papillomavirus (CRPV). One agent which had shown significant success in achieving these goals was ribavirin. Ribavirin was administered intradermally shortly prior to infection at multiple sites with CRPV. Following daily injections of this drug for eight weeks, we have shown a dose-dependent response which had markedly reduced the number of warts, the time of first appearance of warts and reduced the tumor mass as compared to placebo-treated control animals. At the highest dose of ribavirin tested, 30 mg/kg/day, compared to controls, the average reduction in the number of warts was 52%, the average time of first appearance of warts was 49% longer, and the average mass of the warts was reduced by 98%. No detectable antibodies to CRPV were observed in any of the animals. The only side effects which were observed was focal alopecia, and a decrease in body growth upon prolonged treatment, both of which were completely reversible. Pharmacokinetic studies established the metabolism of ribavirin over a 24-h period of time. Ribavirin administered beginning 12 or 30 days post-infection, while not reducing the number of warts, slightly retarded the growth of warts as determined by date of first appearance of warts and mass of warts.

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 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.

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.

Immunobiologic effects of cytokine gene transfer of the B16-BL6 melanoma.

OBJECTIVE: The genetic modification of tumors offers an approach to modulate the host immune response to relatively weak native tumor antigens. We examined the immunobiologic effects of various cytokine genes transferred into the poorly immunogenic B16-BL6 murine melanoma. DESIGN: Retroviral expression vectors containing cDNAs for interleukin 2, interleukin 4, interferon gamma, or a neomycin-resistant control were electroporated into a B16-BL6 tumor clone. Selected transfected clones were examined for in vitro cytokine secretion and in vivo tumorigenicity. RESULTS: When cells from individual clones were injected intradermally into syngeneic mice, the interleukin 4-secreting clone grew significantly slower than did the neomycin-resistant transfected control, while the growth of the interleukin 2- and interferon gamma-expressing clones was not affected. Despite minimal cytokine secretion by interferon gamma-transfected cells, these cells expressed upregulated major histocompatibility class I antigen and were more susceptible to lysis by allosensitized cytotoxic T lymphocytes compared with parental or neomycin-resistant transfected tumor targets. CONCLUSIONS: We observed diverse immunobiologic effects associated with cytokine gene transfer into the B16-BL6 melanoma. Interleukin 4 transfection of tumor resulted in decreased in vivo tumorigenicity that may be related to a host immune response. Further studies to evaluate the host T-cell response to these gene-modified tumors are being investigated.

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.

Studies on the neuromuscular junction with a special preference to nicotinic receptors in normal delivering cows and cows suffering from parturient paresis.

Acetylcholine synthesizing (ACh-s) activity, and binding of 3H-alpha-bungarotoxin (3H-Btx) and 3H-d-tubocurarine (3H-TC) were analysed in gluteus media muscle from normal cows and from cows suffering from parturient paresis, both at parturition and 3 months later. At parturition, the ACh-s activity was 50% lower in the muscle of paretic cows than in non-paretic cows. No difference was found in the number of 3H-Btx and 3H-TC binding sites at parturition, while 3 months after parturition the numbers of 3H-TC and 3H-Btx binding sites were significantly higher in normal than in paretic cows. These significant differences in the number of receptors and a possible underlying receptor regulation defect might be a plausible etiological factor for the disease parturient paresis.

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.