Mental illness in the biological and adoptive families of adopted individuals who have become schizophrenic

In a sample of 5483 adults who had been legally adopted early in life by persons not biologically related to them, 33 were identified, from mental hospital records, for whom a diagnosis of definite schizophrenia (chronic, latent, or acute) could be agreed upon by four raters. An equal number of matched controls were selected from the sample of adopted individuals who had never been admitted to a mental hospital. Ninety percent of the living parents, siblings, and half-siblings, biological and adoptive, cooperated in an extensive psychiatric interview permitting a consensus diagnosis by three blind raters. Schizophrenia and uncertain schizophrenia were found to be significantly concentrated in the population genetically related to the schiziphrenic adoptees. Their adoptive relatives did not differ from the control populations in the prevalence of schizophrenic illness.This was presented at the Annual Meeting of the American Society of Human Genetics, Portland. Oregon, October 18, 1974.     

Clinical findings and prognostic factors in chronic myeloid leukemias

Ninety-one previously untreated patients with chronic myeloid leukemia admitted to three Stockholm hospitals 1973-1978 were studied. There were 49 men and 42 women with a mean age of 56 years (range 15-93). Sixty-five patients were Philadelphia chromosome (Ph1) positive and 17 were Ph1 negative (mean age 51 and 70 years, respectively). After a mean observation time of 5.2 years, 64 patients had deceased, 45 of them in blast transformation. A low hemoglobin value and a high total blast cell count at diagnosis were associated with a poor prognosis in the Ph1 positive group. Other routine clinical and laboratory variables were of subordinate prognostic importance. Early splenectomy in 15 Ph1 positive patients did not improve survival. Median survival from diagnosis was 38 months for Ph1 positive patients as compared to 12 months for the Ph1 negative group.     

Hormonal responses to high- and moderate-intensity strength exercise

The hormonal responses of nine male, strength athletes to strength exercise were examined. The athletes performed one moderate- and one high-intensity strength exercise workout. In the high-intensity workout, the load was 100% of each subject's three-repetition maximum (3-RM) for squats and front squats, and 100% of each subject's six-repetition maximum (6-RM) for leg extensions. In the moderate-intensity workout, the load was 70% of the high-intensity protocol. Rest periods between sets were 4–6 min for both workouts. Blood samples were taken before, 30 min into, and every 15 min for the 1st h after exercise, and then 3, 7, 11, 22 and 33 h after exercise, thus allowing examination of both the acute and prolonged hormonal responses. Blood samples were analyzed for testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), cortisol, adrenocorticotrophic hormone (ACTH), growth hormone (GH), insulin-like growth factor (IGF-1), insulin, sex hormone binding globulin, creatine kinase, total protein, glucose and lactate. The acute responses of testosterone and cortisol were greater during the high-intensity protocol as compared to the moderate-intensity protocol. The cortisol response was associated with an increase in ACTH concentration. LH and FSH showed no response to either protocol. Acute GH responses were not different between protocols. There were great inter-individual differences in acute GH responses to both protocols. There were no significant differences between protocols with regard to prolonged responses for any hormone. In both trials, IGF-1 concentrations were significantly lower at 0800 hours the morning after exercise as compared to concentrations found at 0800 hours the morning before exercise. The mechanisms responsible for reducing IGF-1 concentration in these trials are unclear, and it is not known if this reduction observed 22 hours after exercise is of physiological significance. Accepted: 13 December 1999     

Antibody responses to honey-bee venom and monomethoxy-polyethylene glycol-modified honey-bee venom in mice

Antibody responses of the IgE isotype were raised in mice with honey-bee venom (HBV) administered in alum or by daily injections without adjuvant. The sensitized mice were treated with single injections of HBV modified with monomethoxy-polyethylene glycol. By such treatment with modified but not with natural HBV, suppression of the IgE antibody responses was achieved. The IgG antibody responses, in contrast, were unchanged or enhanced.     

Specific IgE, IgG, and IgA antibody response to oral immunotherapy in birch pollinosis

Thirty-nine patients with birch pollinosis participated in a double-blind, placebo-controlled trial of oral immunotherapy (OIT) for 18 months. They were treated with increasing doses of freeze-dried birch-pollen antigens for 16 months, reaching a cumulative dose of 280 x 10(6) biologic units. This is about 200 times more than the dose used in conventional subcutaneous immunotherapy (IT). In the placebo-treated group, but not in the actively treated group, there was a rise in postseasonal birch-specific IgE antibody levels. A significant decline in postseasonal values after 1 year of treatment was recorded in the actively treated, but not in the placebo-treated, group. Compared to the placebo treatment, there was a significant rise in birch-specific IgG antibodies in patients administered active treatment; however, the rise was less than that usually observed during subcutaneous IT. No significant change in birch-specific serum IgA was found in either group. The changes in IgE and IgG antibody levels demonstrate that OIT affects the immune system. This supports our recent findings that OIT demonstrates a beneficial effect in the treatment of birch pollinosis in adults. But, as with subcutaneous IT, there was no clear relationship between antibody response and clinical findings in the patients. The underlying mechanisms responsible for the relief of symptoms thus remain unknown.     

Serotonergic regulation of canine enteric motility (measured as electrical activity) and absorption: physiologic and morphologic evidence

To explore the effect of serotonin (5-HT) on enteric electrical activity, transit and absorption, four dogs were prepared with 50 cm jejunal and ileal Vella loops. Electrodes for recording enteric electrical activity were attached to the loops and to the main small bowel. After recovery, both loops were perfused with a [14C-]PEG-glucose-electrolyte solution via the proximal stomas, while effluent was collected from the distal stomas and enteric electrical activity was monitored. Control periods were compared with periods when 5-HT was infused intravenously at a rate of 10 micrograms kg-1 min-1 for 60 min. Serotonin increased the mean +/- SEM % of jejunal and ileal pacesetter potentials with spike potentials from 33 +/- 7% and 35 +/- 9%, before infusion to 63 +/- 4% and 61 +/- 5% after infusion (P less than 0.05). Serotonin also induced distally-migrating bursts of spikes in the incontinuity small bowel. The changes were blocked by atropine, but not by ketanserin. Absorption of water, sodium and glucose from the jejunal and ileal loop and transit through the loops was not changed by 5-HT. At autopsy, all layers of the jejunum and ileum contained varicose nerve fibres with a positive immunoreaction to 5-HT, while positive nerve cell bodies were largely confined to the submucosa.     

Drug development strategies for asthma: in search of a new paradigm

The spiraling costs of asthma treatment seem set to continue rising, given the equivocal performance of the latest generation of specific anti-inflammatory drugs in trials in adult asthmatics. We argue that the continuation of this trend is inevitable unless there is a substantial realignment of entrenched drug development policy in the pharmaceutical industry and a parallel shift in licensing policy by regulatory authorities to encourage the development of drugs capable of halting the progression from acute to chronic asthma when the disease first manifests in childhood. The theoretical framework for such an approach, including proof-of-principle data from studies in children with early-stage disease and a range of candidate drugs, already exists. What is needed is informed debate on the risks versus potential benefits of this approach.     

A TLR4 polymorphism is associated with asthma and reduced lipopolysaccharide-induced interleukin-12(p70) responses in Swedish children

BACKGROUND: Bacterial signals play an important role in the maturation of the immune system. Polymorphisms in genes coding for receptors to bacterial components can alter the immune responsiveness of the host to microbial agents and may indicate the development of aberrant immune responses that are associated with immune-mediated diseases such as atopic diseases. OBJECTIVE: The study's objective was to investigate the relationship between TLR4 and CD14 gene polymorphisms, the LPS responsiveness of PBMCs, and the presence of asthma and allergic rhinoconjunctivitis in children. METHODS: The TLR4 (Asp299Gly) and CD14/-159 polymorphisms were determined in 115 Swedish children aged 8 and 14 years. LPS-induced IL-12(p70), IL-10, and IFN-gamma responses of PBMCs from 69 of the children were analyzed by means of ELISA. The levels of soluble CD14 in serum samples were analyzed by means of ELISA, and the total IgE levels were analyzed by means of UniCAP Total IgE (Pharmacia Diagnostics, Uppsala, Sweden). RESULTS: Decreased LPS-induced IL-12(p70) and IL-10 responses were associated with the TLR4 (Asp299Gly) polymorphism and independently with asthma, especially atopic asthma. The TLR4 (Asp299Gly) polymorphism was associated with a 4-fold higher prevalence of asthma in school-aged children (adjusted odds ratio 4.5, 95% CI 1.1-17.4) but not to allergic rhinoconjunctivitis. CONCLUSION: A TLR4 polymorphism modifies innate immune responses in children and may be an important determinant for the development of asthma. This may influence the outcome of intervention studies that use microbial stimuli as immune modulators.