Of sleep state and postnatal age on arousal responses induced by mild hypoxia in infants

STUDY OBJECTIVES: It has been suggested that mild hypoxia may not be a potent stimulus for arousal during sleep in infants because infants frequently fail to arouse from quiet sleep (QS). Our aim was to characterize arousal responses of sleeping infants in both active sleep (AS) and QS under normoxic and mildly hypoxic (15% O2) conditions over the first 6 months of life. PARTICIPANTS: Five healthy term and 6 healthy preterm infants were each studied at 2 to 5 weeks, 2 to 3 months, and 5 to 6 months postterm. All infants underwent daytime polysomnography during which nasal airflow was monitored using a purpose-built pneumotachograph. All infants were studied under both normoxic (21% O2) and hypoxic (15% O2, balance N2) conditions (presentation order randomized) in each sleep state at each study age. Tests were terminated at arousal, O2 saturation falling below 85%, or 5 minutes (failure to arouse). MEASUREMENTS: Probability of failure to arouse and mean arousal latency were compared between each experimental condition, with each infant serving as its own control. RESULTS: Infants aroused more frequently under hypoxic conditions than under normoxic conditions. Overall, arousal latencies were shorter during hypoxia compared to normoxia in both sleep states at each age. Arousal latencies were longer in QS compared to AS in both hypoxic and normoxic conditions. CONCLUSION: In sleeping infants, mild hypoxia serves as a stimulus for arousal in both AS and QS. Of particular significance is our finding that arousal from AS is readily elicited by mild hypoxia.     

Clinical and molecular study in congenital muscular dystrophy with partial laminin alpha 2 (LAMA2) deficiency

Complete laminin alpha2 (LAMA2) deficiency causes approximately half of congenital muscular dystrophy (CMD) cases. Many loss-of-function mutations have been reported in these severe, neonatal-onset patients, but only single missense mutations have been found in milder CMD with partial laminin alpha2 deficiency. Here, we studied nine patients diagnosed with CMD who showed abnormal white-matter signal at brain MRI and partial deficiency of laminin alpha2 on immunofluorescence of muscle biopsy. We screened the entire 9.5 kb laminin alpha2 mRNA from patient muscle biopsy by direct capillary automated sequencing, single strand conformational polymorphism (SSCP), or denaturing high performance liquid chromatography (DHPLC) of overlapping RT-PCR products followed by direct sequencing of heteroduplexes. We identified laminin alpha2 sequence changes in six of nine CMD patients. Each of the gene changes identified, except one, was novel, including three missense changes and two splice-site mutations. The finding of partial laminin alpha2 deficiency by immunostaining is not specific for laminin alpha2 gene mutation carriers, with only two patients (22%) showing clear causative mutations, and an additional three patients (33%) showing possible mutations. The clinical presentation and disease progression was homogeneous in the laminin alpha2-mutation positive and negative CMD patients.     

Effect of mebendazole againstEchinococcus granulosus andTaenia hydatigena cysts in naturally infected sheep and relevance to larval tapeworm infections in man

The ability of three treatment schedules of mebendazole to kill well-established hydatid cysts was studied. Pregnant sheep, naturally infected withEchinococcus granulosus and/orTaenia hydatigena, were treated daily with mebendazole at a dose rate of 50 mg/kg body weight for either five days, one month, or three months.At autopsy, seven months after the commencement of treatment, no evidence was found that the 5-day treatment schedule had any damaging effect onE. granulosus cysts. The effects of the one month treatment were equivocal. There was evidence of a damaging effect from the 3-month treatment schedule and protoscoleces were not infective to dogs. NoT. hydatigena cysts survived the 1- and 3-month treatments, but organisms from the 5-day treatment were infective to dogs.These results forE. granulosus in sheep suggest that long-term treatment with mebendazole may be required in hydatid disease in man. The results obtained forT. hydatigena in sheep are discussed in relation to the treatment of cysticercosis fromT. solium in man. Mebendazole showed no untoward effect on the sheep or their lambs.     

Tg cells in peripheral blood lymphocytes from patients with rheumatoid arthritis

Using combinations of methods for detecting Fc receptors and B lymphocytes, non-B, non-T lymphocytes and T lymphocytes we have shown T_G cells to be significantly increased in rheumatoid arthritis (RA) patients' peripheral blood lymphocytes (PBL). The possible significance of this finding to the disease process is discussed.     

Infant feeding and overweight in two Oxfordshire towns

In a study of feeding and growth in the first year of life in two Oxfordshire market towns, the frequency of overweight babies was the same for the 'intervention' town (where a research health visitor gave intensive advice to mothers on feeding) as for the control town. Eighteen per cent of bottle-fed infants and three per cent of those breast fed were overweight at one year. It seems that an increase in the number of health visitors does not affect the frequency of overweight infants, but it may be that a greater emphasis on breast feeding might reduce the frequency.     

The effect of hydrolytic enzymes on the acetylcholine sensitivity of the skeletal muscle cell membrane

Isometric tension developed by rat soleus and extensor digitorum longus (EDL) muscles in response to acetylcholine (Ach) applied in vitro was recorded. Tension of contractures elicited in response to Ach increased after muscles had been incubated with phospholipase C, pepsin, or soluble fractions prepared from muscle homogenate.Using intracellular microelectrodes, resting membrane potential (RMP) and depolarisation in response to Ach added to the bathing medium were recorded in endplate-free regions of the muscle fibres. No significant change in RMP was observed in muscles incubated with soluble muscle fraction or phospholipase C, but depolarisation in response to Ach or carbachol was significantly increased. The time course for the increase in depolarisation and the contracture response to Ach was similar.When all available receptors were blocked with -bungarotoxin prior to incubation so that no response to Ach could be elicited, with subsequent incubation in muscle soluble fraction or phospholipase C, both contractures and depolarisation in response to Ach returned. These results support the hypothesis that receptors, not previously available to interact with Ach or -bungarotoxin were revealed following incubation.     

Cellular immunity in Guamanians with amyotrophic lateral sclerosis and Parkinsonism-dementia.

To test the hypothesis that host resistance factors may be abnormal in Guamanians in whom amyotrophic lateral sclerosis and Parkinsonism-dementia develop, cellular immunity was evaluated in both diseases and compared to that of Guamanians with other nervous-system diseases, normal adult Guamanians and non-Guamanians with amyotrophic lateral sclerosis and Parkinsonism. Diminished responses to skin-test antigens, lymphopenia, diminished per cent and total T cells and, less frequently, decreased mitogen responses were seen in Guamanian patients with amytorophic lateral sclerosis and Parkinsonism-dementia but not in the other patient or normal groups. Guamanian patients with amyotrophic lateral sclerosis and diminished cellular immunity had an increased frequency of HLA-Bw35 (P less than 0.005) and shorter mean duration of disease (P less than 0.05) than those with normal cellular immunity. In Parkinsonism dementia diminished cellular immunity was less strongly associated with HLA-BW35 (P less than 0.05) and was not associated with differences in duration of disease. Normal Guamanians and those with other nervous-system diseases showed no association of diminished cellular immunity with HLA-Bw35. The association appeared disease-related, with onset concomitant with the neurologic expression of Guamanian amyotrophic lateral sclerosis and Parkinsonism-dementia.     

Lipopolysaccharide (LPS) from Brucella abortus is less toxic than that from Escherichia coli, suggesting the possible use of B. abortus or LPS from B. abortus as a carrier in vaccines.

Brucella abortus may be useful as a component of vaccines. This is because it possesses several unique properties as a carrier that enable it to stimulate human B cells even in the relative absence of T cells. Human immunodeficiency virus type 1 proteins conjugated to B. abortus could induce neutralizing antibodies against human immunodeficiency virus type 1. Recently we showed that the characteristics of lipopolysaccharide (LPS) derived from B. abortus are similar to those of the whole bacterium in that the LPS acts as a T-independent type 1 carrier in mice. In this study we wanted to determine whether LPS derived from B. abortus is associated with the adverse effects seen with other bacterial endotoxins. LPS purified from B. abortus by butanol extraction was shown to have less than 2% (wt/wt) contamination by protein and less than 1% (wt/wt) contamination by nucleic acids and to contain 1% (wt/wt) ketodeoxyoctanic acid. Compared with LPS derived from Escherichia coli, B. abortus LPS was 10,000-fold less potent in eliciting fever in rabbits, 268-fold less potent in killing D-galactosamine-sensitized mice, and 1,400-fold and 400-fold less potent in inducing interleukin-1 beta and tumor necrosis factor alpha production, respectively. These results suggest that B. abortus LPS is much less likely than the LPS from E. coli to evoke endotoxic shock; therefore, it may be feasible to incorporate B. abortus as a component of vaccines.     

p21 ras protein expression in benign and malignant

The ras oncogenes encode for GTP binding and GTPase active proteins of relative molecular mass 21 000 (p21^ras) which are involved in the transduction of stimuli for cell proliferation. There have been conflicting reports about the detection and significance of expression of p21^ras protein in human breast disease as determined by immunohistochemistry. The antibody Y13-259, which detects a single protein of M_r 21 000, has been applied immunohistochemically to frozen sections of normal, benign proliferative breast, fibroadenomas, and carcinomas. Uniform staining of normal breast epithelium and myoepithelium was found, with occasional stronger staining in areas of epithelial hyperplasia in benign breast disease. Contrary to previous reports, decreased expression, usually heterogeneous, was found in half of the carcinomas examined. Thirty per cent of the carcinomas exhibited heterogeneous staining stronger than that of normal breast, interpreted as increased expression of p21^ras protein. This did not relate to tumour grade or node status but showed a significant correlation with proliferation rate as determined by the monoclonal antibody Ki-67. This study confirms previous reports that p21^ras protein expression is a feature of normal cells, and has identified increased expression in 30 per cent of tumours associated with higher proliferation rates, which is a lower incidence than previously claimed when a different antibody was employed.