Induction of periodic breathing during sleep causes upper airway obstruction in humans

To test the hypothesis that occlusive apneas result from sleep-induced periodic breathing in association with some degree of upper airway compromise, periodic breathing was induced during non-rapid-eye-movement (NREM) sleep by administering hypoxic gas mixtures with and without applied external inspiratory resistance (9 cmH2O X l-1 X s) in five normal male volunteers. In addition to standard polysomnography for sleep staging and respiratory pattern monitoring, esophageal pressure, tidal volume (VT), and airflow were measured via an esophageal catheter and pneumotachograph, respectively, with the latter attached to a tight-fitting face mask, allowing calculation of total pulmonary system resistance (Rp). During stage I/II NREM sleep minimal period breathing was evident in two of the subjects; however, in four subjects during hypoxia and/or relief from hypoxia, with and without added resistance, pronounced periodic breathing developed with waxing and waning of VT, sometimes with apneic phases. Resistive loading without hypoxia did not cause periodicity. At the nadir of periodic changes in VT, Rp was usually at its highest and there was a significant linear relationship between Rp and 1/VT, indicating the development of obstructive hypopneas. In one subject without added resistance and in the same subject and in another during resistive loading, upper airway obstruction at the nadir of the periodic fluctuations in VT was observed. We conclude that periodic breathing resulting in periodic diminution of upper airway muscle activity is associated with increased upper airway resistance that predisposes upper airways to collapse.     

Light-dependent degradation of the Q(B)-protein in isolated pea thylakoids

The 32 000-dalton Q_B-protein of photosystem II (PS II) is rapidly damaged and removed from isolated pea thylakoids during incubation in the light resulting in a loss of photosynthetic electron flow through PS II. This in vitro photoinhibition is similar to that previously reported with intact Chlamydomonas cells. The damage occurs at a faster rate in vitro, however, due to the inability of isolated thylakoids to synthesize replacement Q_B-protein. The removal of the damaged Q_B-protein does not require any soluble components of the chloroplast stroma and is unaffected by the protease inhibitors phenyl-methylsulfonylfluoride or antipain. Unlike the effect of trypsin, no low mol. wt. membrane-bound or soluble fragments of the labelled Q_B-protein could be identified either by autoradiography or immunologically using polyclonal antibodies specific for the Q_B-protein. The lightinduced damage to the Q_B-protein (indicated by a loss of Q_B functional activity), preceded the removal of the protein from the membrane. We conclude that photodamage of the Q_B-protein generates a conformational change which renders the protein susceptible to attack by a highly efficient, intrinsic membrane protease.     

Polymyalgia rheumatica/giant cell arteritis in a Cambridge general practice.

The aim of this study was to establish the incidence and prevalence of polymyalgia rheumatica/giant cell arteritis in general practice. Patients with this disorder, whether previously diagnosed or not, were ascertained by using a questionnaire administered by interview, and all received full clinical and laboratory assessment. A total of 579 patients aged 65 and over was seen, and 19 (33/1000) had been diagnosed or developed symptoms within the previous eight years. Thus the calculated annual incidence in those aged 65 and over was about 4/1000. The figures from this first large scale study of polymyalgia rheumatica/giant cell arteritis in general practice are much higher than those from studies carried out in hospital. The questionnaire was effective in both identifying known cases of polymyalgia rheumatica/giant cell arteritis and detecting new cases. As this is a treatable disorder, it is important that doctors become aware of how common it is in elderly people.     

Magnesium homeostasis during high-intensity anaerobic exercise in men

This study was conducted to determine whether short-term, high-intensity anaerobic exercise alters Mg homeostasis. Thirteen men performed intermittent bouts of treadmill running at 90% of their predetermined maximum O2 uptake until exhaustion on one occasion during a week in which all men were consuming a standard diet (115 mg Mg/1,000 kcal). Plasma and erythrocyte Mg concentrations and peripheral blood mononuclear cell Mg content were measured before and after the exercise. Complete 24-h urine collections were obtained on control days, on the day of exercise, and on the day after exercise. Exercise induced a transient but significant decrease in plasma Mg content (-6.8%; P less than 0.01); over 85% of the loss could be accounted for by a shift to the erythrocytes. Significant increases in urinary excretion of Mg were observed on the day of exercise (131.5 +/- 6.8 mg/day) compared with control days (108 +/- 6.6 mg/day), with the percent increase correlating with postexercise blood lactate concentration (r = 0.68; P less than 0.01) and oxygen consumption during recovery (r = 0.84; P less than 0.001). The data indicate that high-intensity anaerobic exercise induces intercompartmental Mg shifts in blood that return to preexercise values within 2 h and urinary losses on the day of exercise that return to base line the day after exercise. It is postulated that the exercise-induced increase in Mg excretion may depend on the intensity of the exercise, and the relative contribution of anaerobic metabolism to the total energy expended during exercise.     

Monoclonal antibody against a melanosomal protein in melanotic and amelanotic human melanoma cells

BALB/c mice were immunized with tyrosinase, partially purified in two stages from a human melanoma cell line. A hybridoma was obtained which produced monoclonal antibody (MoAb 1C11) reactive with 8/10 melanoma cell lines and 10/10 primary cultures of human melanocytes, neval cells, and melanomas. Immunoreactivity correlated to a certain extent with tyrosinase activity but not with melanin content. No crossreactivity was obtained with neuroblastoma, medulloblastoma, fibroblasts, keratinocytes, lymphoid cells, or murine melanomas. Purification of the antigen directly from cell lysates with a MoAb 1C11 CNBr-Sepharose affinity column gave a green-brown protein of 56 kDa with no detectable tyrosinase activity. This protein was therefore different from 60 kDa active tyrosinase, identified by enzyme activity and Western blotting with a MoAb derived previously (MoAb 5C12). Unlike 5C12, 1C11 reactivity was not destroyed by pretreatment of the antigen with periodate. Immunogold labelling showed that the 1C11-reactive antigen was associated with melanosomes, and there was close correlation between 5C12 and 1C11 reactivity in resistance to trypsin and in staining various melanocytic cell populations. MoAb 1C11 may therefore recognise a polypeptide epitope in a molecule closely linked to melanin biosynthesis.     

Increased incidence of developmental anomalies among descendants of carriers of methylenebisacrylamide-induced balanced reciprocal translocations

N,N'-Methylenebisacrylamide (MBA), a dimer of the monomeric acrylamide, was studied for induction of clastogenic effects in germ cells of male mice. It was found to be effective in inducing dominant-lethal mutations and heritable translocations in maturing sperm. The semisterile translocation carriers and their normal counterparts were used to determine the health impact of transmitted chromosomal rearrangements through anatomical analysis of their immediate descendants in utero. As expected, semisterility resulted primarily from embryonic death during the periimplantation stages presumably caused by sperm segregants with unbalanced chromosome complement fertilizing some of the eggs. Among conceptuses that survived to mid- and late-gestation stages, there was an increased incidence of developmental anomalies including fetal death and phenotypic defects. These anomalies are assumed to be caused by certain types of unbalanced segregants that are compatible with survival beyond the periimplantation period. This class of unbalanced segregants represent in humans a major health problem to the mother and her conceptus.     

Quantal melatonin suppression by exposure to low intensity light in man

Plasma melatonin concentrations were examined following three relatively low intensities of artificial light. Six normal, healthy control subjects were all exposed to (a) 200 lux, (b) 400 lux and (c) 600 lux for a three hour duration from midnight to 0300 h. Blood was also collected on a control night where light intensity was less than 10 lux throughout. Significant suppression of melatonin was observed following light of 400 lux and 600 lux intensity when compared to the control night (p less than 0.05; Mann-Whitney U-test). 200 lux light did not produce a statistically significant melatonin suppression when compared with control samples. Each light intensity produced its own individual maximal melatonin suppression by one hour of exposure. Increased duration of exposure to the light had no further influence on melatonin plasma concentrations. These data confirm a dose response relationship between light and melatonin suppression, and indicate that there is no reciprocal relationship between the effects of light intensity and the duration of exposure on maximal melatonin suppression in man.     

Parallel processing of mechanosensory inputs from the locust ovipositor by intersegmental and local interneurones

The neural pathways underlying the processing of signals from locust (Schistocerca gregaria) ovipositor hairs by different classes of interneurones are investigated.Spikes in the sensory neurones from these hairs evoke chemically-mediated, unitary EPSPs with a short and constant latency in six identified non-giant projection interneurones with cell bodies in the terminal abdominal ganglion. Five of these interneurones receive direct inputs from the valves ipsilateral to their neuropilar branches, whereas the other receives direct inputs from valves on both sides. The sensory neurone from a single hair makes divergent connections with several interneurones and those from different hairs make convergent connections with a given interneurone. The amplitude of the EPSPs evoked depends on the position of a hair along the proximal-distal axis of the valve, with sensory neurones from more distal hairs generating larger amplitude EPSPs.Deflection of hairs also excites three of the four giant projection interneurones through polysynaptic pathways and some local interneurones in the terminal abdominal ganglion through monosynaptic connections. Branches of non-giant projection interneurones, local interneurones, but not those of the giant interneurones, overlap the axon terminals of the ovipositor hair afferents in the terminal abdominal ganglion.