Evidence for the presence of components of the alternative (properdin) pathway of complement activation in respiratory secretions

Activation of the alternative complement pathway by respiratory secretory IgA was demonstrated by incubating purified, aggregated preparations of serum and secretory IgA with neat human serum. No depletion of the early components (C1-4) was observed, but 63 and 70% of C3-9, respectively, were consumed. The C3-9-consuming capacity of heat-aggregated nasal secretions from an IgA-deficient volunteer was compared with heat-aggregated nasal secretions from a normal volunteer known to have secretory IgA. The deficient secretions consumed C3-9, whereas the IgA deficient secretions did not. Reconstitution of the nasal secretions from the IgA-deficient volunteer with purified secretory IgA produced alternative pathway activation. Factor B of the alternative complement pathway was found to be present in 16 of 18 bronchoalveolar lavage samples (BALF) from normal volunteers. Simultaneous measurement of lavage and serum albumin and Factor B concentrations rendered it unlikely that Factor B was merely a transudative product from serum in half the samples but rather suggested that it may be a component of lower respiratory tract secretions. The presence of an intact alternative complement pathway in BALF was indicated by showing that cobra venom factor and endotoxin cleaved functionally pure human C3 when mixed with BALF, but had no effect on C3 in the absence of BALF.     

Platelet density and size: the interpretation of heterogeneity

Platelets have been separated according to buoyant density using a colloidal silica-polyvinylpyrrolidone system and subjected to electronic sizing. All density populations were found to be heterogeneous in size, the most dense platelets ranging from less than 3 fl to greater than 21 fl in both man and rat. Light platelet fractions contained no platelets greater than 13 fl in either species. Cohort labeling with [75Se]selenomethionine showed no indication of significant change in platelet buoyant density with ageing; greater specific activity found in young, dense platelets appears to be related to increased protein synthetic activity shown in vitro and likely to occur also in their precursor megakaryocytes. It is postulated that dense, intermediate and light platelets are released synchronously by the three different ploidy classes of megakaryocyte, that varying density indicates differing structural characteristics and presumably differences in function. The present findings do not deny the possibility that platelets decrease in size with ageing but if such occurs, it is not associated with a significant change in platelet buoyant density.     

Nondisjunction in aging female mice

Oocytes from CBA mice varying in age from 2 to 11 months were cultured to the metaphase II stage of meiosis and the chromosomes analyzed. The oocytes from three maternal age groups were compared with respect to the mean number of oocytes obtained per mouse, the frequency of maturation to metaphase II, and the frequency of numerical chromosomes abnormalities. Both the mean number of oocytes obtained per mouse and the frequency of maturation decreased markedly with maternal age. The frequency of chromosome abnormalities in the oocytes increased with maternal age from the young to the middle-aged mice but dropped off in the oldest maternal age group. No hyperploid (n + 1) oocytes were observed in the young or old group of mice, but 5.2% hyperploidy occurred in the middle-aged group. It is suggested that the lack of hyperploid oocytes in the old CBA females might be due to a threshold effect in which oocytes that are damaged by the number of univalents present at metaphase I become atretic and do not progress to metaphase II. The frequency of diploid (2n) oocytes was 1.7% and was not maternal-age dependent.     

Recovery of ventilatory response to carbon dioxide after thiopentone, morphine and fentanyl in man

Ventilatory responses to CO2 (delta VI/delta PCO2) were measured half, one, two and four hours after infusions of thiopentone, morphine, fentanyl and saline in healthy men in order to test the idea that variation in clinical recovery and control of breathing after anaesthetic drugs are associated with interindividual differences in control measurements of delta VI/delta PCO2. Ventilatory response to CO2 was profoundly reduced one half hour after each drug, in contrast to the observation during air breathing that ventilation and end tidal PCO2 had returned to within 10 per cent of control. Mean delta VI/delta PCO2 increased progressively at one, two, and four hours, returning to near control after thiopentone, but remaining less than 80 per cent of control four hours after morphine and fentanyl. From the regression equations of each ventilatory response, ventilation at PCO2 of 58 and 70 mmHg (VI58 and VI70) were computed to estimate displacement of the response curves by the drugs. Following thiopentone there was no significant change of V158. In contrast ther was a highly siginificant fall of VI58 one half hour after fentanyl (p less than 0.01), with progressive return towards control at one, two, and four hours; similar changes were observed after morphine. For each drug, changes of VI70 were substantially greater than corresponding changes of V158. At all times during these recovery measurements, subjects were conscious and co-operative and, by traditional clinical criteria, were judged to have recovered from the effects of the drugs. Differences between high and low responding subjects were assessed by plotting control measurements against values obtained half and one hour after drugs. No systematic differences were found. These findings suggest that delta VI/delta PCO2 is a sensitive indicator of central nervous activity, but do not support the concepts that individuals with low delta VI/delta PCO2 might be more susceptible to the ventilatory depressant effects of anaesthetic drugs, or that low delta VI/delta PCO2 might be associated with delayed return of spontaneous breathing after general anaesthesia. Plasma thiopentone levels at half, one, and four hours were highly reproducible, in contrast to the wide variation of delta VI/delta PCO2 among subjects in this study. These findings together support the notion that wide variation in clinical recovery from anaesthesia may have a primary physiological basis in addition to variation caused by interindividual differences in drug dosage, biotransformation and excretion.     

Morphological and physiological characteristics of Gemmiger formicilis isolated from chicken ceca

Morphological and physiological studies were made on chicken cecal isolates of the strictly anaerobic bacterial species Gemmiger formicilis. Structural features (phase-contrast and electron microscopy) of these microorganisms indicate they (i) are highly pleomorphic, (ii) possess a trilaminar cell wall like gram-negative bacteria, (iii) exhibit an unusual growth process characterized by polar swelling (resembling budding bacteria), and (iv) grow into elongated cells when exposed to a subinhibitory concentration of penicillin. The morphological data presented suggest that this species has a rod-shaped structure. These bacteria ferment a variety of sugars to produce formic, butyric, and lactic acids. There appear to be two groups of Gemmiger, one producing primarily lactate and the other producing formate as major fermentation metabolites. Growth of six strains in a basal medium, consisting of Trypticase, minerals, carbohydrate, Na2CO3 buffer, and cysteine as reducing agent, was stimulated by rumen fluid and yeast extract. Volatile fatty acids partially replaced the requirement for rumen fluid with some strains. Single deletions of vitamins (from a defined vitamin mixture) indicated that pantothenate, riboflavin, and thiamine were highly stimulatory to growth of the organism in a medium containing rumen fluid and Trypticase as source of vitamins. Other vitamin requirements were not studied.     

Plasma progestins, estradiol, and luteinizing hormone following prostaglandin F2 alpha injection

Dairy animals, ranging from days 8 to 13 of the estrous cycle, were fitted with indwelling jugular catheters 1 day prior to either intramuscular injection of prostaglandin F2alpha free acid (30 mg, n=4) or intrauterine deposition of prostaglandin F2alpha free acid (10 mg, n = 3). Blood samples were collected at 6, 4, 2, and 0 h prior to administration of prostaglandin F2alpha and at 1, 3, and every 2 h thereafter until ovulation. Progestins, estradiol, and luteinizing hormone in plasma were measured by radioimmunoassay. Hormonal changes and interrelationships within animals were evaluated by least squares analyses. Decreases in progestins of plasma within 24 h indicated prostaglandin F2alpha induced luteolysis in six of the seven animals. Estradiol increased linearly from time of injection to 52 h postinjection. Intervals from administration of prostaglandin to onset of estrus, peak of luteinizing hormone, and ovulation were 74.9 +/- 21, 78.8 +/- 21, and 99.5 +/- 19 h.     

Circadian rhythms of serum renin activity and serum corticosterone, prolactin, and aldosterone concentrations in the male rat on normal and low-sodium diets

To investigate the control of aldosterone secretion, non-stress levels of serum aldosterone, corticosterone, and prolactin, and renin activity were determined at 4-h intervals during 24-h light-dark cycles in adult male rats on regular and low-sodium diets. Circadian rhythms of plasma aldosterone, prolactin, and corticosterone concentrations and of serum renin activity were demonstrated during a regular sodium diet. When the rats were on a low-sodium diet, a circadian rhythm of serum corticosterone and aldosterone concentration was observed, but there was no circadian variation in serum renin activity or in serum prolactin concentration. Serum aldosterone concentration correlated with serum corticosterone concentration (r = 0.48) and serum renin activity (r = 0.36) during a low-sodium diet. Serum prolactin concentration did not correlate with serum aldosterone concentration or serum osmolality. These data are compatible with a role for renin and ACTH, but not for prolactin, in the modulation of aldosterone secretion in the rat.