Search PubMed⌕ Search

Biomedical subjects

C L Williams

Publications and source records attributed to C L Williams.

At least 163 records · Page 9Linked to original sources

Radiotelemetric monitoring of hypothalamic gonadotropin-releasing hormone pulse generator activity throughout the menstrual cycle of the rhesus monkey.

Continuous monitoring of the electrophysiological manifestations of GnRH pulse generator activity was achieved by radiotelemetry throughout the menstrual cycles of unrestrained rhesus monkeys. The characteristic increases in hypothalamic multiunit activity (MUA volleys) associated with each LH pulse measured in the peripheral circulation were of lower frequency during the luteal phase than in the follicular phase of the cycle. Multiunit activity volley frequency increased as functional luteolysis progressed and achieved maxima of approximately one volley per hour within the first few days of the follicular phase. Unexpectedly, a dramatic decline in pulse generator frequency was observed coincidentally with the initiation of the preovulatory LH surge. Evidence is presented to support the conclusion that this deceleration of pulse generator activity is the consequence of the preovulatory rise in plasma estrogen concentration. As reported in women, a significant reduction in GnRH pulse generator frequency was observed at night during the follicular phase, but not during the luteal phase, of the menstrual cycle.

Animals↗

Activation of M3 muscarinic acetylcholine receptors inhibits voltage-dependent calcium influx in small cell lung carcinoma.

Small cell carcinoma of the lung (SCC) expresses several characteristics of neuronal cells, including voltage-gated Ca2+ channels (VGCC), and also expresses muscarinic acetylcholine receptors (mAChR). In testing the possibility that VGCC may be functionally coupled to mAChR in SCC cell lines, we found that depolarization-dependent Ca2+ influx was inhibited by carbachol (IC50 = 0.78 microM) and oxotremorine (IC50 = 0.69 microM). Equilibrium dissociation constants for several mAChR antagonists indicated that a mAChR of M3 subtype was involved. Exposure of SCC to carbachol induced the hydrolysis of phosphoinositides and increased the cytosolic free Ca2+ concentration ([Ca2+]i). The carbachol-mediated inhibition of depolarization-dependent Ca2+ influx did not directly correlate with increased [Ca2+]i but did correlate with inositol poly-phosphate generation. The protein kinase C activators phorbol 12-myristate 13-acetate or 1-oleoyl-2-acetyl-sn-glycerol neither mimicked nor amplified the inhibitory effect of carbachol on Ca2+ influx. However, phorbol 12-myristate 13-acetate suppressed the carbachol-induced inositol polyphosphate generation and inhibition of depolarization-dependent Ca2+ influx. The inactive compound 4 alpha-phorbol had no effect. These data suggest that the inhibition of VGCC caused by carbachol is not due to protein kinase C activation, but rather is due to events mediated by inositol polyphosphates. This is the first documentation of a role for phosphoinositide hydrolysis in the functional coupling of mAChR and VGCC. The expression of M3 mAChR functionally coupled to VGCC could have therapeutic implications for SCC, in light of recent demonstrations that cell proliferation can be influenced by activation of neurotransmitter receptors.

Calcium↗

Metastatic pneumococcal endophthalmitis: report of two cases and review of literature.

Two patients with pneumococcal bacteraemia complicated by endophthalmitis are described. While this condition appears to have been relatively common in the preantibiotic era, a review of the literature since 1950 only identified six additional case reports. Analysis of these eight cases reveals two patterns: unilateral disease in six patients and bilateral disease with simultaneous onset in two patients. The potential pathogenic mechanisms--direct bacterial invasion or immunologically mediated processes--are discussed in relation to these clinical presentations. The critical importance of seeking ophthalmological advice early in the course of the disease is emphasised, as the risk of visual loss with systemic antimicrobials alone is very high, particularly if the infective process involves the vitreous humour.

Ampicillin↗

Organizational effects of early gonadal secretions on sexual differentiation in spatial memory.

Neonatally castrated (MNC) and control male rats (MC) and female rats treated neonatally with estradiol benzoate (FNE) and female controls (FC) were studied. In Exp. 1 spatial memory was assessed using a 12-arm radial maze. During acquisition, MC and FNE groups were more accurate in choice behavior than FC and MNC groups. In Exp. 2 the discriminative control exerted by different types of cues was evaluated. Alteration of the geometry of the room but not movable landmarks disrupted performance of MC and FNE groups. For the FC and MNC groups, alteration of either geometry or landmarks did not disrupt performance. In Exp. 3 the effect of a 15-min delay was determined. MC and FNE groups were more disrupted by a delay than MNC and FC groups. Together, these data suggest that early exposure to gonadal steroids (probably estradiol) improves acquisition of spatial tasks by reorganizing and simplifying associational-perceptual processes that guide spatial ability.

Animals↗

Duration of phasic electrical activity of the hypothalamic gonadotropin-releasing hormone pulse generator and dynamics of luteinizing hormone pulses in the rhesus monkey.

The secretion of luteinizing hormone (LH) by the pituitary gland is a pulsatile phenomenon. In the rhesus monkey, each pulse of LH in the peripheral circulation is associated with a characteristic increase in multiunit electrical activity (MUA) recorded from the medial basal hypothalamus. These "volleys" of electrical activity initiate the release of gonadotropin-releasing hormone (GnRH) into the pituitary portal circulation from the terminals of neurosecretory cells. Their duration varies from 1-3 min in normal, adult intact females to 10-25 min in long-term ovariectomized monkeys. A variety of pharmacological interventions also modify volley duration. The purpose of this investigation was to determine the physiological significance of alterations in volley duration. The dynamics of LH pulses in ovariectomized animals were observed in a number of experimental circumstances in which MUA volley duration was reduced from a maximum of 23 min to a minimum of 4 min without significantly altering their frequency. The magnitude of each LH pulse was assessed by calculating the area under the curve delineated by the time course of LH above baseline. In eight experiments, a linear regression of these values on volley duration failed to reveal a significant correlation between MUA volley duration and the magnitude of LH pulses. These results suggest that all of the GnRH secreted per pulse is released at the onset of each MUA volley, the remainder of the increase in electrical activity having no further action on GnRH secretion, although effects on other systems cannot be excluded.

Activity Cycles↗

External validity of the new Devereux Adolescent Behavior Rating scales.

The discriminant and concurrent validity of the five new scales for the Devereux Adolescent Behavior Rating Scale (DAB) was explored using a heterogeneous sample of psychiatric and substance abuse patients. Consistent with predictions, the substance abuse patients scored higher on the Acting Out Behaviors (AOB) and Heterosexual Interests (HI) scales, and psychiatric patients scored higher on the Psychotic Behaviors scale. Gender differences also were found, including boys being rated higher on Acting Out Behaviors, and girls higher on Heterosexual Interests. The new DAB scales demonstrated sufficient concurrent validity using a thorough record review and a patient rating scale (the Child Behavior Checklist [CBCL]). The Neurotic/Dependent Behaviors scale (NDB) showed a consistent relationship with substance abuse and several other measures of more externalizing behaviors, in addition to the predicted relationships with anxious, tense, and dependent behaviors. The Withdrawn/Timid Behaviors scale (WTB) proved to be a purer measure of internalizing behaviors in both sexes.

Acting Out↗

Corticotropin-releasing factor and gonadotropin-releasing hormone pulse generator activity in the rhesus monkey. Electrophysiological studies.

The effect of corticotropin-releasing factor (CRF) on the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator, the central neuronal system governing pulsatile pituitary luteinizing hormone (LH) secretion, was studied electro-physiologically in 6 ovariectomized rhesus monkeys bearing bilateral arrays of recording electrodes implanted in the mediobasal hypothalamus. 'Volleys' of increased multiunit activity (MUA) were recorded for 6-10 h in animals placed in primate chairs. The circulating concentrations of LH and cortisol were determined by radioimmunoassay in blood samples taken every 10 min for 3-4 h prior to the administration of CRF (200 micrograms, i.v.) and for 3-6 h thereafter. CRF resulted in a significant decrease in the frequency of pulse generator activity in 4 of 6 animals, a significant decrease in the duration of MUA volleys and a rise in circulating cortisol levels in all 6 monkeys. Treatment with metyrapone (30 mg/kg, i.m.), an inhibitor of adrenal steroidogenesis that prevented the CRF-induced rise in serum cortisol levels, did not reverse the inhibitory effects of CRF on the frequency or duration of MUA volleys. The opiate antagonist naloxone (0.8 mg/kg, i.v., 10 min prior to CRF followed by 0.8 mg/kg/h infusion) blocked the effects of CRF on MUA volley frequency in 2 of 3 animals, but failed to block the effect of CRF on MUA volley duration, suggesting that endogenous opioids may mediate the action of CRF on pulse generator frequency but not on duration.

Animals↗

Duration and frequency of multiunit electrical activity associated with the hypothalamic gonadotropin releasing hormone pulse generator in the rhesus monkey: differential effects of morphine.

The effects of morphine on the frequency and duration of the characteristic bursts or 'volleys' of multiunit electrical activity (MUA) associated with pulsatile pituitary luteinizing hormone (LH) secretion were studied in unanesthetized ovariectomized rhesus monkeys bearing bilateral arrays of electrodes implanted in the mediobasal hypothalamus. Morphine administration resulted in a dose-dependent decrease in MUA volley duration and frequency. When morphine was infused at 10 micrograms/kg/h, the inhibiting effect on volley duration was observed without a change in volley frequency. It is concluded that the frequency and duration of hypothalamic MUA volleys associated with pulsatile LH secretion may be independently regulated.

Animals↗

Rhabdomyolysis and myoglobinuric renal failure following cardioversion and CPR for acute MI.

A 50-year-old man suffered an MI with VFIB at work, and efforts at resuscitation were initiated immediately. Ninety minutes of CPR and 14 cardioversions were given by trained personnel before VFIB converted to sinus rhythm. Reversible myoglobinuric renal failure ensued, requiring two weeks of hemodialysis. Scanning with technetium-99m pyrophosphate revealed extensive muscle injury in the regions of cardioversion and a large anterolateral MI. Prolonged resuscitative efforts involving repeated cardioversion may predispose to myoglobinuric renal failure.

Acute Kidney Injury↗

Lyme disease in childhood: clinical and epidemiologic features of ninety cases.

In 1982 and 1983 practicing pediatricians in a Lyme disease-endemic county, reported 90 cases of Lyme disease among children 19 years of age and younger (median age, 9 years). Three-fourths of the children had initial symptom onset in the summer months, with peak incidence in July. Infection occurred twice as often in boys than in girls, and tick bites were recalled by less than half (49%) of the children or parents. Erythema chronicum migrans was present in two-thirds (67%) of the cases with median onset 7 days after a definite tick bite. Arthritis or arthralgia occurred in 59% and neurologic symptoms, especially seventh nerve palsy, occurred in 14%. Asymmetric involvement of a few large joints, especially the knee, was most commonly reported for those with joint involvement. antibiotics were prescribed for 79% of the children, three-fourths of whom were treated with oral penicillin. Initial diagnosis of Lyme disease is usually made on clinical grounds alone because serologic tests are often negative. Serologic tests for antibody to Borrelia burgdorferi were more often positive in cases with neurological or joint involvement, in addition to erythema chronicums migrans (80%), than in cases presenting with erythema chronicums migrans only.

Adolescent↗

Teaching preventive cardiology in the pediatric setting.

This article presents both the rationale behind and a framework for incorporating pediatric preventive cardiology into undergraduate medical education and pediatric residency training. Such education of physicians in the practice of preventive cardiology requires provision of not only didactic information but also training and practice in clinical skills. A combination of didactic lectures, small group discussions, interactive programs utilizing video tapes and computer programs, family and patient simulation, preventive cardiology clinics, and community cardiovascular health promotion activities all help to provide the optimal framework for an effective medical student and pediatric resident training program in pediatric preventive cardiology. Since pediatricians are in the best position to practice true primary prevention of cardiovascular disease beginning in childhood, it is essential that physicians in training understand the concepts and learn the skills needed to practice this critical component of pediatric medicine.

Adolescent↗

Novel redistribution of myosin-containing filaments in cultured keratinocytes identified by a human monoclonal autoantibody.

A time-dependent redistribution of microfilaments was observed in cultured human keratinocytes using a human monoclonal autoantibody specific for myosin. Immunofluorescent staining revealed that 5 days after plating keratinocytes in either 0.1 mM or 2.0 mM Ca++, myosin was distributed uniformly throughout the cytoplasm. At day 6, parallel arrays of myosin-containing microfilaments were prominent in the cell peripheries. At day 7 the microfilaments formed circumferential rings. The distribution of the microfilaments was disrupted by cytochalasin but not by colchicine, indicating that this novel distribution of myosin was not dependent on colchicine-sensitive vimentin intermediate filaments. The time-dependent redistribution of myosin was not influenced by cell population density, cell shape or cell cycle phase, except for mitotic cells in which myosin was distributed diffusely through the cytoplasm. If, as suggested by Kolega (9), microfilaments align parallel to the direction of applied tension, the redistribution of myosin-containing microfilaments in cultured keratinocytes may reflect the increased tension between cells resulting from increasing strength of cell-cell junctions over time. In sectioned human skin, myosin was localized in the peripheral cytoplasm of stratified epidermal cells. Tensions arising from the numerous desmosomal junctions between cells in vivo could account for this distribution of myosin.

Actin Cytoskeleton↗

Organizational changes in cholinergic activity and enhanced visuospatial memory as a function of choline administered prenatally or postnatally or both.

This experiment was an examination of the effects of supplemental dietary choline chloride given prenatally (to the diet of pregnant rats) and postnatally (intubed directly into the stomachs of rat pups) on memory function and neurochemical measures of brain cholinergic activity of male albino rats when they became adults. The data demonstrate that perinatal choline supplementation causes (a) long-term facilitative effects on working and reference memory components of a 12-arm radial maze task, and (b) alternations of muscarinic receptor density as indexed by [3H]quinuclidinyl benzilate (QNB) binding and choline acetyltransferase (ChAT) levels in the hippocampus and frontal cortex of adult rats. An analysis of the relationship between these organizational changes in brain and memory function indicated that the ChAT-to-QNB ratio in the hippocampus is highly correlated with working memory errors, and this ratio in the frontal cortex is highly correlated with reference memory errors.

Age Factors↗

Group process and social climate of GROW, a community mental health organisation.

GROW, a community based mutual-help organisation, aims to provide the means for those who have been mentally ill to rehabilitate themselves and grow personally. We measured psychiatric symptoms, group processes, social environment and perceived social support in a sample of GROW group members. We found that GROW does provide the opportunity for and encourages some personal changes and does provide social support. We could not draw any conclusions about GROW's efficacy as a rehabilitative agent.

Australia↗

Assessment of life events during adolescence: the use of self-report inventories.

The assessment of stressful life events during adolescence is important to both research and clinical practice. Stressful events are studied to determine their etiological significance in physical and mental illnesses, and also their relevance in the clinical assessment of individual patients. In recent years, a number of self-report inventories of life events for adolescents have been developed, some very carefully, others as one-time endeavors. This article reviews these measures, with an emphasis on the conceptual and methodological issues which created problems in earlier inventories. These issues need to be considered when choosing an instrument to study or assess stressful life events in adolescents.

Adolescent↗

Steroids induce hypothalamic progestin receptors and facilitate female sexual behavior in neonatal rats.

This report provides the first evidence that two activational actions of estrogen can occur within the first week of life in the rat. Priming 4-day-old rats with exogenous estradiol benzoate facilitates lordosis and ear wiggling-like behavior, and induces cytosol progestin receptors in the medial basal hypothalamus and preoptic region (Hyp-PoA) 44 h later. Moreover, unprimed male infants show more intense lordosis and higher concentrations of cytosol progestin receptors in Hyp-PoA than infant females. Neonatal castration of male infants decreases their concentration of cytosol progestin receptors in Hyp-PoA to the levels normally seen in infant females. In addition, priming 6-day-old infants with progesterone alone facilitates lordosis in male but not female infants. Together, these data demonstrate that in the male infant, endogenous steroids of testicular origin have activational as well as organizational actions.

Animals↗

Role of mu 1-opiate receptors in supraspinal opiate analgesia: a microinjection study.

Microinjection of opiates into either the periaqueductual gray, locus coeruleus, nucleus raphe magnus, or nucleus reticularis gigantocellularis elicits a profound naloxone-sensitive analgesia. mu-Opioid receptors have been implicated in supraspinal analgesia and studies from our laboratory have demonstrated the importance of the mu 1-receptor subtype. In an effort to examine the receptor subtypes responsible for opioid analgesia in specific brain regions, we examined dose-response relationships and naloxonazine sensitivity of morphine and two enkephalin derivatives in the above 4 brain regions. Both morphine and [D-Ser2,Leu5]enkephalin-Thr6 (DSLET) were effective analgesics in all regions examined. The poor affinity of DSLET for mu 2-receptors and of morphine for delta-receptors, combined with their similar, high affinity for mu 1-receptors, implied a mu 1-mechanism of action. The mu 1-selective antagonist naloxonazine effectively blocked the analgesic responses of both compounds in all regions. [D-Pen2,D-Pen5]enkephalin (DPDPE), a potent delta-ligand which does not interact with mu 1-receptors, did not elicit analgesia in either the periaqueductal gray or locus coeruleus at any dose tested. These results suggest that opiates and opioid peptides produce analgesia in these 4 brain regions through mu 1-receptors. The inactivity of DPDPE argues against a role for delta-receptors and the similar analgesic potencies of morphine and DSLET makes a significant role for mu 2-receptors unlikely.

Analgesia↗

Pre- and postnatal choline supplementation produces long-term facilitation of spatial memory.

Although research has demonstrated that short-term improvement in memory function of adult rats can occur when the availability of precursors for the neurotransmitter acetylcholine is increased, little is known about whether memory function of adult rats can be permanently altered by precursor supplementation during early development. In the present study, male albino rats were exposed to choline chloride supplementation both prenatally (through the diet of pregnant rats) and postnatally (subcutaneous injections). At 60 days of age rats were tested on a 12- and 18-arm radial maze task. Results indicated that compared to control littermates, perinatal choline-treated rats showed more accurate performance on both working and reference memory components of the task. This performance difference was apparent on the first block of sessions and continued throughout training. Further analysis revealed that the difference between choline and control rats is not due to use of differential response or cue-use strategies. Instead, it appears that choline induced performance differences are due to long-term enhancement of spatial memory capacity and precision.

Animals↗