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A L Morrow

Publications and source records attributed to A L Morrow.

At least 19 recordsLinked to original sources

Fluorescence imaging of GABAA receptor-mediated intracellular [Cl-] in P19-N cells reveals unique pharmacological properties.

This study describes the pharmacological properties of GABAA receptors expressed in P19-N cells using fluorescence imaging of intracellular chloride with 6-methoxy-N-ethylquinolinium iodide (MEQ). We show that application of the GABA agonist, muscimol (10-200 microM), produces time- and concentration-dependent increases in intracellular [Cl-] that are blocked by bicuculline. Diazepam (10 microM) and pentobarbital (1 mM) potentiate muscimol-stimulation. These receptors exhibit novel pharmacological properties. The neurosteroid, 3alpha-hydroxy-5alpha-pregnane-20-one (1-10 microM) exhibited weak potency in enhancement of muscimol-stimulation. Ethanol (50 and 100 mM) exhibited high efficacy on muscimol responses, a 4- to 5-fold potentiation, respectively, of muscimol (10 microM) alone. GABA and muscimol allosterically modulated specific binding of [3H]flunitrazepam to differentiated P19 cells. Modulation of GABAA receptor mediated increases in intracellular [Cl-] demonstrated stability in response magnitude from 7 to 15 days following removal of retinoic acid. In concert, GABAA receptor subunit mRNA and protein expression patterns in these neuron-like cells were stable over the same period. Using RT-PCR we determined that differentiated P19 cells lack gamma1, gamma2L, alpha6 and delta subunit mRNAs while expressing alpha1, alpha2, alpha3, alpha4, alpha5, beta1, beta2, beta3, gamma2S and gamma3. Furthermore, subunit specific antibody immunocytochemical labeling of cells with a neuronal morphology indicated the presence of alpha1, alpha2, alpha4, and gamma2 subunits (the only subunits tested). Therefore, P19-N cells should prove useful to researchers in need of a model cell culture system in which to study function and regulation of neuronal GABAA receptors.

Animals

Efficacy of home-based peer counselling to promote exclusive breastfeeding: a randomised controlled trial.

BACKGROUND: Exclusive breastfeeding is recommended worldwide but not commonly practised. We undertook a randomised controlled study of the efficacy of home-based peer counselling to increase the proportion of exclusive breastfeeding among mothers and infants residing in periurban Mexico City. METHODS: Two intervention groups with different counselling frequencies, six visits (44) and three visits (52), were compared with a control group (34) that had no intervention. From March, 1995, to September, 1996, 170 pregnant women were identified by census and invited to participate in the study. Home visits were made during pregnancy and early post partum by peer counsellors recruited from the same community and trained by La Leche League. Data were collected by independent interview. Exclusive breastfeeding was defined by WHO criteria. FINDINGS: 130 women participated in the study. Only 12 women refused participation. Study groups did not differ in baseline factors. At 3 months post partum, exclusive breastfeeding was practised by 67% of six-visit, 50% of three-visit, and 12% of control mothers (intervention groups vs controls, p<0.001; six-visit vs three-visit, p=0.02). Duration of breastfeeding was significantly (p=0.02) longer in intervention groups than in controls, and fewer intervention than control infants had an episode of diarrhoea (12% vs 26%, p=0.03). INTERPRETATION: This is the first reported community-based randomised trial of breastfeeding promotion. Early and repeated contact with peer counsellors was associated with a significant increase in breastfeeding exclusivity and duration. The two-fold decrease in diarrhoea demonstrates the importance of breastfeeding promotion to infant health.

Breast Feeding

Gender-selective effects of ethanol dependence on NMDA receptor subunit expression in cerebral cortex, hippocampus and hypothalamus.

Previous investigations have shown subunit-selective alterations in NMDA receptors in ethanol dependent male rats. In the present study, we found pronounced gender differences in the effects of ethanol dependence on NMDA receptor subunit expression in all brain regions investigated. Ethanol dependent female rats exhibited increased NR1 subunit levels in cerebral cortex and hypothalamus, whereas males displayed increased NR1 levels only in hippocampus. NR2A subunit levels were significantly increased only in hippocampus from ethanol dependent male rats, whereas NR2B subunit levels significantly increased in cerebral cortex of both female and male rats. These findings suggest that gender influences neuroadaptations elicited by ethanol dependence at the level of NMDA receptor subunit expression.

Animals

Rapid ethnographic assessment of breastfeeding practices in periurban Mexico City.

Before carrying out a breastfeeding promotion programme in a periurban area of Mexico City, we conducted a rapid ethnographic study to determine the factors associated with absence of exclusive breastfeeding. The responses to pilot interviews were used to develop a standardized questionnaire regarding reasons for infant feeding choice, sources of advice, and barriers to breastfeeding. We interviewed a random sample of 150 mothers with a child < 5 years of age; 136 (91%) of them had initiated breastfeeding; but only 2% exclusively breastfed up to 4 months. The mothers consistently stated that the child's nutrition, health, growth, and hygiene were the main reasons for the type of feeding selected; cost, comfort, and the husband's opinion were less important. Physicians were ranked as the most important source of advice. Reduction or cessation of breastfeeding occurred on the doctor's advice (68%); or when the mothers encountered local folk illnesses such as "coraje" (52%) or "susto" (54%), which are associated with anger or fright; or had "not enough milk" (62%) or "bad milk" (56%); or because of illness of the mother (56%) or child (43%). During childhood illnesses and conditions, breastfeeding was reduced and the use of supplementary foods was increased. This study emphasizes the importance of cultural values in infant feeding choices, defines specific barriers to breastfeeding, and provides a basis for interventions to promote exclusive breastfeeding in the study population.

Adolescent

Influence of gender on chronic ethanol-induced alterations in GABAA receptors in rats.

Ethanol dependence, arising from chronic ethanol exposure, is associated with neuroadaptations of GABAA receptors, evidenced by alterations in various behaviors, receptor responsiveness and subunit gene expression. The present studies explored the effects of ethanol dependence in female rats for comparison with previous studies in our laboratory using male rats. We found that ethanol dependence resulted in differential effects on GABAA receptor gene expression in female rat cerebral cortex compared to ethanol dependent male rats. Notably, chronic ethanol consumption did not change GABAA receptor alpha 1 subunit peptide levels in ethanol dependent female rat cortex, in contrast to previously observed decreases in alpha 1 subunit expression in ethanol dependent male rat cortex. The effects of ethanol dependence on additional GABAA receptor subunit peptide levels (alpha 4, beta 2/3 and gamma 2) were similar, but not identical, between female and male rat cortex. When directly compared within the experiment, male and female rats had similar baseline bicuculline seizure thresholds and displayed a similar increase in seizure susceptibility during ethanol withdrawal. Ethanol withdrawn female rats were cross tolerant to the anticonvulsant effects of diazepam, similar to the findings in ethanol withdrawn male rats. Ethanol withdrawn female rats showed a dose-dependent enhancement of the anticonvulsant effect of the neuroactive steroid, THDOC (3 alpha,21-dihydroxy-5 alpha-pregnan-20-one) compared to control animals. This finding is similar to previous observations of increased sensitivity to the anticonvulsant effect of 3 alpha,5 alpha-THP (3 alpha-hydroxy-5 alpha-pregnan-20-one) in ethanol withdrawn male and female rats. In addition, low dose administration of THDOC elevated seizure thresholds in ethanol withdrawn female but not male rats, suggesting that ethanol withdrawn female rats were more responsive to the anticonvulsant effects of this neurosteroid than were ethanol withdrawn male rats. These findings show that gender impacts on adaptations in GABAA receptors elicited by ethanol dependence. However, the physiological outcomes of the differential alterations are not clear. Taken together, these studies suggest that additional mechanisms, beyond effects on GABAA receptor gene expression are involved in the mediation of ethanol dependence and withdrawal.

Animals

Role of human-milk lactadherin in protection against symptomatic rotavirus infection.

BACKGROUND: Human milk contains a 46 kDa mucin-associated glycoprotein, lactadherin, which binds specifically to rotavirus and inhibits its replication. This study tested the hypothesis that lactadherin protects against symptoms of rotavirus infection. METHODS: 200 infants in Mexico City were recruited at birth and monitored by regular stool EIA for rotavirus, serology, and recording of feeding and stool patterns. Milk samples were obtained from the mothers weekly until 4 weeks post partum then monthly. The sample taken immediately before an infant's episode of rotavirus infection was assayed for lactadherin, butyrophilin, mucin, and secretory IgA. An infection was defined as symptomatic if diarrhoea occurred in the 5 days before or after detection of the virus. FINDINGS: 31 infants developed rotavirus infection; 15 were symptomatic and 16 had no symptoms. The median concentration of lactadherin in the milk samples (obtained 4-41 days [median 13] before the infection) was 48.4 (range 5.6-180) microg/mL in the asymptomatic group and 29-2 (6.2-103-4) microg/mL in the symptomatic group. Although these medians did not differ significantly, in logistic regression analysis adjusted for age at infection and secretory IgA concentration there was a significant difference between the groups (p=0O01). No association between symptom status and concentrations of butyrophilin, mucin, or secretory IgA was found. INTERPRETATION: Protection against rotavirus by human milk is associated with the glycoprotein lactadherin. This association is independent of products of the secretory immune system.

Adult

The role of GABA(A) receptors in the acute and chronic effects of ethanol.

GABA(A) receptors are sensitive to ethanol in distinct brain regions and are clearly involved in the acute actions of ethanol, ethanol tolerance, ethanol dependence and ethanol self-administration. Data from a variety of perspectives such as molecular, cellular and behavioral analysis have elucidated the role of GABA(A) receptors in these processes. GABA(A) receptor activation mediates many of the behavioral effects of ethanol including motor incoordination, anxiolysis and sedation. The actions of ethanol at GABA(A) receptors are influenced by endogenous modulators such as the neuroactive steroids. Sensitization to these compounds influences ethanol dependence and withdrawal and may explain gender differences in the molecular effects of ethanol. Furthermore, GABA(A) receptors may also play a role in ethanol self-administration via the mesolimbic reward system. Ethanol tolerance and dependence may be explained, in part, by changes in the function of GABA(A) receptors. We have proposed that alterations in native GABA(A) receptor subunit assembly could alter the functional properties of these receptors. However, post-translational modifications or other post-synaptic mechanisms may also explain changes in GABA(A) receptor function. Genetic animal models of ethanol dependence have also identified GABA(A) receptor genes as likely mediators of the behavioral adaptations associated with ethanol dependence and withdrawal. A better understanding of the effects of ethanol at GABA(A) receptors has highlighted important potential mechanisms involved in the development of alcoholism.

Alcohol Drinking

Differential regulation of GABA(A) receptor gene expression by ethanol in the rat hippocampus versus cerebral cortex.

Previous research has shown that chronic ethanol consumption dramatically alters GABA(A) receptor alpha1 and alpha4 subunit gene expression in the cerebral cortex and GABA(A) receptor alpha1 and alpha6 subunit gene expression in the cerebellum. However, it is not yet known if chronic ethanol consumption produces similar alterations in GABA(A) receptor gene expression in other brain regions. One brain region of interest is the hippocampus because it has recently been shown that a subset of GABA(A) receptors in the hippocampus is responsive to pharmacologically relevant concentrations of ethanol. Therefore, we directly compared the effects of chronic ethanol consumption on GABA(A) receptor subunit gene expression in the hippocampus and cerebral cortex. Furthermore, we investigated whether the duration of ethanol consumption (14 or 40 days) would influence regulation of GABA(A) receptor gene expression in these two brain regions. Chronic ethanol consumption produced a significant increase in the level of GABA(A) receptor alpha4 subunit peptide in the hippocampus following 40 days but not 14 days. The relative expression of hippocampal GABA(A) receptor alpha1, alpha2, alpha3, beta(2/3), or gamma2 was not altered by either period of chronic ethanol exposure. In marked contrast, chronic ethanol consumption for 40 days significantly increased the relative expression of cerebral cortical GABA(A) receptor alpha4 subunits and significantly decreased the relative expression of cerebral cortical GABA(A) receptor alpha1 subunits. This finding is consistent with previous results following 14 days of chronic ethanol consumption. Hence, chronic ethanol consumption alters GABA(A) receptor gene expression in the hippocampus but in a different manner from that in either the cerebral cortex or the cerebellum. Furthermore, these alterations are dependent on the duration of ethanol exposure.

Animals

A prospective study of astrovirus diarrhea of infancy in Mexico City.

AIM: To describe the epidemiologic and clinical characteristics of astrovirus-associated diarrhea in a cohort of young children from a periurban community in Mexico City. METHODS: From November, 1988, through December, 1991, a total of 214 children were enrolled in a longitudinal study of diarrhea and monitored from birth to 18 months of age. A stool specimen was collected during each episode of diarrhea. Specimens from a total of 510 diarrhea episodes were tested for astrovirus by enzyme immunoassay and examined for other enteric pathogens. The antigenic types of astrovirus were determined by a typing enzyme immunoassay. RESULTS: Astrovirus was detected in 26 (5%) of 510 diarrhea episodes, with an incidence rate of 0.1 episode/child year; the highest rate was in children 13 to 18 months of age. Astrovirus-associated diarrhea was characterized by a median of 4 stools (range, 2 to 10) during the first 24 h, a median duration of 3 days (range, 1 to 21), vomiting (20%), and fever (7%). No cases of dehydration or repeat symptomatic infections were observed. Coinfection with another pathogen was detected in 11 of the 26 episodes (42%). Serotype 2 (35%) was most common, followed by serotypes 4 (15%), 3 (11%), and 1 and 5 (4% each); 31% were nontypable. Astrovirus-associated diarrhea was less severe, as measured by the number of stools (4.3 +/- 1.9), than diarrhea caused by rotavirus (7.1 +/- 2.8) or when coinfections occurred (5.5 +/- 1.6; P = 0.008). CONCLUSIONS: Astrovirus was associated with 5% of the episodes of diarrhea in this cohort of young Mexican children and presented as a mild secretory diarrhea. Five predominant antigenic types were detected with type 2 being the most common.

Astroviridae Infections

Immunization coalitions that work: training for public health professionals.

Coalition development is a major strategy to increase immunization rates. However, if local and state coalitions are to succeed, their staffs need training and technical assistance in coalition development, community planning, and program implementation. The National Coalition Training Institute trains key health agency staff in 87 state, territorial, and urban sites to perform needs assessments, use data to guide planning, plan comprehensive strategies, and evaluate their coalitions. The curriculum is based on training needs that are identified by a national survey of immunization coalitions, effective approaches, and participant evaluation. According to evaluations conducted during its first year, the National Coalition Training Institute is meeting the needs of participants.

Curriculum

Transient increase in cerebellar transcriptional activity precedes the expression of GABA(A) receptor alpha6 subunit mRNA during postnatal maturation.

The purpose of this study was to investigate the postnatal expression of GABA(A) receptor alpha6 subunit genes in the context of cerebellar differentiation. We examined steady-state levels of GABA(A) receptor alpha1 and alpha6 subunit mRNAs, polyadenylated (polyA+) mRNA and beta-actin mRNA in7-, 14-, 21-, 28-, 35-, 49- and 120-day-old rats. Messenger RNA expression and splicing were evaluated in parallel using Northern blot analysis and in situ hybridization histochemistry. The expression of mature GABA(A) receptor alpha6 subunit mRNA species (2.7 kb) was found 1 week after birth in cerebellar granule cells. Prior to stable expression of the mature alpha6 subunit gene, we detected large alpha6 subunit premessengers (3.8 and 3.5 kb) by Northern blot analysis. These premessenger species were detected in prenatal day (PND) 15 and neonatal rat cerebellum, when the mature alpha6 subunit mRNAs (2.7 kb) were not yet expressed. The maximal expression of mature alpha6 subunit mRNA species was observed at PND 21 when the peak level of cerebellar transcriptional activity was measured by polyA+ RNA levels. In contrast, beta-actin mRNA expression was decreased at PND 21 compared to birth levels. These major transcriptional events take place during a period of about 1 week (between PND 14 and 21), immediately following the most active phase of cell division in the external granule layer and migration of granule cells to the internal granule cell layer. Comparison between the relative abundance of these genes shows that differential regulation of each gene occurs during postnatal development. The induction of GABA(A) receptor alpha6 subunit gene expression is preceded by a reduction in beta-actin mRNA levels and a transient increase in total transcriptional activity. The expression of alpha6 subunit mRNA is maintained at the PND 21 level through adulthood, but the alpha1 subunit mRNA levels decrease drastically within the following week (from PND 21 to 28). These results suggest that tissue-specific expression of the GABA(A) receptor alpha6 subunit gene is correlated with a series of developmentally regulated morphologic and transcriptional events.

Animals

Prenatal exposure to the pesticide dieldrin or the GABA(A) receptor antagonist bicuculline differentially alters expression of GABA(A) receptor subunit mRNAs in fetal rat brainstem.

We have previously shown that GABA acts as a trophic signal for monoamine neurons in embryonic day 14 (E14) rat brainstem cultures [Liu et al., J Neurosci 1997a; 17:2420-2428]. The organochlorine pesticide dieldrin and the classical GABA(A) receptor antagonist bicuculline interfere with the trophic actions of GABA and alter expression of several GABA(A) receptor subunit mRNA transcripts in these cultures [Liu et al., J Neurosci Res 1997b;49:645-653]. In the present study, we investigated whether prenatal exposure to dieldrin or bicuculline from E12-17 would alter mRNA expression of alpha1, beta3, gamma1, gamma2S and gamma2L GABA(A) receptor subunits in fetal (E17) rat brainstem using competitive RT-PCR to absolutely quantify these transcripts. The effects of dieldrin and bicuculline on expression of GABA(A) receptor subunit transcripts were similar across subunits. Dieldrin and bicuculline decreased expression of alpha1, beta3 and gamma1 transcripts compared to vehicle-injected controls, but did not significantly alter expression of gamma2S and gamma2L transcripts. Taken together, these studies indicate that in utero exposure to organochlorine pesticides acting as GABA(A) receptor antagonists may alter the expression and subunit composition of developing GABA(A) receptors. If these changes persist, they could have long-lasting effects on developing GABAergic neural circuitry, GABA(A) receptor function and GABA-mediated behaviors.

Animals

CINCH: an urban coalition for empowerment and action. Consortium for the Immunization of Norfolk's Children.

CINCH (Consortium for the Immunization of Norfolk's Children) is an urban coalition that was developed in 1993 to improve childhood immunization rates in Norfolk, Virginia. CINCH involves diverse citizens and institutions in effective community-based assessment, planning, and action. A needs assessment from 1993 found that only 49% of Norfolk 2-year-olds were adequately immunized. Using this data, CINCH developed a plan focused on education and communication, support for at-risk families, increased access to immunizations, and improved immunization delivery. After federal funding ended in 1995, members voted to expand the scope of the coalition to address additional child health needs and to broaden the membership. CINCH is a model for a sustainable city-citizen learning environment that intervenes to "help families help themselves to better health." The coalition is presented as an organization that focuses on community empowerment and development. The stages of coalition development and implications for coalition implementation in other sites are discussed.

Child

A population-based study of access to immunization among urban Virginia children served by public, private, and military health care systems.

BACKGROUND: Pediatric immunization rates have increased in the United States since 1990. Nevertheless, national survey data indicate that up to one third of 2-year-old children in some states and urban areas lack at least one recommended dose of diphtheria-tetanus-pertussis (DTP)-, polio-, or measles-containing vaccines. Immunization has become a key measure of preventive pediatric health care in the United States. To achieve and maintain the national immunization goal that 90% of children receive all recommended immunizations by 2 years of age, the role of the health care system in immunization delivery must be examined. Urban eastern Virginia has a diverse population that obtains immunization services from public, private, and military providers and insurers. At the time of this survey, immunization services in Virginia were available free to all children through public health clinics and to military families when using a military facility. OBJECTIVE: To examine access to pediatric immunization services and health system factors associated with underimmunization in a representative sample of children at 12 and 24 months of age. METHODS: We conducted a household survey in urban eastern Virginia from April through September 1993. A total of 12 770 households in Norfolk and Newport News, VA, were selected for inclusion in the study using probability-proportionate-to-size cluster sampling. Use of probability-proportionate-to-size sampling ensured that children within each city had equal probability of being included in the survey. Selected households were visited by trained interviewers to determine their eligibility, defined as having at least one child 12 to 30 months of age residing in the household. In eligible households, parents were asked to participate in a standardized, 15-minute interview. Survey respondents were asked about household demographics, and for each eligible child, the immunization history, health insurance, the name and location of all immunization providers, the usual immunization provider, and any problems the parent had experienced accessing immunization services with that child. Up-to-date (UTD) immunization status was defined as having all recommended doses of DTP, polio, and measles-mumps-rubella at 12 months (three DTP and two polio immunizations) and 24 months (four DTP, three polio, and one measles-mumps-rubella immunizations). The child's immunization history was assessed from parent and provider records only. Data analysis accounted for the survey's cluster sampling design (ie, within-cluster correlation). Because the immunization rates of the two cities did not differ significantly, unweighted analyses were used for ease of computation. Significance was determined for contingency tables by Wald's chi2 test. RESULTS: A total of 749 children (91% of eligible households) participated in the survey. Study children were born between October, 1990, and July, 1992. Immunization records were obtained for 705 children (94%). Eighty-seven percent of respondents were mothers, 44% were African-American, 40% of children were military dependents, and 40% were enrolled in the Women, Infants and Children (WIC) program. Sixty-five percent of children were UTD at 12 months and 53% at 24 months. Parents reported that their children's usual immunization providers were private doctors (34%); public health, hospital clinics, or community health centers (32%); and military clinics or a military contract provider (34%). At least one problem accessing immunization services was reported by 35% of respondents, ranging from 29% among those who used a private doctor as their child's usual immunization provider to 46% among those using a military contract provider. Overall, the most commonly reported problem was clinic waiting time (12%), with reports of waiting time as a problem occurring most often among those using the military contract provider (22%) and public health clinics (17%). (ABSTRACT TRUNCATED)

Child, Preschool

GABA(A) receptor alpha1, alpha4, and beta3 subunit mRNA and protein expression in the frontal cortex of human alcoholics.

Animal studies have shown that chronic ethanol consumption produces physical dependence upon ethanol and alters gamma-aminobutyric acid-A (GABA(A)) receptor subunit gene expression in brain. Although extensive investigation has been conducted in animal models, relatively little work has been performed directly on human alcoholic brain tissue to determine if there are alterations in GABA(A) receptor gene expression. In this study, GABA(A) receptor alpha1, alpha4, and beta3 subunit mRNA and peptide expression in postmortem frontal cortex from human alcoholics (n = 15) and age- and sex-matched controls (n = 13) were measured by quantitative, competitive reverse transcription polymerase chain reaction and Western blot analysis. GABA(A) receptor beta3 subunit mRNA expression was 35% greater (p < 0.05) in alcoholics, compared with nonalcoholic controls. We found no significant difference in alpha1 and alpha4 subunit mRNA levels between groups. However, there was a trend toward greater (21%) alpha1 subunit mRNA expression. There was no difference in alpha1, alpha4, or beta2/3 subunit peptide levels in frontal cortex between controls and alcoholics. Neither the age of the subjects nor the postmortem interval correlated with mRNA or peptide levels. Blood ethanol content also did not correlate with mRNA or peptide expression in alcoholic samples. These data suggest that GABA(A) receptor adaptations, resulting from prolonged alcohol consumption in human alcoholics, may differ from animal models of alcohol dependence. These differences may be related to the longevity of alcohol exposure in human alcoholics, as well as variability in the dependence/withdrawal state of the human subjects. Therefore, further studies in human postmortem brain tissue are warranted.

Adult