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Biomedical subjects

J M Gardner

Publications and source records attributed to J M Gardner.

At least 19 recordsLinked to original sources

Effect of accommodating sucking and nosing on the behaviour of artificially reared piglets.

Neonatal piglets are often used in biomedical research applications that require artificial rearing. Social housing can be problematic because the piglets develop belly nosing, navel and ear sucking that can result in injury. Our objective was to determine the effectiveness of using feeding devices that provide various opportunities for sucking and nosing behaviour on reducing piglet-directed behaviour of group-housed laboratory piglets. Fifteen piglets were used in each of four trials. The piglets nursed their dam for approximately 72 h to obtain passive immunity before transfer to a laboratory facility where they were allotted, five per group, to one of three stainless steel isolator units. Each unit featured a different style of feeding system for the delivery of milk replacer: a plastic trough (T), a nipple (N) mounted on a smooth plexiglass wall, or a nipple mounted on a pliant bag of sterile water (artificial udder [AU]). Each system had five feeding spaces so that all piglets fed simultaneously. Milk was provided at 6-h intervals, and behaviour was recorded on alternate days for 12 days post-weaning. Although trough-fed piglets began to eat much sooner than those piglets fed from nipples, time spent nosing, chewing or sucking on pen-mates and belly nosing were markedly higher in T piglets than in either N or AU, overall (mean: P<0.05) and over time (quadratic: P<0.05). Over time, N piglets developed a stereotypic snout rubbing on the wall behind the nipples, while AU piglets massaged and often fell asleep in contact with the udder from day 2 of the trial. Resting patterns were also affected. N and AU piglets settled down to rest more quickly (P<0.01) and spent significantly more time resting in the hour following feeding than T piglets (P<0.05). A feeding device that accommodates both sucking and massage can significantly reduce piglet-directed behaviour and may facilitate social housing of artificially reared piglets.

Animal Husbandry↗

Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4.

Oculocutaneous albinism (OCA) affects approximately 1/20,000 people worldwide. All forms of OCA exhibit generalized hypopigmentation. Reduced pigmentation during eye development results in misrouting of the optic nerves, nystagmus, alternating strabismus, and reduced visual acuity. Loss of pigmentation in the skin leads to an increased risk for skin cancer. Two common forms and one infrequent form of OCA have been described. OCA1 (MIM 203100) is associated with mutations of the TYR gene encoding tyrosinase (the rate-limiting enzyme in the production of melanin pigment) and accounts for approximately 40% of OCA worldwide. OCA2 (MIM 203200), the most common form of OCA, is associated with mutations of the P gene and accounts for approximately 50% of OCA worldwide. OCA3 (MIM 203290), a rare form of OCA and also known as "rufous/red albinism," is associated with mutations in TYRP1 (encoding tyrosinase-related protein 1). Analysis of the TYR and P genes in patients with OCA suggests that other genes may be associated with OCA. We have identified the mouse underwhite gene (uw) and its human orthologue, which underlies a new form of human OCA, termed "OCA4." The encoded protein, MATP (for "membrane-associated transporter protein") is predicted to span the membrane 12 times and likely functions as a transporter.

Adult↗

Belly-nosing in early-weaned piglets is not influenced by diet quality or the presence of milk in the diet.

Early weaning of piglets can lead to an increase in belly-nosing and other oral-nasal behavior (nosing, chewing, or sucking other piglets), but the causative factors involved in these behavior patterns are largely unknown. Because these behavior patterns resemble massaging the udder and sucking, they may be associated with feeding. The objectives of this study were to determine any effect of diet quality or the presence of milk in the diet on belly-nosing behavior of piglets weaned at 14 to 18 d. During the first 2 wk after weaning, piglets were fed diets differing in quality and inclusion of milk products. Six replicates of eight piglets per replicate, blocked by initial body weight, (n = 192) were offered one of four dietary treatments: HQM: high quality, high in milk products; HQ: high quality, no milk products; PQ: poor quality, no milk products; HQ+MR: high quality, no milk products (as HQ) sprayed with milk replacer five times daily. Thereafter, the piglets were fed a standard nursery diet. Feed intake was measured daily for wk 1 and again at the end of wk 2. Behavior was recorded every 5 min during two 4-h periods on d 2 to 7, 10, 14, 17 and 21 after weaning. Dietary treatment influenced ADFI and ADG during wk 1. Average daily feed intake (P < 0.05) and ADG (P < 0.05) of piglets on PQ were less than those of piglets on the other treatments. During wk 2, ADFI (P > 0.10) and ADG (P > 0.10) were the same across all treatments. Overall, ADFI was not influenced by the inclusion of milk products in the diet or the addition of milk replacer (P > 0.10); however, ADG was. Piglets on HQM had higher ADG than those on HQ during wk 2 (P < 0.05) and 3 after weaning (P < 0.05). However, milk replacer did not influence ADG (P > 0.10). Although the dietary treatments did affect ADFI and ADG, there were no effects on any behavior pattern recorded, including time spent at the feeder (P > 0.10). Lower weight-for-age piglets performed more oral-nasal behavior, in total, than higher weight-for-age piglets (P < 0.03). Neither feeding a poor-quality diet nor the presence of milk in the diet had an effect on belly-nosing or other oral-nasal behavior patterns during the first 3 wk after weaning. Belly-nosing does not seem to be associated with feeding.

Animal Nutritional Physiological Phenomena↗

Aberrant pH of melanosomes in pink-eyed dilution (p) mutant melanocytes.

In past studies, we cloned the mouse p gene and its human homolog P, which is associated with oculocutaneous albinism type 2. Both mouse and human genes are expressed in melanocytes and encode proteins predicted to have 12 membrane-spanning domains with structural homology to known ion transporters. We have also demonstrated that the p protein is localized to the melanosomal membrane and does not function as a tyrosine transporter. In this study, immunohistochemistry and confocal microscopy were used to show that the p protein plays an important role in the generation or maintenance of melanosomal pH. Melanosomes (and their precursor compartments) were defined by antiserum directed against the melanosomal marker tyrosinase related protein 1. Acidic vesicles were identified by 3-(2, 4-dinitroanilino)-3'-amino-N-methyldipropylamine incorporation, visualized with anti-dinitrophenol. In C57BL/6+/+ (wild-type) melanocytes, 94.2% of vesicles demonstrated colocalization of tyrosinase related protein 1 and 3-(2, 4-dinitroanilino)-3'-amino-N-methyldipropylamine, indicating that almost all melanosomes or their precursors were acidic. By contrast, only 7%-8% of the staining vesicles in p mutant cell lines (pJ/pJ and pcp/p6H) showed colocalization of tyrosinase related protein 1 and 3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine. Thus, without a functional p protein, most melanosomes and their precursors are not acidic. As mammalian tyrosinase activity in situ is apparently dependent on low pH, we postulate that in the absence of a low pH environment brought about by ionic transport mediated by the p protein, tyrosinase activity is severely impaired, leading to the minimal production of melanin that is characteristic of p mutants. Additionally (or alternatively), an abnormal pH may also impair the assembly of the normal melanogenic complex.

Animals↗

Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials.

BACKGROUND: Zinc deficiency is prevalent in children in developing countries. Supplemental zinc provides therapeutic benefits in diarrhea. OBJECTIVE: We sought to measure the effect of supplemental zinc given with oral rehydration therapy during recovery from acute or persistent diarrhea. DESIGN: We conducted pooled analyses including all available published and unpublished randomized controlled trials of the effects of supplementary oral zinc in children aged <5 y with acute or persistent diarrhea. We used Cox survival regression analysis to evaluate the overall effect of zinc on continuation of diarrhea and possible differential effects in subgroups divided by sex, age, weight-for-height, and initial plasma zinc concentration. Dichotomous outcomes were analyzed by logistic regression. To assess the effects of excluding studies without original data from the pooled analyses, effect-size was estimated for all studies by using random-effects models. RESULTS: Zinc-supplemented children had a 15% lower probability of continuing diarrhea on a given day (95% CI: 5%, 24%) in the acute-diarrhea trials and a 24% lower probability of continuing diarrhea (95% CI: 9%, 37%) and a 42% lower rate of treatment failure or death (95% CI: 10%, 63%) in the persistent-diarrhea trials. In none of the subgroup analyses were the 2 subgroups of each pair significantly different from each other; however, in persistent diarrhea there tended to be a greater effect in subjects aged <12 mo, who were male, or who had wasting or lower baseline plasma zinc concentrations. CONCLUSION: Zinc supplementation reduces the duration and severity of acute and persistent diarrhea.

Acute Disease↗

The use of herbal teas and remedies in Jamaica.

We investigated the prevalence of the use of herbs among adults and children in Jamaica in 1996. Two concurrent surveys were conducted in randomly selected urban and rural areas: among adults and among caretakers of young children. From over 90% of the selected households, all caretakers of children under 6 years and one randomly selected adult (18 years or older) were interviewed using structured questionnaires. The 457 adults reportedly used 156 types of herbs: a mean of 6 +/- 3 (mean +/- standard deviation) by the urban adults, and 10 +/- 6 by the rural adults (t-test, p < 0.001). Almost 100% of respondents had at some time used herbs for teas or for treating illnesses. The most common method of preparation was by infusion or boiling in water, then adding sugar. Urban respondents, women and those who were employed were more likely to buy medicines than to use herbal remedies. One hundred and sixty-seven caretakers of 203 children under 6 years were interviewed. The mean number of herbs given to each child was between 2 and 3. The most common herbs were introduced within the first 6 months of life. Many caretaker factors were associated with herbal use. Public health implications include the potential toxicity of some herbs, the possibility that herbal teas given to young children may displace more nutritious foods and delay presentation to health care facilities. The findings will allow policy makers to target those most likely to use herbal preparations or to give them to young children, and target herbs to be analyzed for toxic or beneficial properties.

Adolescent↗

Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group.

OBJECTIVES: This study assessed the effects of zinc supplementation in the prevention of diarrhea and pneumonia with the use of a pooled analysis of randomized controlled trials in children in developing countries. STUDY DESIGN: Trials included were those that provided oral supplements containing at least one half of the United States Recommended Daily Allowance (RDA) of zinc in children <5 years old and evaluated the prevention of serious infectious morbidity through household visits. Analysis included 7 "continuous" trials providing 1 to 2 RDA of elemental zinc 5 to 7 times per week throughout the period of morbidity surveillance and 3 "short-course" trials providing 2 to 4 RDA daily for 2 weeks followed by 2 to 3 months of morbidity surveillance. The effects on diarrhea and pneumonia were analyzed overall and in subgroups defined by age, baseline plasma zinc concentration, nutritional status, and sex. The analysis used random effects hierarchical models to calculate odds ratios (OR) and 95% CIs. RESULTS: For the zinc-supplemented children compared with the control group in the continuous trials, the pooled ORs for diarrheal incidence and prevalence were 0.82 (95% CI 0.72 to 0.93) and 0.75 (95% CI 0.63 to 0.88), respectively. Zinc-supplemented children had an OR of 0.59 (95% CI 0.41 to 0.83) for pneumonia. No significant differences were seen in the effects of the zinc supplement between the subgroups examined for either diarrhea or pneumonia. In the short-course trials the OR for the effects of zinc on diarrheal incidence (OR 0.89, 95% CI 0.62 to 1.28) and prevalence (OR 0.66, 95% CI 0.52 to 0.83) and pneumonia incidence (OR 0.74, 95% CI 0.40 to 1.37) were similar to those in the continuous trials. CONCLUSIONS: Zinc supplementation in children in developing countries is associated with substantial reductions in the rates of diarrhea and pneumonia, the 2 leading causes of death in these settings.

Child↗

Feeding-based arousal effects on visual recognition memory in early infancy.

Arousal effects on a 1-trial visual recognition paired-comparison task were studied at newborn, 1-month, and 4-month test ages. Infants were tested before and after feeding, with arousal assumed to be lower after feeding. Newborns and 1-month-olds shifted from a familiarity preference before feeding to a novelty preference after feeding. A control group tested only after feeding confirmed that this shift was not due to increased stimulus exposure from the prefeeding test. By 4 months, infants showed novelty preferences independent of feeding. This age by arousal interaction for recognition memory extends previous knowledge by including endogenous arousal with age, stimulus, and length of exposure as contributors to familiarity-novelty preferences. It also extends and provides converging evidence for arousal effects on visual attention in early infancy found previously with preferential looking. A shift from subcortical to cortical dominance is supported.

Age Factors↗

In vivo evaluation of a novel epitope-tagged human factor VIII-encoding adenoviral vector.

Haemophilia A is caused by a deficiency in coagulation factor VIII (FVIII) and is an attractive target for gene therapy. Adenoviral vectors encoding a human B-domain deleted (BDD) FVIII cDNA have been shown previously to mediate expression of high levels of human FVIII and correct the bleeding defect in haemophiliac mice and dogs. While vector assessment in a non-human primate model would have a significant preclinical benefit, a haemophiliac non-human primate model is not available, and assays that distinguish human FVIII from monkey FVIII have not been developed successfully. As a first step to enable vector evaluation in non-human primates, we have constructed an epitope-tagged FVIII molecule by the addition of 16 amino-acids to the carboxy terminus of the BDD protein (BDD-E). Following vector administration to normal mice, therapeutic levels of BDD-E FVIII were expressed for at least 20 weeks. Treatment of haemophiliac mice revealed that the BDD-E protein was biologically active in vivo. To distinguish the BDD-E protein from non-human primate FVIII, a sensitive immunoprecipitation/Western assay was developed that reproducibly detected 1 ng mL-1 of the epitope-tagged human FVIII in the presence of monkey plasma. These data demonstrate that the addition of an epitope tag had no effect on FVIII function or immunogenicity, and suggest that the BDD-E vector will be an effective reagent for non-human primate studies.

Adenoviridae↗

Behaviour and development of stunted and nonstunted Jamaican children.

In order to examine the mechanism whereby stunted children have poor developmental levels, we compared the behaviour of stunted (N = 78) and nonstunted (N = 26) children aged 12 to 24 months, and examined the relationship of their behaviour to their developmental levels. The effect of nutritional supplementation with or without psychosocial stimulation on the stunted children's behaviour was also examined. The children were observed at home during 4 days over a period of 6 months. The stunted children showed significantly more apathy, and less enthusiasm and variety in exploring, were less happy and more fussy. Caretakers' vocalisations to them were less warm or instructive. Stunted children's activity level, exploratory and happy behaviours were predictive of change in developmental levels measured on the Griffiths Scales, from enrolment to 12 and 24 months later. Supplementation predicted mental age at 12 and 24 months after enrolment, however, it had no significant effect on behaviour.

Child↗

Perinatal death: uncovering the needs of midwives and nurses and exploring helpful interventions in the United States, England, and Japan.

Perinatal death is a crisis for midwives and nurses as well as for bereaved parents and extended families. Surveys and interviews conducted in the United States, England, and Japan described the needs and responses of nurses and midwives as they coped with their own feelings while caring for bereaved parents. Results emphasized common needs of caregivers for increased knowledge, mentored experience, communication skills, and personal support to confidently provide sensitive care to families. Although need for education regarding cultural-specific care was revealed, participants identified helpful strategies of care for bereaved parents that could extend and improve care universally.

Attitude of Health Personnel↗

Folylpoly-gamma-glutamate carboxypeptidase from pig jejunum. Molecular characterization and relation to glutamate carboxypeptidase II.

Jejunal folylpoly-gamma-glutamate carboxypeptidase hydrolyzes dietary folates prior to their intestinal absorption. The complete folylpoly-gamma-glutamate carboxypeptidase cDNA was isolated from a pig jejunal cDNA library using an amplified homologous probe incorporating primer sequences from prostate-specific membrane antigen, a protein capable of folate hydrolysis. The cDNA encodes a 751-amino acid polypeptide homologous to prostate-specific membrane antigen and rat brain N-acetylated alpha-linked acidic dipeptidase. PC3 transfectant membranes exhibited activities of folylpoly-gamma-carboxypeptidase and N-acetylated alpha-linked acidic dipeptidase, while immunoblots using monoclonal antibody to native folylpoly-gamma-glutamate carboxypeptidase identified a glycoprotein at 120 kDa and a polypeptide at 84 kDa. The kinetics of native folylpoly-gamma-carboxypeptidase were expressed in membranes of PC3 cells transfected with either pig folylpoly-gamma-carboxypeptidase or human prostate-specific membrane antigen. Folylpoly-gamma-carboxypeptidase transcripts were identified at 2.8 kilobase pairs in human and pig jejunum, human and rat brain, and human prostate cancer LNCaP cells. Thus, pig folylpoly-gamma-carboxypeptidase, rat N-acetylated alpha-linked acidic dipeptidase, and human prostate-specific membrane antigen appear to represent varied expressions of the same gene in different species and tissues. The discovery of the jejunal folylpoly-gamma-carboxypeptidase gene provides a framework for future studies on relationships among these proteins and on the molecular regulation of intestinal folate absorption.

Amino Acid Sequence↗

Mutations of the human P gene associated with Type II oculocutaneous albinism (OCA2). Mutations in brief no. 205. Online.

Mutations in the human P gene lead to oculocutaneous albinism type 2 (OCA2, MIM #203200), the most common type of albinism in humans. The P gene encodes a 110 kDa protein that is associated with melonosomal membranes and contains 12 potential membrane spanning domains. The specific function of the P protein is currently unknown. We report 7 new mutations in the P gene associated with OCA2. This includes 6 missense mutations (S86R, C112F, A368V, T592I, A724P and A787V) and one frameshift mutation (1047del7). We also report 8 polymorphisms including one amino acid substitution, D/A257. We and others have found many polymorphisms of the P gene in the coding region, several of which result in amino acid substitutions, making molecular diagnosis problematic. In contrast to this is the tyrosinase gene associated with OCA1, with a limited number of polymorphic variations in the coding region. There is also no apparent clustering of P gene missense mutations in contrast to the clustering observed by the tyrosinase gene missense mutations that define functional domains of the protein. Further mutational analysis is needed to help define the critical functional domains of the P protein and to allow a definitive diagnosis of OCA2.

Albinism, Oculocutaneous↗

Identification of a novel transcript produced by the gene responsible for the Hermansky-Pudlak syndrome in Puerto Rico.

Hermansky-Pudlak Syndrome (HPS) is a rare, autosomal recessive disorder that is characterized by oculocutaneous albinism, a predisposition to mild bleeding caused by storage-pool deficient platelets, and a ceroid storage disorder. A gene responsible for HPS in Puerto Rico maps to chromosome 10q2 and isolation of the gene has been reported. We have now identified a variant HPS cDNA that contains the same 5' sequence as the published HPS gene and a unique 3' sequence. Analysis of genomic DNA suggests that the two cDNA are derived from alternative transcripts of a single gene; two polyadenylated transcripts were found in normal human melanocytes, human bone marrow cells, human melanoma cells, lymphoblastoid cell lines, and megakaryocytic leukemia cells by reverse transcriptase polymerase chain reaction and northern analysis. The splicing exhibited by this gene is identical to the splicing found to produce two alternative transcripts of the Chediak-Higashi Syndrome gene, another pigment disorder exhibiting platelet storage pool deficiency. These studies show that the HPS gene on chromosome 10 is complex and may have more than one biologically active transcript.

Albinism, Oculocutaneous↗

Undernutrition and elevated blood lead levels: effects on psychomotor development among Jamaican children.

OBJECTIVE: We examined whether or not the effect of elevated blood lead levels on children's psychomotor development was modified by their nutritional status. DESIGN: Anthropometry, developmental quotients (DQs), blood lead levels and haemoglobin were measured in lead exposed and unexposed children with different levels of nutritional status. Social background and maternal height and verbal intelligence were also measured. Testers, anthropometrists and interviewers established reliabilities with a trainer before the study began. SETTING: Children were from two suburban areas in Kingston, Jamaica. All measurements on the children were carried out at a research unit. Social background and maternal measurements were carried out at the children's homes. SUBJECTS: The exposed group comprised 58 children (3-6 years) attending the same preschool which was situated in a lead contaminated environment. The unexposed group comprised 53 children attending a nearby preschool without lead contamination. RESULTS: The exposed children had significantly higher blood lead levels and lower DQs, and their homes had poorer facilities than the unexposed children. The deficit in DQ was greater (10.6 points) among children with weight for height less than -1 SD (National Center for Health Statistics references) than among better nourished children (2 points). CONCLUSIONS: Undernourished children exposed to lead may have more serious developmental deficits than better nourished children.

Child↗