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Biomedical subjects

M Smith

Publications and source records attributed to M Smith.

At least 1,549 records · Page 86Linked to original sources
PubMedDate not supplied

Clinical and pathologic study of two siblings with arrhythmogenic right ventricular cardiomyopathy.

ARVC is a cardiomyopathy in which the right ventricular myocardium is replaced by fibroadipose tissue. Males are affected slightly more often than females and, in those cases which are familial, the pattern of inheritance is usually autosomal dominant with incomplete penetrance. We examined the hearts of two sisters, ages 17 and 14, with no family history of heart disease. The older sibling, who was previously considered healthy, died suddenly, while the younger sibling developed congestive heart failure and received a cardiac transplant. An autopsy of the older sibling and examination of the younger sibling's excised heart revealed severe examples of ARVC with minor differences. A thick cap of fibroadipose tissue covered most, if not all, of each right ventricle and was transmural in some areas. Microscopically, lelt ventricles contained extensive myocyte disarray and multifocal fibrosis. The coronary arteries displayed intimal hyperplasia with disruption of the internal elastic lamina, similar to fibromuscular dysplasia. These two cases comprise a unique familial grouping in a polymorphic disease. Despite the male predominance and autosomal dominant inheritance in ARVC, the only members affected in this family were female, and an autosomal dominant pattern of inheritance, even with incomplete penetrance, would be unusual. In addition, we identified changes in the coronary arteries similar to fibromuscular dysplasia and corroborated recently reported changes in the left ventricle of patients with ARVC, providing evidence that this disease, in its most severe form, involves the entire heart.

Adolescent↗
PubMedDate not supplied

DNA sequences of two yeast promoter-up mutants.

The yeast Saccharomyces cerevisiae has three genetic loci encoding different alcohol dehydrogenase (ADH) isozymes: ADC1, which encodes the classical fermentative isozyme ADHI; ADR2, which encodes the glucose-repressed isozyme ADHII; and ADM, which encodes an ADH isozyme found associated with mitochondria. When yeast are grown on glucose, the ADC1 gene is expressed, and the ADR2 gene repressed. Conversely, growth on a non-fermentable carbon source such as ethanol or glycerol results in derepression of ADR2, and repression of ADC1. The ADC1 and ADR2 genes have been cloned and sequenced, and a number of cis-acting mutations identified that cause constitutive expression of ADR2, and seem to fall into two classes. The most abundant class consists of mutants that cannot be fully derepressed, and do not revert to wild type at a detectable level: these are caused by the insertion of a transposable element into the 5'-flanking region of the gene. The second class of mutants do revert to a glucose-repressed phenotype at a detectable frequency, and when grown on non-fermentable carbon sources derepress ADR2 to levels up to five times those found in wild-type cells. We report here the sequencing of the 5'-flanking regions of two such promoter-up, constitutive ADR2 mutants, in both of which the mutant phenotype is associated with an increase in length of a poly(A) X poly(T) tract 222 base pairs (bp) upstream of the gene.

Alcohol Oxidoreductases↗
PubMedDate not supplied

Site-directed mutagenesis of cytochrome c shows that an invariant Phe is not essential for function.

Phenylalanine 87 of yeast iso-1-cytochrome c (Phe 82 in horse heart and bonito) is phylogenetically conserved and occurs near the surface of the protein. It has been suggested that this residue is directly involved in electron transfer between cytochrome c and cytochrome c peroxidase (CCP) and may also control the polarity of the haem environment. Because Phe residues are not susceptible to chemical modification, no direct means of studying the functional role of Phe 87 has been available, so we have chosen Phe 87 as our initial target here to test the feasibility of using site-directed mutagenesis as a means of studying structure-function relationships in cytochrome c. We have changed the codon for Phe 87 to that of either a Ser, a Tyr or a Gly. The mutated genes have been introduced into a yeast strain lacking both isozymes of cytochrome c. Unlike the recipient strain, transformants grow on a non-fermentable carbon source, indicating that the mutant proteins can reduce cytochrome oxidase. The purified mutant proteins are similar to wild type with respect to their visible spectra, 20-70% as active as wild-type protein in the CCP assay, and their reduction potentials are lowered by as much as 50 mV. Thus Phe 87 is not essential for cytochrome c to transfer electrons but is involved in determining the reduction potential.

Amino Acid Sequence↗
PubMedDate not supplied

Homoeo-domain homology in yeast MAT alpha 2 is essential for repressor activity.

The MAT alpha locus of the yeast Saccharomyces cerevisiae encodes two regulatory proteins, alpha 1 and alpha 2, which are responsible for determining the alpha-cell type. MAT alpha 1 is a positive regulator of alpha-cell-type-specific genes, and MAT alpha 2 is a negative regulator of a-cell-type-specific genes. MAT alpha 2 also determines the a/alpha diploid cell type, in conjunction with the MATa product, a1, by repressing haploid cell-type-specific genes. The MAT alpha 2-encoded protein binds specifically in vitro to a DNA sequence found upstream of several a-specific genes and is thus thought to exert its control directly at the transcriptional level of target genes. In an initial attempt to understand the molecular basis of the interaction of alpha 2 with DNA, we have saturated with missense mutations the segment of alpha 2 that is weakly homologous to a conserved prokaryote DNA-binding structure and to a portion of the higher eukaryote homoeo domain to ascertain the possible functional significance of this homology in alpha 2. We report here that most of the amino-acid residues in alpha 2 which correspond to conserved amino acids in the prokaryote DNA-binding proteins and in the homoeo domain are essential for the two repressor activities of alpha 2, that is, the repression of a-specific genes and of haploid-specific genes. Mutations in a subset of these amino-acid residues more severely affect the ability to repress a-specific genes than haploid-specific genes.

Genes, Regulator↗
PubMedDate not supplied

Genetic mapping of X-linked loci involved in skewing of X chromosome inactivation in the human.

We have analyzed X-chromosome inactivation patterns in lymphocytes of 264 females from 38 families not known to have any genetic disease. Quantitative measures of X-inactivation showed strong sister-sister correlation in the degree of departure from equal numbers of cells having each X chromosome active, suggesting heritability of this phenotype. Strong sister-sister correlation was also observed for the fraction of cells having the same parent's X chromosome active, consistent with the possibility that this trait might be controlled by a cis-acting, X-linked gene. We used a sib-pair approach to determine whether X-inactivation phenotype was linked to loci in any region of the X chromosome. Both quantitative and discrete measures of X-inactivation phenotype showed evidence of linkage to markers in the region of the X inactivation center (XIC). The quantitative measure of X-inactivation phenotype used in our study also showed linkage to loci at Xq25-q26. This study provides the first evidence for X-linked inheritance of X chromosome inactivation phenotype derived from linkage analysis in phenotypically normal human families.

Base Sequence↗
PubMedDate not supplied

Use of whole body hyperthermia as a method to heat inaccessible tumours uniformly: a phase III trial in canine brain masses.

In this study, whole body hyperthermia (WBH) was assessed as a means of heating intracranial tumours uniformly. Twenty-five dogs received radiation therapy and 20 the combination of radiation and WBH. Total radiation dose was randomly assigned and was either 44, 48, 52, 56 or 60 Gy. Because of WBH toxicity, intercurrent disease or tumour progression, seven of the 45 dogs received less than the prescribed radiation dose. For WBH, the target rectal temperature was 42 degrees C for 2h and three treatments were planned. In five of the 20 dogs randomized to receive WBH, only one WBH treatment was given because of toxicity. WBH toxicity was severe in six dogs, and resulted in death or interruption in treatment. Most tumours did not undergo a complete response, making it impossible to differentiate tumour recurrence from brain necrosis as a cause of progressive neuropathy. Therefore, survival was the major study endpoint. There was no survival difference between groups. One-year survival probability (95% CI) for dogs receiving radiation therapy alone was 0.44 (0.25, 0.63) versus 0.40 (0.19, 0.63) for dogs receiving radiation and WBH. There was no difference in the incidence of brain necrosis in the two treatment groups. Results suggest that use of WBH alone to increase the temperature of intracranial tumours as a means to improve radiation therapy outcome is not a successful strategy.

Animals↗
PubMedDate not supplied

Hyperglycemia as a predictor for mortality in veterans with pneumonia.

The elderly may have multiple problems including diabetes mellitus and pneumonia. This study was undertaken to evaluate the effect of hyperglycemia on the length of stay (LOS) and mortality of elderly veterans admitted for pneumonia. Forty-seven and forty-eight patients over the age of 60 admitted for the diagnosis of pneumonia at the Lexington, Kentucky and Iron Mountain, Michigan VAMC's respectively were evaluated. The mean age at Lexington was 72 and at Iron Mountain was 73.9. At Lexington the mean LOS was 39.5 days with a standard deviation of 9.2 for those with hyperglycemia (n = 18) and 16.5 days with a standard deviation of 2.5 for those without hyperglycemia (n = 29). At Iron Mountain the mean LOS was 21.5 days with a standard deviation of 3.3 for those with hyperglycemia (n = 10) and 13.6 days with a standard deviation of 1.2 for those without (n = 38). These differences were significant at p less than .01 using the 2-sample independent t-test. At Iron Mountain 5 of 38 (13%) of the patients with normoglycemia died during the hospital stay compared to 3 of 10 (30%) those with hyperglycemia. For Lexington the figures were 4 of 29 (13%) and 6 of 18 (33%) respectively. These differences were significant at p less than .05. Age did not have any significant effect on either mortality or length of stay. Hyperglycemia appears to be a significant predictor of a longer hospital course and increased mortality in elderly veterans hospitalized for pneumonia.

Aged↗
PubMedDate not supplied

Short-range functional interaction between connexin35 and neighboring chemical synapses.

Auditory afferents terminating as mixed, electrical, and chemical, synapses on the goldfish Mauthner cells constitute an ideal experimental model to study the properties of gap junctions in the nervous system as well as to explore possible functional interactions with the other major form of interneuronal communication--chemically mediated synapses. By combining confocal microscopy and freeze-fracture replica immunogold labeling (FRIL), we found that gap junctions at these synapses contain connexin35 (Cx35), the fish ortholog of the neuron-specific human and mouse connexin36 (Cx36). Conductance of gap junction channels at these endings is known to be dynamically modulated by the activity of their co-localized chemically mediated glutamatergic synapses. By using simultaneous pre- and postsynaptic recordings at these single terminals, we demonstrate that such functional interaction takes place in the same ending, within a few micrometers. Accordingly, we also found evidence by confocal and FRIL double-immunogold labeling that the NR1 subunit of the NMDA glutamate receptor, proposed to be a key regulatory element, is present at postsynaptic densities closely associated with gap junction plaques containing Cx35. Given the widespread distribution of Cx35- and Cx36-mediated electrical synapses and glutamatergic synapses, our data suggest that the local functional interactions observed at these identifiable junctions may also apply to other electrical synapses, including those in mammalian brain.

Animals↗
PubMedDate not supplied

Replacement of cysteine-107 of Saccharomyces cerevisiae iso-1-cytochrome c with threonine: improved stability of the mutant protein.

Site-directed mutagenesis has been used to change the codon for cysteine-107 of Saccharomyces cerevisiae iso-1-cytochrome c to a threonine codon. The resulting protein is active in vivo, is methylated as in the wild-type protein and has optical properties indistinguishable from those of the wild-type protein. The threonine-107 iso-1-cytochrome c demonstrated fully reversible electrochemical behaviour and a mid-point reduction potential of 272 mV versus NHE. In addition, this mutant does not demonstrate a tendency to autoreduce or to dimerize as does the wild-type protein. These properties of the threonine-107 mutant establish that it will provide a useful background in which to make subsequent mutations for mechanistic and physical studies of yeast iso-1-cytochrome c.

Amino Acid Sequence↗
PubMedDate not supplied

Language and behavior in children with Sotos syndrome.

OBJECTIVE: To examine language and behavior in children with Sotos syndrome, an overgrowth syndrome involving advanced bone age, characteristic facies, and developmental disability. METHOD: Twenty-seven children with Sotos syndrome were compared with 20 children with overgrowth, intellectual disability, and facies not characteristic of Sotos syndrome. Ages ranged from 5 to 16 years. Direct assessment was undertaken with standardized measures of intelligence and language abilities. Behavior was examined by parent and teacher report. RESULTS: Children with Sotos syndrome had levels of intelligence in the severely disabled to average range, with the majority falling in the borderline range. Mean level of intelligence was significantly higher than that observed for children in the comparison group. Language abilities were developed to a level consistent with overall level of intelligence. Rates of parent- and teacher-reported behavior problems were significantly higher than normal, but, with the exception of temper tantrums, did not differ from those observed in children in the comparison group. Attention-deficit hyperactivity disorder was observed in 38% of children with Sotos syndrome. They were more irritable and had more stereotypic behavior and inappropriate speech than is expected in children with intellectual disabilities, and they were more withdrawn and had more stereotypic behavior than children in the comparison group. CONCLUSIONS: Assessment of language abilities revealed no specific language impairment. High rates of behavior problems were observed, but these were not higher than those observed for other large, delayed, dysmorphic children.

Abnormalities, Multiple↗
PubMedDate not supplied

Alternate antimicrobial therapy for vancomycin-resistant enterococci burn wound infections.

Survival after a major thermal burn is precarious and fraught with difficult complications associated with hypermetabolism, gut or respiratory dysfunction, and infection. Clinicians must be cognizant of a new threat to the patient with burn injuries--the emergence of vancomycin-resistant enterococci (VRE). In an analysis of 31 clinical isolates obtained during acute burn hospitalization, an optimal antimicrobial therapy for VRE has been identified. All VRE cultures were inoculated to the MicroScan Gram-Positive Breakpoint Combo Panel #8 (Dade Microscan, Inc, Sacramento, Calif), which speciates the enterococci, provides antimicrobial susceptibility patterns (including vancomycin) and a biotype, and examines streptomycin and gentamicin synergy. Eleven (35.5%) of the 31 isolates were identified as E faecium and 20 (64.5%) as E faecalis. All isolates were susceptible to chloramphenicol and tetracycline, whereas only half were sensitive to gentamicin synergy screen. All other antimicrobials screened against VRE were either ineffective or of limited effect. Our preliminary data supports the initiation of chloramphenicol therapy when a VRE burn wound infection is encountered or suspected.

Anti-Bacterial Agents↗
PubMedDate not supplied

Measurement of the milk intake of breast-fed infants.

Infant test weighing and maternal test weighing are two independent methods for determining milk intake by the breast-fed infant. The sources of error in both these test weighing methods were examined with particular emphasis on the importance of evaluating and correcting for evaporative water loss (EWL). EWL ranged from 3 to 94% of the mother's change in weight after a single breast feed and from 3 to 55% of the infant's change in weight after a single breast feed. Correcting for EWL during a breast feed involved determining the time between the pre- and postfed weighings and measuring the rate of EWL after breast feeding. Significant correlations (p less than 0.001) were found between milk volume intake measured by test weighing the mother and correcting for maternal EWL, and milk volume intake measured by test weighing the infant and correcting for infant EWL. An improved method for measuring 24-h milk intakes by maternal test weighing using a sensitive electronic balance and correcting for EWL is described. The milk intakes, corrected for EWL, ranged from 690-1,041 g/24 h. If no correction for EWL was made then the average overestimate of milk intake by maternal test weighing was 14 +/- 6%.

Body Water↗
PubMedDate not supplied

An innovative, interdisciplinary educational experience in field research.

Although interdisciplinary practice is necessary to meet the complex health needs of populations, there are few planned interdisciplinary learning experiences within educational programs for the health professions. The authors describe an interdisciplinary learning experience in field research for students and faculty members from schools of nursing and medicine.

Education, Medical, Undergraduate↗
PubMedDate not supplied

A decade of distance education: RN to BSN.

TELETECHNET represents a major commitment on the part of the university. The university's strategic plan and resource allocations indicate that this educational strategy is a growing enterprise. Although challenges exist in implementing a nursing education program by television, the TELETECHNET program provides opportunities for the place-bound student to achieve advanced education.

Copyright↗
PubMedDate not supplied

Regulation, emotionality, and preschoolers' socially competent peer interactions.

In this study, the relations of regulatory control to the qualities of children's everyday peer interactions were examined. Effortful control (EC) and observations of peer interactions were obtained from 135 preschoolers (77 boys and 58 girls, mean ages = 50.88 and 50.52, respectively). The results generally confirmed the prediction that children who are high in EC were relatively unlikely to experience high levels of negative emotional arousal in response to peer interactions, but this relation held only for moderate to high intense interactions. Socially competent responding was less likely to be observed when the interaction was intense or when negative emotions were elicited. Moreover, when the interactions were of high intensity, highly regulated children were likely to evidence socially competent responses. The relation of EC and intensity to social competence was partially mediated by negative emotional arousal. The results support the conclusion that individual differences in regulation interact with situational factors in influencing young children's socially competent responding.

Arousal↗
PubMedDate not supplied

Comprehensive health assessment for newly arrived refugee children in Australia.

Providing appropriate and responsive care to refugees from diverse backgrounds and with unique health needs is challenging. Refugee children may present with a wide range of conditions, which may be unfamiliar to health professionals in developed countries. Additionally, refugees may experience unfamiliarity with the Australian health system and distrust of authority figures and/or medical practitioners. This article provides an overview of the priority areas in health and health management for paediatric refugee patients for paediatricians as well as other relevant health care providers caring for this group. Specific issues covered include general health assessment, infectious diseases, immunization, growth and nutrition, oral health, development and disability, mental health and child protection. Comprehensive health assessment can assist in identifying children at risk of poor health and to provide them with timely and effective care, advocacy and appropriate referral.

Australia↗
PubMedDate not supplied

An issue of access: delivering equitable health care for newly arrived refugee children in Australia.

Newly arrived refugees and asylum seekers are faced with many difficulties in accessing effective health care when settling in Australia. Cultural, language and financial constraints, lack of awareness of available services, and lack of health provider understanding of the complex health concerns of refugees can all contribute to limiting access to health care. Understanding the complexities of a new health care system under these circumstances and finding a regular health provider may be difficult. In some cases there may be a fundamental distrust of government services. The different levels of health entitlements by visa category and (for some) detention on arrival in Australia may further complicate the provision and use of health services for providers and patients. Children are particularly at risk of suboptimal health care due to the impact of these factors combined with the effect of resettlement stresses on parents' ability to care for their children. Unaccompanied and separated children, and those in detention experience additional challenges in accessing care. This article aims to increase awareness among health professionals caring for refugee children of the challenges faced by this group in accessing and receiving effective health care in Australia. Particular consideration is given to the issues of equity, rights of asylum seekers, communication and cultural sensitivities in health care provision, and addressing barriers to health care. The aim of the paper is to alert practitioners to the complex issues surrounding the delivery of health care to refugee children and provide realistic recommendations to guide practice.

Australia↗