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Biomedical subjects

M M Smith

Publications and source records attributed to M M Smith.

At least 37 records · Page 2Linked to original sources
PubMed2000

Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes.

Phosphorylation of histone H3 at serine 10 occurs during mitosis and meiosis in a wide range of eukaryotes and has been shown to be required for proper chromosome transmission in Tetrahymena. Here we report that Ipl1/aurora kinase and its genetically interacting phosphatase, Glc7/PP1, are responsible for the balance of H3 phosphorylation during mitosis in Saccharomyces cerevisiae and Caenorhabditis elegans. In these models, both enzymes are required for H3 phosphorylation and chromosome segregation, although a causal link between the two processes has not been demonstrated. Deregulation of human aurora kinases has been implicated in oncogenesis as a consequence of chromosome missegregation. Our findings reveal an enzyme system that regulates chromosome dynamics and controls histone phosphorylation that is conserved among diverse eukaryotes.

Animals↗
PubMed2000

Nodulisporic acid opens insect glutamate-gated chloride channels: identification of a new high affinity modulator.

Nodulisporic acid (NA) is an indole diterpene fungal product with insecticidal activity. NA activates a glutamate-gated chloride channel (GluCl) in grasshopper neurons and potentiates channel opening by glutamate. The endectocide ivermectin (IVM) induces a similar, but larger current than NA. Using Drosophila melanogaster head membranes, a high affinity binding site for NA was identified. Equilibrium binding studies show that an amide analogue, N-(2-hydroxyethyl-2,2-(3)H)nodulisporamide ([(3)H]NAmide), binds to a single population of sites in head membranes with a K(D) of 12 pM and a B(max) of 1.4 pmol/mg of protein. A similar K(D) is determined from the kinetics of ligand binding and dissociation. Four lines of evidence indicate that the binding site is a GluCl. First, NA potentiates opening of a glutamate-gated chloride current in grasshopper neurons. Second, glutamate inhibits the binding of [(3)H]NAmide by increasing the rate of dissociation 3-fold. Third, IVM potently inhibits the binding of [(3)H]NAmide and IVM binds to GluCls. Finally, the binding of [(3)H]IVM is inhibited by NA. The B(max) of [(3)H]IVM is twice that of [(3)H]NAmide, and about half of the [(3)H]IVM binding sites are inhibited by NA with high affinity (K(I) = 25 pM). In contrast, [(3)H]IVM binding to Caenorhabditis elegans membranes is not inhibited by NA at 100 nM, and there are no high affinity binding sites for NA on these membranes. Thus, half of the Drosophila IVM receptors and all of the NA receptors are associated with GluCl. NA distinguishes between nematode and insect GluCls and identifies subpopulations of IVM binding sites.

Amides↗
PubMed2000

The genetics of ivermectin resistance in Caenorhabditis elegans.

The ability of organisms to evolve resistance threatens the effectiveness of every antibiotic drug. We show that in the nematode Caenorhabditis elegans, simultaneous mutation of three genes, avr-14, avr-15, and glc-1, encoding glutamate-gated chloride channel (GluCl) alpha-type subunits confers high-level resistance to the antiparasitic drug ivermectin. In contrast, mutating any two channel genes confers modest or no resistance. We propose a model in which ivermectin sensitivity in C. elegans is mediated by genes affecting parallel genetic pathways defined by the family of GluCl genes. The sensitivity of these pathways is further modulated by unc-7, unc-9, and the Dyf (dye filling defective) genes, which alter the structure of the nervous system. Our results suggest that the evolution of drug resistance can be slowed by targeting antibiotic drugs to several members of a multigene family.

Animals↗
PubMed2000

Oronasal fistula repair.

Oronasal fistula is a relatively common complication associated with maxillary canine tooth extraction, problematic healing of maxillectomy, and repair of secondary cleft palate in small animals. Regardless of the clinical scenario associated with oronasal fistula, therapy requires surgical treatment. Principles for surgical repair of oronasal fistula include development of mucosal flaps with excellent vascular supply to transpose over the defect to restore continuity of the nasal and oral cavities. The specific surgical technique may vary but includes either single or double mucosal flaps. Oronasal fistula refractory to multiple attempts at surgical repair may be obturated by using a prosthodontic device.

Animals↗
PubMed2000

Exclusive breast-feeding: does it have the potential to reduce breast-feeding transmission of HIV-1?

Exclusive breast-feeding is unambiguously the optimal infant feeding practice and is universally promoted in the absence of human immunodeficiency virus (HIV-1). It is associated with reduced morbidity and mortality from diarrheal and respiratory diseases. Recent findings suggest that exclusive breast-feeding may pose less risk of HIV-1 transmission than the more common practice of mixed feeding (i.e., breast-feeding concurrent with the feeding of water, other fluids, and foods), which has important infant feeding policy implications for low-resource settings. This paper reviews the biologic mechanisms associated with exclusive breast-feeding that provide protection against gastrointestinal, respiratory, and atopic diseases, and evaluates the relevance of these mechanisms for HIV-1 transmission. Potential mechanisms include reduction in dietary antigens and enteric pathogens that may maintain integrity of the intestinal mucosal barrier and limit inflammatory responses of the gut mucosa; promotion of beneficial intestinal microflora that may increase resistance to infection and modulate the infant's immune response; alteration in specific antiviral or anti-inflammatory factors in human milk that may modulate maternal hormonal or immunologic status; and maintenance of mammary epithelial integrity that may reduce viral load in breast milk.

Breast Feeding↗
PubMed2000

Histone-histone interactions and centromere function.

Cse4p is a structural component of the core centromere of Saccharomyces cerevisiae and is a member of the conserved CENP-A family of specialized histone H3 variants. The histone H4 allele hhf1-20 confers defects in core centromere chromatin structure and mitotic chromosome transmission. We have proposed that Cse4p and histone H4 interact through their respective histone fold domains to assemble a nucleosome-like structure at centromeric DNA. To test this model, we targeted random mutations to the Cse4p histone fold domain and isolated three temperature-sensitive cse4 alleles in an unbiased genetic screen. Two of the cse4 alleles contain mutations at the Cse4p-H4 interface. One of these requires two widely separated mutations demonstrating long-range cooperative interactions in the structure. The third cse4 allele is mutated at its helix 2-helix 3 interface, a region required for homotypic H3 fold dimerization. Overexpression of wild-type Cse4p and histone H4 confer reciprocal allele-specific suppression of cse4 and hhf1 mutations, providing strong evidence for Cse4p-H4 protein interaction. Overexpression of histone H3 is dosage lethal in cse4 mutants, suggesting that histone H3 competes with Cse4p for histone H4 binding. However, the relative resistance of the Cse4p-H4 pathway to H3 interference argues that centromere chromatin assembly must be highly regulated.

Centromere↗
PubMed2000

Arsenic-induced skin lesions among Atacameño people in Northern Chile despite good nutrition and centuries of exposure.

It has been suggested that the indigenous Atacameño people in Northern Chile might be protected from the health effects of arsenic in drinking water because of many centuries of exposure. Here we report on the first intensive investigation of arsenic-induced skin lesions in this population. We selected 11 families (44 participants) from the village of Chiu Chiu, which is supplied with water containing between 750 and 800 microg/L inorganic arsenic. For comparison, 8 families (31 participants) were also selected from a village where the water contains approximately 10 microg/L inorganic arsenic. After being transported to the nearest city for blind assessment, participants were examined by four physicians with experience in studying arsenic-induced lesions. Four of the six men from the exposed village, who had been drinking the contaminated water for more than 20 years, were diagnosed with skin lesions due to arsenic, but none of the women had definite lesions. A 13-year-old girl had definite skin pigmentation changes due to arsenic, and a 19-year-old boy had both pigmentation changes and keratoses on the palms of his hands and the soles of his feet. Family interviews identified a wide range of fruits and vegetables consumed daily by the affected participants, as well as the weekly intake of red meat and chicken. However, the prevalence of skin lesions among men and children in the small population studied was similar to that reported with corresponding arsenic drinking water concentrations in both Taiwan and West Bengal, India--populations in which extensive malnutrition has been thought to increase susceptibility.

Adolescent↗
PubMed2000

Cell block cytology. Improved preparation and its efficacy in diagnostic cytology.

Cell blocks prepared from residual tissue fluids and fine-needle aspirations can be useful adjuncts to smears for establishing a more definitive cytopathologic diagnosis. They can be particularly useful for categorization of tumors that otherwise may not be possible from smears themselves. A modified cell block technique using an improvised ethanol formalin fixative (Nathan alcohol formalin substitute) followed by a simple paraffin processing schedule is described. This improved preparation offers excellent cytomorphologic features corresponding closely to cells in Papanicolaou-stained smears and ensures optimal preservation of histochemical and immunocytochemical properties. The technique is simple and reproducible and uses routine safe laboratory chemicals. The efficacy of cell blocks also is discussed.

Biopsy, Needle↗
PubMed2000

Neurosyphilis as a cause of facial and vestibulocochlear nerve dysfunction: MR imaging features.

The prevalence of syphilis increased for several decades before the mid-1990s in the United States, particularly in the southern states. We report a case of neurosyphilis causing bilateral facial and vestibulocochlear nerve dysfunction in which the diagnosis was not initially suspected based on the patient's demographics and history. The MR imaging features helped to make the diagnosis in this case and to exclude other possible causes of multiple cranial nerve dysfunction in this patient. Hearing loss associated with neurosyphilis is one of the few treatable forms of progressive hearing loss, and it is essential that a diagnosis of neurosyphilis be made expeditiously.

Facial Nerve↗
PubMed1999

Microendoscopic approach to far-lateral lumbar disc herniation.

The purpose of this study was to determine the feasibility of performing far-lateral lumbar discectomy by using the microendoscopic discectomy (MED) technique. The authors studied 11 consecutive patients with unilateral, single-level radiculopathy secondary to far-lateral disc herniation. There were eight men and three women, with an average age of 43 years. In all patients magnetic resonance imaging and/or computerized tomography scanning documented far-lateral disc herniations. Six patients experienced motor deficits, nine patients sensory abnormalities, and five depressed reflexes. All patients complained of radicular pain, which failed to improve with conservative care. After induction of epidural anesthesia, single-level, unilateral percutaneous discectomies were performed using the MED technique. Five discectomies were performed at L3-4 and six at L4-5. There were four contained and seven sequestered disc herniations. All surgeries were performed on an outpatient basis. Follow up ranged from for 12 to 27 months. Improvement was shown in all patients postoperatively. Using modified Macnab criteria to assess results of surgery, there were 10 excellent results and one good result. None of the patients experienced residual motor deficits, four had residual decreased sensation, and one still had some degree of nonradicular pain. There were no complications. Although various open techniques exist for the treatment of far-lateral disc herniation, MED is unique in that far-lateral pathological entities can be directly visualized and removed via a 15-mm paramedian incision. The percutaneous approach avoids larger, potentially denervating and destabilizing procedures. The need for general anesthesia can be avoided, and surgery is performed on an outpatient basis, thereby reducing hospital cost and length of stay.

Journal Article↗
PubMed1999

Development of internal controls for probe-based nucleic acid diagnostic assays.

A method is described for the design, evaluation, and application of internal control targets and probes for use in probe-based nucleic acid diagnostic assays (i.e., PCR-ELISA). The technique is a modified version of oligonucleotide-directed mutagenesis in conjunction with PCR amplification to develop a novel probe-annealing sequence in a cloned IS1111a gene fragment of Coxiella burnetii. The internal control probe-recognition site with its complementary probe was identical to the wild-type-specific probe in length, base composition, location, and annealing temperature. Neither the internal control nor the wild-type probes annealed to the recognition sequence of the other. As both of the amplified nucleic acid fragments, internal control and wild type, were identical in length and base composition, the amplification conditions for the diagnostic assay were not affected. This allowed small copy numbers of the internal control clone to be loaded into a diagnostic assay without negatively affecting it. In a single reaction we were able to differentiate between an assay reporting a true or false-negative signal. A negative signal is defined as the absence of detectable pathogen genetic material (true) or inhibition/failure of the reaction (false).

Base Sequence↗
PubMed1999

Put prevention into practice. Evaluation of program initiation in nine Texas clinical sites.

INTRODUCTION: Put Prevention Into Practice (PPIP) is a program designed to improve the delivery of clinical preventive services by primary care providers, through the use of specific office materials for providers and clinic staff, as well as an educational booklet for patients. The purpose of this study was to identify potential predictors of successful initiation of PPIP among 9 Texas public health clinics participating in a demonstration project funded by the Texas Department of Health (TDH). METHODS: The PRECEDE model was utilized as a theoretical framework for the study. A qualitative, case study methodology was employed, with structured interviews and open-ended questions asked of each site's PPIP personnel. Information from the sites' report to the TDH on the number of charts containing PPIP forms was also used for purposes of data triangulation. RESULTS: Sites that initiated PPIP successfully were characterized by a medium patient load, the ability to serve low-resource populations, prior attempts to implement categorical programs, existence of a philosophy of prevention, and pre-implementation planning. Barriers to successful initiation were identified as systems-related, patient-related, and staff-related. CONCLUSIONS: We identified factors that might predict the successful initiation of PPIP in public health primary care settings. Implications of present findings for implementation of similar health promotion programs in clinical settings are discussed.

Attitude of Health Personnel↗
PubMed1999

Psychosocial profile of pregnant adolescents in a large Australian regional area.

A psychosocial profile was developed of 122 pregnant adolescents attending a public hospital antenatal clinic in a large regional Australian area. Participants completed the Rosenberg Self-Esteem Scale and the Support Behaviours Inventory and were interviewed to obtain psychosocial and demographic information. Results revealed that those who were most likely to have either or a combination of poor self-esteem, lack of social support, be unemployed or smoke, were more likely to be living alone or with friends, not have a partner or have a partner for a shorter period, have a partner who was older, have previous children, have not planned their pregnancy and have less education. The degree of social support was significantly associated with self-esteem. Over half of the sample smoked, and over half were unemployed. These results underscore the importance of addressing psychosocial factors in the implementation of care for the pregnant adolescent.

Adolescent↗
PubMed1999

Nonsquamous cell neoplasms of the adult head and neck.

The purpose of the article is to describe the magnetic resonance imaging characteristics of the most frequently encountered nonsquamous neoplasms of the adult head and neck. The lesions are divided into those arising from the parapharyngeal or carotid spaces, salivary gland neoplasms, neoplasms of the thyroid and parathyroid glands, mesenchymal neoplasms, and lymphoreticular neoplasms. When appropriate, correlative features of other imaging modalities are included in the discussion. Although magnetic resonance imaging can provide critical information in the evaluation of patients with these neck masses, the imaging features of many of the lesions may be nonspecific and complementary data must be obtained from other modalities or biopsy may be necessary.

Adult↗
PubMed1999

Chart documentation of clinical preventive services at 9 Texas clinics.

Documentation of clinical preventive services at 9 Texas family practice residency programs, community health centers, and public health regional clinics was examined. Assessment of 11 risks, counseling on those risks, and timeliness of 8 screening tests and immunizations were abstracted. Documentation of clinicians' risk assessment focused on tobacco use (56.4%), alcohol/drug abuse (45.8%), and excess weight (21.6%). Counseling was documented most often for nutrition (20.5%), family planning (11.6%), and physical activity (10.3%). Of the sites studied, public health regional clinics had the highest documentation of assessment and counseling. Community health centers were most up-to-date for diabetes and cholesterol screening. Family practice residencies documented the highest rate of counseling for obesity risk. Clinicians do not document risk assessment, counseling, or up-to-date screening tests and immunizations for most of their adult patients. Texas practitioners may need support or assistance to provide universal access to clinical preventive services.

Adult↗
PubMed1998

Cse4p is a component of the core centromere of Saccharomyces cerevisiae.

Histones are fundamental structural components of chromatin and are expected to play important roles in chromosome dynamics. Here, we present direct evidence that Cse4p, a histone H3 variant, is a structural component of the core centromere of S. cerevisiae. In histone H4 and Cse4p mutants, the core centromere chromatin structure is disrupted at restrictive temperature. Overexpression of Cse4p suppresses this defect in the H4 mutant, implying that the two proteins act together in centromere structure. We show by chromatin immunoprecipitation experiments that Cse4p is specifically cross-linked to centromeric DNA. Furthermore, by immunofluorescence microscopy, Cse4p is found in discrete foci consistent with that expected for centromeres. These results suggest the kinetochore is assembled on a specialized centromeric nucleosome containing Cse4p.

Centromere↗
PubMed1998

Genetic dissection of histone function.

Mutational analysis is an essential tool for understanding the functions of genes within a living organism. The budding yeast Saccharomyces cerevisiae provides an excellent model system for dissecting the genetics of histone function at the molecular and cellular levels. A simple gene organization, plus a wide variety of genetic strategies, makes it possible to directly manipulate a specific histone gene in vitro and then examine the expression of mutant alleles in vivo. Recent methods for manipulating the yeast histone genes have been designed to facilitate both side-directed analysis of structure/function relationships and unbiased screens targeted at specific functional pathways. The conservation of histone and nucleosome structure throughout evolution means that the principles discovered through genetic studies in yeast will be broadly applicable to the chromatin of more complex eukaryotes.

Cell Cycle↗