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Biomedical subjects

T Holt

Publications and source records attributed to T Holt.

35 records · Page 2Linked to original sources
PubMed1996

Fumonisins and Alternaria alternata lycopersici toxins: sphinganine analog mycotoxins induce apoptosis in monkey kidney cells.

Fusarium moniliforme toxins (fumonisins) and Alternaria alternata lycopersici (AAL) toxins are members of a new class of sphinganine analog mycotoxins that occur widely in the food chain. These mycotoxins represent a serious threat to human and animal health, inducing both cell death and neoplastic events in mammals. The mechanisms by which this family of chemical congeners induce changes in cell homeostasis were investigated in African green monkey kidney cells (CV-1) by assessing the appearance of apoptosis, cell cycle regulation, and putative components of signal transduction pathways involved in apoptosis. Structurally, these mycotoxins resemble the sphingoid bases, sphingosine and sphinganine, that are reported to play critical roles in cell communication and signal transduction. The addition of fumonisin B1 or AAL toxin, TA, to CV-1 cells induced the stereotypical hallmarks of apoptosis, including the formation of DNA ladders, compaction of nuclear DNA, and the subsequent appearance of apoptotic bodies. Neither mycotoxin induced cell death, DNA ladders, or apoptotic bodies in CV-1 cells expressing simian virus 40 large T antigen (COS-7) at toxin concentrations that readily killed CV-1 cells. Fumonisin B1 induced cell cycle arrest in the G1 phase in CV-1 cells but not in COS-7 cells. AAL toxin TA did not arrest cell cycle progression in either cell line. The induction of apoptosis combined with the widespread presence of these compounds in food crops and animal feed identifies a previously unrecognized health risk to humans and livestock. These molecules also represent a new class of natural toxicants that can be used as model compounds to further characterize the molecular and biochemical pathways leading to apoptosis.

Alternaria↗
PubMed1996

Characterization of the covalent binding of thiostrepton to a thiostrepton-induced protein from Streptomyces lividans.

Thiostrepton is a highly modified multicyclic peptide antibiotic synthesized by diverse bacteria. Although best known as an inhibitor of protein synthesis, thiostrepton is also a potent activator of gene expression in Streptomyces lividans. In these studies, we characterize the nature of the interaction between thiostrepton and two proteins that it induces, TipAL and TipAS. In the absence of added cofactors, thiostrepton formed a complex with either TipAL or TipAS in aqueous solution. The TipA-thiostrepton complex was not dissociated by denaturants such as SDS, urea, or disulfide reducing agents. The mass of the TipAS-thiostrepton complex as determined by both sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry (MS) was equivalent to the sum of TipAS and thiostrepton. Thiostrepton also reacted spontaneously with free cysteine (but not with other amino acids tested) to generate stable compounds having masses equivalent to thiostrepton plus 3 to 4 cysteines. Blocking experiments indicated that complex formation required dehydroalanine residues on thiostrepton and cysteine residues on TipAS. When the TipAS-thiostrepton complex was digested with trypsin and analyzed by MS, the thiostrepton adduct was found bound only to the unique cysteine-containing TipAS peptide fragment. Amino acid analysis confirmed that the TipAS-thiostrepton complex contained lanthionine, the product of a reaction between dehydroalanine and cysteine. Together, these data document a covalent attachment of thiostrepton to TipA proteins mediated by bond formation between dehydroalanine of thiostrepton and cysteine of TipAS. Implications regarding the function of TipAS as a thiostrepton (electrophile)-sequestering protein and thiostrepton-mediated activation of TipAL as a model of irreversible transcriptional activation are discussed.

Alanine↗
PubMed1993

Computerized tomography in the diagnosis of appendicovesical fistula.

Appendicitis and its complications are among the causes of an enterovesical fistula, with approximately 100 such cases reported. This condition is seldom diagnosed preoperatively and surgery is often delayed. We report 2 cases of an appendicovesical fistula that were diagnosed preoperatively by computerized tomography (CT). We describe a CT finding consistent with the diagnosis, namely calcification in the thickened bladder wall adjacent to the cecum on noncontrast CT, which is a fecalith in the lumen of the fistula.

Adult↗
PubMed1991

Evaluation of growth and changes in body composition following neonatal diagnosis of cystic fibrosis.

Early deficits in nutritional status that might require specific treatment and early response to nutritional therapy were studied longitudinally in 25 infants with cystic fibrosis (CF) diagnosed by neonatal screening, using anthropometric and research body composition methodology, and evaluation of pancreatic function. At the time of confirmed diagnosis (mean 5.4 weeks), body mass, length, total body fat (TBF), and total body potassium (TBK) were all significantly reduced. Following diagnosis and commencement of therapy there was a normalization of weight, length, and TBK by 6-12 months of age, indicating catch-up growth. But in some individuals the response was incomplete, and as a group, mean total body fat remained significantly lower than normal at 1 year of age. Seven of 25 (28%) were pancreatic sufficient at diagnosis, and all but one had evidence of declining pancreatic function requiring the institution of pancreatic enzyme therapy during the next 1-9 months. The median age of commencement of enzyme therapy was 10 weeks (range 5 weeks to 11 months). These longitudinal assessments emphasize the dynamic changes occurring in absorptive function, body composition, and nutritional status following neonatal diagnosis of cystic fibrosis and may reflect previously described abnormalities of energy metabolism in this age group. Abnormal body composition is evident in most CF infants following diagnosis by neonatal screening but pancreatic damage may still be evolving. We suggest that early active nutritional therapy and surveillance for changes in pancreatic function are warranted in CF infants diagnosed by neonatal screening.

Body Composition↗
PubMed1989

Histological evaluation of the effect of a miniature carbon dioxide laser on oral mucosa.

Carbon dioxide lasers emit infra-red radiation at a wavelength of 10600 nm, making them suitable for tissue vaporisation, incision and vessel coagulation. A miniature CO2 laser (length 24 cm), with an output of 4 Watts focused on to a spot of 0.2 mm diameter at a distance of 2.5 mm from the nozzle tip, has been developed. This hand-held, water-cooled device operates off a 12 V D.C. source and provides good access to most areas of the mouth. In order to evaluate the use of the miniature laser, a series of lesions were produced on the lateral margins of sheep's tongues, and histological examination of tissues carried out immediately after treatment and at 1 h; 1, 2, 4, 7, 14, 21, and 28 day intervals. Wounds showed clean cut margins with even removal of epithelium and superficial connective tissue. Damage appeared to be restricted to a 100 microns deep zone in the lamina propria. Epithelial regeneration had commenced at between 2 and 4 days, and re-covered the surface by 14 days. A residue of chronic inflammatory cells was present within the stroma at 21 days, but this had resolved by 28 days. The miniature carbon dioxide laser is effective in vaporising oral mucosa and also achieving haemostasis by vessel coagulation; its manoeuvrability and relatively low cost warrant further clinical evaluation for the treatment of mucosal lesions, such as leukoplakia.

Animals↗
PubMed1989

Vital links. Hospital's geriatric program integrates the spectrum of care.

In July 1988 St. Mary Medical Center (SMMC), Long Beach, CA, established Older Adult Services (OAS) to help the elderly of the community. At the time, SMMC was already providing a number of services for the elderly, but OAS enables it to provide a continuum of care. In addition, the medical staff committee developing the geriatric program recommended establishing a geriatric assessment team headed by a fellowship-trained geriatrician, having that geriatrician serve as medical director of the inpatient skilled nursing facility (SNF), having the geriatric team develop treatment protocols in various aspects of care, and extending OAS within the community. The categories of service within the continuum are extended care, acute care, ambulatory care, home care, outreach, wellness, and housing. SMMC does not directly provide all services; rather, through integrating mechanisms, it uses community-based services or services provided by other institutions to meet some patient needs. A key element to integrating the continuum is the involvement of OAS in the SNF. The SNF medical director can bring the expertise of the geriatric assessment team to a wide sphere of the medical community. This sphere of influence quickly spreads to the hospital's entire medical community. Through direct participation in utilization review and quality assurance in the SNF, the OAS director can influence the quality of care.

Aged↗
PubMed1988

Profound muscle weakness and hypokalemia due to clay ingestion.

We have presented the case of a 43-year-old woman with severe myositis due to clay ingestion and hypokalemia. EMG studies revealed a pattern consistent with myositis, and muscle biopsy showed a nonspecific diffuse myositis. The clay was shown to act as a potassium binder. With potassium replacement and discontinuance of clay ingestion, the symptoms and signs abated and laboratory values returned to normal.

Adult↗
PubMed1985

Efficacy of routine annual studies in the care of elderly patients.

The authors reviewed the results of annual laboratory screening (SMA 20, T3, T4, UA, EKG, chest x-ray) performed on a population of 500 institutionalized and ambulatory patients retrospectively followed from 1 to 19 years. With 30 laboratory values recorded for each annual exam, there were an average of 1.56 new abnormal laboratory findings per year per patient. A sample of 100 patients was further reviewed to determine the incidence of new diagnoses and treatment initiated by the appearance of new abnormal laboratory findings; 756 new abnormalities were recorded out of a possible 15,000, and 66 medical work-ups were initiated, which lead to new diagnoses in 21 cases and a treatment plan in 12 cases. The authors suggest that, in view of the rapid increase in the number of elderly persons and the consequent need to conserve limited health care resources, "standard" laboratory screening may not be warranted on a yearly basis in the elderly population.

Aged↗