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P A Bauman

Publications and source records attributed to P A Bauman.

11 recordsLinked to original sources
PubMed2006

Critical factors influencing prion inactivation by sodium hydroxide.

BACKGROUND AND OBJECTIVES: Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases caused by aberrantly folded cellular proteins (PrP(Sc); prions) that are generally resistant to conventional pathogen-inactivation techniques. To ensure effective decontamination and inactivation of prions that could be present in source material, we investigated critical factors that influence prion inactivation by NaOH. MATERIALS AND METHODS: A decrease in prion infectivity correlates with the disappearance of the protease-resistant core of PrPSc (PrPRES) observed in biochemical assays. To model prion inactivation, hamster scrapie (strain 263K) brain homogenate (SBH) was incubated for specific periods of time in 0.1 m NaOH at 4 or 18 degrees C, with or without detergent. Neutralized samples were subjected to limited digestion with proteinase K (PK) and then analysed using an endpoint dilution western blot assay and antibody 3F4. Structural changes in prions exposed to NaOH were examined using differential immunoprecipitation. RESULTS: Treatment of SBH with 0.1 m NaOH for 15 min, in the absence of detergent, at 4 and 18 degrees C caused a reduction in the PrP(RES) signal of 3.5 and 4.0 log10 units, respectively, with some residual signal remaining. The presence of the detergent sarkosyl during a 60-min incubation in NaOH further enhanced PrPRES reduction to > or = 4.5 log10 units (i.e. below the limit of detection). NaOH treatment induced conformational changes in PrP that resulted in the exposure of a hidden epitope and enabled prion immunoprecipitation by antibody 3F4. CONCLUSIONS: The use of NaOH can effectively reduce prion levels in an in vitro inactivation assay. After pretreatment of SBH with detergent, NaOH completely eliminates the PrPRES signal. Detergent may liberate lipid membrane-protected PrPSc to improve access to NaOH, which can then inactivate PrPSc by altering its structure. In cases of unidentified exposure to PrPSc during manufacturing, sanitizing procedures combining the use of detergent and NaOH may help to ensure minimal levels of contamination carryover in products.

Animals↗
PubMed1999

Masters athletes: factors affecting performance.

In recent years there has been an increase in interest in issues related to the enhancement of the performance of the masters athlete. Many of the changes in health status that have been thought to be the normal result of aging have been found to be actually the result of a long-standing sedentary lifestyle. Thus, masters athletes may be able to increase their athletic performance to higher levels than what was once thought. Decreases in muscle strength thought to be the result of aging do not appear to be so. The masters athlete may be able to maintain and increase strength in situations where strength training has not been previously engaged in. However, the literature lacks longitudinal studies demonstrating improvements in strength with age in masters athletes who have maintained habitual strength training. Studies in the past have shown that aging results in changes in fibre type, with a shift towards a higher percentage of type I fibres. This again may be an adaptation to lack of use. Decreases in heart function and aerobic capacity appear to be immutable, but in the masters athlete the rate of this decrease can be slowed. The masters athlete has certain elevated nutritional needs over younger athletes. Degenerative joint disease, although effecting most persons as they age, is not a certain result of aging and disability as the condition is reduced in the active person. Some orthopaedic conditions are related to decreases in flexibility of soft tissues that appear to accompany the aging process. Performance improvement in the masters athlete requires the same commitment to hard training that it requires from younger athletes, with some modifications for changes that are associated with aging.

Adult↗
PubMed1996

Cytokeratin expression results in a drug-resistant phenotype to six different chemotherapeutic agents.

The cytokeratin network is an abundant cytoplasmic system whose function is largely unknown. Recently, we have found that the introduction of a cytokeratin network into eukaryotic cells results in a drug resistance phenotype. The current study was undertaken to determine the universal nature of this phenomenon by investigating the survival response of two different cell lines to six different DNA-damaging agents using two different assays of cell survival. To correlate our in vitro assays of survival with known in vivo responses to DNA damage, we compared the apoptotic response of cytokeratin-positive and cytokeratin-negative cell lines. The results show that the introduction of a cytoskeletal network confers a resistant phenotype to mitoxantrone, doxorubicin, melphalan, bleomycin, and mitomycin C in the different cytokeratin-positive cell lines. No survival advantage was noted when damage was conferred by cisplatin or UV irradiation. We found the cytokeratin-positive cell lines were protected from apoptosis, while the cell lines without cytokeratins showed apoptosis in response to mitoxantrone exposure. Cytokeratin-dependent drug resistance is observed in different cell lines but is not observed with all DNA-damaging agents. The data suggest that the mechanism of this drug resistance may be attributed, in part, to a cytokeratin-conferred protection against apoptosis.

3T3 Cells↗
PubMed1994

Expression of cytokeratin confers multiple drug resistance.

The cytokeratin network is an extensive filamentous structure in the cytoplasm whose biological function(s) is unknown. Based upon previous data showing the modification of cytokeratin by mitoxantrone, we investigated the ability of cytokeratin networks to influence the survival response of cells to chemotherapeutic agents. We have compared the survival of mouse L fibroblasts lacking cytokeratins with that of L cells transfected with cytokeratins 8 and 18 in the presence of chemotherapeutic drugs. The expression of cytokeratins 8 and 18 conferred a multiple drug resistance phenotype on cells exposed to mitoxantrone, doxorubicin, methotrexate, melphalan, Colcemid, and vincristine. The degree of drug resistance was 5-454 times that of parental cells, depending upon the agent used. Drug resistance could not be attributed to altered growth characteristics, altered drug accumulation, or an altered drug efflux in the transfected cells. Cytokeratin does not confer resistance to ionizing radiation, which damages DNA independently of intracellular transport mechanisms. These data suggest a role for cytokeratin networks in conferring a drug resistance phenotype.

Animals↗
PubMed1994

Femoral neck anteversion in ballerinas.

The elite ballet dancer has greater-than-average turnout, or external rotation, in the hip. Anatomic constraints, such as the angle of version of the femoral neck, or the femoral neck anteversion (FNA) angle, may limit the amount of external rotation or turnout in the hip. The purpose of this study was to determine whether dancers who have better-than-average turnout have lower-than-average FNA angles. Fourteen elite female dancers from three major American ballet companies were studied. The FNA angles were measured in 28 hips by magnetic resonance imaging techniques. The mean FNA angle in the dancers measured 11.9 degrees (range, 4 degrees-24 degrees), and was similar to the mean FNA angle in the general population (11.4 degrees). It was concluded that the average femoral neck anteversion angle in this select group of dancers is similar to that of the general population, although none of the dancers in this study had severe femoral neck anteversion.

Adult↗
PubMed1991

Ribonuclease inhibits Ah receptor transformation in vitro.

The aryl hydrocarbon (Ah) receptor undergoes a ligand-dependent transformation to a heteromeric structure which has the ability to bind DNA sequence-specifically with high affinity. By this mechanism, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related xenobiotics modify gene expression. We observed that transformation was inhibited in vitro by the presence of ribonuclease A (RNAase) during incubation of rat hepatic cytosol with TCDD. This effect was detected as a decreased ability of the TCDD-receptor complex to bind to calf thymus DNA covalently linked to Sepharose, and to a dioxin-responsive enhancer which is upstream of the cytochrome P450IA1 structural gene. RNAase had no effect on previously transformed TCDD-receptor complexes. These observations indicated that RNAase acted during ligand binding and/or transformation of the Ah receptor. Saturation binding analyses demonstrated that RNAase decreased the receptor affinity for TCDD without changing the total number of binding sites. RNAase also inhibited transformation of the TCDD-bound, partially purified, untransformed, receptor. Thus RNAase does not interfere with ligand binding, but inhibits the subsequent transformation of the receptor monomer to the heteromeric, transcriptionally active, form.

Animals↗
PubMed1991

Prolactin-provoked alterations of cytosolic, membrane, and nuclear protein kinase C following partial hepatectomy.

The adenohypophyseal polypeptide hormone prolactin is a potent liver mitogen, stimulating cell cycle progression, an effect that appears coupled to increasing protein kinase C activity in membrane and nuclear fractions. Here, we examine whether hepatocyte proliferation, stimulated by partial hepatectomy, is associated with altered serum prolactin or protein kinase C activation. Within 5-15 min of liver resection, serum prolactin concentrations elevate significantly. Protein kinase C activity in hepatic cytosol decreases significantly, and membrane and nuclear PKC activity increase by 30 min. Hypophysectomy prior to partial hepatectomy abrogates any effect of liver resection on protein kinase C activation in the hepatic remnant. Based upon these data, it is suggested that the rapid increase in serum prolactin seen after partial hepatectomy may be linked to protein kinase C activation, which in turn stimulates the hepatic proliferative response that is essential for hepatic regeneration.

Animals↗
PubMed1987

Heterogeneity of the rat hepatic Ah receptor and evidence for transformation in vitro and in vivo.

The characteristics of the Ah receptor from rat liver were investigated following the incubation of cytosol with [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) under various conditions, and using DEAE- and DNA-Sepharose chromatography and sucrose density gradient centrifugation. These studies indicated that the Ah receptor can exist in three distinct forms in vitro that are dependent on the presence or absence of TCDD and the duration and temperature of incubation. The unoccupied receptor was distinguished by its elution from DEAE-Sepharose columns at 0.20-0.23 M NaCl and lack of affinity for DNA-Sepharose. Following the incubation of the unoccupied receptor with [3H]TCDD, two occupied forms were distinguished based on their overall surface charges and affinities for DNA. One of these forms was predominant following short incubations (2 h) with [3H]TCDD at a low temperature (0 degree C) and was characterized by having the same elution profile on DEAE-Sepharose as the unoccupied form, but demonstrated some affinity for DNA. Another occupied form was predominant following an incubation for a longer time (20 h, 0 degree C) or at an elevated temperature (2 h, 20 degrees C). This form had an overall surface charge that was less negative and a greater affinity for DNA. These changes in receptor characteristics were dependent on the presence of TCDD and were not accompanied by apparent changes in the sedimentation coefficients of the two occupied forms. Anion exchange chromatography of the [3H]TCDD-receptor complex extracted from hepatic nuclei of [3H]TCDD-treated rats indicated that the ligand-induced change of the unoccupied receptor to a less negatively charged form had occurred in vivo. These results indicated a biochemical heterogeneity of the Ah receptor and suggested the occurrence of a ligand- and temperature-dependent transformation process in vivo and in vitro.

Animals↗
PubMed1987

Obturator hip dislocation with ipsilateral fractures of the femoral head and femoral neck. A case report.

A 28-year-old female pedestrians, struck by an automobile, sustained an obturator hip dislocation with concomitant ipsilateral fractures of both the femoral head and femoral neck. This unusual hip injury seems not to have been previously reported. The femoral neck fracture was widely separated from the shaft, and unfortunately, a 6-mm deep indentation fracture involved the anterosuperior portion of the articulating surface of the femoral head. This complex injury was treated with a press-fit bipolar prosthesis.

Adult↗
PubMed1985

Metabolism of N-nitrosodi-n-propylamine and N-nitrosodiallylamine by isolated rat hepatocytes.

Isolated rat hepatocytes were incubated with approximately equimolar amounts of N-nitrosodi-n-propylamine (NDPA) and N-nitrosodiallylamine (NDAA) in order to compare their metabolism. The principal metabolite of NDPA was N-nitroso-(2-hydroxypropyl)propylamine, which was present as a glucuronide. N-Nitroso-(3-hydroxypropyl)propylamine and N-nitrosopropyl-(carboxyethyl)amine were minor metabolites; no N-nitrosomethylpropyl-amine (NMPA) was detected. A single N-nitroso metabolite of NDAA was found and identified as N-nitroso-(2,3-dihydroxypropyl)allylamine. These data indicate that the allyl group of N-nitrosodiallylamine is readily oxidized by hepatocytes in vitro. It appears unlikely that N-nitrosomethylpropylamine is an intermediate in N-nitrosodi-n-propylamine metabolism.

Animals↗