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Biomedical subjects

J S Smith

Publications and source records attributed to J S Smith.

At least 37 records · Page 2Linked to original sources

Methionine as a methyl group donor in growing cattle.

Holstein steers were used in two 5 x 5 Latin square experiments to evaluate the sparing of methionine by alternative sources of methyl groups (betaine and choline). Steers were housed in metabolism crates and limit-fed a soybean hull-based diet high in rumen degradable protein. To increase energy supply, ruminal infusions of volatile fatty acids and abomasal infusions of glucose were provided. An amino acid mixture, limiting in methionine, was infused abomasally to ensure that nonsulfur amino acids did not limit protein synthesis. Treatments for Exp. 1 were abomasal infusion of 1) water, 2) 2 g/d L-methionine, 3) 1.7 g/d L-cysteine, 4) 1.6 g/d betaine, and 5) 1.7 g/d L-cysteine + 1.6 g/d betaine. Treatments for Exp. 2 were abomasal infusion of 1) water, 2) 2 g/d L-methionine, 3) 8 g/d betaine, 4) 16 g/d betaine, and 5) 8 g/d choline. In both experiments, nitrogen retention increased in response to methionine (P < 0.05), demonstrating a deficiency of sulfur amino acids. Responses to cysteine, betaine, and choline were all small and not significant. The lack of response to cysteine indicates that the response to methionine was not due to transsulfuration to cysteine or that cysteine supply did not alter the flux of methionine through transsulfuration. The lack of response to betaine suggests that the steers' needs for methyl groups were met by the dietary conditions or that betaine was relatively inefficient in increasing the remethylation of homocysteine to methionine and, thereby, reducing the synthesis of cysteine from homocysteine. Under our experimental conditions, responses to methionine were likely due to a correction of a deficiency of methionine per se rather than of methyl group donors.

Abomasum↗

Identification of a series of oxadiazole-substituted alpha-isopropoxy phenylpropanoic acids with activity on PPARalpha, PPARgamma, and PPARdelta.

A series of oxadiazole-substituted alpha-isopropoxy phenylpropanoic acids with dual agonist activity on PPARalpha and PPARgamma is described. Several of these compounds also showed partial agonist activity on PPARdelta. Resolution of one analogue showed that PPARalpha and PPARgamma activity resided in mainly one enantiomer, whereas PPARdelta activity was retained in both enantiomers.

Chromatography, High Pressure Liquid↗

PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme.

BACKGROUND: Survival of patients with anaplastic astrocytoma is highly variable. Prognostic markers would thus be useful to identify clinical subsets of such patients. Because specific genetic alterations have been associated with glioblastoma, we investigated whether similar genetic alterations could be detected in patients with anaplastic astrocytoma and used to identify those with particularly aggressive disease. METHODS: Tissue specimens were collected from 174 patients enrolled in Mayo Clinic Cancer Center and North Central Cancer Treatment Group clinical trials for newly diagnosed gliomas, including 63 with anaplastic astrocytoma and 111 with glioblastoma multiforme. Alterations of the EGFR, PTEN, and p53 genes and of chromosomes 7 and 10 were examined by fluorescence in situ hybridization, semiquantitative polymerase chain reaction, and DNA sequencing. All statistical tests were two-sided. RESULTS: Mutation of PTEN, amplification of EGFR, and loss of the q arm of chromosome 10 were statistically significantly less common in anaplastic astrocytoma than in glioblastoma multiforme (P =.033, P =.001, and P<.001, respectively), and mutation of p53 was statistically significantly more common (P<.001). Univariate survival analyses of patients with anaplastic astrocytoma identified PTEN (P =.002) and p53 (P =.012) mutations as statistically significantly associated with reduced and prolonged survival, respectively. Multivariate Cox analysis of patients with anaplastic astrocytoma showed that PTEN mutation remained a powerful prognostic factor after adjusting for patient age, on-study performance score, and extent of tumor resection (hazard ratio = 4.34; 95% confidence interval = 1.82 to 10.34). Multivariate classification and regression-tree analysis of all 174 patients identified EGFR amplification as an independent predictor of prolonged survival in patients with glioblastoma multiforme who were older than 60 years of age. CONCLUSION: PTEN mutation and EGFR amplification are important prognostic factors in patients with anaplastic astrocytoma and in older patients with glioblastoma multiforme, respectively.

Adolescent↗

Epidemiologic characteristics of rabies virus variants in dogs and cats in the United States, 1999.

OBJECTIVE: To evaluate epidemiologic features of rabies virus variants in dogs and cats in the United States during 1999 and assess the role of bat-associated variants. DESIGN: Epidemiologic survey. SAMPLE POPULATION: Rabies viruses from 78 dogs and 230 cats. PROCEDURE: Brain specimens from rabid dogs and cats were submitted for typing of rabies virus. Historical information, including ownership and vaccination status, was obtained for each animal. Specimens were typed by use of indirect fluorescent antibody assay or reverse transcriptase polymerase chain reaction assay and nucleotide sequence analysis. RESULTS: Nearly all animals were infected with the predicted terrestrial rabies virus variant associated with the geographic location of the submission. A bat-associated variant of rabies virus was found in a single cat from Maryland. More than half (53%) of submitted animals were classified as owned animals, and most had no known history of vaccination. One vaccination failure was reported in a dog that did not receive a booster dose of rabies vaccine after exposure to a possibly rabid animal. CONCLUSIONS AND CLINICAL RELEVANCE: Bat-associated rabies virus variants were not a common cause of rabies in dogs and cats during 1999. Vaccine failures were uncommon during the study period. Because most rabid dogs and cats were unvaccinated and were owned animals rather than strays, educational campaigns targeting owners may be useful.

Animals↗

Pho23 is associated with the Rpd3 histone deacetylase and is required for its normal function in regulation of gene expression and silencing in Saccharomyces cerevisiae.

The Rpd3 histone deacetylase (HDAC) functions in a large complex containing many proteins including Sin3 and Sap30. Previous evidence indicates that the pho23, rpd3, sin3, and sap30 mutants exhibit similar defects in PHO5 regulation. We report that pho23 mutants like rpd3, sin3, and sap30 are hypersensitive to cycloheximide and heat shock and exhibit enhanced silencing of rDNA, telomeric, and HMR loci, suggesting that these genes are functionally related. Based on these observations, we explored whether Pho23 is a component of the Rpd3 HDAC complex. Our results demonstrate that Myc-Pho23 co-immunoprecipitates with HA-Rpd3 and HA-Sap30. Furthermore, similar levels of HDAC activity were detected in immunoprecipitates of HA-Pho23, HA-Rpd3, or HA-Sap30. In contrast, HDAC activity was not detected in immunoprecipitates of HA-Pho23 or HA-Sap30 from strains lacking Rpd3, suggesting that Rpd3 is the HDAC associated with these proteins. However, HDAC activity was detected in immunoprecipitates of HA-Sap30 or HA-Rpd3 from cells lacking Pho23, although levels were significantly lower than those detected in wild-type cells, indicating that Rpd3 activity is compromised in the absence of Pho23. Together, our genetic and biochemical studies provide strong evidence that Pho23 is a component of the Rpd3 HDAC complex, and is required for the normal function of this complex.

Acid Phosphatase↗

Differential expression of kcnq2 splice variants: implications to m current function during neuronal development.

The KCNQ family of K(+) channels has been implicated in several cardiac and neurological disease pathologies. KCNQ2 (Q2) is a brain-derived gene, which in association with KCNQ3 (Q3) has been shown to provide a molecular basis for the neuronal M current. We have cloned a long (Q2L) and a short (Q2S) splice variant of the human KCNQ2 gene; these variants differ in their C-terminal tail. Northern blot analysis reveals that Q2L is preferentially expressed in differentiated neurons, whereas the Q2S transcript is prominent in fetal brain, undifferentiated neuroblastoma cells, and brain tumors. Q2L, transfected into mammalian cells, produces a slowly activating, noninactivating voltage-gated K(+) current that is blocked potently by tetraethylammonium (TEA; IC(50), 0.14 mm). Q2S on the other hand produces no measurable potassium currents. Cotransfection of Q2S with either Q2L, Q3, or Q2L/Q3 heteromultimers results in attenuation of K(+) current, the suppression being most profound for Q3. Inclusion of Q2S in the heteromultimer also positively shifts the voltage dependence of current activation and alters affinity for the TEA block, suggesting that under these conditions, some Q2S subunits incorporate into functional channels on the plasma membrane. In view of the crucial role of M currents in modulating neuronal excitability, our findings provide important insight into the functional consequences of differential expression of KCNQ2 splice variants: dampened potassium conductances in the developing brain could shape firing repertoires to provide cues for proliferation rather than differentiation.

Alternative Splicing↗

Strategic management simulations is a novel way to measure resident competencies.

BACKGROUND: The Strategic Management Simulation (SMS) has been used extensively to test and train higher cognitive functions in persons who occupy professional and leadership positions (i.e., skills like those needed by a surgeon). METHODS: The SMS was used to predict surgical residents' competency in decision making. Skills required for integrative surgical decision making including critical thinking, crisis management, flexibility, factual knowledge, and team building were assessed. Surgical residents with at least 2 years of experience participated. In additional, attending faculty familiar with the residents' work evaluated each resident with a standard comprehensive rating scale. Simulation performance on multiple measures was compared with faculty ratings. RESULTS: A number of measures obtained on simulation performance (eg, activity level, response speed, initiative, adequate usage of and appropriate search for relevant information) generated high correlations with comprehensive faculty assessment (eg, measures of crisis management, team interactions, flexibility of approach). CONCLUSION: The simulation technique is able to accurately assess performance of surgical residents (on a number of parameters) in a relatively brief time period. Simulation data were highly similar to faculty ratings that were based on at least 2 years of experience with the resident.

Clinical Competence↗

Limits of body mass index to detect obesity and predict body composition.

Body mass index (BMI) is commonly used to identify obesity. In this study, we determined how accurately BMI could determine body composition and identify obese from non-obese individuals. Fat-free mass and body fat were determined with bioelectrical impedance. Adiposity was calculated as body fat per body mass and as body fat divided by body height (m2). Obesity was defined as a BMI of at least 30 kg/m2 or an amount of body fat of at least 25% of total body mass for men and at least 30% for women. Obesity as defined by percentage of body fat was always present with a BMI of at least 30 kg/m2. However, 30% of men and 46% of women with a BMI below 30 kg/m2 had obesity levels of body fat. The greatest variability in the prediction of percentage of body fat and body fat divided by height (m2) from regression equations using BMI was at a BMI below 30 kg/m2. In conclusion, using impedance-derived body-fat mass as the criterion, people with BMI of at least 30 kg/m2 are obese. However, significant numbers of people with a BMI below 30 kg/m2 are also obese and thus misclassified by BMI. Percent of body fat and body fat divided by height (m2) are predictable from BMI, but the accuracy of the prediction is lowest when the BMI is below 30 kg/m2. Therefore, measurement of body fat is a more appropriate way to assess obesity in people with a BMI below 30 kg/m2.

Adipose Tissue↗

Schizophrenia-like psychosis following traumatic brain injury: a chart-based descriptive and case-control study.

BACKGROUND: Head injury has been reported to increase the likelihood of the development of schizophrenia-like psychosis (SLP), but its features and risk factors have been insufficiently investigated. METHOD: Between 1987 and 1997, we examined 45 referred patients with SLP following brain trauma. These subjects were matched with 45 head-injured subjects without SLP on age (current and at injury) and gender, and their case records reviewed systematically. The groups were compared and logistic regression analyses performed. RESULTS: The psychoses had a mean age of onset of 26.3 years, a mean latency of 54.7 months after head injury, usually a gradual onset and a subacute or chronic course. Prodromal symptoms were common and depression often present at onset. Paranoid delusions and auditory hallucinations were the predominant features, with formal thought disorder, catatonic features and negative symptoms being uncommon. The SLP group had more widespread brain damage on neuroimaging, especially in the left temporal and right parietal regions, and were more impaired cognitively. Fewer (non-significantly) SLP subjects had epilepsy which was more likely to be well-controlled in this group. On regression analysis, a positive family history of psychosis and duration of loss of consciousness were the best predictors of SLP. CONCLUSIONS: Head injury-related psychosis is usually paranoid-hallucinatory and subacute or chronic in its presentation. A genetic predisposition to schizophrenia and severity of injury with significant brain damage and cognitive impairment may be vulnerability factors.

Adolescent↗

Losses of chromosomal arms 1p and 19q in the diagnosis of oligodendroglioma. A study of paraffin-embedded sections.

Comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), polymerase chain reaction-based microsatellite analysis, and p53 sequencing were performed in paraffin-embedded material from 18 oligodendrogliomas and histologically similar astrocytomas. The study was undertaken because of evidence that concurrent loss of both the 1p and 19q chromosome arms is a specific marker for oligodendrogliomas. Of the six lesions with a review diagnosis of oligodendroglioma, all had the predicted loss of 1p and 19q seen by CGH, FISH, and polymerase chain reaction. Other lesions, including some considered oligodendroglioma or mixed glioma by the submitting institution, did not. There were no p53 mutations in any of the six oligodendrogliomas, whereas 5 of the 10 remaining, successfully studied cases did have p53 mutations. The results suggest that CGH and FISH performed on current or archival tissue can aid in classification of infiltrating gliomas such as oligodendrogliomas and astrocytomas. The results of the p53 studies are consistent with findings of previous investigations that such mutations are less common in oligodendrogliomas than they are in astrocytomas.

Adult↗

Bilateral orbitomedial leucotomy for obsessive-compulsive disorder: a single-case study using positron emission tomography.

OBJECTIVE: The objective of this report is to correlate the clinical outcome of neurosurgery for obsessive-compulsive disorder (OCD) with regional cerebral glucose metabolic changes. CLINICAL PICTURE: The patient was a 37-year-old female patient with severe and intractable OCD. TREATMENT: The patient was treated with bilateral stereotactic lesions in the frontal white matter superior to the orbito-medial cortex. OUTCOME: She had a remarkable improvement in her obsessive-compulsive symptoms, which was sustained up to 3 years of follow up. A positron emission tomography (PET) scan performed 18 days after surgery demonstrated an obvious reduction of metabolism in the caudate head, anterior cingulate and orbital, medial and lateral prefrontal cortices and the thalamus. At 1 year postsurgery, metabolic rate was still reduced in the anterior cingulate gyrus, caudate and thalamus compared with preoperative baseline. The patient demonstrated no long-term cognitive effects of the surgery. CONCLUSIONS: This case supports some of the cortical-subcortical circuit dysfunction models of OCD and argues for the further evaluation of neurosurgery for the treatment of a severe and intractable disorder.

Adult↗

Use of a human patient simulator in the development of resident trauma management skills.

BACKGROUND: Computerized human patient simulators (HPSs) have been used to improve diagnostic and therapeutic decision making. The goal of this study was to investigate the impact of HPSs and Advanced Trauma Life Support (ATLS) on the development of trauma management skills and self-confidence in surgical interns. METHODS: Three teams of interns completed two ATLS-like trauma scenarios on the HPS (pre-ATLS). They then took the ATLS provider course. After ATLS, the interns were evaluated on two different HPS trauma scenarios (post-ATLS). Two teams of senior residents, experienced in trauma care, completed the same HPS scenarios and were used as controls. Trauma management skills were scored in three areas--critical treatment decisions, potential for adverse outcomes, and team behavior--by staff trauma surgeons. After participating in the HPS trauma scenarios, the interns completed self-confidence questionnaires and a course evaluation survey. RESULTS: Trauma management skill scores increased 23% in critical treatment decisions, 25% in potential for adverse outcomes, and 47% in team behavior after ATLS/HPS (p < 0.002). Senior residents' performance on HPS trauma scenarios was better than the interns (p < 0.05) in all three areas evaluated. The interns' self-confidence scores rose significantly after the course. (p < 0.01) The HPS course evaluation survey averaged 8.3 out of a maximum 10. CONCLUSION: Use of HPSs in conjunction with ATLS appears to enhance the development of trauma management skills. The surgical interns participating in the study deemed the HPS to be a worthwhile experience and a confidence-building tool. In particular, trauma team behavior improved significantly after ATLS/HPS.

Clinical Competence↗

Prevalence and risk factors for herpes simplex virus type 2 infection among middle-age women in Brazil and the Philippines.

BACKGROUND: Data comparing type-specific herpes simplex virus type 2 (HSV-2) seroprevalence and risk factors between comparable populations are largely unavailable, particularly from less-developed countries. GOAL: To examine the seroprevalence of HSV-2 infection and the risk factors for this infection among women in São Paulo, Brazil, and Manila, the Philippines. STUDY DESIGN: Altogether, 552 middle-aged women participating as control subjects in two cervical cancer studies were screened for type-specific HSV-2 antibodies. RESULTS: Herpes simplex virus type 2 seroprevalence was higher in Brazil (42%) than in the Philippines (9.2%). The mean ages of Brazilian (n = 181) and Filipino (n = 371) women were 52.4 and 46.6 years, respectively. Brazilian participants had more lifetime sexual partners, less education, and more often a husband with other sexual partners than Filipino women. Herpes simplex virus type 2 was independently associated with younger age at first intercourse in both countries. More than one lifetime sexual partner, a husband with other sexual partners, urban/semi-urban residence, and no history of condom use were HSV-2 risk factors in Brazil, but not in the Philippines, where long-term hormonal contraceptive use was associated with increased risk. CONCLUSIONS: The higher HSV-2 seroprevalence in Brazil than in the Philippines may be explained largely by differences in the sexual behavior of women and their husbands. Herpes simplex virus type 2 seroprevalence data may be used as a marker of past sexual behavior for the direct comparison of different population groups.

Antibodies, Viral↗

High prevalence of antibodies to herpes simplex virus type 2 among middle-aged women in Mexico City, Mexico: a population-based study.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) is among the most prevalent sexually transmitted diseases worldwide. In Mexico there is a lack of population-based HSV-2 surveys. GOALS: To determine population-based HSV-2 seroprevalence and risk factors among women in Mexico City. STUDY DESIGN: A random sample of 730 women was identified among the residents of Mexico City. Women ages 25 to 85 years were selected from 3,694 households. Western blot serology testing was conducted on serum samples to determine HSV-2 type-specific serostatus. A structured questionnaire was administered, and multivariate analyses were performed to identify risk factors for HSV-2 seropositivity, which were stratified into two age categories: younger than 50 years of age and 50 years of age or older. RESULTS: The HSV-2 seroprevalence among female participants was 29.8%, with a significant trend of increasing HSV-2 prevalence for each higher level of age (P < 0.001). Female participants had a median age of 46 years and were predominantly monogamous (82.6%). The overall population-based seroprevalence estimated in Mexico City among women was 35.8%. The independent risk factors for HSV-2 seropositivity included a history of two or more sexual partners (odds ratio [OR], 2.2; 95% CI, 1.4-3.4), two or more sexual partners before first pregnancy (OR, 2.3; 95% CI, 1.4-3.7), cohabitation with partner (OR, 2.5; 95% CI, 1.3-4.7), and current vaginal douching (OR, 1.7; 95% CI, 1.2-2.6). CONCLUSIONS: Population-based HSV-2 seroprevalence is endemically high among middle-age women in Mexico City, and clearly is correlated with higher-risk sexual behavior. This elevated HSV-2 seroprevalence may reflect unrecognized HSV-2 transmission throughout life.

Adolescent↗

Genetic alterations and chemotherapeutic response in human diffuse gliomas.

Although for many years adjuvant chemotherapy has been used in the management of human diffuse gliomas, the survival of a large proportion of patients with these tumors has remained unchanged. To date, little is known about the factors that render some of these patients resistant to cytotoxic drugs. Since response to chemotherapy has been heterogeneous irrespective of glioma type, it has been proposed that some genetic alterations associated with glioma formation and progression may be responsible for the variations in the sensitivity of these tumors to adjuvant chemotherapy. In this paper, we review the literature and discuss the usefulness of some of the common genetic alterations in predicting chemotherapeutic response in gliomas.

Antineoplastic Agents↗