Biomedical subjects

L A Jones

Publications and source records attributed to L A Jones.

At least 55 records · Page 3Linked to original sources

PubMed1999

p53 mutations and expression in ovarian cancers: correlation with overall survival.

The p53 gene is altered in approximately 50% of all human malignancies. p53 overexpression, identified by immunohistochemistry, and p53 mutations, identified by single-strand conformational polymorphism (SSCP) and DNA sequencing, have been described in ovarian cancers. p53 overexpression has been correlated with poor outcome for women with ovarian cancer in some studies. With only limited data, the assumption has been made that p53 overexpression corresponds to p53 mutations. The purpose of this investigation was to assess p53 alterations in ovarian cancer to determine if p53 overexpression corresponds with mutations in the p53 gene, and to assess whether either predicts clinical outcome in ovarian carcinoma. Frozen ovarian carcinoma tumor specimens from 105 patients were analyzed by immunohistochemical staining for p53 expression. SSCP was used to screen for mutations and DNA sequencing was used to confirm the specific mutation in exons 2 to 11, encompassing the entire p53 open reading frame. Those ovarian carcinomas identified as wild-type p53 by SSCP were subjected to automated DNA sequence analysis of the entire open reading frame. Relative to DNA sequence analysis, the sensitivity of SSCP was 85% and the specificity was 98%. Immunohistochemical staining demonstrated that 72 of the 105 (69%) cases had positive immunostaining. SSCP and DNA sequencing identified and confirmed mutations in 60 of the 105 carcinomas (57%). Although there was a statistically significant association between p53 immunostaining and p53 mutations (p = 0.0002), false-negative and -positive results were identified. Tumor grade (p = 0.03), stage (p = 0.08), and overall survival (p = 0.15) were moderately associated with positive p53 immunostaining. Patients with p53 mutations and overexpression had shorter overall patient survival (p = 0.02). The findings demonstrated that, individually, p53 mutations and p53 overexpression were each related to shorter patient survival, but the strongest predictor of outcome was a combination of both mutations and overexpression. Comparisons of overall survival for women with mutations in loop 2, loop 3, and the loop-sheet-helix domains together showed a statistically significant difference in survival compared to survival of women whose ovarian cancers had other mutations (p = 0.046).

Adult↗

PubMed1999

Symptoms of ocular irritation in patients diagnosed with dry eye.

PURPOSE: The purpose of this study was to develop a pilot survey to evaluate ocular irritation symptom frequency, severity, and impact on daily activity in patients previously diagnosed with dry eye. METHODS: Forty-five patients previously diagnosed with dry eye (ICD-9 code 375.15) completed the 17-item symptom survey. Analog-scale response questions concerning the frequency, severity, and effect on daily activity were asked for the following symptoms: dryness, scratchiness and soreness, burning and stinging, light sensitivity, blurry vision, and ocular itching. RESULTS: Dryness and soreness were the most frequently reported symptoms of ocular irritation. Although the occurrence of symptoms of ocular irritation was reported as frequent by patients diagnosed with dry eye, the symptoms had minimal to moderate impact on daily activity. CONCLUSIONS: Patient expression of the symptoms of dryness and soreness at more frequent and/or more severe levels may lend more validity to a diagnosis of dry eye.

Activities of Daily Living↗

PubMed1999

Repeated delivery of adeno-associated virus vectors to the rabbit airway.

Efficient local expression from recombinant adeno-associated virus (rAAV)-cystic fibrosis (CF) transmembrane conductance regulator (CFTR) vectors has been observed in the airways of rabbits and monkeys for up to 6 months following a single bronchoscopic delivery. However, it is likely that repeated administrations of rAAV vectors will be necessary for sustained correction of the CF defect in the airways. The current study was designed to test the feasibility of repeated airway delivery of rAAV vectors in the rabbit lung. After two doses of rAAV-CFTR to the airways, rabbits generated high titers of serum anti-AAV neutralizing antibodies. Rabbits then received a third dose of a rAAV vector containing the green fluorescent protein (GFP) reporter gene packaged in either AAV serotype 2 (AAV2) or serotype 3 (AAV3) capsids. Each dose consisted of 1 ml containing 5 x 10(9) DNase-resistant particles of rAAV vector, having no detectable replication-competent AAV or adenovirus. Three weeks later, GFP expression was observed in airway epithelial cells despite high anti-AAV neutralizing titers at the time of delivery. There was no significant difference in the efficiency of DNA transfer or expression between the rAAV3 and rAAV2 groups. No significant inflammatory responses to either repeated airway exposure to rAAV2-CFTR vectors or to GFP expression were observed. These experiments demonstrate that serum anti-AAV neutralizing antibody titers do not predict airway neutralization in vivo and that repeated airway delivery rAAV allows for safe and effective gene transfer.

Animals↗

PubMed1999

Therapeutic potential of dendritic-based vaccines.

Involving a delicate balance of cell types, the interaction between the immune system and disease or abnormality in the human body is complex. Moreover, the mere presence of antigen and immune cells is necessary, yet insufficient to elicit immune reactivity. In order to elicit an immune response, an antigen in some form must be processed and presented to the immune system. Arguably, the most efficient antigen-presenting cell, the dendritic cell (DC), is the centre of intense investigation. The elicitation or cessation of an immune response is not a simple matter. The body must be able either to up-regulate (e.g., in the case of infectious disease) or down-regulate (e.g., in the case of transplantation) immunity to antigens located anywhere in the body. This sentinel role is capably filled via the distribution of Langerhans cells in the epidermis of the skin, and the migration of DCs throughout the lymphatic and circulatory systems. DCs are potent, as well as efficient: small numbers of cells and low levels of antigen still induce clinically relevant immunity. Lastly, they are capable of tolerance induction to self components by helping to delete self-reactive thymocytes and generating anergy in committed T-cells. Since DCs both initiate and modulate immunity, they are a component of a vast array of vaccines. This review highlights some of the intriguing basic research involving the development of DC-based therapeutics. Furthermore, whenever an area of study has progressed to human treatment, recent and on-going clinical trials are discussed.

Journal Article↗

PubMed1999

Are there critical bands in kinesthesia?

The effect of changing the bandwidth of noise on the ability of human subjects to detect a 10-Hz sinusoidal movement signal was measured in two experiments. The objective of these studies was to investigate whether critical bands exist for the kinesthetic system, as has been demonstrated for the auditory and tactile systems. It was found that subjects' ability to detect a 10-Hz sinusoidal movement stimulus embedded in noise was not influenced by the bandwidth of the noise over a range of 4-10 Hz. These findings suggest that, if a critical filter does exist for this system, it would have to be greater than 10 Hz.

Auditory Perception↗

PubMed1999

Tonic accommodation, age, and refractive error in children.

PURPOSE: An association between tonic accommodation, the resting accommodative position of the eye in the absence of a visually compelling stimulus, and refractive error has been reported in adults and children. In general, myopes have the lowest (or least myopic) levels of tonic accommodation. The purpose in assessing tonic accommodation was to evaluate it as a predictor of onset of myopia. METHODS: Tonic accommodation was measured in children enrolled in the Orinda Longitudinal Study of Myopia using an infrared autorefractor (model R-1; Canon, Lake Success, NY) while children viewed an empty lit field or a dark field with a fixation spot projected in Maxwellian view. Children aged 6 to 15 years were measured from 1991 through 1994 (n = 714, 766, 771, and 790 during the 4 years, successively). Autorefraction provided refractive error and tonic accommodation data, and videophakometry measured crystalline lens curvatures. RESULTS: Comparison of the two methods for measuring tonic accommodation shows a significant effect of age across all years of testing, with the lit empty-field test condition yielding higher levels of tonic accommodation compared with the dark-field test condition in children aged 6 through 11 years. For data collected in 1994, mean (+/-SD) tonic accommodation values for the lit empty-field condition were significantly lower in myopes, intermediate in emmetropes, and highest in hyperopes (1.02 +/- 1.18 D, 1.92 +/- 1.59 D, and 2.25 +/- 1.78 D, respectively; Kruskal-Wallis test, P < 0.001; between-group testing shows each group is different from the other two). Age, refractive error, and Gullstrand lens power were significant terms in a multiple regression model of tonic accommodation (R2 = 0.18 for 1994 data). Lower levels of tonic accommodation for children entering the study in the first or third grades were not associated with an increased risk of the onset of myopia, whether measured in the lit empty-field test condition (relative risk = 0.90; 95% confidence interval = 0.75, 1.08), or the dark-field test condition (relative risk = 0.83; 95% confidence interval = 0.60, 1.14). CONCLUSIONS: This is the first study to document an association between age and tonic accommodation. The known association between tonic accommodation and refractive error was confirmed and it was shown that an ocular component, Gullstrand lens power, also contributed to the tonic accommodation level. There does not seem to be an increased risk of onset of juvenile myopia associated with tonic accommodation.

Accommodation, Ocular↗

PubMed1999

Ocular predictors of the onset of juvenile myopia.

PURPOSE: The purpose of this study was to identify reliable predictors of the onset of juvenile myopia. METHODS: The data from 554 children enrolled in the Orinda Longitudinal Study of Myopia (OLSM) as nonmyopes with baseline data from the third grade were evaluated to develop a predictive profile for later onset of juvenile myopia. Myopia was defined as at least -0.75 D of myopia in the vertical and horizontal meridians of the right eye as measured by cycloplegic autorefraction (n = 45 children). Chosen predictors were refractive error and the ocular components: corneal power, Gullstrand crystalline lens power, and axial length. Sensitivity and specificity were calculated. Receiver operating characteristic (ROC) curves were generated to evaluate and compare these predictors singly and combined. RESULTS: Refractive error, axial length, Gullstrand lens and pod corneal power were all significant predictive factors for the onset of juvenile myopia. The best single predictor of future myopia onset in the right eye was the right eye's cycloplegic autorefraction spherical refractive error value (mean sphere across 10 readings) at baseline. For a cut point of less than +0.75 D hyperopia in the third grade, sensitivity was 86.7% and specificity was 73.3%. The area under the ROC curve for this mean sphere was 0.880. Producing a logistic model combining mean sphere, corneal power, Gullstrand lens power, and axial length results in a slight improvement in predictive ability (area under the ROC curve = 0.893). CONCLUSIONS: Onset of juvenile myopia can be predicted with moderate accuracy using the mean cycloplegic, spherical refractive error in the third grade. Measurement of other ocular components at this age improves predictive ability, albeit incrementally. Further improvements in the prediction of myopia onset will require the use of longitudinal data in addition to one-time measurement of refractive error and the ocular components.

Adolescent↗

PubMed1998

A simple screening test for variant transthyretins associated with familial transthyretin amyloidosis using isoelectric focusing.

Variant forms of the plasma protein transthyretin (TTR) are associated with the most frequently occurring type of familial systemic amyloidosis. Organ system involvement in transthyretin type amyloidosis (ATTR) is often similar to that which occurs in light chain amyloid disease (AL). The proper diagnosis of ATTR is important since treatment (liver transplantation) differs from that in AL (chemotherapy). We present a two-step test to screen sera for variant TTRs using non-denaturing gel electrophoresis performed in 7.5% acrylamide (PAGE) followed by isoelectric focusing (IEF) between pH 4.0 and 7.0 in 2.5 M urea. Serum samples from 110 patients with amyloidosis and their relatives were tested using this IEF technique and compared to genetic mutation results. Sera from patients with ATTR who underwent liver transplantation were also examined prior to and following surgery. IEF analysis showed the presence of both wild-type and variant TTR in 74 of the 110 serum samples tested. Genomic DNA from peripheral blood was used to identify TTR gene mutations in 77 of the 110 patients. Fifteen variants including Val122Ile, preponderant in the African-American population, could be demonstrated by IEF. The sensitivity of IEF was 96% (74/77) and the specificity was 100% (33/33). The predictive values for a positive or negative result were 100% (74/74) and 92% (33/36), respectively. There were no false-positive results and 4% (3/77) false-negative results. In sera from patients with ATTR who underwent liver transplantation, variant TTR was detected by IEF before, but not after, surgery. A simple, accurate, sensitive method is presented as a useful screening test for variant transthyretins associated with ATTR.

Amyloidosis↗

PubMed1998

A cross-sectional case control study of work-related injuries among Ohio farmers.

The agricultural industry has consistently been ranked among the most hazardous in the U.S. To date, few analytic studies of occupational injury among farm operators and workers have been conducted. A case control study was undertaken to investigate risk factors for agricultural work-related injury among Ohio farm operators. Cases were selected from among 1,793 respondents to a questionnaire administered during the first phase of the NIOSH-sponsored Ohio Farm Family Health and Hazard Study (OFFHHS). Analysis consisted of description of the injury experience of the sample as a whole, followed by logistic estimation of prevalence odds ratios (pORs) measuring the effect of potential risk factors on injury risk. The case series consisted of 90 white male principal operators (POs) injured doing farm work in the 12 months prior to questionnaire completion. Controls consisted of 1,475 white male POs who reported no injuries. The overall rate of injury was 5 per 100 person-years. The most notable result is the relationship between self-reported neurotoxic symptoms and injury, suggesting those with more reported symptoms were at greater risk of injury. The crude OR, when compared to the reference score of < or = 27, increased from 1.74 (95% CI = 0.60-5.09) in the 28-30 category, to 1.89 (95% CI = 0.71-5.03) in the 31-35 category, to 2.96 (95% CI = 1.10-7.96) in the highest category of test score. The P value for trend was 0.0218. These associations largely persisted after controlling for potential confounders with multiple logistic regression. Risk was inversely related to age. The results show marked increases in risk of injury associated with farmers younger than 30 and increased severity of self-reported neurological symptoms, controlling for potential confounding.

Accidents, Occupational↗

PubMed1998

Sibling pairs with schizophrenia or schizoaffective disorder: associations of subtypes, symptoms and demographic variables.

BACKGROUND: Affected sibling pairs provide a valuable means of investigating the familial basis of clinical heterogeneity in schizophrenia. METHODS: Associations of schizophrenia subtypes, psychotic symptoms (defined by SAPS/SANS and OPCRIT), affective episodes and demographic variables were studied in 109 sibling pairs with DSM-IV schizophrenia or schizoaffective disorder. RESULTS: None of the subtypes or affective episodes were significantly associated within pairs. A broad definition of positive formal thought disorder, grandiose delusions and delusions of influence (all from OPCRIT) were modestly associated. There was no excess of same-sex pairs. There were modest associations for age of illness onset, pre-morbid adjustment and illness severity. Caution is required in interpreting the results because many statistical tests were carried out. CONCLUSIONS: None of the variables appears to be closely associated with specific genetic or shared environmental factors that contribute liability to schizophrenia. They are at best only weakly associated with such factors, and/or are associated with factors unrelated to the aetiology of schizophrenia.

Adult↗

PubMed1998

Linked polymorphisms upstream of exons 1 and 2 of the human cholecystokinin gene are not associated with schizophrenia or bipolar disorder.

The evidence for a significant genetic contribution to the functional psychoses (schizophrenia and bipolar disorder) is now well established. However, in both cases, the non-mendelian mode of inheritance has made the identification of susceptibility loci particularly challenging. The neuropeptide cholecystokinin (CCK) is present both in the gut and the CNS. Studies of CCK-like immunoreactivity and CCK mRNA levels in human brains have revealed high concentrations in numerous loci and shown colocalisation of CCK with, for example, dopamine and tyrosine hydroxylase. Furthermore, antagonists of CCK-B receptors, which are found most frequently in the brain, inhibit the activity of brain dopamine neurons. Such findings suggest that, with respect to neuropsychiatric disorders, CCK is a suitable candidate for analysis using methods to detect gene variations which have the potential to affect protein structure or expression. In the present study, mutation analyses were carried out on the human CCK gene. Linked polymorphisms were found in the promoter region and in intron 1 close to the 3' mRNA splice acceptor site. However, the allele frequencies of these polymorphisms in samples of individuals affected with either schizophrenia (n=117) or bipolar disorder (n=124) did not differ from those of control subjects (n=234), suggesting that these variations do not confer a predisposition to either of the functional psychoses.

Alleles↗

PubMed1998

Further support for an association between a polymorphic CAG repeat in the hKCa3 gene and schizophrenia.

A recent study has suggested that a polymorphism in the hKCa3 potassium channel may be associated with raised susceptibility to schizophrenia. Despite its modest statistical significance, the study is intriguing for two reasons. First, hKCa3 contains a polymorphic CAG repeat in its coding sequence, with large repeats more common in schizophrenics compared with controls. This is interesting in view of several repeat expansion detection (RED) studies that have reported an excess of large CAG repeats in psychotic probands. Second, the hKCa3 gene is a functional candidate gene because studies of antipsychotic and psychotogenic compounds suggest that glutamatergic systems modulated by SKCa channels may be important in schizophrenia pathogenesis. In the light of the above, we have tested the hypothesis of an association between schizophrenia and the hKCa3 CAG repeat polymorphism using a case control study design. Under the same model of analysis as the earlier study, schizophrenic probands had a higher frequency of alleles with greater than 19 repeats than controls (chi 2 = 2.820, P = 0.047, 1-tail). Our data therefore provide modest support for the hypothesis that polymorphism in the hKCa3 gene may contribute to susceptibility to schizophrenia.

Alleles↗

PubMed1998

"5 A Day" achievement badge for urban boy scouts: formative evaluation results.

BACKGROUND: Certain cancers are more common among African Americans (AA). Fruit and vegetables (F&V) reduce cancer risk, but Americans, and African Americans in particular, do not meet the "5 A Day" goal. Scouting organizations, particularly urban Boy Scout groups that target inner-city youth, provide promising channels for nutritional behavioral change programs. METHODS: Focus groups were conducted with urban Boy Scouts and their parents to identify factors influencing F&V consumption and evaluate potential intervention activities. Twenty-four-hour dietary recalls were collected from 85 area Boy Scouts. A national data set was used to obtain values for F&V consumption by African American and European American (boys age 0-16). RESULTS: Vegetable preferences were low and a negative peer influence for vegetables was reported. The group has limited food-preparation skills, but both parents and scouts reported that F&V were available in their homes. Use of goal setting and use of problem-solving techniques were limited. The local scouts' mean F&V intake was 3.2 servings per day. Ethnic differences in F&V consumption were identified in the national data. CONCLUSIONS: Based on these results and previous interventions in schools, an overall structure for the intervention was developed to include eight weekly troop sessions and two camping sessions, parent newsletters, seven weekly home badge assignments, and ten comic books.

Adolescent↗

PubMed1998

Development of phoria in children.

BACKGROUND: Although the prevalence of phoria in adults is well documented, data are scarce on phoria in children. We present results using modified clinical technique vision screening and data from the Orinda Longitudinal Study of Myopia on a large, population-based sample of nonstrabismic children to document the prevalence of phoria with age. METHODS: We collected cross-sectional (N = 1495) and longitudinal (N = 469) data. Phoria data were collected by cover tests administered by one observer who subjectively classified phoria as orthophoria, esophoria, or exophoria in 2 delta steps. RESULTS: Ninety-seven percent of the children were orthophoric at distance, and there were no significant changes with age. Near phoria showed a more normal distribution, with a 10.8% decrease in the prevalence of exophoria (from 31.8 to 21.0%) and a 5.5% increase in the prevalence of esophoria (from 6.7 to 12.2%) between kindergarten and fifth grade. CONCLUSIONS: Children are typically orthophoric or exophoric at near, but convergent shifts occur with age.

Child↗

PubMed1998

Effects of rigid contact lens prism ballasting on oxygen access to the cornea under static and dynamic conditions.

The effects of rigid contact lens material [polymethyl methyacrylate (PMMA) and itabisfluorofocon A] and prism ballasting (0, 1.5, 2.25, and 3 delta) on tear pump efficiency were studied by measuring corneal oxygen uptake rates on the right eyes of six human subjects under three conditions: (1) normal open eye; (2) after 5 min of static (without blinking) wear of the contact lens; and (3) after 5 min of dynamic (with blinking once every 5 s) wear of the same lens. As expected, corneal oxygen uptake rates (i.e., demand for oxygen) measured with the itabisfluorofocon A material were significantly lower (p < 0.0001) than those measured with PMMA under both static and dynamic conditions. Under static conditions, no significant differences were found across materials among the corneal oxygen uptake rates associated with the four amounts of prism ballasting (p = 0.0514). However, under dynamic conditions, significant differences (p < 0.0001) were found across materials among corneal oxygen uptake rates associated with the four amounts of prism ballasting, with the lower amounts of prism ballasting being associated with lower corneal oxygen uptake rates. The changes in the measured corneal oxygen uptake rates from static to dynamic conditions, relative to those measured for the normal open eye, served as an index of tear pump efficiency. There were no significant differences in these changes for the prism amounts studied; however, static condition data were significantly higher than dynamic condition data for the 0 delta and 1.5 delta lenses only, whereas greater amounts of prism ballasting resulted in no reduction in oxygen uptake under dynamic conditions. In addition, significantly greater differences between static and dynamic condition data were found for the PMMA material than for itabisfluorofocon A.

Adult↗

PubMed1998

Association between functional psychosis and expanded CAG/CTG repeats is not explained by health stratification.

A number of studies have reported an association between large CAG/CTG repeats and both schizophrenia and bipolar disorder. Recently, we reported an inverse correlation between CAG/CTG repeat size and age in a health-selected population, raising the possibility that selection of control groups for physical health was a confounding factor in our previous association studies. We investigated this by health-selection of patients with schizophrenia and bipolar disorder. The maximum CAG/CTG repeat size remained significantly larger in probands with functional psychosis compared with control individuals, and in probands with a diagnosis of schizophrenia compared with control individuals. The number of probands in the healthy bipolar group was small, and although on average this group also had longer CAG/CTG repeats than control individuals, this failed to reach statistical significance. Our findings do not support the notion that the original results with psychosis as a whole, and schizophrenia specifically, are attributable to a stratification effect consequent on health selection. Nevertheless, we are unable formally to reject the hypothesis that the previously observed difference between bipolar probands and control individuals is the result of this phenomenon.

Bipolar Disorder↗

PubMed1998

Polydactyly and psychosis. Five cases of co-occurrence.

BACKGROUND: Abnormalities presumed to occur during foetal life have been associated with schizophrenia. Polydactyly is a developmental abnormality but no previous association has been reported between polydactyly and functional psychotic illness. METHOD: Individuals with both polydactyly and a functional psychosis were ascertained during a study of familial schizophrenia. RESULTS: Five such individuals were ascertained in the course of assessing 234 individuals with familial psychosis, giving a rate of polydactyly in the sample of around 10 times the general population rate. CONCLUSIONS: This study provides preliminary evidence that polydactyly is over-represented in individuals with familial schizophrenia and related psychotic illnesses.

Adult↗

PubMed1998

Radiotherapy, toxicity and dosimetry of copper-64-TETA-octreotide in tumor-bearing rats.

UNLABELLED: The efficacy of 64Cu [T1/2 = 12.7 hr; beta+ (0.655 MeV; 19%); beta- (0.573 MeV; 40%)] as a radioisotope for radiotherapy has been recently established. Here we demonstrate that 64Cu-1,4,8,11 -tetraazacyclotetradecane-N,N',N",N'''-tetraacetic acid (TETA)-octreotide, a somatostatin receptor ligand, inhibits the growth of CA20948 rat pancreatic tumors in Lewis rats at doses that cause minimal toxicity. METHODS: Tumor-bearing rats were administered a single 15 mCi (555 MBq) dose, a fractionated dose of 15 mCi given in 2-3 doses over 2-8 days, or control agents of buffer, unlabeled octreotide or 64Cu-labeled TETA. In certain experiments, blood was removed at times from 4-23 days post-treatment, and a complete blood count along with blood chemistry analyses were obtained. RESULTS: Tumor-growth inhibition was significantly greater in rats injected with a single 15 mCi dose than in rats injected with control agents (p < 0.05). Dose fractionation in two doses, either 1 or 2 days apart, induced significantly increased tumor-growth inhibition compared with rats given a single dose (p < 0.05). The only toxicity observed in treated rats was a decrease in the white blood cell count. This drop was more pronounced in rats treated with a single dose compared with those treated with a fractionated dose. Human absorbed doses of 64Cu-TETA-octreotide to normal organs were estimated from biodistribution data in Lewis rats, and these data indicate that radiotherapy with 64Cu-TETA-octreotide in humans would be feasible. CONCLUSION: Copper-64-TETA-octreotide is a promising radiopharmaceutical for targeted radiotherapy of somatostatin receptor-positive tumors.

Animals↗