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Biomedical subjects

L A Jones

Publications and source records attributed to L A Jones.

At least 73 records · Page 4Linked to original sources
PubMed1997

Dietary fiber, Hispanics, and breast cancer risk?

The cancer rates of immigrant populations in the United States must be taken into account when looking at the importance of diet and culture as it relates to cancer prevention. Unfortunately, some nutrition studies targeted toward nontraditional white populations have not adequately confronted the issue of cultural meaning in efforts to gather dietary data accurate enough to support nutritional analyses, identify marginal diets, or relate risk to dietary patterns. The study presented here resolves many of the culturally specific issues utilizing awareness, attention, and judicious combination of culturally sensitive qualitative and quantitative research techniques. The importance of such a study in an Hispanic population is based on the fact that the age-adjusted rate of breast cancer in countries such as Mexico is among the lowest in the world. In addition, although one of the fastest-growing minority groups in the United States, Hispanic women living in this country have been shown to have the lowest incidence of the mortality rates from this disease across most geographic regions of the United States. Therefore, one might speculate that dietary factors, which have been shown to play a role in breast cancer prevention, may account for this difference. It is well recognized that the traditional Hispanic diet is rich in protective nutrients such as dietary fiber. It is known that through complex mechanisms, dietary fiber works to reduce the amount of estrogens in the body. Research also indicates that it is the level of endogenous estrogen in the body that may influence the onset of breast cancer. In order to better understand how dietary factors may be associated with breast cancer in Hispanic women, it is important that one develop the proper tools to discern any potential differences. Therefore, we developed an approach to obtaining dietary fiber information from a small cohort of 22 Houston-area Hispanic women as a vanguard study for a larger breast cancer prevention trial. Two separate dietary assessment instruments were utilized, a three-day food record and the Southwest Food Frequency Questionnaire. The mean intake of dietary fiber was 16 g/day according to the food record and 21 g/day according to the SWFFQ. Fruits, vegetables, breads, cereals, and beans provided for most of the participants' dietary fiber intake. These results support evidence that the Hispanic population's dietary fiber intake is higher than that for other groups, and this may help explain the lower incidence of breast cancer among some Hispanic populations.

Aged↗
PubMed1997

Linkage study of chromosome 6p in sib-pairs with schizophrenia.

Following reports of linkage between schizophrenia and markers in the chromosomal region 6p24-22 we have studied nine microsatellite markers spanning 40 cM of this region in our sample of 102 affected sibling pairs from 86 families. Allele sharing identity by descent was examined using likelihood based sib-pair analysis as implemented by the program SPLINK. No evidence for linkage was obtained and the highest lod score was only 0.192 for D6S309. We conclude that if there is a susceptibility locus for schizophrenia in this region then its effect size is so small as to render our study insufficiently powerful to detect it.

Adult↗
PubMed1997

No evidence for an allelic association between schizophrenia and markers D22S278 and D22S283.

We report a case control association study using markers D22S278 and D22S283 in 90 unrelated patients with DSMIII-R schizophrenia and 90 controls matched for ethnicity, age and sex. No differences between allele frequencies for either marker were observed when the two groups were compared (D22S278: chi 2 = 6.53, df = 7, P = 0.51; D22S283: chi 2 = 14.73, df = 15, P = 0.48). These findings fail to support previous work by others suggesting the presence of allelic association between the markers D22S278 and D22S283 and schizophrenia.

Alleles↗
PubMed1997

Bone mineral changes in young women with hypothalamic amenorrhea treated with oral contraceptives, medroxyprogesterone, or placebo over 12 months.

OBJECTIVES: The objectives of this study were to assess (1) whether treatment with oral contraceptives, in comparison with medroxyprogesterone and placebo, improved bone mineral in women with hypothalamic amenorrhea and (2) whether treatment with medroxyprogesterone, in comparison with placebo, improved bone mineral in women with hypothalamic oligomenorrhea. STUDY DESIGN: The study was a randomized, controlled clinical trial. Twenty-four white women, aged 14 to 28 years, with hypothalamic amenorrhea or oligomenorrhea were prospectively enrolled for a 12-month intervention period. Amenorrheic subjects were randomized to receive oral contraceptives, medroxyprogesterone, or placebo. Oligomenorrheic subjects were randomized to receive medroxyprogesterone or placebo. Bone mineral was measured by dual-energy x-ray absorptiometry at baseline and at 6 and 12 months. RESULTS: In amenorrheic subjects spine and total body bone mineral measurements at 12 months were greater in the oral contraceptive group than in the medroxyprogesterone and placebo groups when baseline bone mineral measurements, body weight, and age were controlled for (p < or = 0.05). There were no differences in hip bone mineral calcium and bone mineral density measurements at 12 months among the three groups. In oligomenorrheic subjects there was no detectable improvement in bone mineral associated with medroxyprogesterone use. CONCLUSIONS: This study supports the hypothesis that oral contraceptive use in women with hypothalamic amenorrhea will improve lumbar spine and total body bone mineral.

Adolescent↗
PubMed1997

A CD2/CD28 chimeric receptor triggers the CD28 signaling pathway in CTLL.2 cells.

We are evaluating strategies to enhance the in vivo proliferation and function of adoptively transferred antigen-specific T cells. Although the CD28 costimulatory pathway is important for T cell activation and proliferation, the expression of the ligands for CD28 is highly restricted. We have generated a chimeric receptor composed of the signaling domains of CD28 and the extracellular domain of CD2 which binds the widely expressed ligand CD58. The CD2/CD28 chimeric receptor was introduced into CTLL.2 cells via retrovirus infection and was shown to be expressed on the cell surface. By monitoring early and late components of the CD28 signaling pathway, the chimeric receptor was demonstrated to trigger the CD28 pathway in response to CD2 cross-linking. The possible utility of the CD2/CD28 chimeric receptor for adoptive immunotherapy is discussed.

Animals↗
PubMed1997

Association between schizophrenia and a microsatellite polymorphism at the dopamine D5 receptor gene.

An association study of 97 patients with DSM-III-R schizophrenia and 97 matched controls was performed using a polymorphic microsatellite repeat at the dopamine D5 receptor gene. We observed a significant difference between the allele frequencies of patients and controls (chi 2 = 23.4, df = 12, p = 0.019). This reflects an excess of allele 4 (140 bp) in the patients when compared with the control sample (chi 2 = 7.087, p < 0.01; odds ratio = 2.98, 95% CI 1.29-6.86). However, this association remains tentative until confirmation in other samples.

Alleles↗
PubMed1997

During development, 17alpha-estradiol is a potent estrogen and carcinogen.

Neonatal administration of estradiol-17beta (E2-17beta) increases the nuclear DNA content in the mouse reproductive tract. Similar responses have been demonstrated for synthetic estrogens such as diethylstilbestrol. One of the questions raised regarding environmental estrogens such as organochlorines is whether they are potent enough to result in abnormal changes such as those demonstrated by both natural and synthetic estrogens. To test this hypothesis, female BALB/c mice were treated neonatally (days 1-5) with either E2-17beta or estradiol-17alpha (E2-17alpha), an inactive stereoisomer in adult reproductive tissues. We also proposed whether neonatal administration of (E2-17alpha) was tumorigenic and whether the effects were age dependent. To answer these questions, one set each of 10 day-old treated and control mice received short-term secondary administration of E2-17beta, E2-17alpha, or cholesterol. Cervicovaginal tracts from intact BALB/c mice were examined histologically and by flow cytometry at 70 days of age and by histology alone at 18 to 22 months of age. The results include several important findings: a) like E2-17beta, neonatal E2-17alpha treatment induced persistent vaginal cornification, hypospadias, vaginal concretions, and hyperproliferation in nearly 100% of the animals regardless of the secondary treatment for most groups; b) neonatal E2-17alpha treatment increased the nuclear DNA content of cervicovaginal epithelium at one-half both the level (mean DNA index of 1.02 vs 1.04) and incidence (22 vs 46% of the animals) of E2-17beta; c) short-term secondary treatment with E2-17alpha, unlike E2-17beta, did not significantly augment the increase in DNA content (13% for E2-17alpha vs 37 and 56% for control and E2-17beta, respectively); and d) neonatal administration with E2-17alpha induced adenosquamous tumors in the reproductive tract in 25% of the animals. Therefore, the biological effects (estrogenic potency) of E2-17alpha may be age dependent.

Animals↗
PubMed1997

WAF1/Cip1 gene polymorphism and expression in carcinomas of the breast, ovary, and endometrium.

The p53 gene is altered in approximately 50% of human cancers and is considered to be important in the pathogenesis of these malignancies. The p53 protein product regulates the transition from G1 to S phase of the cell cycle and entry to the DNA damage repair pathway. As alterations in this pathway appear to be important in a variety of human cancers, downstream effector proteins of p53 are potential sites for somatic alterations. WAF1/Cip1, also known as WAF1, Cip1, sdi1, or CAP20, codes for a 21-kd protein (p21WAF1/Cip1), which was recently described as a universal inhibitor of cyclins and is thus critical in cell cycle control. Mutations in WAF1/Cip1 are potentially important in human malignancies because they could affect the control of the cell cycle. To understand whether mutations of WAF1/Cip1 occur in cancer, we screened 53 cases of invasive breast carcinoma, 35 cases of ductal carcinoma in situ (DCIS), 53 ovarian carcinomas, and 47 endometrial carcinomas in the second exon of WAF1/Cip1 (90% of the open reading frame). p21WAF1/Cip1 expression was characterized with immunohistochemistry. Cells from the blood of 21 normal individuals were also characterized using single-strand conformational polymorphism analysis, DNA sequencing and restriction analysis. Single-strand conformational polymorphism analysis demonstrated an altered mobility pattern for exon 2 in 12 invasive breast cancers (22.6%), 5 DCIS of the breast (14%), 8 invasive ovarian carcinomas (15%), and 9 endometrial carcinomas (19%). In total, 209 samples were screened, and 38 cases (18.2%) had an altered codon 31. Each case with altered single-strand conformational polymorphism, analyzed by DNA sequencing and/or restriction analysis, showed the same alteration of codon 31, a C to A transversion encoding a change in amino acid sequence from serine to arginine (31Ser-->31Arg). DNA from the blood of 21 normal individuals showed the same alteration in WAF1/Cip1 in 4 cases (19%). Furthermore, paired normal tissue was available for 3 of 20 breast carcinomas with the Ser31Arg transversion. Normal DNA from all 3 cases showed the same 31Arg alteration as found in the tumor tissue. These results indicate that codon 31 is a polymorphic site and that the serine to arginine shift is a polymorphism. p21WAF1/Cip1 expression, identified by immunohistochemistry, was found to vary in a pattern that depended both on the tissue type and on the presence or absence of the codon 31 polymorphism. Using pair-wise comparisons in breast DCIS, we found higher protein expression in tumor nuclei as compared with benign stromal cell nuclei (P = 0.002) or normal ductal epithelium (P = 0.005). Invasive breast cancer specimens showed a trend in p21WAF1/Cip1 immunostaining similar to DCIS but did not reach statistical significance (P = 0.12). However, when cases with extensive desmoplastic reaction were excluded, a statistically significant association (P = 0.019) similar to that in DCIS was noted. In contrast to the breast tumors, ovarian carcinomas exhibited significantly greater p21WAF1/Cip1 expression in the benign stromal (fibroblast) nuclei surrounding the tumor than in the carcinoma cell nuclei (P = 0.016). Endometrial carcinoma revealed no difference in staining when comparing benign tissue with carcinoma (P = 0.99); however, unlike breast and ovarian carcinomas in which there was no correlation between p21WAF1/Cip1 expression and the presence or absence of the alteration at the 31st codon, endometrial carcinomas showed an increased percentage of immunopositive nuclei associated (P = 0.056) with 31Arg. These results demonstrate tissue-specific expression patterns of WAF1/Cip1 in different tumors which appears to be characteristic of the tumor type.

Breast Neoplasms↗
PubMed1996

Factor analysis of schizophrenic symptoms using the OPCRIT checklist.

Factor analysis was performed on OPCRIT checklist psychotic symptoms rated on 102 patients with DSM-III-R schizophrenia. An initial three-factor solution produced positive, negative, and disorganisation factors. However, application of the scree test suggested five substantive factors, with the positive factor dividing into three factors characterised, respectively, by paranoid symptoms, first rank delusions and first rank hallucinations.

Adult↗
PubMed1996

Molecular genetic analysis of clear cell adenocarcinomas of the vagina and cervix associated and unassociated with diethylstilbestrol exposure in utero.

BACKGROUND: Prenatal exposure to the synthetic estrogen diethylstilbestrol (DES) is associated with the subsequent development of clear cell adenocarcinoma of the lower reproductive tract in young women, and data concerning the molecular genetic alterations involved in the etiology of this tumor type have not previously been reported. Such knowledge would be of potential value by providing insight into the molecular mechanisms of hormonal carcinogenesis in general, as well as by suggesting molecular markers for risk assessment in the estrogen-exposed population. METHODS: A total of 24 samples of clear cell adenocarcinoma of the vagina or cervix, 16 associated with exposure in utero to DES and 8 with no history of DES exposure, were obtained as archival fixed and embedded tissue specimens. DNA was purified from these tissues and used to examine a number of biologically plausible molecular genetic endpoints for tumor specific alterations. RESULTS: No evidence was found for mutations in the K-ras or H-ras protooncogenes, the Wilms' tumor (WT1) tumor suppressor gene, or the estrogen receptor gene. Sporadic overexpression of the p53 tumor suppressor gene was detected in some tumor cell nuclei by immunohistochemistry, but in the absence of detectable p53 gene mutation. Genetic instability as manifested by somatic mutation of microsatellite repeats was widespread in these tumors, with evidence of microsatellite instability in all DES-associated tumors examined, and in 50% of those tumors not associated with DES exposure. CONCLUSIONS: These data are consistent with the hypothesis that the induction of genomic instability may be an important mechanism of DES-induced carcinogenesis.

Adenocarcinoma, Clear Cell↗
PubMed1996

Treatment of 100 patients with primary amyloidosis: a randomized trial of melphalan, prednisone, and colchicine versus colchicine only.

PURPOSE: A clinical trial designed to test whether treatment with melphalan, prednisone, and colchicine (MPC) is superior to colchicine (C) alone was performed in patients with primary amyloidosis (AL), a nonmalignant plasma cell dyscrasia. PATIENTS AND METHODS: Patients were randomized to MPC or C with stratification according to sex, time from diagnosis to study entry (ie, less than 3 months or 3 to 12 months), and dominant organ system involvement (ie, cardiac, renal, neurologic, or others). Data were gathered monthly from patients, quarterly from physicians, and annually in the Clinical Research Center. One hundred consecutive patients with AL amyloidosis admitted between 1987 and 1992 who met eligibility requirements were treated and followed for a minimum of 18 months. Fifty patients (group A) received daily oral colchicine and 50 patients (group B) received cycles of oral melphalan and prednisone every 6 weeks for 1 year as well as colchicine. RESULTS: The principal outcome measure was median survival, which was compared in the two treatment groups and in the subgroups. The overall survival of all patients from study entry was 8.4 months. Comparing group A (C) to group B (MPC), the survival was 6.7 months versus 12.2 months (P = 0.087). Both treatment groups had poor survival for patients in the cardiac subgroup, longest survival in the renal group, and significant differences favoring MPC treatment only in patients whose major system manifestations were neurologic (P = 0.037) or other (P = 0.007). Multivariate analysis showed a strongly significant treatment effect (P = 0.003) and improved survival associated with not having cardiac or gastrointestinal involvement. CONCLUSIONS: MPC was advantageous for patients whose major manifestations of amyloid disease were other than cardiac or renal. Better survival regardless of treatment was noted in patients for whom a satisfactory supportive treatment such as transplant or dialysis exists for their organ failure.

Amyloidosis↗
PubMed1996

No evidence for allelic association between schizophrenia and a polymorphism determining high or low catechol O-methyltransferase activity.

OBJECTIVE: Catechol O-methyltransferase (COMT) inactivates catecholamines by methylating their m-hydroxy group. Some previous studies using biochemical methods have found higher levels of COMT activity in schizophrenic patients. Recently, the genetic polymorphism that underlies variation in COMT activity, which results in the creation of a NlaIII restriction site in the low-activity allele, has been elucidated. METHOD: This study investigated this polymorphism in 78 unrelated schizophrenic patients and 78 comparison subjects matched for age and ethnicity. High-molecular-weight DNA was isolated from lymphocytes with routine procedures, and each individual was typed for high and low COMT activity. RESULTS: The frequency of the NlaIII polymorphism was 0.51 in the schizophrenic patients and 0.53 in the comparison subjects, and no significant allelic or genotypic associations were observed. CONCLUSIONS: There was no evidence for variation in COMT activity between a group of schizophrenic patients and matched comparison subjects.

Alleles↗
PubMed1996

Expanded CAG/CTG repeats in schizophrenia. A study of clinical correlates.

BACKGROUND: Schizophrenia is associated with expanded CAG/CTG trinucleotide repeats. We wished to determine whether the presence of such expansions correlated with specific subsyndromes or other clinical features of schizophrenia. METHOD: Seventy patients from England and Wales and 44 patients from Portugal with a DSM-III-R diagnosis of schizophrenia were rated on the OPCRIT checklist. Patient's maximum CAG/CTG repeat length was measured using repeat expansion detection (RED). Significant differences were sought for repeat lengths in subjects categorised according to dimensional and categorical schizophrenia subsyndromes, affective episodes, individual symptoms, and a range of demographic variables. RESULTS: Maximum CAG/CTG repeat length did not differ significantly for any of the clinical or demographic variables studied. CONCLUSION: There are no subsyndromes or other clinical features of schizophrenia associated with CAG/CTG repeat expansion. Therefore, the identification of the gene(s) that contain expanded CAG/CTG repeats and which are associated with schizophrenia is unlikely to be facilitated at present by using any subsyndromes of schizophrenia as phenotypes.

Adult↗
PubMed1996

Chromosomal radiosensitivity in G2-phase lymphocytes as an indicator of cancer predisposition.

Sanford et al. (Int. J. Radiat. Biol. 55, 963-981, 1989) have reported that G2-phase cells from many heritable cancer-prone conditions exhibit higher yields of X-ray-induced chromosome damage than those found in the majority of healthy controls. We have applied their protocol to lymphocytes of a group of control and cancer-prone individuals to see if we could confirm these observations. For control donors we observed higher aberration yields, different kinetics and more interexperiment variability than found by Sanford et al. These differences could not be attributed to unavoidable minor variations in procedures (e.g. serum batches, glassware washing methods), but the difference in X-ray qualities used in the two laboratories may have made a small contribution to the discrepancies. We attribute some of our experimental variability to the fact that, to varying extents in different experiments, centrifugation of cells prior to irradiation can slow down the progression of cells into metaphase and that cells can continue to repair during the harvesting procedure (centrifugation and hypotonic treatment). We have applied the assay to cases of ataxia telangiectasia (AT, homozygotes and heterozygotes), xeroderma pigmentosum (homozygotes and heterozygotes), familial adenomatous polyposis and the syndromes Li-Fraumeni, basal cell nevus, Down's and Fanconi's but have been unable to discriminate between these groups and controls except for AT homozygotes. By including a control sample in parallel with samples from cancer-prone groups we found a significant difference in mean aberration yields between controls and AT homozygotes and heterozygotes, but not for the other groups. Since technical features could explain the discrepancies between our laboratories, we have devised our own G2-phase assay which appears to be giving promising results.

Adenomatous Polyposis Coli↗
PubMed1995

Amplification and overexpression of HER-2/neu (c-erbB2) in endometrial cancers: correlation with overall survival.

Few molecular genetic alterations have been identified in endometrial cancers that are associated with poor clinical outcome. Overexpression of HER-2/neu, transforming growth factor alpha, and p53 proteins have all been associated with poor prognosis in women with endometrial cancer. In this study, the level of HER-2/neu gene amplification and expression was characterized in 92 endometrial cancers. Fluorescence in situ hybridization (FISH) was used to characterize HER-2/neu gene copy number, and immunohistochemistry was used to characterize expression. Forty-seven of the 90 (52%) endometrial cancers were characterized as showing moderate or high immunostaining. HER-2/neu gene amplification was detected in 17 of 81 (21%) cases. Immunohistochemical staining and FISH results were both available for 80 cases. Fourteen of these cases showed both moderate or high immunostaining and gene amplification. Clinical follow-up information was available for 76 women in this study. Women whose endometrial cancer exhibited HER-2/neu gene amplification by FISH had a shorter overall survival than women whose endometrial cancer lacked amplification (P = 0.018). Likewise, tumors with moderate or high HER-2/neu immunostaining were associated with a lower cumulative overall survival than tumors with low immunostaining by log rank analysis (P < 0.0001). Multivariate analysis of survival rates revealed HER-2/neu overexpression to be an independent predictor of overall survival (P = 0.0163). Among those patients with HER-2/neu overexpression, adjuvant chemotherapy or radiation therapy was associated with an improved overall survival (P = 0.039). However, among those women whose tumor lacked overexpression, overall survival was not improved by adjuvant treatment.

Adult↗
PubMed1995

The senses of effort and force during fatiguing contractions.

The sensory basis upon which judgments of force are made during fatiguing isometric contractions is reviewed. At issue is whether the perception of force is based on centrally generated sensations arising from the motor command, known as the sense of effort, or from peripheral sensations originating in the muscle, and termed a sense of force. The results from a number of studies indicate during sustained constant-force contractions the perceived magnitude of the force increases, which is consistent with the idea that judgments of force are based on centrally generated signals. It is, however, possible for some subjects to dissociate effort and force and to make accurate judgments of the magnitude of forces during fatigue.

Humans↗
PubMed1995

Ophthalmic microsurgical robot and associated virtual environment.

An ophthalmic virtual environment has been developed as part of a teleoperated microsurgical robot built to perform surgery on the eye. The virtual environment is unique in that it incorporates a detailed continuum model of the anatomical structures of the eye, its mechanics and optical properties, together with a less detailed geometric-mechanical model of the face. In addition to providing a realistic visual display of the eye being operated on, the virtual environment simulates tissue properties during manipulation and cutting and the forces involved are determined by solving a mechanical finite element model of the tissue. These forces are then fed back to the operator via a force reflecting master and so the surgeon can experience both the visual and mechanical sensations associated with performing surgery. The virtual environment can be used to enhance the images produced by the camera on the microsurgical slave robot during surgery and as a surgical simulator in which it replaces these images with computer graphics generated from the eye model.

Computer Graphics↗