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Biomedical subjects

R Barnes

Publications and source records attributed to R Barnes.

At least 19 recordsLinked to original sources

Development of delta-opioid receptor subtypes and the regulatory role of weaning: radioligand binding, autoradiography and in situ hybridization studies.

Evidence from behavioral studies suggests that the process of weaning activates the development of a delta-opioid receptor subtype. We now report the influence of weaning on the development of delta receptors in the central nervous system assessed by membrane homogenate binding and autoradiography with selective delta radioligands and by in situ hybridization using a cRNA probe for the delta receptor. Binding was carried out by using [3H][D-Ala2]deltorphin I (DELT I), [3H]IIe5,6-deltorphin II (IIe5,6-DELT II) and [3H]naltrindole (NTI). [3H]IIe5,6-DELT II and [3H]NTI labeled an equivalent number of sites in brain and spinal cord from both weaned and nonweaned 25-day-old rats. The number of sites labeled by [3H]DELT I was similar in nonweaned rats but significantly higher in the brain and cord from weaned animals. Furthermore, the ontogenetic profile of these three ligands was distinct. Quantitative autoradiography showed identical levels of [3H]IIe5,6-DELT II binding in all brain regions in weaned and nonweaned rats. In contrast, levels of [3H]DELT I binding were significantly higher in weaned rats and this difference was localized to the deep layers of the frontal-parietal cortex and to the pontine nucleus. In situ hybridization experiments showed no differences in delta-opioid receptor mRNA density between weaned and nonweaned groups in the regions in which binding differences were observed. Weaning stimulates the development of a subpopulation of delta receptors recognized by [3H]DELT I but not by [3H]IIe5,6-DELT II or NTI. This effect is localized to specific brain regions and does not appear to reflect increased synthesis of mRNA coding for the delta receptor.

Animals

Gene for familial psoriasis susceptibility mapped to the distal end of human chromosome 17q.

A gene involved in psoriasis susceptibility was localized to the distal region of human chromosome 17q as a result of a genome-wide linkage analysis with polymorphic microsatellites and eight multiply affected psoriasis kindreds. In the family which showed the strongest evidence for linkage, the recombination fraction between a psoriasis susceptibility locus and D17S784 was 0.04 with a maximum two-point lod score of 5.33. There was also evidence for genetic heterogeneity and although none of the linked families showed any association with HLA-Cw6, two unlinked families showed weak levels of association. This study demonstrates that in some families, psoriasis susceptibility is due to variation at a single major genetic locus other than the human lymphocyte antigen locus.

Alleles

Cytomegalovirus/herpesvirus and carotid atherosclerosis: the ARIC Study.

Ubiquitous viruses such as members of the human herpes virus group, particularly cytomegalovirus (CMV), have been proposed to be clinically important agents in the initiation and progression of atherosclerosis. Antibodies to CMV and herpes simplex virus type 1 (HSV1) and type 2 (HSV2) were determined in 340 matched case-control pairs from the Atherosclerosis Risk in Communities (ARIC) Study. Cases were defined by B-mode ultrasonography as persons with thickened carotid artery walls consistent with early atherosclerosis but without a history of cardiovascular disease. Controls were defined as persons without thickened walls or history of cardiovascular disease. The case-control odds ratio for CMV antibodies was 1.55 (P = .03), for HSV 1.41 (P = .07), and for HSV2 0.91 (P = .63). When adjustment was made for potential confounders, the odds ratios were 1.36 for CMV (P = .24), 1.21 for HSV1 (P = .45), and 0.61 (P = .05) for HSV2. These results suggest a modest association between CMV and asymptomatic carotid wall thickening consistent with early atherosclerosis.

Antibodies, Viral

Clear cell epithelial-myoepithelial carcinoma arising in pleomorphic adenoma of the lacrimal gland.

BACKGROUND: A 63-year-old man had an 8-year history of painless proptosis, which had noticeably increased over the last 2 months. A mass was palpable in the left lateral canthus. Computed tomographic studies showed a globular mass with small foci of calcification involving the lacrimal gland. After an incisional biopsy, a histologic diagnosis of clear cell epithelial-myoepithelial carcinoma was made and an orbital exenteration was performed. FINDINGS: Results of histologic examination of the mass showed a partially encapsulated, clear cell epithelial-myoepithelial carcinoma with an associated pleomorphic adenoma (benign mixed tumor). Immunohistochemical studies disclosed strong immunoreactivity to cytokeratin (AE1/AE3), epithelial membrane antigen, S-100 protein, and alpha-actin. CONCLUSION: Although a clear cell myoepithelial carcinoma rarely has been reported in association with a pleomorphic adenoma of the submandibular gland, to the authors' knowledge, this combination has never been reported in the lacrimal gland, nor has a clear cell epithelial-myoepithelial carcinoma ever been reported in this anatomic location. The differential diagnosis of lesions with prominent clear cells involving the lacrimal gland is extensive and includes clear cell variants of acinic cell carcinoma and oncocytoma, mucoepidermoid carcinoma, and others.

Adenocarcinoma, Clear Cell

B-mode-detected carotid artery plaque in a general population. Atherosclerosis Risk in Communities (ARIC) Study Investigators.

BACKGROUND AND PURPOSE: There is little information on the distribution of atherosclerotic lesions of the extracranial carotid artery wall in free-living populations. The purpose of the present study was to describe the prevalence from 1987 through 1989 of extracranial carotid artery plaque and plaque with acoustic attenuation (shadowing) lesions in a general population of white and black adults from four US communities. METHODS: B-mode ultrasound was used to characterize wall lesions in the common and internal carotid arteries and at the carotid artery bifurcation in 14,046 men and women 45 to 64 years old who participated in the Atherosclerosis Risk in Communities Study baseline survey. RESULTS: Thirty-four percent of participants had plaque and 6.4% had plaque with acoustic shadowing. The prevalence of plaque with acoustic shadowing increased steadily with age from 2.5% at ages 45 to 49 to 12.4% at ages 60 to 64. Overall, whites had more plaque with acoustic shadowing lesions than blacks (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.02 to 1.46), and men had more than women (OR, 1.42; 95% CI, 1.22 to 1.63). However, plaque lesions in the common carotid artery were less common among whites than among blacks, and no racial difference was observed in the prevalence of plaque with acoustic shadowing at this segment. CONCLUSIONS: Although these prevalence rates are likely to be underestimated because of the emphasis on arterial boundary visualization of the scanning protocol, they show a large, mostly asymptomatic burden of atherosclerosis in these populations, especially among older individuals. Site-specific frequency rates of plaque varied between blacks and whites. Among those with plaque, however, whites had more lesions with acoustic shadowing attenuation.

Adult

A 4.5-megabase yeast artificial chromosome contig from human chromosome 13q14.3 ordering 9 polymorphic microsatellites (22 sequence-tagged sites) tightly linked to the Wilson disease locus.

We have previously performed a genetic analysis of multiply affected families to map a locus responsible for Wilson disease (WND) to a 0.3-centimorgan (cM) region within chromosome 13q14.3, between D13S31 and D13S59. Here we describe the construction of a contig of approximately 4.5 Mb, which spans this region and extends from D13S25 to D13S59. This contig consists of 28 genomic yeast artificial chromosome (YAC) clones. Five critical crossover events have been defined in this interval in two unaffected (Centre d'Etudes du Polymorphisme Humain) and three WND families. The combination of sequence tagged site content mapping of YACs with both polymorphic and nonpolymorphic markers and recombination breakpoint mapping resulted in the following order of polymorphic markers: centromere-RB1-D13S25-AFM205vh2-D13S31-D13S22 7-D13S228-AFM238vc3-D13S133- AFM084xc5-D13S137-D13S169, D13S155-D13S59-telomere. The recombination/physical distance ratio varies from approximately 3000 kb per cM in the region between D13S31 and D13S25 to 6000 kb per cM in the region between D13S31 and D13S59. Three WND families exhibiting recombination between the disease locus and D13S31 or D13S59 were genotyped for additional markers in this region and further refined the location of the WND gene to between D13S155 and D13S133. Nine of the markers in this region of < 1 cM are polymorphic microsatellites (seven have observed heterozygosities of 70% or above) that will be extremely useful in prenatal and preclinical diagnosis of this disease. This physical map is an essential step in the isolation of the WND gene and is a framework for the identification of candidate genes.

Base Sequence

Microsatellite polymorphism linkage map of human chromosome 13q.

Twelve polymorphic (CA)n microsatellites were isolated from a flow-sorted chromosome 13 genomic library. These, and two others that have been previously described, were genotyped in 41 families from the CEPH (Centre d'Etude Polymorphisme Humain, Paris), and a primary linkage map with considerable support for order (odds > 10,000:1) was constructed. Two RFLP-based markers, COL4A1 and D13S52, with heterozygosities above 0.67 and an RFLP-based centromeric marker at D13Z1 were included in this map which extends from 13cen to 13q34. The heterozygosity of all of the PCR-based markers is above 60%. The total map spans a genetic distance of 144 cM, extending from D13Z1 to D13S52 with a single maximum intermarker recombination distance of 35 cM. All other intermarker recombination distances are 18 cM or less. Marker order was confirmed by sublocalizing many of the microsatellite containing clones on a panel of rodent-human somatic cell hybrids with deletions and rearrangements of chromosome 13. One spontaneous new mutation for these 14 (CA)n repeat markers was identified from a total of 8006 gametes, giving an overall observed spontaneous mutation rate of 0.00012 per locus per gamete. An integrated map of chromosome 13q was constructed with the microsatellite markers described here and previously genotyped RFLP-based markers. This sex-average map spans 209 cM with an average distance between unique map locations of 4.5 cM; the maximum intermarker distance was 14 cM.

Base Sequence

Influence of polar route schedules on the duty and rest patterns of aircrew.

The duty and rest periods of aircrew operating the polar route from London via Anchorage were recorded during five schedules which involved 1-, 2- or 3-day sojourns in Japan. Sleep throughout each schedule was fragmented, with naps before duty and short sleeps after arrival at a new location. Sleep disturbance rather than cumulative sleep loss appeared to be the overriding problem, and the shorter schedules had the most marked disturbances in sleep during the trip and during the immediate recovery period. Electroencephalographic studies are necessary to confirm these observations, and information on circadian rhythmicity is needed to define the circumstances which lead to persistence of sleep disturbance on return to Europe.

Adult

Diastasis of bipartite sesamoids of the first metatarsophalangeal joint.

Injury to the metatarsophalangeal (MP) joint of the great toe, often termed "turf-toe", is a common occurrence in football. We have identified four cases of first MP plantar capsular injury with diastasis of a bipartite sesamoid. In three cases, observation and protection resulted in progressive widening of the fragments associated with pain and disability. These players required resection of the distal sesamoid fragment and repair of the volar capsule. The fourth player underwent acute repair of the medial retinaculum and capsule. All players have had a full return to sports activity. Diastasis of components of a partite sesamoid provides objective evidence of disruption of the plantar capsular mechanism. Early recognition of this condition confirmed by stress radiographs is recommended. Treatment may include early protection followed by resection, if painful, or acute repair of the retinaculum. Previous descriptions of turf-toe have not included injuries to the sesamoid complex of the first MP joint. In our opinion, the term turf-toe should represent the consequences of a hyperextension injury to the first MP joint in which the volar capsule has been disrupted proximal to the sesamoid. A classification for first MP joint injuries is presented.

Adult

A pilot study of pi-class glutathione S-transferase expression in breast cancer: correlation with estrogen receptor expression and prognosis in node-negative breast cancer.

PURPOSE AND METHODS: Previous studies have indicated that RNA levels for pi-class glutathione S-transferase (GST pi), a phase II, drug-metabolizing enzyme, were inversely related to estrogen receptor (ER) and progesterone receptor (PR) levels in human breast tumors. Because GST pi also is expressed in normal breast epithelium, an immunohistochemical assay that uses affinity-purified polyclonal antibodies to GST pi was developed to examine the possible relationship between GST pi expression in breast cancer cells and hormone receptor expression, as well as prognosis, in patients with primary breast cancer. RESULTS: A strong inverse correlation between GST pi expression and ER (two-sided P [P2] = .002) and PR status (P2 = .023) was found in our study of 189 patients with primary breast cancer. GST pi expression was not related to tumor size, nodal metastasis, nuclear grade, histology, or age of the patient. In node-negative breast cancer (n = 72), increased GST pi expression was associated with decreased disease-free survival (DFS) and overall survival (OS). When GST pi expression was divided into categories of negative (no GST pi-positive tumor cells), intermediate (1% to 70% GST pi-positive tumor cells), and high (> 70% GST pi-positive tumor cells), the relative risk of tumor recurrence in patients with node-negative breast cancer was increased 3.39-fold for each successive category of expression (P2 = .0045; 95% confidence interval, 1.46 to 7.87) and the relative risk of death was increased 4.49-fold for each successive category (P2 = .0003; 95% confidence interval, 2.02 to 10.42). The actuarial 5-year OS was 100%, 79%, and 51%, and the DFS was 94%, 77%, and 44%, for the negative, intermediate, and high tumor groups, respectively. Among the factors studied in multivariate analysis (ER status, PR status, nuclear grade, and tumor size), GST pi expression was the factor that most accurately predicted shorter DFS and OS in node-negative patients. CONCLUSION: GST pi expression is inversely related to hormone receptor status in breast cancer. This pilot study also suggests that increased GST pi expression may be an important predictor of early recurrence and death in node-negative breast cancer patients that merits additional investigation.

Breast Neoplasms

Hospital response to psychosocial needs of AIDS inpatients.

Compassionate care for HIV-infected persons requires response to psychosocial needs. With no new external funding, Women's College Hospital, a 270-bed urban teaching hospital, provided effective psychosocial services for HIV-infected inpatients by developing a comprehensive policy, educating staff, organizing existing services into a psychosocial support team to provide crisis intervention, and developing liaisons with community AIDS organizations. A retrospective chart review of epidemiologic and psychosocial patient data was carried out for 59 HIV inpatients (58 men, 1 woman) admitted 1987-89. Of the cohort, 91% indicated homosexual contact as the only risk factor. A psychosocial support team contacted 90% of these inpatients. One third (36%) of the patients designated as next of kin individuals who were not legally or biologically related. Approximately 25%-30% made active arrangements for impending death, e.g. wills and funeral plans. Thirteen patients, 22%, died in hospital, and three, 5%, on first admission. Experience showed that psychosocial interventions that focus on human dignity and quality of life, normally seen as elements of palliative care, are critically important from the earliest stages of HIV disease and should not be reserved only for those who are terminally ill.

Acquired Immunodeficiency Syndrome

Increased risk for polycystic ovary syndrome associated with human leukocyte antigen DQA1*0501.

OBJECTIVE: The objective of this investigation was to identify genes that confer susceptibility to polycystic ovary syndrome. STUDY DESIGN: Nineteen subjects with polycystic ovary syndrome, hirsutism, and elevated plasma androgen levels and 46 fertile, female control subjects were studied. Alleles at the human leukocyte antigen DQA1 locus were identified with dot-blot hybridizations with allele-specific oligonucleotide probes. Associations between human leukocyte antigen DQA1 alleles and polycystic ovary syndrome were examined with logistic regression analysis. RESULTS: The frequency of the human leukocyte antigen DQA1*0501 was 0.50 and 0.26 in subjects with polycystic ovary syndrome and control subjects, respectively (corrected for multiple comparisons, p = 0.067). Homozygosity for this allele was also increased among subjects with polycystic ovary syndrome (p = 0.054). The odds ratios for having polycystic ovary syndrome associated with the *0501 allele and the *0501/*0501 homozygous genotype were 2.8 and 5.8, respectively. CONCLUSION: These data suggest that a polycystic ovary syndrome susceptibility allele is linked to human leukocyte antigen and that the susceptibility allele is recessive.

Alleles

Association of coagulation factors and inhibitors with carotid artery atherosclerosis. Early results of the Atherosclerosis Risk in Communities (ARIC) Study.

Several population studies have shown that plasma levels of fibrinogen and factor VII are significantly associated with ischemic cardiovascular events. However, there is little information regarding the association of hemostatic factors with early atherosclerosis. To evaluate this, we compared the plasma concentrations of several coagulation proteins (fibrinogen, factor VII, factor VIII, von Willebrand factor, protein C, and antithrombin III) between 385 case patients, defined by high-resolution B-mode ultrasonography as having carotid arterial wall thickening, and 385 age-, race-, and sex-matched control subjects. These case patients and control subjects were selected from participants in a prospective population investigation, the Atherosclerosis Risk in Communities (ARIC) Study, who were examined between May 1987 and May 1989. Plasma fibrinogen, factor VII, protein C, and antithrombin III levels were significantly higher in case patients than in control subjects (P < 0.05). Factor VIII and von Willebrand factor were not different. These findings were supported by quartile distribution and univariate analysis. However, only fibrinogen remained significantly associated with carotid atherosclerosis on multivariate analysis taking other atherosclerosis risk factors into consideration. A one standard deviation increase in fibrinogen (67 mg/dL) was associated with a 1.6-fold increase in the odds of carotid atherosclerosis univariately (P < 0.001) and with a 1.3-fold increase in the odds multivariately (P = 0.010). Further analysis revealed that the association of fibrinogen with carotid atherosclerosis was somewhat stronger in cigarette smokers than in nonsmokers. This early case-control analysis of the ARIC Study demonstrates a significant association between plasma fibrinogen concentration and early atherosclerosis in the carotid arteries. In the context of published findings from population studies, our results indicate that plasma fibrinogen concentrations may be a useful marker for identifying individuals at high risk of developing arterial thrombotic disorders.

Antithrombin III

Drug use and suicide ideation and behavior among North Carolina public school students.

We used data from 3064 respondents to the 1990 North Carolina Youth Risk Behavior Survey to examine the relationship between adolescent drug use and suicide ideation and behavior. Principal components analysis followed by varimax rotation was performed separately on the drug use and suicide items. Correlation coefficients computed between the two sets of factor scores and comparison of mean drug use factor scores revealed that drug use, particularly of crack/cocaine, was related to increased suicide ideation and behavior.

Adolescent

Carotid atherosclerosis measured by B-mode ultrasound in populations: associations with cardiovascular risk factors in the ARIC study.

To assess whether carotid atherosclerosis measured by B-mode ultrasound is related to cardiovascular risk factors, 386 cases with carotid artery wall thickening and an equal number of controls free of arterial intima-media thickening were drawn from the cohort of the Atherosclerosis Risk in Communities (ARIC) Study examined in four communities in the United States between 1988 and 1990. Cases and controls were individually matched on sex, race, age group, study center, and date of examination. The mean values of total cholesterol, low density lipoprotein (LDL) cholesterol, total triglyceride, blood pressure, and pack-years of cigarette smoking were higher in cases than controls. Mean high density lipoprotein (HDL) cholesterol was lower in cases than controls. Case-control differences were all statistically significant. Multivariable-adjusted odds ratios point to differences of considerable magnitude in the risk of carotid atherosclerosis between groups defined by clinical and public health-oriented risk factor cut-points.

Arteriosclerosis