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Biomedical subjects

T O'Brien

Publications and source records attributed to T O'Brien.

At least 127 records · Page 7Linked to original sources
PubMed1995

Distribution of GAGA protein on Drosophila genes in vivo.

GAGA protein binds specific CT.GA-rich DNA sequences in vitro, and many of these sequences are required for transcription in vivo. GAGA protein has been implicated in the transcription of numerous Drosophila genes, including hsp70, hsp26, actin 5C, and Ubx. Here, we examine the in vivo distribution of GAGA protein on a number of Drosophila genes that do and do not have CT-rich sequences by use of a UV cross-linking technique. Prior to heat shock, GAGA protein is associated with the promoter regions of the uninduced hsp70 and hsp26 genes. Upon heat shock induction, GAGA protein is recruited to their transcription units with its distribution coincident with that of RNA polymerase II. The recruitment of GAGA protein to the hsp70 gene after an instantaneous heat shock occurs in a 5' to 3' manner with kinetics similar to RNA polymerase. GAGA protein has been shown to disrupt nucleosome both in vivo and in vitro. We propose that GAGA protein may function in vivo both by binding constitutively to its high-affinity binding sites and by spreading through the induced gene opening the chromatin structure allowing polymerase to elongate efficiently.

Actins↗
PubMed1995

Different angiogenic pathways characterize superficial and invasive bladder cancer.

We have investigated by RNase protection analysis the expression of 2 angiogenic factors in 45 primary bladder tumors and 8 normal bladders. Expression of vascular endothelial growth factor (VEGF) was 3-fold higher and that of platelet-derived endothelial cell growth factor was 40-fold higher in tumors compared to normal bladder. However, the factors were differentially expressed in different stages of the cancer. Expression of VEGF in superficial tumors was 4-fold higher than in invasive tumors and 10-fold higher than in normal bladder (superficial versus invasive, P < 0.0006; superficial versus normal, P < 0.0002). Expression of platelet-derived endothelial cell growth factor in invasive tumors was 33-fold higher than in superficial tumors and 260-fold higher than in normal bladder (invasive versus superficial, P < 0.0001; invasive versus normal, P < 0.0003). In well differentiated or moderately differentiated superficial tumors which had invaded the lamina propria (pT1G1/2) VEGF expression was 4-fold higher in tumors which subsequently recurred at 3 months compared to those which did not recur (P < 0.002). Thus there are two distinct angiogenic pathways involved in different stages of bladder cancer, which is in keeping with the evidence for two different genetic pathways. Elevated VEGF expression predicts early recurrence of pT1G1/2 tumors.

Antisense Elements (Genetics)↗
PubMed1995

Multiple endocrine neoplasia type 2B: more than an endocrine disorder.

BACKGROUND: Multiple endocrine neoplasia type 2B (MEN 2B) is a rare disorder differentiated from MEN 2A primarily by its extraendocrine features. This report describes the clinical spectrum and outcome of MEN 2B. METHODS: Twenty-one patients underwent operation for manifestations of MEN 2B between 1970 and 1993. Median follow-up was 16.9 years. Diagnosis was made through family screening in nine, the development of medullary thyroid carcinoma (MTC) in seven, phenotypic features in four, and constipation in one. Median age at presentation of colonic dysfunction, MTC, and pheochromocytoma was 0.1, 16, and 28 years, respectively. RESULTS: Every patient had MTC. Fifteen (94%) of 16 patients undergoing primary thyroidectomies had multicentric disease, and seven (44%) had nodal metastases. Seven patients (33%) had pheochromocytoma, six bilateral and one malignant. Adrenalectomy was curative in every patient. Nineteen patients (90%) had colonic disturbances, typically chronic constipation from birth. Megacolon developed in 14 patients, and eight required colonic surgery. Every patient had the characteristic phenotype. Dominant features included neuromas of the tongue, buccal mucosa, lips, conjunctivae, and eyelids and a marfanoid habitus. Other features included high arched palate, corneal nerve thickening, and dental and skeletal abnormalities. Four patients died, two of metastatic MTC, one after operation for metastatic MTC, and one as a consequence of colonic perforation. Of 17 survivors, three have hepatic metastases from MTC, eight have nodal metastases, and six are well with normal or mildly elevated calcitonin levels. CONCLUSIONS: MEN 2B is characterized by a relatively aggressive form of MTC, bilateral pheochromocytoma, severe colonic dysfunction, and a multitude of other extraendocrine abnormalities. Early recognition of MEN 2B and early prophylactic thyroidectomy are essential. Colonic dysfunction has previously received little attention, and further investigation of the pathogenesis and treatment of this disorder is warranted.

Adolescent↗
PubMed1995

Polydactylous Bowen's disease of the nail bed.

A case is presented with tender swelling and nail bed hyperplasia in 2 fingers. Histopathology revealed Bowen's disease in both fingers and after amputation, invasive squamous cell carcinoma in one finger.

Amputation, Surgical↗
PubMed1995

The role of lipoprotein A-I and lipoprotein A-I/A-II in predicting coronary artery disease.

The aim of this study was to examine the role of HDL subparticles with apolipoprotein (apo) A-I alone (LpA-I) and with apoA-I and apoA-II (LpA-I/A-II) in predicting coronary artery disease. Concentrations of these HDL subparticles were compared in 184 subjects with angiographically confirmed significant coronary artery disease (> 50% stenosis of at least one vessel) and 191 age- and sex-matched control subjects without clinical coronary artery disease. LpA-I and LpA-I/A-II were measured with magnetic beads coated with anti-apoA-II antibodies to separate particles containing apoA-II from plasma. Total plasma cholesterol and triglyceride levels were similar in both groups. Although subjects with coronary artery disease had lower HDL cholesterol, plasma apoA-I, LpA-I, and LpA-I/A-II than age- and sex-matched control subjects without coronary artery disease, plasma apoA-I was the best predictor of coronary artery disease. In conclusion, LpA-I and LpA-I/A-II are lower in subjects with coronary artery disease but do not add to plasma apoA-I in predicting the presence of coronary artery disease.

Aged↗
PubMed1995

Refractory pelvic stress fracture in a female long-distance runner.

Stress fractures of the pelvis are uncommon. They tend to occur in female long-distance runners. We present the case of a female jogger with amenorrhea and osteoporosis who presented with left hip and groin pain. An initial bone scan yielded normal results. Symptoms persisted and subsequent plain radiographs and a repeat bone scan revealed evidence of public rami stress fractures. She developed a delayed union that ultimately healed with an electrical bone growth stimulator.

Adult↗
PubMed1994

Phosphorylation of RNA polymerase II C-terminal domain and transcriptional elongation.

The carboxy-terminal domain (CTD) of the large subunit of RNA polymerase II is essential in vivo, and is found in either an unphosphorylated (IIa) or hyperphosphorylated (IIo) form. The Drosophila uninduced hsp70 and hsp26 genes, and the constitutively expressed beta-1 tubulin and Gapdh-2 genes, contain an RNA polymerase II complex which pauses after synthesizing a short transcript. We report here that, using an in vivo ultraviolet crosslinking technique and antibodies directed against the IIa and IIo forms of the CTD, these paused polymerases have an unphosphorylated CTD. For genes containing a 5' paused polymerase, passage of the paused RNA polymerase into an elongationally competent mode in vivo coincides with phosphorylation of the CTD. Also, the level of phosphorylation of the CTD of elongating polymerases is shown not to be related to the level of transcription, but is promoter specific.

Animals↗
PubMed1994

Fatherhood without apparent spermatozoa after vasectomy.

Fatherhood after vasectomy is rare. We describe 6 cases of DNA-proven fatherhood after vasectomy in association with persistently negative semen examination. All vasectomy patients and their partners should be counselled about the small possibility of late failure, and warning of failure should be recorded.

Female↗
PubMed1994

Psychometric properties of the children's atypical development scale.

The Children's Atypical Development Scale (CADS) is a 53-item rating scale designed to measure unusual behaviors in children. Principal-factor analysis on a clinic-referred and pediatric sample of 474 children resulted in a four-factor solution: Communication Deficits, Lability, Social Relatedness Deficits, and Preoccupation. The CADS is internally consistent and has adequate temporal stability. CADS factor scores were differentially associated with parent and teacher rating scales, IQ, and Continuous Performance Test errors. The scale shows promise as a clinical and research tool for assessing atypical behaviors associated with pervasive developmental disorder and other neurobehavioral disorders.

Adolescent↗
PubMed1994

Lipids and Lp(a) lipoprotein levels and coronary artery disease in subjects with non-insulin-dependent diabetes mellitus.

OBJECTIVE: To determine whether increased Lp(a) lipoprotein levels are associated with either non-insulin-dependent diabetes mellitus (NIDDM) or coronary artery disease (CAD) in patients with NIDDM and to examine the relationship between Lp(a) levels and glycemic control. DESIGN: We conducted a cross-sectional study of subjects with NIDDM who were participants in the Rochester Diabetic Neuropathy Study and healthy control subjects from the population of Rochester, Minnesota. MATERIAL AND METHODS: Lipids and Lp(a) lipoprotein levels were compared in 227 subjects with NIDDM and 163 control subjects and, among the subjects with NIDDM, in those with (N = 96) and without (N = 131) CAD. The correlation between Lp(a) levels and glycosylated hemoglobin was investigated. RESULTS: Subjects with NIDDM had higher triglyceride and lower high-density lipoprotein cholesterol levels than did control subjects. Subjects with NIDDM and CAD had higher total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels and lower high-density lipoprotein cholesterol levels than did subjects with NIDDM without CAD. Subjects with NIDDM had significantly higher Lp(a) levels than did control subjects, but subjects with NIDDM and CAD did not have significantly higher Lp(a) levels than did those without CAD. Among subjects with NIDDM, the level of Lp(a) was not significantly correlated with glycosylated hemoglobin. CONCLUSION: Although subjects with NIDDM have higher Lp(a) levels than do control subjects, Lp(a) does not seem to be associated with CAD in subjects with NIDDM. In this study, no association was found between Lp(a) level and glycemic control.

Adult↗
PubMed1994

Nonmelanoma skin cancer: number of cancers and their distribution in outpatients.

BACKGROUND: Nonmelanoma skin cancer (NMSC) is increasing in incidence and more are developing on the trunk and limbs. The objectives were to determine how many outpatients have more than one NMSC at the time they present for treatment and to determine the anatomical distribution of the cancers. METHODS: All outpatients with histologically confirmed NMSC visited by the authors during 1992 received a total body examination and the number and sites of NMSC were recorded. RESULTS: A total of 952 outpatients were seen. A single NMSC was present in 69.4%, two in 16%, three in 6.4%, four in 3.5%, five to nine in 4.2%, and 0.5% had ten or more. Of the 291 patients with more than one NMSC, one anatomical region was involved in 53.4%, two were involved in 38.4%, and 8.2% had three or more regions involved. CONCLUSION: Patients with NMSC required a total body examination to detect unsuspected skin cancers.

Adult↗
PubMed1994

Anaerobic flora of the conjunctival sac in patients with AIDS and with anophthalmia compared with normal eyes.

Relatively few investigations of anaerobic bacteria as ocular flora have been conducted, and their results have been contradictory. The conjunctival sacs of 22 normal subjects and of 14 patients with acquired immunodeficiency syndrome, and 22 anophthalmic sockets were cultured for anaerobic bacteria Thirty-four (77.3%) of the 44 eyes of normal subjects harbored anaerobic bacteria; Propionibacterium acnes was present in 28 eyes (63.6%), Lactobacillus species in 6 eyes (13.6%), and Veillonella species in 7 eyes (15.9%). The finding were very similar for anophthalmic sockets (p = 0.01), with 17 (77.3%) of the 22 sockets harboring anaerobes; Propionibacterium acnes was the organism identified in 16 (72.7%) of these sockets; Veillonella was identified in 4 (18.1%), Peptococcus niger in 3 (13.6%) and P. granulosum in 2 (9.0%) of these sockets. Acquired immunodeficiency syndrome patients had the highest incidence of anaerobic organisms, with positive cultures obtained from 24 (85.7%) of the 28 eyes. Propionibacterium species were isolated from 16 (57.1%) of these eyes. Clostridium species from 10 (35.7%) eyes and Actinomyces species from 8 (28.6%) eyes. It thus appears that anaerobic organisms are common flora in normal conjunctival sacs and in anophthalmic sockets, as well as in the sacs of acquired immunodeficiency syndrome patients, but the latter group had a higher incidence (x2 = 0.87) and a spectrum of organisms that was different from that of the other two groups.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Coordinate pulsatile insulin secretion by chronic intraportally transplanted islets in the isolated perfused rat liver.

In the present studies we sought to address the following questions: do chronically transplanted intrahepatic islets (IHI-Tx) secrete insulin in a coordinate pulsatile manner, and, if so, is reestablishment of this coordinate pulsatility a function of time after transplantation? We studied isolated perfused livers at 10 mM glucose from 27 rats rendered diabetic with streptozotocin and then transplanted with approximately 2 x 10(3) islets, 2 (n = 5), 7 (n = 5), 30 (n = 5), and 200 (n = 12) d after transplantation. 12 out of 12 of the 200-d IHI-Tx secreted insulin in coordinate pulses (frequency 3.9 +/- 0.3 pulses/h, amplitude 15.2 +/- 2.4 nmol/min). In contrast, one out of five 2-d, zero out of five 7-d, and one out of five 30-d IHI-Tx showed pulsatile insulin secretion. Insulin secretion was markedly greater (76 +/- 13 vs 13 +/- 3 nmol/min, P < 0.0001) in the 200-d versus early IHI-Tx. Pentobarbital 25 micrograms/ml had no effect on total (13.9 +/- 3.9 vs 15.9 +/- 3.9 nmol/min), nonpulsatile (12.9 +/- 3.5 vs 14.1 +/- 3.3 nmol/min), or pulsatile (pulse amplitude 17.6 +/- 4.5 vs 20.0 +/- 4.2 nmol/min, pulse frequency 4.1 +/- 0.3 vs 4.0 +/- 0.7 pulses/h) insulin secretion. Using synaptophysin, islet innervation was documented in 12 out of 12 200-d IHI-Tx but in none of the early IHI-Tx. We conclude that established (approximately 200 d) IHI-Tx secrete insulin in a coordinate pulsatile manner and that establishment of coordinate pulsatile insulin secretion by IHI-Tx is accompanied by increased total insulin secretion and is associated with islet reinnervation.

Animals↗
PubMed1994

Low intelligence but not attention deficit hyperactivity disorder is associated with resistance to thyroid hormone caused by mutation R316H in the thyroid hormone receptor beta gene.

Resistance to thyroid hormone (RTH) is a syndrome of reduced responsiveness of tissues to thyroid hormone. The clinical manifestations are variable and 46-50% of children with RTH have attention deficit hyperactivity disorder (ADD). We present a new family with RTH (F120) found to have a mutation R316H in the thyroid hormone receptor beta (TR beta) gene identical for that reported in an unrelated family. Assignment of the mutant allele and haplotyping based on CA repeat polymorphism were done on 16 family members. Semistructured diagnostic interviews and psychometric testing were used to determine the psychiatric diagnosis of 12 family members by examiners blinded to the genotype. Three subjects were identified to have the R316H allele as well as mildly elevated free T4 index (168 +/- 12; normal range 77-135) and nonsuppressed TSH (4.1 +/- 1.7 mU/L). Only 2 of the subjects with RTH were found to have ADD, while one family member homozygous for the wild type TR beta and normal thyroid function tests also had ADD. Unaffected family members had higher full scale intelligence quotients (IQ) (93 +/- 7) than any of the 3 family members with RTH (77 +/- 5, p = 0.006). These data do not support the genetic linkage of ADD and RTH, but do suggest that RTH is associated with lower IQ scores that may confer a high likelihood of exhibiting ADD symptoms.

Adolescent↗
PubMed1994

Medullary thyroid carcinoma in multiple endocrine neoplasia types 2A and 2B.

BACKGROUND: Considerable emphasis has been placed on early diagnosis and surgery for multiple endocrine neoplasia (MEN)-related medullary thyroid carcinoma (MTC) during the past two decades. Genetic screening now promises earlier and more accurate diagnosis. We examine our experience with MTC in MEN 2A and MEN 2B and assess the benefits of biochemical screening during the past 20 years. PATIENTS AND METHODS: Seventy-seven patients undergoing 63 primary total thyroidectomies and 14 reoperative procedures for MEN-related invasive MTC and/or preinvasive C-cell hyperplasia are reported. Fifty-eight patients had MEN 2A and 19 had MEN 2B; 79% of patients had a family history of MTC; 27% had pheochromocytoma, and 25% had hyperparathyroidism. RESULTS: Patients with MEN 2B had more advanced disease than those with MEN 2A, in spite of presentation at a younger age (15 years versus 24 years). Every patient with MEN 2B had invasive carcinoma, whereas 14% of patients with MEN 2A had C-cell hyperplasia without invasive disease. Nodal metastases were found less frequently in MEN 2A (14%) than MEN 2B (38%), and biochemical cure was achieved in 56% of patients with MEN 2A compared with none in patients with MEN 2B. Among patients with MEN 2A the occurrence of invasive carcinoma increased with age (p = 0.0003); 40% of patients for less than 5 years had invasive MTC compared with 100% at more than 20 years. Cause-specific mortality among patients with MEN and invasive tumors at 6, 12, and 18 years was 2%, 4%, and 7%, respectively, lower than that of patients with sporadic MTC (12%, 17%, and 23%, respectively) treated during the same time period (p = 0.028). CONCLUSIONS: Intensive biochemical screening of MEN 2 kindreds for MTC can result in detection of early disease and a significant prospect of surgical cure. Genetic testing promises additional benefits through more reliable detection of preinvasive disease, allowing prophylactic thyroidectomy in infancy. In MEN 2B, MTC is considerably more aggressive than in MEN 2A. A policy of routine thyroidectomy in infants with MEN 2B, regardless of serum calcitonin levels, is justified.

Adolescent↗
PubMed1993

Separation of high-density lipoproteins into apolipoprotein E-poor and apolipoprotein E-rich subfractions by fast protein liquid chromatography using a heparin affinity column.

The aim of this paper is to describe a new methodology for the separation of human high-density lipoproteins (HDL) into apolipoprotein (apo) E-poor and apo E-rich subfractions by fast protein liquid chromatography (FPLC) using a heparin affinity column. Recoveries for apolipoproteins AI, AII, CI, CII, CIII, and E were 68.9, 74.7, 71.9, 73.5, 40.0, and 55.8%, respectively. We provide suggestive evidence that apo E-rich HDL is produced from apo E-poor HDL by the displacement of apo AI by apo E. Apo E-poor HDL was the predominant fraction. The molar ratio of apo E to apo AI in apo E-poor HDL was 0.02 and 0.01 for the subjects studied while in apo E-rich HDL it was 1.86 and 1.25. The molar ratios of the C apolipoproteins to apo AI are markedly different between the subfractions.

Apolipoproteins↗