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Biomedical subjects

J Roberts

Publications and source records attributed to J Roberts.

At least 433 records · Page 24Linked to original sources
PubMed1990

Simian virus 40 origin auxiliary sequences weakly facilitate T-antigen binding but strongly facilitate DNA unwinding.

The complete simian virus 40 (SV40) origin of DNA replication (ori) consists of a required core sequence flanked by two auxiliary sequences that together increase the rate of DNA replication in monkey cells about 25-fold. Using an extract of SV40-infected monkey cells that reproduced the effects of ori-auxiliary sequences on DNA replication, we examined the ability of ori-auxiliary sequences to facilitate binding of replication factors and to promote DNA unwinding. Although the replicationally active form of T antigen in these extracts had a strong affinity for ori-core, it had only a weak but specific affinity for ori-auxiliary sequences. Deletion of ori-auxiliary sequences reduced the affinity of ori-core for active T antigen by only 1.6-fold, consistent with the fact that saturating concentrations of T antigen in the cell extract did not reduce the stimulatory role of ori-auxiliary sequences in replication. In contrast, deletion of ori-auxiliary sequences reduced the efficiency of ori-specific, T-antigen-dependent DNA unwinding in cell extracts at least 15-fold. With only purified T antigen in the presence of topoisomerase I to unwind purified DNA, ori-auxiliary sequences strongly facilitated T-antigen-dependent DNA conformational changes consistent with melting the first 50 base pairs. Under these conditions, ori-auxiliary sequences had little effect on the binding of T antigen to DNA. Therefore, a primary role of ori-auxiliary sequences in DNA replication is to facilitate T-antigen-dependent DNA unwinding after the T-antigen preinitiation complex is bound to ori-core.

Animals↗
PubMed1990

Out-of-hours duties in public health medicine: a survey of doctors in the Yorkshire Region.

A survey of doctors involved in out-of-hours public health medicine was conducted in the Yorkshire Region. Although the majority were satisfied with their present arrangements and had received some formal training for such duties, the study revealed potential areas for improvement. A review of current responsibilities and education is indicated.

Attitude of Health Personnel↗
PubMed1990

Transcutaneous oxygen tension in preterm neonates during neonatal behavioral assessments and heelsticks.

This study evaluates the effects of neonatal behavioral assessments and heelsticks on transcutaneous oxygen tension (TcPO2) in 37 preterm neonates from a neonatal intensive care unit. Two behavioral assessments were evaluated, the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) and the Neurobehavioral Assessment for Preterm Infants (NAPI). TcPO2 during heelsticks was used as a comparison because reliable decreases have typically been noted during heelsticks. Although the heelsticks resulted in significant declines in TcPO2, the behavioral assessments led to only negligible changes in TcPO2. Observed changes during the behavioral assessments occurred in a small number of infants, primarily during the few test procedures administered to the infants outside of their isolettes. Accordingly, it is suggested that time outside the isolette and associated temperature changes may be more critical variables than the assessments per se.

Arousal↗
PubMed1990

Role of calcium in adrenergic neurochemical transmission in the aging heart.

The effect of modification of extracellular Ca2+ concentration ([Ca2+]0), the administration of the neuronal Ca2+ channel blocker, omega-conotoxin, and the calcium (Ca2+) ionophore, ionomycin, were examined in the isolated heart of male Fisher-344 rats 6 and 24 months of age. Hearts with the right cardiac sympathetic nerve intact were isolated and perfused with Krebs-Ringer solution containing cocaine (10(-6) M) to block uptake 1, metanephrine (10(-6) M) to block uptake 2 and yohimbine (3 X 10(-6) M) to prevent alpha 2 receptor inhibition of Ca2+ influx. The nerve was stimulated with frequencies of 2, 6 and 12 Hz for 1 min and NE output was determined by high-performance liquid chromatography/electrochemical methods. Effluent of hearts from 6-month-old rats contained higher levels of NE than effluent of hearts from 24-month-old rats at all frequencies of stimulation when perfused with either normal (1.2 mM), low (0.3 mM) or high (4.8 mM) [Ca2+]0. Even when high [Ca2+]0 was used to make more Ca2+ available, the amount of NE in the effluent of 24-month-old animal hearts was only approximately 54% of that found in the effluent of 6-month-old animal hearts perfused with normal [Ca2+]0. omega-Conotoxin caused a greater decrease in NE release in the older preparations suggesting that the neuronal Ca2+ channels of older preparations are more susceptible to blockade than those of younger preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1989

Severe delayed-onset hypersensitivity reactions to amoxicillin in children.

Amoxicillin, a semisynthetic aminopenicillin, has achieved widespread use in recent years for the treatment of respiratory tract and otic infections. Serious reactions have been relatively infrequent. From July 1986 to June 1987, 11 children aged 6 months to 10 years presented with delayed-onset hypersensitivity reactions. In 10 the symptoms were consistent with a serum-sickness-like illness, including urticaria, angioedema, arthritis and arthralgia. Radioallergosorbent testing for IgE antibodies to penicillin yielded negative results, and lymphocyte transformation testing gave a positive result in only one patient. Because of the negative immunologic test results and the occurrence of reactions only in children, who had received an amoxicillin solution, the reactions may have been caused by the excipient.

Amoxicillin↗
PubMed1989

Cytotoxic effects of methionine alkyl esters and amides in normal and neoplastic cell lines.

Homologous series of L-methionine alkyl ester hydrochlorides and tosylates were synthesized and evaluated for in vitro growth inhibitory activity in Meth A sarcoma. Cytotoxicity, as determined by [3H]thymidine incorporation, was found to be directly proportional to alkyl chain length and surface tension lowering activity. L-Methionine decyl and dodecyl ester hydrochlorides possessed optimum cytotoxic activity (IC50 = 29, 28 microM) which was not reversible by the addition of L-methionine. Surface tension of a 50 microM solution of the decyl and dodecyl ester hydrochlorides were 35.4 and 32.7 dyn/cm, respectively. The corresponding decyl and dodecyl ester tosylates and amide hydrochlorides were less active. The N-t-butoxycarbonyl analogues were essentially inactive, demonstrating the necessity of an unsubstituted and/or potentially cationic amino group. Methionine dependence characteristics and cytotoxicity were also determined for three human (IMR-90, LX-1, MCF7) and four additional murine (L1210, L5178Y, 3T3, SV-T2) cell lines. The human cell lines Meth A, LX-1, and SV-T2 were found to be methionine independent. The LX-1 tumor cell line and the SV-T2 transformed line exhibited two to four times more sensitivity to the cytotoxic and cytolytic properties of the decyl and dodecyl ester hydrochlorides than their normal counterparts. The dodecyl amide hydrochloride derivative demonstrated enhanced cytotoxic activity in vivo relative to the corresponding ester, possibly due to decreased metabolic hydrolysis.

Animals↗
PubMed1989

Upregulation of adrenergic beta receptor subtypes in the senescent rat heart.

Beta receptors in older hearts respond to procedures which cause upregulation (N. Tumer et al., J. Gerontol., 1989, in press). To determine whether a particular beta receptor subtype is responsible for the development of upregulation as a function of age, we studied the ratio of beta 1- to beta 2-adrenergic receptors in the membrane preparations from the ventricles of Fischer-344 hearts at 6 and 24 months of age. The animals were injected with 6-hydroxydopamine hydrobromide (6-OHDA) (2 x 50 mg/kg, i.v.) on days 1 and 8 and they were decapitated on day 15. The depletion of norepinephrine in the heart was about 86% in each age group. [125I]iodopindolol (IPIN) was used as the radioligand at the final concentration of 110 pM. Inhibition of specific IPIN binding was studied by adding ICI 89,406 (beta 1-selective antagonist) and ICI 118,551 (beta 2-selective antagonist) at 25 pM to 40 microM. The relative proportions of the beta receptor subtypes were determined using a competition radioligand selective binding and computer modeling technique. The ventricles contained about 67% beta 1 and 33% beta 2-adrenergic receptors in hearts isolated from 6- and 24-month old rats; the ratio remained the same in sympathectomized animals. These data suggest that both subtypes of cardiac adrenergic receptors participate in the response to chemical denervation by 6-OHDA regardless of age.

Aging↗
PubMed1989

Optimal coverage of peritoneal surface in whole abdominal radiation for ovarian neoplasms.

Patterns of failure in ovarian carcinoma include early seeding of the entire peritoneal cavity. Inability to encompass the anatomic extent of the peritoneal cavity is a possible factor leading to relapse. However, little has been published regarding technical advances in optimal coverage of the peritoneal surface in whole abdominal radiation. In the Department of Radiation Oncology at the University of Michigan, 21 consecutive patients were analyzed prospectively in regard to adequate coverage of peritoneum in the treatment of advanced ovarian carcinoma. Simulation and focused blocks were designed to treat the whole abdomen. CT treatment planning studies were obtained with the entire peritoneum identified as the target volume. Simulator designed blocks were projected over the CT scans throughout the treatment volume. Dose volume histograms were used to calculate the amount of target volume missed for each treatment plan. All treatment plans demonstrated different degrees of volume miss, ranging from 1 cm3 to 837.3 cm3 with a median of 137.9 cm3 overall. Volume missed directly correlated with increasing patient weight and flatter pelvic shape, but poorly with AP separation. This was especially evident for patients requiring treatment at extended distances in both the supine and prone positions. We conclude that bony landmarks are poor guidelines in designing pelvic blocks, especially in heavy patients and patients requiring treatment in both prone and supine positions. CT treatment planning is helpful to ensure optimal peritoneal coverage.

Abdomen↗
PubMed1989

Induction of metachromasia in experimentally induced hyperplastic/hypertrophic changes in the prostate of the cynomolgus monkey (Macaca fascicularis).

Metachromasia has been shown to be a stromal marker for human benign prostatic hyperplasia (BPH). So far, it is not known whether comparable changes can be demonstrated in experimentally induced BPH in the dog or in a subhuman primate species. In the present study, the phenomenon of metachromasia could be demonstrated in the prostate of cynomolgus monkeys, too. The reaction was quantitatively intensified by the treatment with androstenedione--an aromatizable androgen which caused hyperplastic and hypertrophic changes--especially a stimulation of the smooth muscle--in the stroma of the prostate. Simultaneous treatment with the aromatase inhibitor 1-methyl-ADD prevented both the phenomenon of metachromasia and the stimulation of the stroma. In conclusion, it is not only possible to induce hyperplastic/hypertrophic changes in the prostate of a subhuman species by means of an aromatizable androgen but, in addition, this effect is accompanied by a phenomenon which is thought to be typical for human BPH suggesting the suitability of this type of experiment for the study of the factors involved in the pathogenesis of BPH.

Androstenedione↗
PubMed1989

Detection of breast cancer by measuring areolar blood flow--a pilot study.

Regional blood flow in the areola was measured by using the non-invasive transient thermal clearance method in normal breasts and in breasts involved with cancer. Areolar blood flow (ABF) in normal breasts was almost constant for women in the age range 20-60y, but decreased at higher ages. ABF in breasts involved with cancer was higher than that in the contralateral breast, and higher than the average normal ABF in the corresponding age group. The effect was more prominent in the left breast. The transient thermal clearance method provides a potential non-invasive means for detection of breast cancer.

Adult↗
PubMed1989

The effect of age on presynaptic alpha 2 adrenoceptor autoregulation of norepinephrine release.

The effect of age on presynaptic alpha 2 adrenoceptor-mediated regulation of norepinephrine (NE) release was studied in hearts isolated from male Fischer 344 rats 6-, 12- and 24-months of age. Cocaine (10(-6)M) and metanephrine (10(-5)M) were added to the perfusion fluid separately and in combination to block neuronal and extraneuronal uptake mechanisms, respectively. The amount of NE overflow in the effluent was significantly lower with increasing age at any given frequency of nerve stimulation. Metanephrine increased NE overflow in heart preparations of 12- and 24-month-old animals only. Yohimbine, a selective alpha 2 adrenoceptor antagonist at concentrations of 10(-6)M and 3 x 10(-6)M significantly increased the amount of NE overflow only in the perfusion effluent of hearts isolated from 6-month-old animals. These results suggest that extraneuronal uptake mechanisms increase with age and that presynaptic alpha 2 adrenoceptor-mediated autoregulation of NE decreases with age. The findings could account, at least in part, for the decrease in adrenergic control of the heart shown to occur with age.

Aging↗