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Biomedical subjects

R G Roberts

Publications and source records attributed to R G Roberts.

At least 19 recordsLinked to original sources
PubMed1996

Sequence and chromosomal location of a human homologue of LRPR1, an FSH primary response gene.

The rat gene Leucine-Rich Primary Response Gene-1 (LRPR1) has been proposed to encode a protein involved in the response of gonadal tissues to follicle-stimulating hormone. We have characterized a human transcript that probably encodes the orthologue of the rat protein, exhibiting 72% identity at the amino acid level. The gene from which the transcript is derived maps to human chromosomal region Xq22 and therefore becomes a potential candidate for human X-linked disorders of gonadal development.

Amino Acid Sequence↗
PubMed1996

The correction of acidosis does not increase dietary protein intake in chronic renal failure patients.

In normal humans and in patients with chronic renal failure (CRF), acidosis increases whole-body protein degradation. Correction of acidosis reduces protein degradation. The mechanisms underlying these changes in protein metabolism are unclear. However, one possibility is that dietary protein intake is reduced in acidosis and that this causes increased protein degradation. This possibility has not been tested. In this study the effects of acidosis on protein intake in patients with CRF have been assessed using 7-day weighed dietary inventories in the acidotic state (venous bicarbonate 15.6 +/- 1.0 mmol/L) and following treatment with oral sodium bicarbonate (venous bicarbonate 21.0 +/- 1.4 mmol/L). Protein intake was also derived from urinary nitrogen excretion. There was no significant difference in protein intake calculated from dietary records (1.0 +/- 0.09 g/kg/d v 1.06 +/- 0.1 g/ kg/d) or calculated from urinary nitrogen (1.13 +/- 0.07 g/kg/d v 1.06 +/- 0.06 g/kg/d) between the untreated and bicarbonate-treated states in eight patients with CRF. We conclude that acidosis in CRF patients does not affect dietary protein intake and that dietary changes therefore do not contribute significantly to the changes in protein metabolism seen in acidosis.

Acidosis↗
PubMed1996

Characterization of DRP2, a novel human dystrophin homologue.

The currently recognised dystrophin protein family comprises the archetype, dystrophin, its close relative, utrophin or dystrophin-related protein (DRP), and a distantly related protein known as the 87K tyrosine kinase substrate. During the course of a phylogenetic study of sequences encoding the characteristic C-terminal domains of dystrophin-related proteins, we identified an unexpected novel class of vertebrate dystrophin-related sequences. We term this class dystrophin-related protein 2 (DRP2), and suggest that utrophin/DRP be renamed DRP1 to simplify future nomenclature. DRP2 is a relatively small protein, encoded in man by a 45 kb gene localized to Xq22. It is expressed principally in the brain and spinal cord, and is similar in overall structure to the Dp116 dystrophin isoform. The discovery of a novel relative of dystrophin substantially broadens the scope for study of this interesting group of proteins and their associated glycoprotein complexes.

Amino Acid Sequence↗
PubMed1996

Capsaicin cough receptor sensitivity test in children.

Capsaicin has been used as a tussive agent in studies in adults to determine cough receptor sensitivity. The aim of this study was to determine the tolerance, repeatability and influence of inspiratory flow on the capsaicin cough receptor sensitivity test in children. Thirty children (mean age 11 yrs; range 6-16 yrs) were tested on two different days, to determine the lowest concentration of capsaicin required to stimulate two or more coughs (cough threshold (Cth)), 2-4 coughs (C2), and five or more coughs (C5). Capsaicin was nebulized through a dosimeter, with an arrangement that allowed the subjects to visualize and regulate their inspiratory flow. Using a constant inspiratory flow of 20 L x min(-1), tests were reproducible for C2, C5 and Cth (doubling dose changes of 1.13, 1.03 and 1.08, respectively). An increase in the inspiratory flow from 20 to 60 L x min(-1) significantly increased C2 (19.5 to 46.8 microM; p=0.016) and C5 (46.8 to 128.8 microM; p=0.008). We conclude that in children, the capsaicin cough challenge test: 1) is well-tolerated; 2) is highly repeatable; and that 3) the inspiratory flow significantly influences cough receptor sensitivity and repeatability of the test and should, thus, be regulated.

Adolescent↗
PubMed1995

Nicotinic acetylcholine receptors on capsaicin-sensitive nerves.

To study the density of nicotinic acetylcholine receptors on primary afferents and central nociceptive pathways, [3H](-)-nicotine binding was conducted in the cerebral cortex and spinal cord including dorsal roots and ganglia (DRG), of control rats and rats desensitized by neonatal capsaicin treatment. [3H](-)-nicotine binding in capsaicin-treated rats was reduced in cerebral cortex by 35% and spinal cord+DRG by 46% (p < 0.05). Functionally, both iontophoretically applied acetylcholine- and capsaicin-evoked flares (measured by laser Doppler flowmetry) were reduced in capsaicin-treated animals (p < 0.05); similarly, electrical stimulation-evoked flares were significantly lower in the same group, compared with controls (p < 0.05). These data provide direct evidence that many neuronal nicotinic acetylcholine receptors are associated with capsaicin-sensitive peptidergic neurones, including primary afferents, DRG and central nociceptive pathways.

Afferent Pathways↗
PubMed1995

Protein truncation test: analysis of two novel point mutations at the carboxy-terminus of the human dystrophin gene associated with mental retardation.

Approximately one-third of the mutations responsible for Duchenne muscular dytrophy (DMD) do not involve gross rearrangements of the dystrophin gene. Methods for intensive mutation screening have recently been applied to this immense gene, which resulted in the identification of a number of point mutations in DMD patients, mostly translation-terminating mutations. A number of data raised the possibility that the C-terminal region of dystrophin might be involved in some cases of mental retardation associated with DMD. Using single-strand conformation analysis of products amplified by polymerase chain reaction (PCR-SSCA) to screen the terminal domains of the dystrophin gene (exons 60-79) of 20 unrelated patients with DMD or BMD, we detected two novel point mutations in two mentally retarded DMD patients: a 1-bp deletion in exon 70 (10334delC) and a 5' splice donor site alteration in intron 69 (10294 + 1G-->T). Both mutations should result in a premature translation termination of dystrophin. The possible effects on the reading frame were analyzed by the study of reverse transcripts amplified from peripheral blood lymphocytes mRNA and by the protein truncation test.

Base Sequence↗
PubMed1995

The identification of point mutations in Duchenne muscular dystrophy patients by using reverse-transcription PCR and the protein truncation test.

The protein truncation test (PTT) is a mutation-detection method that monitors the integrity of the open reading frame (ORF). More than 60% of cases of Duchenne muscular dystrophy (DMD) result from gross frame-shifting deletions in the dystrophin gene that are detectable by a multiplex PCR system. It has become apparent that virtually all of the remaining DMD mutations also disrupt the translational reading frame, making the PTT a logical next step toward a comprehensive strategy for the identification of all DMD mutations. We report here a pilot study involving 22 patients and describe the mutations characterized. These constitute 12 point mutations or small insertions/deletions and 4 gross rearrangements. We also have a remaining five patients in whom there does not appear to be a mutation in the ORF. We believe that reverse-transcription--PCR/PTT is an efficient method by which to screen for small mutations in DMD patients with no deletion.

Base Sequence↗
PubMed1994

The advanced life support in obstetrics course. A national program to enhance obstetric emergency skills and to support maternity care practice.

Unexpected emergencies occur during routine maternity care. Perceived or actual deficiencies in training may decrease the quality of care and increase liability risks and anxiety among providers. This may lead the provider to discontinue obstetrics, which results in problems in access to care. To improve the training for obstetric emergency management, an Advanced Life Support in Obstetrics (ALSO) course was developed. This skill-enhancing course, modeled after other life support courses, is designed to improve the quality and availability of maternity care through standardized training in the management of emergencies and improved communication between maternity care providers. A total of 1315 physicians and nurses attended 35 ALSO courses from 1991 through 1993. Seventy-six percent were family physicians in practice; 20% were from rural areas. About 15% were in hospitals with no obstetricians or pediatricians on staff. Attendees reported a significant increase in their level of comfort in the management of obstetric emergencies and a greater intention to continue maternity care.

Adult↗
PubMed1994

Searching for the 1 in 2,400,000: a review of dystrophin gene point mutations.

The past few years have seen a rapid increase in our knowledge of naturally occurring mutations in the dystrophin gene. Although earlier studies were limited to gross rearrangement mutations, we are now in a position to draw lessons on the molecular etiology of the remaining one-third of cases of Duchenne and Becker muscular dystrophy (DMD, BMD) which are associated with small mutations. This paper reviews 70 published and unpublished small mutations in the dystrophin gene and asks what we can learn about their nature, their distribution, and approaches to their characterisation. Strikingly for such a well-conserved gene, missense mutations are extremely rare, and the vast majority of DMD point mutations, like the gross rearrangements, result in premature translational termination. It seems increasingly likely that almost all cases of DMD arise solely as a result of a reduction in the level of dystrophin transcripts, and we argue that > 95% of DMD mutations contribute nothing to the functional dissection of the dystrophin protein. Most of the few BMD point mutations presented here are missense mutations in the N-terminal or C-terminal domains or are splice-site mutations that probably act, like BMD deletions, via the production of in-frame, interstitially deleted transcripts.

DNA↗
PubMed1994

Prostate cancer, screening and the generalist physician.

The generalist physician (family physician or general internist) provides primary care services and coordinates the care of other specialists for most Americans. These physicians develop continuous relationships with patients that can span decades. This therapeutic relationship is an important aspect of the services that generalist physicians provide. Generalist physicians serve as the first line of defense in screening for cancer and other serious health conditions. Prostate cancer is a prevalent and important condition. However, generalist physicians will encounter 10 times as many older men who will die of heart disease than of prostate cancer. Until more conclusive evidence is available to support the aggressive diagnosis and treatment of early stage prostate cancer, the generalist physician should refrain from screening for prostate cancer without counseling men about the risks, benefits, alternatives and uncertainties of early diagnosis and treatment of prostate cancer.

Aged↗
PubMed1994

BPH: new guidelines based on symptoms and patient preference. The Agency for Health Care Policy and Research.

Benign prostatic hyperplasia (BPH) is the most common tumor in the aging human male. BPH is rarely a life-threatening condition, but it can affect the quality of an older man's life when it causes urinary symptoms. Several interventions are available for BPH: surgery, most often transurethral resection of the prostate (TURP); medication, including alpha blockers and 5-alpha reductase inhibitors; and balloon dilation. An appropriate option for many men is no active treatment but "watchful waiting." The common nature and cost of BPH and the range of available therapies stimulated the development of a guideline by a multidisciplinary panel sponsored by the federal Agency for Health Care Policy and Research (AHCPR).

Aged↗