PubMed HealthSearch

Biomedical subjects

R D Harris

Publications and source records attributed to R D Harris.

At least 19 recordsLinked to original sources

Reduction-driven polypeptide folding by the delta Tt mechanism.

Poly(Gly-Val-Gly-Val-Pro), i.e., poly(GVGVP), exhibits composition and solute dependence of Tt, the temperature of the inverse temperature transition at which hydrophobic folding and assembly occur on raising the temperature. Importantly, a means whereby the value of Tt is lowered from above to below the working temperature becomes an isothermal means of driving folding and assembly, i.e., of achieving free energy transduction. Using poly[0.73(GVGVP),0.27(GK[NMeN]GVP)] where [NMeN] indicates N-methyl nicotinamide attached to the epsilon-NH2 of the Lys(K) residue, chemical and electrochemical reductions are found to remarkably lower the value of Tt; reduction can drive hydrophobic folding and assembly as effectively as decreasing ionization. Changing the redox state of a protein becomes yet another means of achieving free energy transduction by the delta Tt mechanism.

Amino Acid Sequence

Drug and alcohol related health problems in primary care--what do GPs think?

OBJECTIVE: To examine knowledge, attitudes and beliefs of general practitioners (GPs) in the field of drug and alcohol related health problems. DESIGN: A cross-sectional survey in which self-completion postal questionnaires were sent to all identifiable GPs in the Adelaide metropolitan area. Non-responders received a reminder letter and second questionnaire. SETTING, PARTICIPANTS: The target population was doctors whose principal activity was general practice, or who were in training for general practice. MAIN OUTCOME MEASURES: Demographic and "practice characteristic" information on participants. Measures of knowledge, attitudes and beliefs regarding alcohol consumption, smoking and over the counter medication. RESULTS: The response rate was 59.8%. More responders than non-responders were affiliated with the Royal Australian College of General Practitioners. Alcohol consumption was perceived to be a more difficult issue than smoking to raise during consultations. GPs indicated that significant proportions of their patients were participating in hazardous drinking (mean estimate was 13.8% of patients), but only a third of respondents believed their effort in changing alcohol related behaviour would be effective. Sixty-one per cent of respondents identified hazardous daily levels of alcohol consumption for men consistent with National Health and Medical Research Council guidelines. In the case of women this figure was 42%. Longer reported appointment times were associated with greater reported levels of enquiry about alcohol consumption. CONCLUSIONS: New developments in medical training and systems of payment in general practice need to address both the pessimistic attitude of GPs in dealing with drug and alcohol related health problems, and apparent inconsistencies in defining hazardous alcohol consumption.

Adult

Hydrophobicity scale for proteins based on inverse temperature transitions.

In general, proteins fold with hydrophobic residues buried, away from water. Reversible protein folding due to hydrophobic interactions results from inverse temperature transitions where folding occurs on raising the temperature. Because homoiothermic animals constitute an infinite heat reservoir, it is the transition temperature, Tt, not the endothermic heat of the transition, that determines the hydrophobically folded state of polypeptides at body temperature. Reported here is a new hydrophobicity scale based on the values of Tt for each amino acid residue as a guest in a natural repeating peptide sequence, the high polymers of which exhibit reversible inverse temperature transitions. Significantly, a number of ways have been demonstrated for changing Tt such that reversibly lowering Tt from above to below physiological temperature becomes a means of isothermally and reversibly driving hydrophobic folding. Accordingly, controlling Tt becomes a mechanism whereby proteins can be induced to carry out isothermal free energy transduction.

Amino Acid Sequence

Anterior urethral valve presenting in an adult male.

Anterior urethral valves are a rare congenital anomaly which can occur singly or in combination with a proximal urethral diverticulum. A retrograde urethrogram and voiding cystourethrogram can easily make the diagnosis unless the valve is located with the glandular urethra. Cystoscopic examination of the urethra can overlook anterior urethral valves, but by altering the flow of the irrigant, the cystoscope can be used to make these valves very apparent.

Adult

Limited field of view spin echo MR imaging.

Several groups have reported using a method of limiting the field of view (FOV) where the slices excited by the 90 and 180 degree pulses are perpendicular. However, only one slice can be excited during each repetition time, so multislice imaging is not possible. We present a modification of this method that allows multislice imaging. The slices excited by the 90 degrees and 180 degrees pulses are at a small angle; the field of view is limited and multislice imaging is possible. The modifications also allow the center of the FOV to be offset to any position. We describe the conditions that yield optimal images for the given FOV, slice thickness, and interslice gap. Representative images demonstrating the features of the technique are presented. The technique can be used to reduce the number of phase-encoding steps resulting in reduced imaging time, or it can be used to increase the spatial resolution without increasing the imaging time.

Humans

Global glomerular sclerosis and glomerular arteriolar hyalinosis in insulin dependent diabetes.

We studied the lesions of global glomerular sclerosis and arteriolar hyalinosis in 43 (29 females) insulin-dependent diabetes mellitus (IDDM) patients whose creatinine clearance (CCr) was greater than or equal to 45 ml/min/1.73 m2 and whose renal biopsies had at least 20 glomeruli available for study. These patients, ages 17 to 55 years, had IDDM for 7 to 32 (20 +/- 6, means +/- SD) years. CCr ranged from 47 to 139 (91 +/- 25) ml/min/1.73 m2 and urinary albumin excretion (UAE) from 5 to 3386 (median = 127) mg/24 hrs. Eighteen patients were hypertensive. Thus, these patients represented a broad clinical range from normal renal function through overt diabetic nephropathy. The percent of glomeruli which were globally sclerosed was strongly correlated with CCr (r = -0.64, P less than 0.0001) and log UAE (r = +0.67, P less than 0.001). Hypertension was more common in patients with more than 10% sclerosed glomeruli (chi square = 9.5, P less than 0.002). Percent sclerosed glomeruli was highly significantly correlated with the index of severity of the arteriolar hyalinosis lesion (r = +0.66, P less than 0.0001) and mesangial volume fraction (r = +0.61, P less than 0.0001). We hypothesize that arteriolar hyalinosis could contribute to global glomerular sclerosis through severe compromise of glomerular blood flow. Alternately, global glomerular sclerosis may result from marked mesangial expansion and capillary occlusion. However, in this broad range of patients it appeared that global glomerular sclerosis and mesangial expansion were not infrequently independent diabetic renal lesions which could contribute separately to the ultimate development of overt diabetic nephropathy.

Adolescent

Transgenic plants and insect cells expressing the coat protein of arabis mosaic virus produce empty virus-like particles.

The 3' end of the RNA-2 of arabis mosaic virus (ArMV) was cloned and sequenced. The N-terminal amino acid sequence of the virion coat protein was determined by Edman degradation and the corresponding coding region identified. This gene was modified at the 5' and 3' ends by use of mismatched primers in the polymerase chain reaction (PCR), in order to facilitate the cloning of the gene, and to provide it with a methionine initiation codon. The modified cloned gene was expressed in transgenic plants, recombinant baculovirus-infected insect cells and bacteria. Both the insect cells and the plants expressing the modified coat protein gene contained empty virus-like particles (VLPs) similar to the empty virus shells found in plants infected with ArMV. These VLPs were not detected in the Escherichia coli expressing the coat protein. Analysis of the primary amino acid sequence in the ArMV coat protein revealed extensive regions of identity with that of grapevine fanleaf virus. Patterns in these identities may reflect a three-domain organization of the proteins.

Amino Acid Sequence

A randomised study of outcomes in a defined group of acutely ill elderly patients managed in a geriatric assessment unit or a general medical unit.

The aim of this study was to identify differences in the medical management and clinical outcome in a group of elderly patients admitted to a designated geriatric assessment unit (GAU) or to two general medical units (GMUs). A prospective randomised controlled trial was undertaken in 267 patients aged 70 years and over (mean age = 78.3 years). Following discharge from hospital, patients were followed up at three monthly intervals for a total of 12 months. At the time of discharge, no significant differences were found in inpatient management, length of stay, mortality rates, discharge rates to institutional care or utilisation of community services in patients admitted to the GAU and the GMUs. Similarly, no significant differences were found at three, six, nine, and 12 month follow up in case fatality, activities of daily living indices, mental health status, rates of institutional referral and the level of community service support in patients admitted to the GAU and the GMUs studied. These findings do not show any advantage for the unselected 70+ acutely ill elderly patient who is admitted to a designated geriatric assessment unit rather than to a general medical unit. Therefore, an admission policy to GAU, based solely on age 70+ is medically inappropriate and cost-inefficient. Evidence from other sources suggests that an age cohort of acutely admitted patients beyond 80 years may well have returned more optimistic findings for the GAU. In future, GAUs will require a more selective admission policy to maximise the benefits of their rehabilitative and interdisciplinary approach.

Acute Disease

Attained height of lacto-ovo vegetarian children and adolescents.

The relationship between diet and attained height was studied in children and adolescents in Southern California. Diet pattern was determined from an extensive food frequency questionnaire in 1765 Caucasian children of 7-18 years, attending state schools (452 m and 443 f) and Seventh-day Adventist schools (427 m and 443 f). The major difference in diet pattern between state and Adventist school children was in meat consumption. The Adventist children were split evenly between three categories of frequency in meat consumption (less than 1/week, 1/week-less than 1/d, and greater than or equal to 1/d), while 92 percent of state school children consumed meat daily. Vegetarians (those consuming meat less than 1/week) differed significantly in the consumption of other major food groups, such as fruit and vegetables. All school and diet subgroups were at or above the 50th percentile of the National Center for Health Statistics. Age-adjusted regression analysis showed that on average Adventist vegetarian children were taller than their meat-consuming classmates (2.5 and 2.0 cm for boys and girls, respectively). These results did not change materially when adjusting for other food groups. Nor did adjustment for parental height and socioeconomic factors in a sub-sample of 518 children. The results indicate that vegetarian children and adolescents on a balanced diet grow at least as tall as children who consume meat.

Adolescent

Anthropometric parameters of schoolchildren with different life-styles.

Height and weight data obtained from a 2-year longitudinal survey were analyzed for 2272 children aged 6 through 18 years who were attending public schools or Seventh-Day Adventist (SDA) schools in southern California. The SDAs do not use alcohol or tobacco, and many adhere to a lacto-ovovegetarian diet. For both sexes, in each school group, the mean height and weight were at or above national reference values. Age-adjusted regression analysis showed that SDA school-boys were 1.6 cm taller than public schoolboys. There were no significant differences in height for girls. After controlling for height, boys and girls in the SDA schools were found to be leaner than their public school peers, ie, 1.27 and 1.16 kg, respectively. These results suggest that a health-oriented life-style in childhood and adolescence, such as the one followed by SDAs, is compatible with adequate growth and associated with a lower weight for height.

Adolescent

Differential scanning calorimetry studies of the inverse temperature transition of the polypentapeptide of elastin and its analogues.

Differential scanning calorimetry studies have been carried out on the sequential polypeptide of elastin, (L-Val1-L-Pro2-Gly3-L-Val4-Gly5)n, abbreviated as PPP, and its more hydrophobic analogues (L-Leu1-L-Pro2-Gly3-L-Val4-Gly5)n, referred to as Leu1-PPP, and (L-Ile1-L-Pro2-Gly3-L-Val4-Gly5)n, referred to as Ile1-PPP Consistent with inverse temperature transitions, the temperatures of the transitions for which maximum heat absorption occurs are inversely proportional to the hydrophobicities of the polypentapeptides (31 degrees C for PPP, 16 degrees C for Leu1-PPP, and 12 degrees C for Ile1-PPP), and the endothermic heats of the transitions are small and increase with increasing hydrophobicity, i.e., 1.2, 2.9, and 3.0 kcal/mol pentamer for PPP, Leu1-PPP, and Ile1-PPP, respectively. Previous physical characterizations of the polypentapeptides have demonstrated the occurrence of an inverse temperature transition since increase in order, as the temperature is raised above that of the transition, has been repeatedly observed using different physical characterizations. Furthermore, the studies demonstrated identical conformations for PPP and Il21-PPP above and below the transition. Both heats and temperatures of the transitions vary with hydrophobicity, but not in simple proportionality.

Amino Acid Sequence

Expression, characterization, and purification of a phosphorylated rabies nucleoprotein synthesized in insect cells by baculovirus vectors.

A baculovirus expression vector (AcNPV3) derived from the nuclear polyhedrosis virus of Autographa californica (AcNPV) was prepared containing the complete coding region of the nucleoprotein (N) gene of rabies virus (Gif-sur-Yvette clone of the CVS strain). The gene was placed under the control of the AcNPV polyhedrin promoter and was expressed to high levels (66 mg N protein/liter of 2 x 10(9) cells) by the derived recombinant virus using a Spodoptera frugiperda cell line. Using available antisera, it was established that the antigenic characteristics of the N protein were similar by comparison with those of the native N protein of rabies virus. Characterization of the expressed protein established that, like the N protein of mammalian cell-grown CVS virus, the N protein was phosphorylated. The expressed rabies N protein induced antibodies in mice that reacted strongly with the rabies viral protein. The expressed nucleoprotein was recovered from the insect cells by differential centrifugation followed by ion exchange chromatography. The expressed rabies N protein represents a source of authentic protein suitable for virus diagnosis as well as structural studies.

Animals

Unusual cause for recurrent Cushing syndrome and its diagnosis by computed tomography and NP-59 radiocholesterol scanning.

Cushing syndrome can recur following an adrenalectomy. One of the primary causes is recurrence of adrenal carcinoma either locally or from metastases. Hyperplasia and hyperfunction of adrenal remnants may also occur if there is pituitary stimulation. We have a patient in whom recurrent Cushing syndrome developed from small nonmalignant deposits of adrenal tissue in the perirenal adipose tissue following adrenalectomy of a benign adenoma. These deposits were identifiable by computed tomography. A false-negative NP-59 iodocholesterol scan was instructive in pointing out some problems in the interpretation of this type of scan for adrenal tissue.

Adenoma

Placental hypoechoic-anechoic areas and infarction: sonographic-pathologic correlation.

High-resolution ultrasound (US) and pathologic analysis were used to define the relationship between placental hypoechoic-anechoic areas, frequently seen in the third trimester, and the clinically significant entity of placental infarction. Placentas were obtained from three groups of patients: those prospectively demonstrating one or more placental hypoechoic-anechoic areas greater than or equal to 1 cm in diameter on third-trimester sonograms (n = 14), those with risk factors for vascular disease (n = 12), and control patients without risk factors (n = 16). Pathologic analysis demonstrated significantly more infarcts in patients with risk factors than in control patients (17 vs three, P = .047). Of a total of 22 infarcts from all three groups, 19 (86%) were isoechoic to viable placenta and therefore not detected with US. The three infarcts identified with US contained hypoechoic or anechoic foci of fibrin or hemorrhage. Of 26 placental hypoechoic-anechoic areas 23 (88%) were decidual septal cysts or intervillous thrombosis without infarction. The authors conclude that nonhemorrhagic placental infarction cannot be identified with ex utero US and, by inference, that prenatal US is probably insensitive for detection of placental infarction.

Female

MRI of splenic hemangioma associated with thrombocytopenia.

In contrast to the only previously published description, the magnetic resonance appearance of a splenic hemangioma was markedly heterogeneous on T2-weighted images due to extensive infarction and large vascular pools. Magnetic resonance images correlated precisely with the pathological findings. The hemangioma caused thrombocytopenia, a well-documented albeit rare hematologic phenomenon associated with visceral hemangioma.

Adult

MR and CT imaging of perirenal amyloidosis.

The radiographic findings of perirenal amyloidosis have not previously been described. A patient with multiple myeloma and primary amyloidosis (AL) with secondary hydronephrosis as examined on plain film, retrograde ureteropyelography, computed tomography, and magnetic resonance imaging is presented. This case illustrates perirenal amyloidosis and demonstrates the utility of CT and MRI in patient management and surgical treatment.

Aged

Offset electrocardiographic electrode simulating a pulmonary nodule on radiographs.

A recently developed type of electrocardiographic (ECG) monitoring electrode may simulate a pulmonary nodule on chest radiographs. The artifact results from the offset design of the electrode, which contrasts with the configuration of conventional electrodes. Awareness of this potential artifact is important to prevent misdiagnosis.

Diagnostic Errors