Muscle Rad expression and human metabolism: potential role of the novel Ras-related GTPase in energy expenditure and body composition

Ras associated with diabetes (Rad), a new ras-related GTPase, was recently identified by subtractive cloning as an mRNA in skeletal muscle that is overexpressed in NIDDM. To better understand its metabolic significance, we measured skeletal muscle Rad expression in well-characterized insulin sensitive (IS) and insulin resistant (IR) subjects with normal glucose tolerance and in untreated NIDDM patients. We found no differences in expression of Rad mRNA levels among IS, IR, and NIDDM groups using a ribonuclease protection assay (0.22 +/- 0.06, 0.13 +/- 0.01, and 0.16 +/- 0.02 relative units, respectively; NS) and no differences in Rad protein expression using a specific anti-peptide Rad antibody (1.05 +/- 0.18, 1.14 +/- 0.08, and 1.08 +/- 0.21 units/mg protein, respectively; NS). However, Rad protein levels were positively correlated with BMI (r = 0.43, P = 0.03) and percentage body fat (r = 0.55, P < 0.005), two independent measures of obesity, and negatively correlated with resting metabolic rate (r = 0.49, P = 0.01). In multiple regression analyses, percentage body fat and resting metabolic rate independently accounted for 30 and 10% of individual variability in muscle Rad protein expression. In conclusion, Rad expression in skeletal muscle is not altered as a function of insulin resistance or NIDDM in humans. However, these data, for the first time, implicate a role for Rad in regulating body composition and energy expenditure and provide a framework for studies designed to elucidate Rad's cellular functions.     

The incidence of low-pressure urethra as a function of prolapse-reducing technique in patients with massive pelvic organ prolapse (maximum descent at all vaginal sites)

OBJECTIVE: Our aims were to compare several prolapse-reducing techniques during urodynamic evaluation and prospectively evaluate their usefulness in identifying the incidence of low urethral closure pressure in continent patients with massive prolapse. STUDY DESIGN: This preoperative, prospective, repeated-measures urodynamic study evaluated the maximum urethral closure pressure with the use of four different techniques in 30 consecutive continent patients with grade 4 prolapse at all vaginal sites. Twenty patients with grade 0 prolapse served as the control group. All patients from the prolapse group underwent surgical treatment and were followed up clinically for a minimum of 1 year. RESULTS: Use of the Scopette (Birchwood Laboratories, Eden Prairie, Minn.) reduction technique to reduce the prolapse in a linear orientation during multichannel urodynamics revealed a 56% incidence of low-pressure urethra and an overall genuine stress urinary incontinence of 83% in patients with massive pelvic organ prolapse but without clinical urinary incontinence. CONCLUSIONS: There may be an increased indication for sling urethropexy in patients with massive prolapse.     

Paediatric upper gastrointestinal endoscopy: a 2-year review

OBJECTIVE: To review the paediatric upper gastrointestinal endoscopy service in a paediatric department in Hong Kong. METHODS: Records of all endoscopies undertaken in this department from May 1995 to January 1996 were retrieved and analysed. RESULTS: The commonest indication for upper endoscopy was dyspepsia with 88% positive histological findings. Helicobacter pylori (H. pylori) was found in 25% of this group of children. CONCLUSION: Paediatric upper gastrointestinal endoscopy service is invaluable in a paediatric department by providing useful diagnostic information which would otherwise be missed.     

Detection of oxidative stress in heart by estimating the dinitrophenylhydrazine derivative of malonaldehyde

Accurate estimation of the oxidative stress in heart is necessary because the pathogenesis of many heart diseases are believed to be mediated at least in part from the development of oxidative stress resulting from the generation of oxygen free radicals and reduced antioxidant defense system. The most widely used method for this purpose has been the estimation of malonaldehyde (MDA), a lipid peroxidation product, by the thiobarbituric acid (TBA) reaction method. However, because of the nonspecificity of this method, the results are often erroneous. The present report describes a method using high-performance liquid chromatography (HPLC) to estimate MDA. To develop the oxidative stress, two different models were used: ischaemic-reperfused heart and perfusing the heart with a hydroxyl radical (OH+) generating system. The coronary effluents obtained from the isolated rat heart before ischaemia and during the reperfusion of ischaemic heart, as well as during the perfusion of the heart with the OH+ generating system were collected, derivatized with 2,4-dinitrophenylhydrazine (DNPH) and extracted with pentane. Aliquots of 25 microliters in acetonitrile were injected onto a Beckman Ultrasphere C18 (3 microns) column. The products were eluted isocratically with a mobile phase containing acetonitrile-water-acetic acid (40:60:0.1, v/v/v), measured at 307 nm using a Waters M-490 multichannel UV detector and collected for gas chromatography-mass spectrometry (GC-MS). The peaks were identified by co-chromatography with DNPH derivatives of authentic standards, peak addition, and by GC-MS. The retention time for MDA-DNPH was 5.3 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stroke therapy in children

OBJECTIVE: To evaluate the treatment modalities used in children (ages 1-18 years) with cerebral infarction. BACKGROUND: [corrected] Cerebrovascular disease in children is more common than once suspected but its treatment has not been rigorously studied. MATERIAL AND METHODS: We reviewed all cases of cerebral infarction at the James Whitcomb Riley Hospital for Children at the Indiana University Medical Center from 01.01.80 to 31.12.95. RESULTS: Ninety-three children who experienced ischemic strokes were followed over the past fifteen years. Fifty-seven males and thirty-six females comprised the sample. Mean age was 6.9 years at the time of stroke. No medication or surgical intervention was the therapeutic recommendation in 44% of patients. For cardioembolic strokes, warfarin was used later in the course for a few patients who went on to have atrial fibrillation or valve replacement. Aspirin was used in all patients with carotid artery dissections. Aspirin was used in most children with Moya-Moya, with calcium channel blockers and surgical intervention used in later cases. Exchange transfusion followed by monthly transfusion and chelation therapy has been the treatment of choice for children with cerebral infarction complicating sickle cell disease. CONCLUSIONS: In most instances, treatment was widely disparate, probably reflecting the lack of firm therapeutic guidelines for this age group, with a better understanding of the etiology and pathophysiology of strokes in children, multicenter, international, randomized therapeutic trials based strictly on an etiological basis should be organized in the future.     

Human xeroderma pigmentosum group A protein interacts with human replication protein A and inhibits DNA replication

Human replication protein A (RPA; also known as human single-stranded DNA binding protein, or HSSB) is a multisubunit complex involved in both DNA replication and repair. While the role of RPA in replication has been well studied, its function in repair is less clear, although it is known to be involved in the early stages of the repair process. We found that RPA interacts with xeroderma pigmentosum group A complementing protein (XPAC), a protein that specifically recognizes UV-damaged DNA. We examined the effect of this XPAC-RPA interaction on in vitro simian virus 40 (SV40) DNA replication catalyzed by the monopolymerase system. XPAC inhibited SV40 DNA replication in vitro, and this inhibition was reversed by the addition of RPA but not by the addition of DNA polymerase alpha-primase complex, SV40 large tumor antigen, or topoisomerase I. This inhibition did not result from an interaction between XPAC and single-stranded DNA (ssDNA), or from competition between RPA and XPAC for DNA binding, because XPAC does not show any ssDNA binding activity and, in fact, stimulates RPA's ssDNA binding activity. Furthermore, XPAC inhibited DNA polymerase alpha activity in the presence of RPA but not in RPA's absence. These results suggest that the inhibitory effect of XPAC on DNA replication probably occurs through its interaction with RPA.     

An analysis of automatic teller machine usage by older adults: a structured interview approach

Sex differences in the activity of aromatase cytochrome P450 (CYP19) in the rat brain have been reported during pre- and postnatal development. It is unclear, however, whether these differences are reflected by corresponding differences in specific mRNA levels. To address this question, we have examined aromatase mRNA levels in specific regions of male and female rat brains by means of in situ hybridization (ISH). At prenatal stages of development, i.e. at gestational day 18 (GD18) and GD20, aromatase mRNA was detected in several preoptic, hypothalamic and limbic brain regions. Semiquantitative analysis of aromatase mRNA did not reveal sex differences in any of these regions. In contrast, clear-cut sex differences were determined at postnatal day (PN) 2; male animals expressed significantly more aromatase mRNA in the bed nucleus of stria terminalis (BST) and the sexually dimorphic nucleus of the preoptic area (SDN). Smaller but still significant differences (females > males) were obtained in the medial preoptic area (MPO). At PN6, sex differences of aromatase mRNA signals (males > females) were still present in the BST, but were no longer detectable in the SDN and the MPO. At PN15 and in adult animals, aromatase mRNA levels were similar in BST and medical amygdaloid nucleus of male and female rats. Since aromatase mRNA expression decreases during postnatal development, no ISH signals could be detected anymore in MPO, SDN and ventromedial hypothalamic nucleus. Our results are consistent with the concept that differential regulation of aromatase mRNA expression might be important for the establishment of different neuronal circuitry in male and female animals.     

Missed appendicitis a timebomb. Greater number of physicians are reported to the Health Services Disciplinary Board today than 50 years ago

In its early stages appendicitis often manifests itself by uncharacteristic symptoms, which may result in delayed diagnosis and treatment. A greater number of physicians are reported to the Health Services Disciplinary Board (HSDB) for missed appendicitis today than formerly, and disciplinary measures are more severe. This is shown by a unique breakdown of reported cases for three periods between 1945 and 1997.