The Escherichia coli signal transducers PII (GlnB) and GlnK form heterotrimers in vivo: fine tuning the nitrogen signal cascade

The PII protein is Escherichia coli's cognate transducer of the nitrogen signal to the NRII (NtrB)/NRI (NtrC) two-component system and to adenylyltransferase. Through these two routes, PII regulates both amount and activity of glutamine synthetase. GlnK is the recently discovered paralogue of PII, with a similar trimeric x-ray structure. Here we show that PII and GlnK form heterotrimers, in E. coli grown in nitrogen-poor medium. In vitro, fully uridylylated heterotrimers of the two proteins stimulated the deadenylylation activity of adenylyltransferase, albeit to a lower extent than homotrimeric PII-UMP. Fully uridylylated GlnK did not stimulate, or hardly stimulated, the deadenylylation activity. We propose that uridylylated PII/GlnK heterotrimers fine-regulate the activation of glutamine synthetase. The PII/GlnK couple is a first example of prokaryotic signal transducer that can form heterotrimers. Advantages of hetero-oligomer formation as molecular mechanism for fine-regulation of signal transduction are discussed.     

Diverticular fecalith in scleroderma simulating colonic neoplasm: Report of a case

This is a report of a patient with the CRST syndrome, a mild variant of scleroderma consisting of calcinosismraynaud's phenomenon, sclerodactyly, and telangiectasia. Typical changes of scleroderma were present in the extremities, esophagus, duodenum and colon. In addition, there was a polypoid filling defect in a colonic diverticulum due to a fecalith. The radiologic appearance at first resembled a colonic neoplasm, although its location within a diverticulum and its speckled appearance suggested the possibility of a fecalith. This was confirmed at colonoscopy, which disclosed numerous wide-mouthed diverticula, with inspissated fecal material projecting from several diverticula. In patients with scleroderma and polypoid filling defects in the colon, the possibility of a fecalith within a diverticulum should be considered. Where the radiologic study is inconclusive, colonoscopy may provide a definitive diagnosis.     

Hypertrophic osteoarthropathy in association with pulmonary tuberculosis

Three white male patients with advanced cavitary pulmonary tuberculosis presented with HOA. No other pathology to explain the osteoarthropathy was detected. The osteoarthropathy responded symptomatically to NSAI drugs and treatment of tuberculosis but resolved radiologically in only one patient.     

Providing physical health care for people accessing mental health services: Clinicians’ perceptions of their role

The prevalence of health risk behaviours and associated poor physical health is high in people with severe mental illness. Mental health service guidelines and policies stipulate that mental health services should address physical health of people who access services. This study reports results from a large, interdisciplinary, cross‐sectional study exploring mental health clinicians’ (n = 385) views of role legitimacy in physical health service provision. All disciplines reported that mental health clinicians have a role to play in addressing the physical health of consumers. Among mental health clinicians, psychiatrists and mental health nurses received higher endorsement than allied health clinicians in relation to the provision of physical health care, with primary care providers including general practitioners also ranking highly. As community mental health services routinely appoint allied health staff to case management roles, a challenge for services and a challenge for clinicians are to ensure that physical health and the effects of medication are monitored appropriately and systematically. Online and telephone support services received relatively lower endorsement. As the availability of nonface to face services increases, there is a need to explore their utility in this population and where appropriate promote their uptake.     

Changes in Pain Sensitization After Bariatric Surgery

Objective

To evaluate changes in pain (at the knee and elsewhere) and pain sensitization in obese subjects with knee pain who were having bariatric surgery compared with similarly obese individuals who were undergoing medical management.

Methods

This study included a cohort of subjects who were having bariatric surgery and those undergoing medical management. Knee pain severity of the more painful knee (index knee) was assessed at baseline and at 12 months using the Western Ontario and McMaster Universities Osteoarthritis Index. The pressure pain threshold (PPT) was evaluated at the index patella and the right wrist. Low patella PPT may reflect peripheral and/or central sensitization, and low wrist PPT may reflect central sensitization. The mean change in measures of pain and pain sensitization was analyzed in the surgery and medical management groups separately.

Results

A total of 45 subjects in the surgery group and 22 in the medical management group completed baseline and follow‐up visits. The mean weight loss was 32.7 kg (29.0%) and 4.6 kg (4.1%) in the surgery and medical management groups, respectively. Knee pain decreased only in the surgery group, in which the PPT at the patella improved by 38.5% (P = 0.0007) and at the wrist by 30.9% (P = 0.005). There was no significant change in PPT in the medical management group.

Conclusion

Persons who underwent bariatric surgery experienced an improvement in pain sensitization, reflected by improvements in PPT. This improvement was observed not only at the patella, but also at the wrist, suggesting that central sensitization improved after bariatric surgery.

     

Catecholamine effect on HCO3-/Cl- exchange and rabbit myocardial cell pH regulation

The possible effect of isoproterenol on a HCO3-/Cl- exchange in mammalian myocardium and its role on intracellular pH (pHi) regulation was studied in isolated perfused rabbit hearts. pHi was determined from the distribution of 5.5-dimethyl-2,4-oxazolidinedione (DMO). Perfusates contained either 137.4 or 4.4 mM Cl-. In the latter case, Cl- was replaced by glucuronate. Hearts were perfused with low [Cl-] Ringer for 1 h in order to deplete the cell of Cl-. Isoproterenol (10(-5) M) was infused for the last 15 min of perfusion in approximately half of the preparations. Reduction of [Cl-], both in the untreated and in the isoproterenol-treated preparations resulted in an increase in pHi. Isoproterenol increased tissue cAMP concentration by approximately 2.5 fold both in hearts perfused with normal and with low [Cl-] Ringer. In the presence of normal [Cl-], isoproterenol had an alkalinizing effect when acid loads were introduced. This effect was abolished by the reduction of [Cl-]. These results support the idea that the catecholamine-cAMP system stimulates a HCO3-/Cl- exchange in mammalian myocardium.     

Hemodynamic and metabolic effects of venoarterial cardiopulmonary support in coronary artery disease

Coronary angioplasty was performed on 14 high-risk patients supported with venoarterial partial cardiopulmonary bypass. Hemodynamic, metabolic and physiologic parameters were monitored to assess the effect of cardiopulmonary support in conscious patients. Cardiopulmonary support caused a decrease in systolic (45 ± 17 to 27 ± 14 mm Hg, p < 0.001), diastolic (23 ± 12 to 14 ± 8 mm Hg, p < 0.005) and mean (29.7 ± 13.2 to 18 ± 9 mm Hg, p < 0.001) pulmonary artery pressures. Aortic systolic (129 ± 18 to 106 ± 17 mm Hg, p < 0.001), mean (89 ± 19 to 84 ± 19 mm Hg, p < 0.05) and pulse (64 ± 17 to 37 ± 16 mm Hg, p < 0.00001) pressures also decreased. Heart rate and aortic diastolic pressures were unchanged. End-systolic wall stress (122 ± 48 × 10³ to 96 ± 44 × 10³ dynes/cm², p < 0.001) and left ventricular end-diastolic diameter (5.7 ± 0.8 to 5.5 ± 0.9 cm, p < 0.05) were reduced during partial cardiopulmonary bypass. After initiation of cardiopulmonary support, normal lactate extraction across the coronary circulation was diminished or converted to lactate production (38 ± 23 to 2 ± 29%, p < 0.005). There was a marked reduction in hematocrit (41 ± 4 to 28 ± 5%, p < 0.0001) and platelet count (259,000 ± 57,600/ml to 145,900 ± 46,000/ml, p < 0.0001) after bypass. Cardiopulmonary bypass successfully supported all patients during balloon inflation, for an optimal angioplasty result. During balloon inflation, 6 of 8 patients with interpretable electrocardiograms had ST shifts suggestive of ischemia and 1 developed ventricular tachycardia. During balloon inflation, pulse pressure decreased from a mean of 38 ± 15 to 25 ± 15 mm Hg (p < 0.01). It is concluded that cardiopulmonary support provides excellent systemic support but induces cardiac anaerobic metabolism in patients with severe coronary artery disease. Myocardial ischemia when coronary blood flow is interrupted during balloon inflation is still observed despite effective cardiopulmonary support.     

Molecular evidence for Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn''s disease correlates with enhanced TNF-α secretion

BACKGROUND: Support for a role of Mycobacterium avium subspecies paratuberculosis in Crohn's disease is largely based on epidemiological evidence, as no data on mechanisms linking the presence of M. avium subspecies paratuberculosis with gut damage is available. AIMS: To determine whether the presence of M. avium subspecies paratuberculosis contributes to the pathogenesis of Crohn's disease by promoting cytokine secretion within gut mucosa. PATIENTS AND METHODS: A total of 235 subjects were recruited: 63 with Crohn's disease, 53 with ulcerative colitis, 45 with irritable bowel syndrome and 74 normal controls. M. avium subspecies paratuberculosis status was defined by nested PCR using IS900 sequence. Gut mucosal organ cultures were established to detect cytokine secretion patterns. RESULTS: Significantly higher tumour necrosis factor-alpha concentrations were found in culture supernatants for Crohn's disease compared to ulcerative colitis (p<0.05), irritable bowel syndrome (p<0.01) and controls (p<0.0001). When tumour necrosis factor-alpha levels were correlated with the presence of M. avium subspecies paratuberculosis, significantly greater concentrations were only found in M. avium subspecies paratuberculosis-positive Crohn's disease patients (p<0.05). Tumour necrosis factor-alpha levels in M. avium subspecies paratuberculosis-positive Crohn's disease were significantly higher than in M. avium subspecies paratuberculosis-positive ulcerative colitis (p<0.01), M. avium subspecies paratuberculosis-positive irritable bowel syndrome (p<0.05) and M. avium subspecies paratuberculosis-positive controls (p<0.01) and all M. avium subspecies paratuberculosis-negative specimens. CONCLUSIONS: The data link M. avium subspecies paratuberculosis with a pathogenic mechanism in Crohn's disease and is consistent with abnormal macrophage handling of M. avium subspecies paratuberculosis.