Molecular mechanisms in the control of limb regeneration: the role of homeobox genes

The Ca2+ sensitivity of cardiac myofibrillar force production can be decreased by acidosis or inorganic phosphate (P(i)) and increased by caffeine. To investigate whether the source of tissue influences the potency of these agents, we compared the actions of acidosis (change of pH from 7.0 to 6.2), P(i) and caffeine (both 20 mM) on force production of skinned cardiac muscles from adult ventricle, adult atrium and neonate ventricle of the rat. Maximum Ca(2+)-activated force was reduced by all three interventions and the responses of the different muscle types to a given intervention were similar. Acidosis reduced myofibrillar Ca2+ sensitivity by 1.09 and 1.04 pCa units in adult ventricle and atrium, respectively, and P(i) reduced it by 0.19 and 0.22 pCa units. However, each effect was only one-third as great in the neonate ventricle, which showed falls of 0.33 pCa units for acidosis and 0.06 for P(i). In contrast, caffeine raised the Ca2+ sensitivity by the same amount (approximately 0.4 pCa units) in all three muscle types. The differential effect between adult and neonate seen with both acidosis and P(i) suggests some similarity in the mechanisms by which these factors decrease Ca2+ sensitivity. In contrast, the equal effects of caffeine on neonate and adult suggests that caffeine acts by a completely different mechanism. The lower pH- and P(i)-sensitivity of the neonatal ventricle can help to explain why neonatal and adult myocardium exhibit differential force responses to ischaemia (or hypoxia alone).     

The first accurate measurement of systolic and diastolic bloodpressure

Poiseuille, known for his law of fluid flow, which is the analog of Ohm's law, introduced the units (mmHg) by which we measure blood pressure by using the mercury manometer, which he described in his medical school thesis in 1828. For 50 years, mean blood pressure was all that could be measured because of the long response time of the mercury manometer. It is true that the height of the mercury column displayed pulsatile oscillations, but their amplitude was much less than that of pulse pressure. It is interesting to note that the slowly responding mercury manometer was made to display first systolic then diastolic pressure by means of an ingenious device that contained two oppositely directed check valves. It took from 1828 to 1903 for high-fidelity graphic recordings of blood pressure to appear in which systolic and diastolic pressures were believable. However, systolic and diastolic pressures were measurable since 1878 when Golz and Gaule created their ingenious valved device that permitted use of the slowly responding mercury manometer to display these pressures accurately     

Role of newly synthesized cholesterol or its metabolites on the regulation of bile acid biosynthesis after short-term biliary diversion in the rat

Cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the bile acid biosynthetic pathway, is thought to be regulated by hydrophobic bile acids through negative feedback control. The role of cholesterol in the regulation of cholesterol 7 alpha-hydroxylase is more controversial, in part because of incomplete understanding of the relationship between the pathways of cholesterol synthesis and degradation. The main objective of this study was to define the interaction between these two pathways in an experimental model in which the supply of newly synthesized cholesterol was interrupted by sustained infusion of mevinolin (lovastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) or accelerated by a continuous infusion of mevalonate, a cholesterol precursor. The study was carried out in rats subjected to short-term bile fistula. In one set of experiments, rats were treated postoperatively with mevinolin (5 mg/kg loading dose followed by 2 mg/kg/hr infusion), mevalonate (180 mumol/hr infusion) or both for up to 96 hr. In a separate set of experiments, rats were infused intraduodenally with taurocholate (36 mumol/100 gm/hr for up to 96 hr). We determined cholesterol 7 alpha-hydroxylase- and HMG-CoA reductase specific activities at those time intervals, whereas bile acid synthesis rates were determined throughout the study. Compared with rats not subjected to surgery, rats with short-term biliary diversion had increases in cholesterol 7 alpha-hydroxylase activity of 259% and 827% at 48 and 96 hr, respectively. The increase in bile acid biosynthesis was less pronounced. Continuous infusion of mevinolin completely prevented increases in cholesterol 7 alpha-hydroxylase specific activity and bile acid biosynthesis at both time intervals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the antireflux mechanism following laparoscopic fundoplication

BACKGROUND: Laparoscopic Nissen fundoplication is an effective procedure for the treatment of gastro-oesophageal reflux disease (GORD), but the underlying motility mechanisms that explain the success of this operation remain unclear. METHODS: Twenty patients with a history of GORD underwent stationary oesophageal manometry and prolonged ambulatory pH monitoring, both before and 3 months after fundoplication. RESULTS: Eighteen patients were completely cured of reflux symptoms and stopped all antireflux medication after operation. After fundoplication there was a significant increase (P < 0.01) in median resting lower oesophageal sphincter (LOS) pressure and length. Median residual LOS pressure during swallow-induced LOS relaxation also increased significantly after operation (P < 0.01). The number of reflux episodes decreased from a median of 48 to 3 after fundoplication (P < 0.01). The time at pH less than 4 decreased from 5.7 to 0 per cent in the supine position (P < 0.01), and from 9.8 to 0.2 per cent while upright (P < 0.001). CONCLUSION: Early subjective results at 3 months following laparoscopic antireflux surgery show improved symptoms. One of the mechanisms underlying the antireflux action of fundoplication is an increase in median residual LOS pressure at the gastro-oesophageal junction. This may be a purely mechanical effect of the fundic wrap extrinsic to the LOS.     

Cervical esophageal web associated with a patch of heterotopic gastric mucosa

Cervical esophageal webs are a relatively common finding on esophograms. We report a web resulting from the squamocolumnar junction produced by heterotopic gastric mucosa. The clinical significance of this lesion is discussed and the importance of differentiating it from Barrett's esophagus is stressed.     

In search of tuberculosis virulence genes

The identity of the virulence genes that enable tuberculosis organisms to survive in macrophages and to induce the features of tuberculosis remains largely unknown. Numerous putative virulence genes have been identified, but so far there is only conclusive evidence for the role of two genes, KatG and rpoV, in virulence.