Tetracyclines induce changes in accessibility of ribosomal proteins to proteases

It is generally assumed that folding intermediates contain partially formed native-like secondary structures. However, if we consider the fact that the conformational stability of the intermediate state is simpler than that of the native state, it would be expected that the secondary structures in a folding intermediate would not necessarily be similar to those of the native state. beta-Lactoglobulin is a predominantly beta-sheet protein, although it has a markedly high intrinsic preference for alpha-helical structure. We have studied the refolding kinetics of bovine beta-lactoglobulin using stopped-flow circular dichroism and find that a partly alpha-helical intermediate accumulates transiently before formation of the native beta-sheets. The present results suggest that the folding reaction of beta-lactoglobulin follows a non-hierarchical mechanism, in which non-native alpha-helical structures play important roles.     

Expression of somatotropin receptor messenger ribonucleic acid in bovine tissues

The somatotropin receptor mRNA is controlled by at least two different gene promoters that generate two variants with different exon 1 sequences (1A and 1B). The location of 1A and 1B somatotropin receptor mRNA within cattle tissues and, hence, the tissue specificity of the 1A and 1B promoters are unknown. In addition, the cDNA sequence of the 1B somatotropin receptor has not been determined. Our objective, therefore, was to sequence a cDNA for the 1B somatotropin receptor and to analyze bovine tissues for expression of 1A and 1B somatotropin receptor mRNA. Twenty adult tissues and six fetal tissues were collected at slaughter from each of four cows and two fetuses. Messenger RNA was analyzed using ribonuclease protection assays. The adult liver expressed both 1A and 1B mRNA. All other adult tissues expressed 1B mRNA but not 1A mRNA. The greatest amount of 1B mRNA was detected in liver and adipose (abdominal and subcutaneous) tissues. Other tissues had approximately one-half to one-tenth of the amount of 1B mRNA in the liver or adipose tissue. Fetal tissues (including fetal liver) expressed 1B mRNA and not 1A mRNA. Based on cDNA sequencing, the protein encoded by the 1A and 1B mRNA was nearly identical. We concluded that 1A somatotropin receptor mRNA is specific to adult bovine liver. Other adult and fetal bovine tissues expressed 1B somatotropin receptor mRNA with a predicted protein sequence that was similar to the 1A somatotropin receptor.     

Dopamine decreases the excitability of layer V pyramidal cells in the rat prefrontal cortex

In both primates and rodents, the prefrontal cortex (PFC) is highly innervated by dopaminergic fibers originating from the ventral tegmental area, and activation of this mesocortical dopaminergic system decreases spontaneous and evoked activity in the PFC in vivo. We have examined the effects of dopamine (DA), over a range of concentrations, on the passive and active membrane properties of layer V pyramidal cells from the rat medial PFC (mPFC). Whole-cell and perforated-patch recordings were made from neurons in rat mPFC. As a measure of cell excitability, trains of action potentials were evoked with 1-sec-long depolarizing current steps. Bath application of DA (0.05-30 microM) produced a reversible decrease in the number of action potentials evoked by a given current step. In addition, DA reversibly decreased the input resistance (RN) of these cells. In a subset of experiments, a transient increase in excitability was observed after the washout of DA. Control experiments suggest that these results are not attributable to changes in spontaneous synaptic activity, age-dependent processes, or strain-specific differences in dopaminergic innervation and physiology. Pharmacological analyses, using D1 agonists (SKF 38393 and SKF 81297), a D1 antagonist (SCH 23390), a D2 receptor agonist (quinpirole), and a D2 antagonist (sulpiride) suggest that decreases in spiking and RN are mediated by D2 receptor activation. Together, these results demonstrate that DA, over a range of concentrations, has an inhibitory effect on layer V pyramidal neurons in the rat mPFC, possibly through D2 receptor activation.     

Segregation analysis of NIDDM in Caucasian families

Non-insulin-dependent diabetes mellitus (NIDDM) has a substantial genetic component, but the mode of inheritance and the molecular basis are unknown. We have undertaken segregation analysis of NIDDM after studying 247 subjects in 59 Caucasian nuclear pedigrees ascertained without regard to family history of the disorder. The analyses were performed using POINTER and COMDS, which are computer programs which apply statistical models to the data. POINTER analysis was performed defining the phenotype as a presence or absence of hyperglycaemia. Among single locus hypothesis, the analyses rejected a recessive model and favoured a dominant model, but could not statistically show that this fitted better than a mixed model (a single locus against a polygenic background) or a polygenic model. COMDS analysis assumed a continuum of hyperglycaemia from normality to NIDDM, classified family members into a series of diathesis classes with increasing plasma glucose levels and compared the distribution with that found by screening the normal population. This analysis improved the likelihood of a dominant single locus model and suggested a gene frequency of 7.4%. It raised the possibility of a second locus, but cannot identify or exclude a polygenic model. In conclusion, two types of segregation analyses rejected a recessive model and favoured a dominant model of inheritance, although they could not statistically show that this fitted better than the polygenic model. The results raised the possibility of a common dominant gene with incomplete penetrance, but genetic analysis of NIDDM needs to take into account the likelihood of polygenic inheritance with genetic heterogeneity.     

Organometallic flavonoid derivatives as spectroscopic probes

Derivatives of naringenin have been synthesized with organometalcarbonyl reporting groups for IR spectroscopy attached at C-2, C-3', or C-6, and the products have been tested for the induction of nod gene expression using a Rhizobium leguminosarum strain which contains the Escherichia coli lacZ (beta-galactosidase) gene fused to nodABC. Derivatives with an OMe substituent within the reporting group moiety showed residual gene induction activity.     

The effect of wait time on T2 distributions from NMR experiments

BACKGROUND: After liver transplantation there is a fall in lean body mass. AIMS: To determine the risk factors for this fall in lean body mass using univariate and subgroup analyses. PATIENTS AND METHODS: Dual energy X-ray absorptiometry was performed in 36 patients (12 with Child-Pugh Class A, 20 with Class B and 4 with Class C disease) before and up to 24 months after liver transplantation. Univariate and sub-group comparative analyses were performed to assess possible risk factors for the fall in lean body mass post-transplantation. RESULTS: The pre-transplantation serum albumin inversely correlated with the fall lean body mass at 1 month (r = 0.55; p < 0.009) and at 6-9 months (r = 0.51; p < 0.05) post-transplantation. A positive correlation between the fall in lean body mass and: (i) cumulative dose of steroids administered at 2-5 months (r = 0.57; p < 0.05) and (ii) length of hospital stay after transplantation (r = 0.52; p < 0.05) were also observed. Neither the severity or presence of cholestatic liver disease pre-transplant, nor acute cellular rejection post-transplant were risk factors for a fall in lean mass. DISCUSSION: A hypercatabolic state post-transplant (represented by low albumin pre-transplantation), immobility, lack of exercise and steroid induced catabolism of muscle may cause the observed fall in lean mass after liver transplantation. Earlier transplantation of patients with better nutritional status and the use of low dose steroid immunosuppressive regimens may prevent the observed fall in lean body mass after transplantation.     

Invasive sinonasal disease due to Scopulariopsis candida: case report and review of scopulariopsosis

Sinonasal infection with fungi of the order Mucorales--termed mucormycosis or zygomycosis--is sometimes seen in immunosuppressed patients, including those with diabetic ketoacidosis and malignancy. We describe a case of invasive sinonasal infection with Scopulariopsis candida (not among the Mucorales organisms) in a 12-year-old girl who was being treated for non-Hodgkin's lymphoma. Only a few cases of invasive infection with Scopulariopsis species have been reported previously; five of six of these cases were associated with persistent or fatal disease. Our patient survived without undergoing radical surgical debridement and was treated with granulocyte colony-stimulating factor, amphotericin B, and itraconazole; chemotherapy was stopped. In vitro susceptibility testing of our patient's Scopulariopsis isolate showed that it was resistant to amphotericin B and that it was relatively susceptible to itraconazole and miconazole. The case described herein demonstrates the expanding spectrum of fungal organisms that may cause invasive sinonasal infection in immunocompromised hosts and the need for reliable antifungal susceptibility testing.     

Results of bypass to the popliteal and tibial arteries with alternative sources of autogenous vein

PURPOSE: The goal of an all-autogenous policy for infrainguinal arterial bypass requires that many bypasses be performed with alternative autogenous veins (AAV) because an adequate length of ipsilateral or contralateral greater saphenous vein (GSV) is not available. The durability and efficacy of infrainguinal vein bypasses constructed of venous conduits other than a single segment of greater saphenous vein (SSGSV) is, however, questioned. METHODS: AAV and GSV bypasses were reviewed from 1980 through 1994. Patients who required bypass to the popliteal or a tibial artery were compared for vascular surgical history and vascular disease risk factors and life-table survival. AAV and SSGSV procedures were compared for indications for surgery, morbidity and mortality rates, limb salvage rates in patients who underwent surgery for limb-salvage indications, subsequent need for revision, and life-table-assisted primary patency. RESULTS: Nine hundred nineteen autogenous vein bypasses were performed to the popliteal or a tibial artery--187 (20%) with AAVs, including whole or partial arm vein conduits in 144 grafts (77%). One hundred fourteen AAVs (61%) required vein splicing. The mortality rate was 2% for SSGSV bypasses and 1% for AAV bypasses. The morbidity rate was higher for GSV surgery as a result of increased wound complications (11% vs 5%; p=0.02). Sixty-seven percent of patients with AAV bypass extremities had undergone previous ipsilateral arterial surgery, compared with 20% of patients with SSGSV bypasses (p0.0005). AAV bypasses were more likely to be to a tibial artery (71% vs 45%; p<0.0001). Twelve percent of SSGSV and 15% of AAV popliteal bypasses required revision (p=NS). The 5-year assisted primary patencies were 82%, 77%, and 63%, with limb salvage rates of 91%, 86%, and 74% for ipsilateral SSGSV, contralateral SSGSV, and AAV femoropopliteal bypasses, respectively. Twelve percent of SSGSV and 30% of AAV tibial bypasses required revision (p=0.0001). The 5-year assisted primary patencies were 74%, 82%, and 72%, with limb salvage rates of 84%, 92% and 78% for ipsilateral SSGSV, contralateral SSGSV, and AAV femorotibial bypasses, respectively. CONCLUSION: AAV bypasses can provide overall results comparable with SSGSV bypasses.     

Treatment strategies for management of serum lipids: lessons learned from lipid metabolism, recent clinical trials, and experience with the HMG CoA reductase inhibitors

The Adult Treatment Panel (ATP) guidelines, published initially in 1988 and revised in 1993, are based on sentinel observations and early clinical trials in support of treating and preventing coronary artery disease by cholesterol lowering. With the conclusion of several large long-term trials using HMG CoA reductase inhibitors for primary and secondary coronary prevention, the ATP II recommendations, which remain remarkably accurate, can be supplemented with more evidence-based strategies. Increasing evidence suggests that thoughtful lipid management for coronary prevention should include a more complete assessment of lipoproteins with an emphasis on apolipoproteins, triglycerides, and very low-density (VLDL) remnant particles, LDL particle size, and lipoprotein(a). This review summarizes clinically relevant lipid metabolism with an emphasis on the concept of atherogenic plasma lipids, discusses the clinical benefits and specific uses of each of the lipid-lowering drug classes, and provides an analysis of recent cholesterol-lowering primary and secondary coronary prevention trials from which a new treatment strategy can be derived.