Phylogenetic and physiological diversity of sulphate-reducing bacteria isolated from a salt marsh sediment

Xenopus blastula cells activate different mesodermal genes as a concentration-dependent response to activin, which behaves like a morphogen. To understand how cells recognize morphogen concentration, we have bound naturally labeled activin to cells and related this to choice of gene activation. We find that the increasing occupancy of a single receptor type can cause cells to switch gene expression. Cells sense ligand concentration by the absolute number of occupied receptors per cell (100 and 300 molecules of bound activin induce Xbra and Xgsc, respectively, i.e., 2% and 6% of the total receptors) and not by a ratio of occupied to unoccupied receptors. The long duration of occupancy explains a previously described ratchet effect. Our results suggest a new concept of morphogen gradient formation and interpretation that is particularly well suited to the needs of early development.     

The Linear Thermal Expansion of Bulk Nanocrystalline Ingot Iron from Liquid Nitrogen to 300 K

The linear thermal expansions (LTE) of bulk nanocrystalline ingot iron (BNII) at six directions on rolling plane and conventional polycrystalline ingot iron (CPII) at one direction were measured from liquid nitrogen temperature to 300 K. Although the volume fraction of grain boundary and residual strain of BNII are larger than those of CPII, LTE of BNII at the six measurement directions were less than those of CPII. This phenomenon could be explained with Morse potential function and the crystalline structure of metals. Our LTE results ruled out that the grain boundary and residual strain of BNII did much contribution to its thermal expansion. The higher interaction potential energy of atoms, the less partial derivative of interaction potential energy with respect to temperature T and the porosity free at the grain boundary of BNII resulted in less LTE in comparison with CPII from liquid nitrogen temperature to 300 K. The higher LTE of many bulk nanocrystalline materials resulted from the porosity at their grain boundaries. However, many authors attributed the higher LTE of many nanocrystalline metal materials to their higher volume fraction of grain boundaries.     

Molecular alterations in early gastric carcinomas. No apparent correlation with Helicobacter pylori status

The effect of nitric oxide (NO) donors on high-voltage-activated Ca2+ channels in insulin-secreting RINm5F cells was investigated using the patch-clamp technique in the whole-cell configuration. Sodium nitroprusside (SNP, 2-400 microM) induced a dose-dependent reduction in Ba2+ currents with maximal inhibition of 58%. The IC50 for SNP was 45 microM. A different NO donor, (+/-)S-nitroso-N-acetylpenicillamine (SNAP, 500 microM), also produced a 50% decrease in current amplitude. When 200 microM SNP was administered together with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidozoline-1-oxyl-3-oxide (carboxy-PTIO, 300 microM), the Ba2+ current inhibition was lowered to 7%. Administration of 500 microM 8-bromoguanosine 3':5'-cyclic monophosphate sodium salt (8-Br-cGMP) mimicked the effects of SNP, causing a comparable decrease (56%) in peak-current amplitude. When soluble guanylyl cyclase was blocked by 10 microM 1H-[1,2, 4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ), the inhibitory effect of 200 microM SNP was reduced from 39% to 15%. The SNP-induced current decrease was 36% of controls after the blockade of L-type Ca2+ channels and 30% in the presence of 2.5 microM omega-conotoxin-MVIIC. These data indicate that NO inhibits both L-type and P/Q-type Ca2+ channels in RINm5F cells, probably by an increase in the intracellular levels of cGMP. NO may then significantly influence the Ca2+-dependent release of hormones from secretory cells as well as that of neurotransmitters from nerve terminals.     

Transplantation for end stage liver disease related to alpha 1 antitrypsin

Alpha 1 antitrypsin deficiency (AT) is an autosomal recessive disease associated with chronic liver disease in adults and children and emphysema in adults. The disease is one of the most common inherited disorders of the Caucasian population of North Europe and North America and is the most common genetic reason for pediatric orthotopic liver transplantation (OLTx), although it is a rare indication in adults. The natural history of the disease is unpredictable and the pathogenesis of the liver injury unclear. Thirty-five patients with histologically apparent alpha 1 AT accumulation in the liver (22 adults, 13 children) have been transplanted in this center. Clinical features were correlated with the pretransplant phenotype, serum alpha 1 antitrypsin levels and potential precipitating factors. All children were PiZZ homozygotes, most of whom had presented with neonatal hepatitis. The majority of adult patients were heterozygotes presenting with portal hypertension and liver cirrhosis. Current one-year posttransplant survival figures are 73% for adults and 87.5% for children. Replacement of the cirrhotic liver results in acquisition of the donor phenotype, a rise in serum levels of alpha 1 antitrypsin, and apparent prevention of associated disease.     

Primary aortic mural thrombus: presentation and treatment

Schizophrenic patients are extremely heavy tobacco smokers. However, a lower incidence of lung cancer in schizophrenic patients has been observed in comparison to other heavy smokers. Nicotine increases the proliferation of pulmonary neuroendocrine tissue, causing the release of a bombesin-like peptide. Thus, bombesin-like peptide levels in urine may be an indicator of precancerous, cigarette-induced lung damage. Bombesin-like peptide levels of 10 schizophrenic smokers and 11 schizophrenic nonsmokers were compared to those of nonschizophrenic subjects matched for age and pack-years of smoking. The nonschizophrenic smokers showed the expected increase in urinary bombesin-like peptide levels, as compared to nonschizophrenic nonsmokers. Schizophrenic patients had lower bombesin-like peptide levels independent of smoking effects. The mechanism of the difference in bombesin-like peptide levels between schizophrenic patients and nonschizophrenic subjects is unknown, but one possibility involves alteration in the alpha 7-nicotinic acetylcholine receptor, which mediates the growth of some neuroendocrine cell lines in vitro.     

The role of voltage-gated Ca2+ channels in anoxic injury of spinal cord white matter

Dorsal column axons of the rat spinal cord are partially protected from anoxic injury following blockade of voltage-sensitive Na+ channels and the Na+/--Ca2+ exchanger. To examine the potential contribution of voltage-gated Ca2+ channels to anoxic injury of spinal cord axons, we studied axonal conduction in rat dorsal columns in vitro following a 60-min period of anoxia. Glass microelectrodes were used to record field potentials from the dorsal columns following distal local surface stimulation. Perfusion solutions containing blockers of voltage-gated Ca2+ channels were introduced 60 min prior to onset of anoxia and continued until 10 min after reoxygenation. Pharmacological blocking agents which are relatively selective for L- (verapamil, diltiazem, nifedipine) and N- (omega-conotoxin GVIA) type calcium channels were significantly protective against anoxia-induced loss of conduction, as was non-specific block using divalent cations. Other Ca2+ channel blockers (neomycin and omega-conotoxin MVIIC) that affect multiple Ca2+ channel types were also neuroprotective. Ni2+, which preferentially blocks R-type Ca2+ channels more than T-type channels, was also protective in a dose-dependent manner. These data suggest that the influx of Ca2+, through L-, N- and possibly R-type voltage-gated Ca2+ channels, participates in the pathophysiology of the Ca2+-mediated injury of spinal cord axons that is triggered by anoxia.     

Outcome of moderate carotid artery stenosis in patients who are asymptomatic

PURPOSE: The incidence rate of disease progression and stroke after the diagnosis of a moderate (50% to 79%) carotid stenosis was determined by means of color-flow duplex scanning. METHODS: During a 4-year period, 344 male veterans with moderate internal carotid artery stenoses, on one or both sides, were examined at regular intervals for a mean period of 25 months. Carotid color-flow scans were obtained semiannually. Clinical follow-up was performed to determine the incidence rate of amaurosis fugax, transient ischemic attacks, nonhemispheric symptoms, and strokes. RESULTS: New neurologic symptoms developed in 75 patients (21.8%). Fifty-one (14.8%) had ipsilateral symptoms during follow-up: 18 amaurosis fugax (5.2%), 14 transient ischemic attacks (4%), 5 nonhemispheric symptoms (1.4%), and 14 strokes (4%). Twenty-four patients (6.9%) had contralateral symptoms: 20 strokes (5.8%) and 4 transient ischemic attacks (1.2%). Life-table analysis showed that the annual rate of ipsilateral neurologic events was 8.1%, and the annual rate of stroke was 2.1%. Seventy-five patients (22%) died in the follow-up period. Disease progression to 80% to 99% stenosis or occlusion occurred in 71 of 458 vessels (15.5%). The internal carotid arteries that showed evidence of disease progression had a significantly higher initial peak systolic velocity (251 vs 190 cm/s; P <.0001) and end diastolic velocity (74 vs 52 cm/s; P < 0.0001). Black patients and patients with ischemic heart disease were at a higher risk for disease progression. We could not identify any atherosclerotic risk factors that reliably predicted patients in whom future ipsilateral neurologic symptoms were more likely to develop. However, there was an increased risk of stroke associated with progression of disease. CONCLUSION: Patients who are asymptomatic and who have moderate carotid stenoses are at significant risk for neurologic symptoms and death, but have a relatively low incidence rate of ipsilateral events. The initial flow characteristics in the stenotic vessel are predictive of future disease progression, but they are not helpful in identifying patients in whom symptoms will develop.     

A histomorphometric evaluation of heparin-induced bone loss after discontinuation of heparin treatment in rats

Although it is well established that long-term heparin therapy causes osteoporosis, it is unknown whether heparin-induced bone loss is reversible when heparin treatment is stopped. To address this question, we randomized rats to once daily subcutaneous injections of either unfractionated heparin (1.0 U/g or 0.5 U/g) or saline for 28 days and then followed the rats for an additional 28 days off treatment. Based on histomorphometric analysis of the distal third of the right femur proximal to the epiphyseal growth plate, 1.0 U/g heparin caused a 30% loss in cancellous bone volume over the first 28 days. This was accompanied by a 137% increase in osteoclast surface and a 60% decrease in both osteoblast and osteoid surface. One month after cessation of heparin treatment, no recovery in these parameters was observed. Similarly, serum levels of alkaline phosphatase, a biochemical marker of bone formation, which continued to decrease over the course of heparin treatment, showed no signs of recovery in the subsequent 28 days off treatment. To explore the mechanism responsible for the prolonged effect of heparin on bone, we repeated the experiment giving 125I-labeled heparin in place of unlabeled heparin. 125I-labeled heparin was found to accumulate in bone during the course of its administration, and be retained in bone for at least 56 days after stopping heparin treatment. These findings suggest that heparin-induced osteoporosis is not rapidly reversible because heparin is sequestered in bone for an extended period.