shukoor65/lab-rag-model huggingface dataset:
Evidence for a defect in growth hormone-releasing factor signal transduction in the dwarf (dw/dw) rat pituitary. Dwarf (dw/dw) rats exhibit a 40% reduction in body growth, isolated GH deficiency (less than 5% of normal pituitary content), and a decreased number of pituitary somatotrophs (15-20% of normal). Since GH-releasing factor (GRF) stimulates GH synthesis and secretion and somatotroph proliferation, and its effects are probably mediated by cAMP, we have assessed GH secretion and cAMP production in dw rat pituitaries in response to various GH secretagogues. Dispersed pituitary cells from dw rats were less sensitive (2.5-fold) to stimulation of GH secretion by GRF and showed a 25% reduction in the maximal GH response even after normalization of their reduced GH content. Intracellular cAMP was elevated 63-fold over basal levels in normal cells after 4 h in response to maximal GRF stimulation, but only 1.9-fold in dw cells, and even larger differences between the groups were found at earlier time points. The GH responses of dw cells to exogenous cAMP, however, were indistinguishable from normal. Forskolin, a direct stimulator of adenylate cyclase, elicited comparable maximal GH and cAMP responses, but an increased ED50, in dw cells. Activation of GS alpha by cholera toxin showed an increased ED50 and reduced GH and cAMP responses in dw cells, and marked decreases in these responses were observed in response to prostaglandin E1. Phorbol ester stimulation resulted in a reduced maximal GH response in dw cells without a change in sensitivity. These results provide evidence for a defect in the GRF signal transduction pathway associated with a decreased ability of GS alpha to stimulate adenylate cyclase in dw rat somatotrophs that may be causally linked to their GH deficiency.
Reaction time and movement velocity abnormalities in Parkinson's disease under different task conditions. We examined reaction times, movement velocities, and the associated agonist and antagonist muscle behaviors in nine Parkinson's disease (PD) patients and eight normal subjects before and after medications, using a wrist extension task to changing locations of a visual target. Targets changing 500 msec before an auditory "go" signal act as a preparatory cue, while targets changing at the time of the go signal provide a combined auditory and visual stimulus. Late target changes allowed examination of (1) reaction times during an ongoing movement, and (2) movement in the presence and absence of visual targets. PD prolonged the time from the onset agonist electromyographic activity and reduction of antagonist activity to movement onset. Both were shortened by preparatory cues and combined visual and auditory go signals. PD slowed movement only in a subset of trials in which there was movement to a displayed target.
The proximal element of the beta globin locus control region is not functionally required in vivo. In addition to local sequence elements the regulation of the high-level, development- and tissue-specific expression of the human beta globin gene cluster appears to require distant regulatory sequences which have been termed locus control region. In the chromatin of erythroid cells the locus control region is characterized by four DNaseI hypersensitive sites that are located 6-18 kb 5' of the epsilon globin gene. The definition of the sequences minimally required for locus control region activity is likely to further the understanding of its physiology and will be of interest for the development of somatic gene therapy strategies of the hemoglobinopathies. We present here the analysis of a family with a 3,030-bp deletion of sequences upstream of the epsilon globin gene including the most 3' locus control region element and cosegregating beta degree thalassemia. The deletion is linked in cis to a structurally and functionally normal beta globin gene. The proximal element of the locus control region does not therefore appear to be necessary for beta globin gene activity in vivo.
Alterations in the levels of iron, ferritin and other trace metals in Parkinson's disease and other neurodegenerative diseases affecting the basal ganglia. Levels of iron, copper, zinc and manganese were measured by inductively coupled plasma spectroscopy in frozen postmortem brain tissue from patients with Parkinson's disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy with strionigral degeneration (MSA), and Huntington's disease (HD) compared with control subjects. Total iron levels were found to be elevated in the areas of basal ganglia showing pathological change in these disorders. In particular, total iron content was increased in substantia nigra in PD, PSP and MSA, but not in HD. Total iron levels in the striatum (putamen and/or caudate nucleus) were increased in PSP, MSA and HD but not in PD. Total iron levels were decreased in the globus pallidus in PD. There were no consistent alterations of manganese levels in basal ganglia structures in any of the diseases studied. Copper levels were decreased in the substantia nigra in PD, and in the cerebellum in PSP, and were elevated in the putamen and possibly substantia nigra in HD. Zinc levels were only increased in PD, in substantia nigra and in caudate nucleus and lateral putamen. Levels of the iron binding protein ferritin were measured in the same patient groups using a radio-immunoassay technique. Increased iron levels in basal ganglia were generally associated with normal or elevated levels of ferritin immunoreactivity, for example, the substantia nigra in PSP and possibly MSA, and in putamen in MSA. The exception was PD where there was a generalized reduction in brain ferritin immunoreactivity, even in the substantia nigra. An increase in total iron content appears to be a response to neurodegeneration in affected basal ganglia regions in a number of movement disorders. However, only in PD was there an increased total iron level, decreased ferritin content, decreased copper content, and an increased zinc concentration in substantia nigra. These findings suggest an alteration of iron handling in the substantia nigra in PD. Depending on the form in which the excess iron load exists in nigra in PD, it may contribute to the neurodegenerative process.
Revision of failed knee replacements using fixed-axis hinges. Forty failed hinged arthroplasties of the knee were revised by the insertion of another hinged implant. In 14 cases the prosthesis used at the revision operation was similar to the primary implant; in 26, a hinge with an elongated femoral stem was used, usually replacing part of the femoral shaft. In seven of these knees an elongated tibial stem was also required, though the tibial shaft was replaced in only two of them. There were many complications. Fracture of the femur at the tip of the femoral stem was the most frequent. Sixteen first revisions failed and were revised a second time; 12 required replacement of the distal femoral shaft and three required replacement of the proximal tibia. The incidence of complications in knees requiring a second revision was even higher. Four required a third revision after an average interval of three years. Failure of a hinged prosthesis results in bone loss mainly in the femur. Revision of a failed hinged prosthesis with another of the same design is unlikely to be successful and may cause fracture of the femur.
The epidemiology of exposure to electromagnetic fields: an overview of the recent literature. Epidemiologic studies of exposure to electromagnetic fields (EMF) have been reviewed. Possible links to incidences of cancer and abnormal fetal development have been suggested by some investigators. In general, the results have been inconsistent. There are many deficiencies in the studies, and many questions have been raised about the validity of some of the conclusions proposed. There is currently no definitive evidence of an association between exposure to EMF and the alleged risks. Due to problems and limitations inherent in future studies (misconceptions about exposure levels, uncertainty about field variability, criticisms of surrogate measures), this question is unlikely to ever be answered with certainty. Unfortunately, many highly-publicized accounts of speculative and unsubstantiated claims have caused undue concern among the general public.
Increased amino acid transport into brain tumors measured by PET of L-(2-18F)fluorotyrosine The uptake of L-(2-18F)fluorotyrosine (F-Tyr), a newly synthetized amino acid tracer, was studied in 15 patients with various brain tumors by dynamic PET. The higher F-Tyr accumulation in tumors (mean 27% above contralateral tissue) was associated with two-fold transport rates into tumors, while the rate constants describing irreversible incorporation were decreased. The increased F-Tyr transport was not correlated to 68Ga-EDTA accumulation and cannot be explained by disruption of the blood-brain barrier. Kinetic analysis of 2-(18F)-fluoro-deoxy-glucose accumulation in the same patients demonstrated that increased metabolic rates in tumors are mainly caused by altered phosphorylation rates while transport of glucose is less affected. Since F-Tyr transport rates clearly separated tumors from normal tissue and since F-Tyr accumulation was related to tumor grade, PET studies of F-Tyr uptake are of clinical value for diagnosis and classification of brain tumors.
Similar prevalence of renovascular hypertension in selected blacks and whites. Renovascular hypertension is a potentially curable form of high blood pressure that is thought to be extremely rare among blacks. We demonstrate, however, that in a clinically selected population, the prevalence of renovascular hypertension is similar in blacks and whites. We prospectively evaluated 167 hypertensive subjects who had one or more clinical features known to be associated with renovascular hypertension. All subjects had captopril-stimulated peripheral renin measurements and conventional renal arteriography. All significant renal artery stenoses (greater than 50% luminal narrowing) were treated with percutaneous transluminal angioplasty or surgery. Renovascular hypertension was diagnosed if there was a blood pressure response to interventional therapy, according to the criteria established by the Cooperative Study of Renovascular Hypertension. Of the total group evaluated, 24% (39 of 167) had renal artery stenosis and 14% (23 of 167) had renovascular hypertension. Renal artery stenosis or occlusion was found in 27% (26 of 97) of whites and 19% (13 of 67) of blacks (p = 0.27). Renovascular hypertension was diagnosed in 18% (17 of 97) of whites and 9% (6 of 67) of blacks evaluated (p = 0.25). Renovascular hypertension was associated with severe or refractory hypertension and with smoking, but there were no racial differences in these associations. Blacks with renovascular hypertension tended to have low captopril-stimulated peripheral renin activity. We conclude that blacks with clinical features suggestive of renovascular hypertension should be evaluated with angiography. Captopril-stimulated plasma renin may not be useful in detecting blacks with renovascular hypertension, but this and other potential screening tests require further evaluation.
Reversion of recent-onset atrial fibrillation to sinus rhythm by intravenous flecainide. Spontaneous reversion to sinus rhythm is a frequent occurrence in recent-onset atrial fibrillation (AF). In a randomized, double-blind, controlled study, intravenous flecainide (2 mg/kg, maximum dose 150 mg) was compared with placebo in the treatment of recent-onset AF (present for greater than or equal to 30 minutes and less than or equal to 72 hours' duration and a ventricular response greater than or equal to 120 beats/min). Intravenous digoxin (500 micrograms) was administered concurrently to all patients in both groups who had not previously taken digoxin. The trial medication was administered over 30 minutes. Exclusion criteria included hemodynamic instability, severe heart failure, recent antiarrhythmic therapy, hypokalemia and pacemaker dependence. One hundred two consecutive patients with recent-onset AF were enrolled in the study. All patients underwent continuous electrocardiographic monitoring in the intensive care or coronary care unit. Twenty-nine (57%) patients given flecainide and digoxin, but only 7 (14%) given placebo and digoxin, reverted to sinus rhythm in less than or equal to 1 hour after starting the trial medication infusion and remained in stable sinus rhythm (chi-square 18.9, p = 0.000013; odds ratio 8.3, 95% confidence interval 2.9 to 24.8). At the end of the 6-hour monitoring period, 34 patients (67%) in the flecainide-digoxin group were in stable sinus rhythm, whereas only 18 patients (35%) in the placebo-digoxin group had reverted (chi-square 8.83, p = 0.003; odds ratio 3.67, 95% confidence interval 1.5 to 9.1).
Quadrantic visual field defects. A hallmark of lesions in extrastriate (V2/V3) cortex. We report 2 patients with homonymous quadrantic visual field defects. The first patient experienced scintillations in the left lower quadrant, leading to the discovery of an astrocytoma in the cuneus of the right occipital lobe. Postoperatively she had a left lower quadrantanopia that precisely respected the horizontal meridian. The second patient presented with a left lower quadrantanopia, sparing the central 10 degrees of vision that also respected the horizontal meridian. An astrocytoma was resected from the right upper peristriate cortex. We must explain how a lesion in extrastriate cortex produced a homonymous field defect with a sharp horizontal edge in these 2 patients. Areas V2 and V3 are each divided along the horizontal meridian into separate halves flanking striate cortex. Consequently, the upper and lower quadrants in extrastriate cortex are physically isolated on opposite sides of striate cortex. We propose that a lesion involving V2/V3 may be sufficient to create a visual field defect. Although the lesion may have irregular margins, if it crosses the representation of the horizontal meridian in extrastriate cortex, it will produce a quadrantic visual field defect with a sharp horizontal border because of the split layout of the upper and lower quadrants in V2/V3.
Effectiveness of recombinant desulphatohirudin in reducing restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits BACKGROUND. The effectiveness of balloon angioplasty is limited by a restenosis rate of approximately 30%. Recombinant desulphatohirudin (r-hirudin [CGP 39393]) has been found to be highly effective in preventing acute platelet-rich thrombosis after deep arterial injury as compared with heparin. METHODS AND RESULTS. This study evaluated the effect of intravenous r-hirudin, a selective inhibitor of thrombin, on restenosis after balloon angioplasty in 29 rabbits. Focal femoral atherosclerosis was induced by air desiccation endothelial injury followed by a 2% cholesterol diet for 1 month. At angioplasty (2.5-mm balloon with three 60-second, 10-atm inflations 60 seconds apart), the rabbits received heparin (150 units/kg bolus, n = 16) or r-hirudin (1 mg/kg bolus followed by infusions of 1 mg/kg for the first hour and 0.5 mg/kg for the second hour, n = 13). Angiograms performed before and after angioplasty and before death were analyzed quantitatively by a blinded observer. Rabbits were killed 2 hours (n = 14) or 28 days (n = 15) after angioplasty. Femoral arteries were fixed in situ by perfusion of 10% formaldehyde at 100 mm Hg. The mean luminal diameter of the arteries with successful angioplasty (greater than or equal to 20% increase in luminal diameter) in rabbits treated with heparin (n = 8 arteries) increased from 1.18 +/- 0.29 mm before angioplasty to 1.86 +/- 0.24 mm immediately after angioplasty (p less than 0.001) and decreased to 0.94 +/- 0.69 mm (p = 0.0004) at 28 days after angioplasty. In rabbits treated with r-hirudin (n = 11 arteries), the mean luminal diameter increased from 1.14 +/- 0.17 mm before angioplasty to 1.68 +/- 0.20 mm immediately after angioplasty (p less than 0.001) and decreased to 1.37 +/- 0.47 mm (p = 0.01) at 28 days after angioplasty. The mean reduction in luminal diameter by angiography was less in the r-hirudin-treated group than in the heparin-treated group (0.30 +/- 0.33 versus 0.92 +/- 0.61 mm, p = 0.01). Blinded planimetric analysis of stained histological sections of the femoral arteries also showed less cross-sectional area narrowing by plaque in rabbits treated with r-hirudin compared with those treated with heparin (22 +/- 16% verus 48 +/- 29%, p = 0.01). Both groups had similar numbers of arteries with histological evidence of balloon-induced plaque tear (12 of 13 versus 13 of 15). CONCLUSIONS. Rabbits receiving r-hirudin at the time of experimental balloon angioplasty had significantly less restenosis by angiography and by quantitative histopathology than rabbits receiving heparin.
Growth of human breast cancer cell lines is inhibited by the somatostatin analog BIM23014. Somatostatin has been shown to lower plasma levels of various hormones and growth factors involved in regulation of the growth of human breast cells. In the present study we examined the ability of the somatostatin octapeptide analog BIM23014 to modulate the in vitro growth of five human breast cell lines: HBL100, Hs578T, MDAMB231, T47D, and MCF7. BIM23014 inhibited the growth of the two steroid-dependent cell lines, MCF7 and T47D, in a dose-related manner. This inhibitory effect was only observed when MCF7 and T47D cells were cultivated in medium containing steroid-depleted serum. The growth of a MCF7 variant capable of growth in serum-free medium was also inhibited by BIM23014, indicating that serum factors are not required for this inhibition. In the serum-free medium, the addition of estradiol before or during treatment with BIM23014 abolished its inhibitory effects on cell growth. The studies including time course, competitive inhibition, and cross-linking of iodinated BIM23014 to its receptor revealed a specific binding on MCF7 cells and showed a single 57,000 mol wt protein band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results support the hypothesis that BIM23014 inhibits the growth of steroid-receptor positive cells of human breast cancers through its own receptor in estradiol-free conditions.
Coronary vasospasm following subarachnoid hemorrhage as a cause of stunned myocardium. Case report. A patient with subarachnoid hemorrhage was found to have electrocardiographic abnormalities resembling an acute myocardial infarction as well as left ventriculographic findings of cardiac dysfunction. These cardiac abnormalities resolved following surgical clipping of the aneurysm and the patient recovered well from the operation. She died 2 months later from cancer and a postmortem examination at that time revealed no evidence of myocardial necrosis. In this report, the authors discuss coronary vasospasm and reversible postischemic "stunned myocardium," a condition that has not been considered previously in relation to subarachnoid hemorrhage.
Hypertrophy and increased gene expression of neurons containing neurokinin-B and substance-P messenger ribonucleic acids in the hypothalami of postmenopausal women. We have previously described hypertrophy of neurons containing estrogen receptor mRNA in the infundibular nucleus of postmenopausal women. In the present investigation we identified peptide mRNAs in the hypertrophied neurons and determined whether postmenopausal neuronal hypertrophy was accompanied by changes in gene expression. In the first study in situ hybridization was performed on sections from hypothalami of postmenopausal women (n = 3) using synthetic 35S-labeled cDNA probes complementary to mRNAs encoding estrogen receptor, substance-P (SP), neurokinin-B (NKB), POMC, cholecystokinin, dynorphin, CRF, enkephalin, galanin, neuropeptide-Y, GH-releasing hormone, and tyrosine hydroxylase. Neuronal cross-sectional areas and cell densities were measured with the aid of a computer microscope system. Neurons labeled with the NKB and SP probes were comparable in size, morphology, and distribution to the hypertrophied neurons containing estrogen receptor mRNA. In contrast, neurons labeled with other cDNA probes were sparsely distributed (CRF and dynorphin), smaller in size (neuropeptide-Y, galanin, GH-releasing hormone, enkephalin, cholecystokinin, and POMC), or located anterior to the hypertrophied population (tyrosine hydroxylase). In the second study sections from hypothalami of premenopausal (n = 3) and postmenopausal (n = 3) women were incubated with cDNA probes complementary to SP or NKB mRNAs. The mean cross-sectional areas of postmenopausal infundibular neurons containing NKB and SP mRNAs increased to 194% and 176% of premenopausal values, respectively. The autoradiographic grain densities of infundibular neurons labeled with either probe were also significantly increased in the postmenopausal group. Finally, the numbers of labeled neurons/tissue increased 6-fold (SP) and 15-fold (NKB) in the postmenopausal infundibular nucleus. These data demonstrate that human menopause is associated with marked increases in hypothalamic NKB and SP gene expression. We propose that neurons containing estrogen receptor, SP, and NKB mRNAs participate in the hypothalamic circuitry regulating estrogen negative feedback in the human.
Relation of upper gastrointestinal bleeding to non-steroidal anti-inflammatory drugs and aspirin: a case-control study. We conducted a case-control study in five general hospitals in the region of Antwerp, studying 161 patients (102 men, 59 women) and hospital control subjects matched for age and sex to explore the relation between drug use and upper gastrointestinal bleeding from 'erosive lesions' (peptic oesophagitis, gastric erosions, gastric ulcer(s), or duodenal ulcer(s]. There was a highly significant difference between cases and control subjects in the use of non-steroidal anti-inflammatory drugs (NSAIDs, excluding aspirin) (odds ratio 7.4, p less than 0.001; 95% confidence interval odds ratio 3.7 to 14.7). There also was a significant difference in the use of aspirin (odds ratio 2.2, p = 0.025; 95% CI odds ratio 1.3 to 4.0) and a highly significant difference regarding the presence of antecedents of peptic ulcer disease (odds ratio 5.5, p less than 0.001; 95% CI odds ratio 3.2 to 9.6). There was no significant difference in the use of other drugs, paracetamol and corticosteroids in particular, nor in the use of alcohol or tobacco. The patient group using NSAIDs was older, had more women, and had a higher mortality than the group not using NSAIDs. Among patients with bleeding gastric or duodenal ulcer(s), NSAID users were not more or less likely to have had symptoms of peptic ulcer disease, and had no higher frequency of multiple gastric or duodenal ulcers. The attributable risk for NSAID use was 0.30 (95% CI 0.23 to 0.37) and for aspirin use 0.14 (95% CI 0.08 to 0.20).
Coronary arteriography in patients with dextrocardia. Coronary arteriography is described in a patient with dextrocardia and situs inversus totalis. Six cases of coronary arteriography in dextrocardia were reviewed from the literature, and 3 other cases were reported from the authors' institutions. In 9 of the 10 patients, coronary arteriography was performed without difficulty using standard Judkins or Sones catheters. Angiographers encountering patients with dextrocardia may use standard coronary arteriographic techniques with a few subtle modifications.