shukoor65/lab-rag-model huggingface dataset:
A single base mutation in type I procollagen (COL1A1) that converts glycine alpha 1-541 to aspartate in a lethal variant of osteogenesis imperfecta: detection of the mutation with a carbodiimide reaction of DNA heteroduplexes and direct sequencing of products of the PCR. Skin fibroblasts from a proband with a lethal variant of osteogenesis imperfecta synthesized both apparently normal type I procollagen and a type I procollagen that had slow electrophoretic mobility because of posttranslational overmodifications. The thermal unfolding of the collagen molecules as assayed by protease digestion was about 2 degrees C lower than normal. It is surprising, however, that collagenase A and B fragments showed an essentially normal melting profile. Assay of cDNA heteroduplexes with a new technique involving carbodiimide modification indicated a mutation at about the codon for amino acid 550 of the alpha 1(I) chain. Subsequent amplification of the cDNA by the PCR and nucleotide sequencing revealed a single-base mutation that substituted an aspartate codon for glycine at position alpha 1-541 in the COL1A1 gene. The results here confirm previous indications that the effects of glycine substitutions in type I procollagen are highly position specific. They also demonstrate that a recently described technique for detecting single-base differences by carbodiimide modification of DNA heteroduplexes can be effectively employed to locate mutations in large genes.
Significance of CSF immunoglobulins in monitoring neurologic disease activity in Behcet's disease. We examined the intrathecal production of immunoglobulins (Ig) G, A, and M in 16 patients with Behcet's disease, 13 of whom have CNS involvement, and in 40 neurologic controls. Oligoclonal IgA and IgM bands were mainly detected in CSF samples from patients with active neuro-Behcet's disease and were documented to disappear when neurologic manifestations remit. Oligoclonal IgG bands, however, were not related to disease activity and were also found in some neurologic controls. High immunoglobulin index values were detected in both active and quiescent diseases and were high in some patients with impaired blood-CSF barriers. The study presented here demonstrates that CSF oligoclonal IgA and IgM may be helpful in monitoring CNS disease activity in neuro-Behcet's and could be useful in understanding the pathogenesis of this disease.
Radiology in the intensive-care unit. Portable chest radiography is an essential component of clinical patient management in the intensive-care unit. With routine use of this procedure, unexpected cardiopulmonary abnormalities are frequently detected, and malposition or complications of intravascular devices and endotracheal, thoracostomy, or nasogastric tubes are also commonly found. The pulmonary parenchyma may be assessed for changes of acute lung injury, cardiogenic edema, areas of pneumonitis, atelectasis, or other abnormal collections of fluid or air. In mechanically ventilated patients, barotrauma occurs frequently and may be manifested by subtle intrathoracic collections of air. Technical factors may limit the resolution of the anteroposterior chest radiograph obtained at the bedside, but crucial clinical information is often gained. Portable chest radiographic findings, the role of computed tomography and ultrasonography, and interventional radiologic procedures pertinent to patients in the intensive-care unit are reviewed.
Cervical carcinoma: MR imaging with an endorectal surface coil. Ten consecutive patients with biopsy-proved invasive cervical carcinoma underwent magnetic resonance (MR) imaging with both a standard body coil and with an endorectal surface coil. The endorectal coil provided a markedly improved signal-to-noise ratio, enabling the use of small fields of view; thus, the images had significantly improved in-plane resolution. The images were assigned an MR imaging stage based on the clinical staging system of the International Federation of Gynecology and Obstetrics. Vaginal wall, vaginal fornix, parametrium, and pelvic side-wall invasion by tumor were all well demonstrated. When compared with body coil images, the endorectal coil images provided increased anatomic detail and demonstrated tissue planes between tumor and normal structures that were not seen on the body coil images. This preliminary investigation indicates that use of an endorectal surface coil is a promising technique to obtain high-resolution images of the female genital tract. This technique has the potential to improve the accuracy of staging for cervical carcinoma.
Are angiotensin converting enzyme inhibition and aldosterone antagonism equivalent in hypertensive patients over fifty? The effects of inhibiting angiotensin converting enzyme with perindopril and aldosterone with spironolactone were tested in hypertensive patients over fifty. Accordingly, 75 patients with mild hypertension aged 50 to 70 were randomly divided into three groups for a double-blind 8 week comparison of the actions of placebo, 4 to 8 mg/day perindopril, and 37.5 to 75 mg/day spironolactone. Side-effects caused one patient to withdraw from placebo and one from spironolactone treatment. Mean blood pressure rose by 2.4 mm Hg after placebo but dropped by 7.4 and 8.6 after perindopril and spironolactone (P less than .01). Placebo, perindopril, and spironolactone did not alter blood glucose or plasma potassium, but induced, respectively, variations of -0.09, 0, and +0.34 mmol/L in cholesterol (P = .04), and -0.02, -0.05, and +0.27 mmol/L in triglycerides (P less than .01). After the three treatments, changes in angiotensin converting enzyme activity averaged -1, -6, and -1 mU/mL (P less than .01), in active renin -2, +18, and +28 pg/mL (P less than .01), and in aldosterone, +15, +8, and +95 pg/mL (P less than .01). Placebo, perindopril, and spironolactone did not alter microalbuminuria, but reduced urinary kallikrein activity by 0.9, 1.8, and 5.4 mU/mmol creatinine (P = .04). Although short-term administration of spironolactone raised renin and aldosterone markedly and lipids moderately (possibly because of volume contraction), the present results show that perindopril and spironolactone are both safe and effective for treating hypertension at the age of 50 or older.
Squamous carcinoma cell lines produce 1,25 dihydroxyvitamin D, but fail to respond to its prodifferentiating effect. The active metabolite of vitamin D3, 1,25 dihydroxyvitamin D3 [1,25(OH)2D], is produced by normal human keratinocytes (NKC) and regulates their differentiation. Squamous carcinoma cell (SCC) lines lack the ability to differentiate in vitro, which might involve defective 1,25(OH)2D synthesis or response. To address this possibility we obtained four SCC lines (12F2, 12B2, 25, and A431) and first determined whether they could produce 1,25(OH)2D from its substrate 25 hydroxyvitamin D3 (250HD). All could (12F2 greater than NKC greater than 25 greater than 12B2 greater than A431). Furthermore, exogenously added 1,25(OH)2D inhibited 1,25(OH)2D production and stimulated 24,25 dihydroxyvitamin D3 [24,25(OH)2D] production in all cell lines but with different potency (25 = A431 greater than NKC greater than 12B2 greater than 12F2). Cellular binding studies suggested that the high-affinity binding site for 1,25(OH)2D in NKC is not found in 12F2 and 12B2. When the effect of 1,25(OH)2D on differentiation was determined, only NKC responded with an increase in cornified envelope formation, although some of the cell lines responded to the proliferative [at low 1,25(OH)2D concentration] or antiproliferative [at high 1,25(OH)2D concentration] effect of 1,25(OH)2D. Thus, although SCC lines synthesize 1,25(OH)2D and respond to exogenous 1,25(OH)2D with respect to appropriate regulation of endogenous 250HD metabolism, these cell lines fail to respond to the differentiating influence of this vitamin D metabolite.
Small cell carcinoma of the stomach: a clinicopathologic study of 17 cases. Of 17 cases of small cell carcinoma of the stomach, three were early and 14 were advanced. Grossly, the tumors were mostly polypoid at the early stage, and as they advanced, deep ulcerations developed. Histologically, only one tumor was "oat cell type," and the other 16 were "intermediate cell type." With regard to tumor components, five were "pure" tumor, and 12 were "composite" admixing glandular and/or squamous differentiation. Argyrophil cells were seen in eight tumors. Immunohistochemically positive cells for chromogranin, neuron-specific enolase, and keratin were seen in 12, 10, and 7 tumors, respectively. Carcinoembryonic antigen was negative in the small cell component of most tumors as opposed to strong positivity in the glandular component. Electron-dense core granules were evident in seven of nine tumors examined. These findings suggest that histologic variety is quite characteristic of the small cell carcinomas of the stomach, and this type of carcinoma takes an aggressive clinical course like its counterparts in other organs.
Disruption of the blood-brain barrier in open and closed cranial window preparations in rats. The goal of this study was to determine whether the severity of disruption of the blood-brain barrier during acute hypertension is similar in open and closed cranial window preparations. Intravital fluorescent microscopy and fluorescein-labeled albumin were used to evaluate disruption of the blood-brain barrier under control conditions and during acute arterial hypertension in 10 rats equipped with an open cranial window and in six rats equipped with a closed cranial window. Permeability of the blood-brain barrier was quantified by calculating the clearance of fluorescein-labeled albumin and by counting the number of microvascular leaky sites under control conditions and during acute hypertension. Pressure in cerebral venules and intracranial pressure were measured in rats equipped with an open cranial window and a closed cranial window, respectively, under control conditions and during acute hypertension. In rats equipped with an open cranial window, arterial pressure increased from 118 +/- 6 to 189 +/- 3 mm Hg (mean +/- SEM) and pial venous pressure increased from 7 +/- 1 to 22 +/- 3 mm Hg during acute hypertension induced with 30 micrograms/kg/min phenylephrine for 5 minutes. In addition, the clearance of fluorescent albumin increased from 0.11 +/- 0.03 to 1.2 +/- 0.4 ml/sec x 10(-6) and the number of microvascular leaky sites increased from 0 to 25 +/- 1 during phenylephrine infusion. In rats equipped with a closed cranial window, arterial pressure increased from 122 +/- 5 to 187 +/- 7 mm Hg and intracranial pressure increased from 3 +/- 1 to 12 +/- 1 mm Hg during the intravenous infusion of 30 micrograms/kg/min phenylephrine for 5 minutes.
Immunohistochemical study of childhood rhabdomyosarcomas and related neoplasms. Results of an Intergroup Rhabdomyosarcoma study project. The authors assessed a panel of immunohistochemical stains against 109 pediatric solid tumors, primarily rhabdomyosarcomas, under the auspices of the Intergroup Rhabdomyosarcoma Study. Fresh tumor tissue received from participating organizations was divided into portions that were either frozen or fixed in formalin, alcohol, or B5. Immunostaining was performed by the avidin-biotin complex method using monoclonal antibodies to desmin, neurofilaments, vimentin, cytokeratin, and leukocyte common antigen on cryostat sections. Tissue was also embedded in paraffin and stained with antimuscle-specific actin (MSA) and polyclonal antibodies to desmin, creatine kinase M subunit (CKM), myoglobin, and neuron-specific enolase (NSE). Antidesmin staining of cryostat sections was the most sensitive indicator of rhabdomyosarcoma (58 of 62 specimens positive). Results with this reagent in alcohol-fixed and formalin-fixed tissue were similar (46 of 56 positive versus 43 of 56 positive, respectively) and comparable with results with anti-MSA in formalin-fixed tissue (43 of 55 positive). However, the proportion of cells stained by antidesmin was higher in alcohol-fixed tissue than in formalin-fixed tissue. Staining with antimyoglobin and anti-CKM was much less satisfactory, with positivity rates of 17 of 37 and 11 of 57, respectively, in formalin-fixed rhabdomyosarcomas. Immunostaining of muscle markers revealed evidence of myogenesis in six undifferentiated sarcomas and in two sarcomas with inadequate histologic study on hematoxylin-eosin-stained sections. However, positivity was also noticed in samples of fibromatosis, Wilms' tumor, ectomesenchyoma, peripheral primitive neuroectodermal tumor, renal rhabdoid tumor, myositis ossificans, malignant fibrous histiocytoma, and embryonal sarcoma of the liver. The authors conclude that combined use of antidesmin and anti-MSA enhances the diagnosis of childhood sarcomas, especially when employed with other techniques such as electron microscopic study.
Angiotensin II receptor antagonist markedly reduces mortality in salt-loaded Dahl S rats. We investigated the effect of blockade of the renin-angiotensin system (RAS) on morbidity and hypertension in salt-loaded Dahl salt-sensitive (Dahl S) rats. Six-week-old male Dahl S rats (n = 198) were fed a high sodium diet (8% NaCl) for 10 weeks. One group of rats (n = 91) was treated with 30 mg/kg/day of the nonpeptide angiotensin II receptor antagonist, DuP 753, whereas the control group (n = 107) was left untreated. Blood pressure rose steeply in both groups, reaching levels above 200 mm Hg by week 6. DuP 753-treated animals were less hypertensive than controls between weeks 3 and 5 of the study, but had similar blood pressure before and after that time. Although the angiotensin II antagonist had only a transient effect on blood pressure it markedly prolonged survival. After 10 weeks, 68.3% of rats receiving DuP 753, but only 30.1% of controls, were still alive (P less than .0001). Higher morbidity in controls than in DuP 753-treated rats was also suggested by body weights. Following 6 weeks of high salt diet, untreated rats progressively lost weight while DuP 753-treated animals maintained a steady body weight. These results show that the angiotensin II receptor antagonist DuP 753 greatly enhanced survival in salt-loaded Dahl S rats although it reduced blood pressure only transiently. Our data are consistent with a contribution of the RAS to morbidity in this model of hypertension.
Epithelial-myoepithelial carcinoma of salivary glands. Four cases of epithelial-myoepithelial carcinoma of the salivary glands arose as painless masses in patients over 60 years old, three in the parotid and one in the submandibular gland. Histologically, all the tumours were composed of small ducts with a double cell lining surrounded by a basement membrane. The inner cells were epithelial and the outer cells myoepithelial, the latter usually possessing clear cytoplasm. There was a variable degree of intervening hyalinised stroma. All the tumours were partly encapsulated, but also displayed local invasiveness. One of the tumours also showed areas of dedifferentiation when it later recurred and metastasised. The other three were apparently cured by initial excision, with adjuvant radiotherapy in one instance. In the past this tumour has been described as clear cell adenoma, and it was only recently that its true malignant nature, albeit low grade, was recognised. Reports of epithelial-myoepithelial carcinoma are still relatively few, with only one case described from Britain. It is recommended that this histologically distinct neoplasm deserves wider recognition.
Vascular rehabilitation: benefits of a structured exercise/risk modification program. A vascular rehabilitation program was designed to increase exercise tolerance and reduce the risk of cardiovascular disease in patients with lower extremity arterial occlusive disease. Sixty-eight patients (32 men, 36 women); ages 55 to 85 years (mean, 68 years) with claudication 30 (44%), or recovering from lower extremity revascularization 36 (53%), or endovascular procedures 2 (3%) entered the vascular rehabilitation program. Each underwent a physical examination, risk factor assessment, noninvasive arterial studies, and cardiac evaluation. A history was taken from each patient also. Six patients (9%) were excluded on recognition of silent myocardial ischemia. Sixty-two patients (91%) were accepted for exercise training in a program designed to offer 24 (1-hour) monitored exercise sessions, 12 (1-hour) personalized education lectures, and development of a home maintenance exercise program. No deaths or major morbidity occurred. Seventeen patients (27%) did not finish the program, eight (13%) because of development of significant cardiac, extremity, or cerebrovascular disease and nine for nonmedical reasons. Of the 45 patients (73%) who completed the program, 38 (88%) had documented increases in walking distances of greater than 100% (122% to 450%). All 45 patients designed home exercise programs, and 88% of the smokers quit. Long-term follow-up was available on 100% of the patients. Thirty-eight patients (84%) have been followed for 2 years or more. Thirty-eight (84%) maintained or improved walking distances recorded on exit from the program. Thirty of the 36 patients (83%) who stopped smoking remained nonsmokers. Significant reductions in cholesterol were seen at 1 year, and significant reductions in triglycerides were seen at 12 weeks and 1 year.
Overview: diagnosis of ischemic heart disease by noninvasive techniques. Noninvasive tests have greatly improved in their ability to diagnose coronary artery disease. In addition, new testing modalities have been added to our armamentarium. However, no test is clearly superior to all others in every clinical circumstance. Moreover, none have been shown to provide sensitivities and specificities consistently above 90%. Therefore, their use for diagnostic purposes in populations with a lower prevalence of disease is only of moderate value. Conversely, for the assessment of the functional significance of coronary artery disease or prognosis in patients with ischemic heart disease, the addition of noninvasive imaging modalities to exercise testing is of high value.
Screening of gene deletions by polymerase chain reaction in Japanese patients with Duchenne muscular dystrophy. Gene deletions were screened in 49 Japanese Duchenne muscular dystrophy patients from 43 families, using the polymerase chain reaction. Enzymatic amplification was carried out on six regions prone to deletion. Fifteen of 43 families (33%) had gene deletions in at least one of the six regions. This frequency was almost the same as that previously reported in Caucasians. The mid-part of the dystrophin gene was the location most frequently deleted. The frequency of deletion of the region encompassing exon 45 was higher in Japanese families (18.4%) than in Caucasians.
Unexplained displacement of ipsilateral ovary and fallopian tube. During routine laparoscopy, the right fallopian tube and ovary were noted to be displaced. Ovarian and fallopian tube tissue were found on biopsy of adjacent omentum. The most probable cause is asymptomatic torsion of the right adnexum; therefore, evaluation of the renal system with intravenous pyelogram is probably not necessary.
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 less than 0.001), diastolic (23 +/- 12 to 14 +/- 8 mm Hg, p less than 0.005) and mean (29.7 +/- 13.2 to 18 +/- 9 mm Hg, p less than 0.001) pulmonary artery pressures. Aortic systolic (129 +/- 18 to 106 +/- 17 mm Hg, p less than 0.001), mean (89 +/- 19 to 84 +/- 19 mm Hg, p less than 0.05) and pulse (64 +/- 17 to 37 +/- 16 mm Hg, p less than 0.00001) pressures also decreased. Heart rate and aortic diastolic pressures were unchanged. End-systolic wall stress (122 +/- 48 x 10(3) to 96 +/- 44 x 10(3) dynes/cm2, p less than 0.001) and left ventricular end-diastolic diameter (5.7 +/- 0.8 to 5.5 +/- 0.9 cm, p less than 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 less than 0.005). There was a marked reduction in hematocrit (41 +/- 4 to 28 +/- 5%, p less than 0.0001) and platelet count (259,000 +/- 57,600/ml to 145,900 +/- 46,000/ml, p less than 0.0001) after bypass. Cardiopulmonary bypass successfully supported all patients during balloon inflation, for an optimal angioplasty result.
Regional three-dimensional geometry and function of left ventricles with fibrous aneurysms. A cine-computed tomography study. BACKGROUND. To assess the extent and nature of the dysfunction surrounding aneurysms of the left ventricle (LV), we examined the parameters of local and global three-dimensional shape, size, and function of LVs of eight patients with histologically confirmed anterior fibrous aneurysms. METHODS AND RESULTS. Three-dimensional reconstructions of each LV were made from 10-12 short-axis fast cine-angiographic computed tomography (cine-CT) slices encompassing the entire heart at end diastole and end systole. Regional three-dimensional wall thickness, thickening, motion, curvature, and stress index were calculated for 84 elements encompassing the entire LV. The aneurysmal border was defined by a sharp decrease in end-diastolic wall thickness and separated the LV into an aneurysmal zone and a normal zone that was further divided into adjacent normal (AN) and remote normal (RN) zones. As expected, thickening was negligible in both the aneurysmal and the border zones. Although both the AN and the RN zones had normal wall thickness (1.05 +/- 0.20 and 1.09 +/- 0.20 cm, respectively), thickening was depressed in the AN (0.22 +/- 0.08 cm) but not the RN (0.44 +/- 0.19 cm) zones. The size of the dysfunction zone (defined as less than 2 mm thickening) was found to be considerably greater than the anatomic size of the aneurysm (60.9 +/- 13.7% versus 33.6 +/- 7.6% of the left ventricular endocardial area, respectively; p less than 0.001). In addition, the AN zone had a smaller curvature and a higher stress index than the RN zone. CONCLUSIONS. LVs with fibrous aneurysms are characterized by a relatively large region of nonfunction that encompasses the thin aneurysmal area and its transitional border zone, a normally functioning remote zone, and an intermediate region of normal wall thickness but with reduced function, which may be attributed to its low curvature and high stress index.
Delayed postanoxic encephalopathy after strangulation. Serial neuroradiological and neurochemical studies. A 13-year-old boy was the victim of attempted strangulation. His condition had returned to normal by the sixth day after the assault; however, from the seventh day, choreoathetosis, dystonia, and marked pseudobulbar paralysis developed in the boy. The computed tomographic scans and T2-weighted magnetic resonance images that were obtained at this time revealed low-density and high-signal intensities in the region of the bilateral putamen and caudate nucleus. These symptoms and the changes in his computed tomographic scans and magnetic resonance images subsided gradually during a 2-month period. Sequential analysis of the cerebrospinal fluid for gamma-aminobutyric acid and dopamine concentrations during his illness revealed reciprocal changes with normal recovery. Because of the delayed onset of neurological changes and the cerebrospinal fluid showing reversible symptoms, the delayed encephalopathy after strangulation had been related to the biochemical alterations that followed anoxia in the vulnerable basal ganglia.