shukoor65/lab-rag-model huggingface dataset:
Haemolytic effects of exercise. 1. Exercise-induced haemolysis has been implicated in the sub-optimal iron status of endurance-trained athletes. Accordingly, erythrocyte survival studies using 51Cr were performed on male and female distance runners (n = 20) and sedentary control subjects (n = 10) in order to determine whether the rate of erythrocyte destruction was altered as a consequence of repetitive exercise training. 2. The chromium half-disappearance time of the male (25.4 +/- 3.6 days, mean +/- SD) but not the female (28.3 +/- 4.6 days) athletes was significantly lower than that of the male (33.1 +/- 4.5 days) and female (32.3 +/- 2.6 days) control subjects (P less than 0.01). The mean erythrocyte lifespan of the male and female distance runners (67.2 +/- 22.2 and 72.4 +/- 26.0 days, respectively) was significantly shorter than that of the non-exercising male and female subjects (113.4 +/- 31.0 and 114.1 +/- 29.0 days, respectively) (P less than 0.01). 3. There was no correlation between the mean erythrocyte lifespan and the haemoglobin concentration, serum ferritin levels, body mass, weekly training distance, number of years running or daily protein intake. The mean cell volume and reticulocyte count measured in the same athletes before and after completing a standard 42 km marathon race were within the normal range, whereas the plasma haemoglobin levels were elevated (77.0 +/- 50.5 mg/l) and the serum haptoglobin levels were decreased (0.89 +/- 0.4 g/l) at rest, with a further significant decrease after running (0.69 +/- 0.4 g/l) in the latter measurement (P less than 0.05). 4. It is concluded that the demonstrated increase in erythrocyte turnover may be sufficient to precipitate an iron deficiency in endurance athletes when dietary intake or absorption does not meet the accelerated erythropoietic demands.
Cell migration and actin organization in cultured human primary, recurrent cutaneous and metastatic melanoma. Time-lapse and image analysis. Random cell migration and actin organization in seven human primary, recurrent cutaneous, and metastatic melanoma cell lines were studied by time-lapse video recording and image analysis. The migration of over 800 randomly selected cells from the cell lines were recorded using an inverted microscope with an attached incubator housing. The fraction of cells with random migration rates greater than 10 microns/hour was 8% in an established primary melanoma cell line, 2% and 34% in two recurrent cutaneous melanoma cell lines, and 5%, 30%, 31%, and 60% in four metastatic cell lines. The three metastatic cell lines with significantly higher mean migration rates (P less than 0.001) were derived from lymph node metastases, whereas the fourth metastatic cell line was derived from a visceral metastasis. The cellular morphology and presence of cell nests in the original tissue correlated with in vitro cell morphology and the formation of colonies. The ability of cells to organize actin into stress fibers directly correlated with significantly higher random migration rates and lack of colony formation. Characterization of random migration rates and actin organization of human melanoma cells that are isolated from different stages of tumor progression may lend insight into metastasis.
Stasis ulcers: the role of compliance in healing. The goal in treating a stasis ulcer is rapid and permanent reepithelialization of the ulcer bed. The patient can reach this goal by strict compliance with a program taught and continually reinforced by the physician. The program teaches about the effects of the force of gravity on the flow of blood and lymph in the lower extremities in various positions. The program consists of three rules for the patient to follow: (1) Never sit with legs below heart level. (2) Never stand still. Walk in place or even while sitting (if sitting is necessary). (3) Always wear compressive stockings or pneumatic leggings when walking. I present four case histories demonstrating the different rates of healing of stasis ulcers during noncompliance and during compliance with the physiologic methods of controlling edema and venous stasis in the legs.
Embryological and molecular investigations of parental imprinting on mouse chromosome 7 Mouse embryos with duplications of whole maternal (parthenogenetic and gynogenetic) or paternal (androgenetic) genomes show reciprocal phenotypes and do not develop to term. Genetic complementation has identified the distal region of chromosome 7 (Chr 7) as one of the regions for which both a maternal and paternal chromosome copy are essential for normal development, presumably because of the presence of imprinted genes whose expression is dependent on their parental origin. Embryos with the maternal duplication and paternal deficiency of distal Chr 7 are growth retarded and die around day 16 of gestation; the reciprocal paternal duplication embryos die at an unidentified earlier stage. We report here the incorporation of cells with the paternal duplication into chimaeras, resulting in a striking growth enhancement of the embryos. One gene located on mouse distal Chr 7 (ref. 5) is the insulin-like growth factor 2 (Igf2) gene, an embryonic mitogen. In embryos with the maternal duplication of distal Chr 7, the two maternal alleles of the Igf2 gene are repressed. The presence of two paternal alleles of this gene in many cells is probably responsible for the growth enhancement observed in chimaeras. We propose that there are other imprinted genes in this Chr 7 region. We also compare the imprinting of this subgenomic region with phenotypes resulting from the duplication of the whole parental genome in parthenogenones and androgenones.
Initial blood pressure fall on stand up and exercise explained by changes in total peripheral resistance. To elucidate the underlying mechanisms of the initial fall in blood pressure on standing upright from the supine position, we measured the beat-to-beat changes in intra-arterial pressure in eight healthy male subjects in response to standing. Changes in stroke volume, cardiac output, and total peripheral resistance were computed from the pressure waveform using a pulse contour method. To determine possible mechanisms for the changes observed on standing, similar measures were made on passive tilting and a brief (3-s) bout of cycle exercise. Standing elicited a transient 25% (23-mmHg) fall in mean blood pressure as a result of a 36% fall in total peripheral resistance. Head-up tilt elicited a gradual change in haemodynamic parameters, which reached plateau levels in 20-30 s. Cycling elicited a transient 17% (18-mmHg) fall in blood pressure and a 41% fall in total peripheral resistance. In addition, we measured right atrial and esophageal pressures in two subjects on standing and cycling and found a 10- to 15-mmHg rise in right atrial pressure without a corresponding change in esophageal pressure. This points to the cardiopulmonary reflex as the primary effector of peripheral vasodilation, but we cannot exclude the possibility that 1) local metabolic vasodilation and 2) central command-mediated cholinergic vasodilation contributed to the fall in vascular resistance.
Effects of a three-drug antineoplastic protocol of wound healing in rats: a biomechanical and histologic study on gastrointestinal anastomoses and laparotomy wounds. Using biomechanical and histologic approaches, the effect of perioperative administration of a drug protocol containing 5-fluoruracil, Adriamycin, and mitomycin C (FAM) on the healing of gastrointestinal anastomoses and laparotomy wounds in rats was examined. Application of FAM immediately before operation resulted in significant impairment of wound healing in the early postoperative period. Once the proliferation of fibroblasts and collagen synthesis had led to an increase of mechanical strength, no negative effect on wound healing could be detected applying the same chemotherapeutic agents. These findings indicate the early inflammatory phase of the wound healing process to be most vulnerable to the chemotherapeutic effects. This has significant implications if the theoretical advantages of starting adjuvant chemotherapeutic treatment in the immediate postoperative period are implemented.
Involvement of vacuolar H(+)-adenosine triphosphatase activity in multidrug resistance in HL60 cells. HL60 cells isolated for resistance to vincristine (HL60/Vinc cells) or doxorubicin (HL60/Adr cells) contain enhanced levels of an energy-dependent drug efflux pump. HL60/Vinc cells contain the drug transporter P-glycoprotein, whereas the HL60/Adr isolate does not. In the present study, we examined the possible involvement of vacuolar H(+)-adenosine triphosphatase (H(+)-ATPase) activity in drug resistance in HL60 cells. We utilized bafilomycin A1, an agent which selectively inhibits vacuolar H(+)-ATPase activity at low concentrations. The results showed that bafilomycin A1 induced a major increase in drug accumulation and inhibited drug efflux in both HL60/Adr cells and HL60/Vinc cells. Similar results were obtained with 7-chloro-4-nitrobenz-2-oxa 1,3 diazole, an agent which is also capable of inhibiting vacuolar H(+)-ATPase. Azide, an inhibitor of F1F0 mitochondrial ATPase, and vanadate and ouabain, which are inhibitors of E1E2-type ATPase, did not affect drug levels in resistant cells. We also observed that bafilomycin A1 did not compete with [3H]azidopine binding to P-glycoprotein. Thus, bafilomycin A1 does not appear to function as a substrate for P-glycoprotein. These results suggest an involvement of vacuolar H(+)-ATPase activity in the pathway of drug efflux from HL60/Adr cells and HL60/Vinc cells. The mechanism of this action remains to be determined.
Buschke-Ollendorff syndrome of the scalp: histologic and ultrastructural findings. Buschke-Ollendorff syndrome is an association of connective tissue nevi and osteopoikilosis that usually appears in the first decades of life. The nevi occur on the trunk and extremities. In a 48-year-old man with this rare syndrome the connective tissue nevus was located on the scalp and was pruritic. Histologically, involvement of the epidermis with cystic dilatation of the hair follicles and an abnormality of mucopolysaccharides were present. The nevi in this syndrome may involve an alteration in the three components of connective tissue to a variable degree.
Malignant biliary obstruction: percutaneous use of self-expandable stents A total of 83 self-expandable metallic stents were placed percutaneously in 69 patients for palliation of malignant biliary obstruction. Stent diameter was 1 cm; length, 3.5-10.5 cm. Of the 41 patients with common bile duct obstruction, 27 died 0.2-12 months (median, 3.2 months) after stent insertion. Two patients developed recurrent jaundice and cholangitis after 6 and 12 months, respectively. One patient underwent reintervention. Fourteen patients were alive without jaundice 1-8 months (median, 6.3 months) after stent placement. Of the 28 patients with hilar lesions, 13 died 0.7-7.6 months (median, 4.3 months) after stent placement. Fifteen were alive 1-15.5 months (median, 8.1 months) afterward. Recurrent jaundice and cholangitis were seen in eight of the 28 patients (28%) after 1-6 months (median, 3.6 months). The cause of malfunction of the stent(s) was tumor ingrowth in one patient, tumor overgrowth at the proximal end in five patients, and overgrowth at the distal end in two patients. Reintervention was performed in five patients (18%). Stent-related complications were seen in four patients.
Eosinophil-induced chronic active hepatitis in the idiopathic hypereosinophilic syndrome. A 19-yr-old man had features of chronic hepatitis with piecemeal necrosis as the sole clinical feature of the idiopathic hypereosinophilic syndrome. Liver biopsy specimens demonstrated the presence of activated eosinophils and, by immunohistochemical staining, major basic protein in areas of hepatic cell damage. The case demonstrates the clinical presentation of the idiopathic hypereosinophilic syndrome as chronic hepatitis and the association between eosinophil infiltration and degranulation with the presence of hepatocyte necrosis.
Expression of a mutant DNA topoisomerase II in CCRF-CEM human leukemic cells selected for resistance to teniposide. Nuclear extracts from teniposide (VM-26)-resistant sublines of the human leukemic cell line CCRF-CEM have decreased levels of DNA topoisomerase II catalytic activity and decreased capacity to form drug-stabilized covalent protein-DNA complexes. The ATP concentration required for equivalent activity in a DNA-unknotting assay is 2- to 8-fold higher in nuclear extracts from drug-resistant cell lines as compared with the parental line. When adenosine 5'-[beta,gamma-imido]triphosphate is substituted for ATP in complex-formation assays, no significant change is seen with drug-sensitive cells, but a 50-65% reduction is seen with VM-26-resistant cells. Collectively, these results indicate that an alteration in ATP binding may be involved in the resistance phenotype. Therefore, we identified regions of the topoisomerase II sequence that conform to previously identified nucleotide-binding sites. Starting with cDNA as the template we determined the sequence of the topoisomerase II mRNA surrounding these sites by sequencing DNA fragments produced by the polymerase chain reaction. In the region corresponding to the consensus B ATP-binding sequence described by Walker et al. [Walker, J. E., Saraste, M., Runswick, M. J. & Gay, N. J. (1982) EMBO J. 1, 945-951], the cDNA from the two VM-26-resistant sublines contained an altered sequence having a G----A base change. This base substitution results in the replacement of the conserved arginine at position 449 with a glutamine. Hybridization with allele-specific oligonucleotides confirmed the presence of both the normal and the altered sequence in the resistant cell lines, whereas only the normal sequence was found in the sensitive CEM cells. A chemical mismatch cleavage procedure for the detection of mispaired bases in DNA duplexes identified no other alterations in the 5' third of the mRNA coding sequence, which contains the complete ATP-binding domain of topoisomerase II. The presence of mRNA encoding topoisomerase II with Gln449 correlates both with the presence of a topoisomerase II protein whose interaction with ATP is altered and with increased resistance to the cytotoxicity of VM-26.
Relation of risk factor levels in young adulthood to parental history of disease. The CARDIA study BACKGROUND. The relation between self-reported parental disease and risk factor levels was examined in 2,637 black and 2,478 white men and women aged 18-30 years at the Coronary Artery Risk Development in Young Adults (CARDIA) Study baseline examination (1985-1986). METHODS AND RESULTS. The prevalence of parental disease (at least one parent) in white versus black participants was 44% and 56% for hypertension, 47% and 44% for obesity, 16% and 13% for myocardial infarction, 11% and 17% for diabetes, and 6% and 10% for stroke, respectively. Among these young adults, parental hypertension was associated with higher sex- and age-adjusted systolic and diastolic blood pressure levels. Parental myocardial infarction was associated with higher plasma cholesterol, higher blood pressure levels, and lower high density lipoprotein cholesterol levels in white participants. Parental diabetes was associated with higher fasting blood glucose and insulin levels in all race-sex groups and with higher triglycerides and lower high density lipoprotein cholesterol in black participants only. Parental history of obesity was related to less favorable age- and sex-adjusted lipid levels in white participants and higher blood pressure levels in black participants. Parental history of stroke was associated with higher systolic blood pressure levels in black participants. In general, these differences across family history were predicted only in part by obesity. The prevalence of more than one disease reported in parents occurred more frequently than would have been expected due to chance alone. CONCLUSIONS. These associations between parental disease and risk factors in their adult children probably reflects the impact of both environmental and genetic factors. Parental history may be a useful marker for high risk individuals.
Morphine pharmacokinetics and pain assessment after intracerebroventricular administration in patients with terminal cancer. Morphine pharmacokinetics and pain relief were evaluated after intracerebroventricular administration of morphine (0.4 +/- 0.11 mg) in seven patients with cancer suffering from intractable pain. Ventricular cerebrospinal fluid (CSF), lumbar CSF, and plasma morphine concentrations were analyzed by a specific morphine radioimmunoassay. A two-compartment model was sufficient to describe the kinetics of morphine in ventricular CSF. Morphine diffuses to the lumbar level, and the mean maximum concentration was 192 +/- 105 ng/ml at 4.5 +/- 1.3 hours. Ventricular and lumbar CSF morphine kinetics showed a similar decline during the elimination phase, with terminal half-lives of 3.8 +/- 0.6 hours and 4.2 +/- 1.6 hours, respectively. Pain relief was evaluated by a visual analog scale: the test showed a rapid onset of analgesia (less than 10 minutes). Analgesic effectiveness reached a maximum between 6 and 10 hours. The relationship between pharmacologic effect and morphine concentrations in ventricular CSF resulted in an anticlockwise hysteresis curve. The presence of morphine in lumbar CSF suggested an additive spinal action of morphine, which probably plays a role in the duration of analgesia.
Carcinoembryonic antigen levels in peritoneal washings can predict peritoneal recurrence after curative resection of gastric cancer. Carcinoembryonic antigen (CEA) levels were determined in the peritoneal washings from 120 patients with gastric cancer and 9 patients with benign diseases. Elevated values (greater than 100 ng/g of protein) were observed in 20 of 25 patients with gastric cancer with visible dissemination and 16 of 25 patients with serosal invasion but no dissemination. The same elevation was found in only 9 of 70 patients with no serosal invasion and none of the patients with benign disease. The 2-year survival rates after curative operation for the patients with and without elevation of CEA levels were 21% (19 patients) and 100% (66 patients), respectively (P less than 0.001). A negative correlation was found between CEA levels and survival times after noncurative operation. These results indicate that the CEA level in peritoneal washings could be a sensitive detector of invisible peritoneal dissemination and a new predictor for the postoperative prognosis of gastric cancer.
Effect of preoperative stabilization on respiratory system compliance and outcome in newborn infants with congenital diaphragmatic hernia. To determine whether preoperative stabilization and delay of operative repair of congenital diaphragmatic hernia (CDH) may decrease operative risk, we performed serial pulmonary function tests on 22 newborn infants with CDH and on four infants without pulmonary hypoplasia (two with ileal atresia and two with tracheoesophageal anomalies) who served as control subjects. We used 2 passive respiratory mechanics technique to measure respiratory system compliance. All patients with CDH had respiratory distress immediately after birth, and required mechanical ventilation. Thirteen babies underwent emergency repair (six survived, seven died); nine of them received extracorporeal membrane oxygenation (ECMO) after the operation (two survived, seven died). Operative repair was delayed deliberately for 2 to 11 days in nine infants with severe hypoxemia. Six immediately received ECMO for 4 to 10 days; one died of intraventricular hemorrhage, and five survived and later underwent surgical repair. The seventh patient did not receive ECMO but appeared to have respiratory distress syndrome of infancy and improved after administration of synthetic surfactant. Improvement was seen in two additional infants who received conventional assisted ventilation during a 48-hour delay before surgery, and survived. In all, eight of nine infants who underwent preoperative stabilization survived (p less than 0.05 compared with survival after emergency surgery). Following surgical repair immediately after birth, respiratory system compliance improved only slightly during the first week of life, a time when control infants had a rapid increase in respiratory system compliance (p less than 0.001). In contrast, respiratory system compliance increased nearly twofold in the nine patients undergoing preoperative stabilization (p less than 0.02). Preoperative ECMO was associated with an increase in respiratory system compliance of more than 60% for 1 week, a significant difference from respiratory system compliance among patients undergoing emergency CDH repair (p less than 0.05). These observations provide physiologic evidence of possible benefits of preoperative stabilization before repair of CDH.
Acute pseudobulbar or suprabulbar palsy. We studied 13 patients with supranuclear lower cranial nerve ("pseudobulbar" or "suprabulbar") palsy of acute onset. While seven patients had had a prior stroke, six patients had no history of stroke. Eight patients experienced a complete bilateral supranuclear lower cranial nerve palsy, which was isolated in five patients and associated with hemiplegia and with hemiparesis in three patients. Pseudobulbar palsy was partial in five patients. Only one patient had neuropsychologic impairment. The pseudobulbar features improved or recovered within a few weeks in all patients. The common characteristic of the lesions on computed tomography or magnetic resonance imaging was the interruption of the corticonuclear pathways contrasting with marked sparing of the corticospinal pathways in both hemispheres. These lesions were either an opercular infarct, or a deep infarct in the corona radiata or internal capsule, or a lenticular hemorrhage. Hypertension was the most prevalent concomitant. Our findings suggest that acute pseudobulbar or suprabulbar palsy has rather stereotyped anatomic-vascular correlates and time course.
Rupture of hepatocellular carcinoma as a result of blunt abdominal trauma. Spontaneous rupture of hepatocellular carcinoma occurs frequently in populations in which this tumor is common, but rarely in populations with a low incidence of the tumor. Rupture caused by blunt abdominal trauma has previously been reported in a single patient only. We describe three southern African black men who presented with an acute hemoperitoneum after blunt trauma to the abdomen, and in whom a moderate-size hepatocellular carcinoma was found at laparotomy to have ruptured. In two of the patients, it was possible to resect the tumor. This resectability rate is unusual in blacks with hepatocellular carcinoma, because the tumor is characteristically far advanced at the time of presentation and is rarely amenable to resection.