123rc/medical_text huggingface dataset:
Studies on autoimmunity for initiation of beta-cell destruction. VI. Macrophages essential for development of beta-cell-specific cytotoxic effectors and insulitis in NOD mice. NOD mice were treated with silica (which is selectively toxic to macrophages) from 4 or 20.5 wk of age. Syngeneic neonatal pancreases were transplanted into the renal subcapsular space of the NOD mice at 21 wk of age. Silica treatment was continued until 24 wk of age, and then the mice were killed for examination of islet morphology. Neither the islets in transplanted pancreases nor the host pancreatic islets from the early long-term silica-treated animals revealed insulitis. In contrast, most of the islets in transplanted pancreases from the late short-term silica-treated animals showed severe insulitis and beta-cell necrosis, as did the host islets. A further experiment was performed to compare the effect of late short-term silica treatment with that of anti-L3T4-antibody treatment of the same time and duration. In contrast to the late short-term silica-treated animals, the transplanted pancreases in the anti-L3T4-antibody-treated animals revealed intact islets, although most of the host islets showed insulitis. The control group, which received no treatment but did receive neonatal pancreases, revealed severe insulitis and beta-cell necrosis of both transplanted and host islets. These results suggest that early macrophage depletion can abolish the development of beta-cell-specific immunologic effectors but that late macrophage depletion, after the development of insulitis, does not affect the destruction of beta-cells by preexisting effectors other than macrophages. We conclude that macrophages are essential for the development of beta-cell-specific cytotoxic effectors in the initial phase of insulitis in NOD mice.
Angioplasty from the contralateral approach: use of a guiding catheter and coaxial angioplasty balloons. An 8-F guiding catheter has been developed for use with coaxial angioplasty balloon catheters in angioplasty of the femoral artery from the contralateral approach when antegrade puncture of the ipsilateral femoral artery is not possible. The catheter may be used for angioplasty of the femoral artery bifurcation and the superficial femoral artery and for arterial stenoses in patients with renal transplants.
Triiodothyronine in the recovery of stunned myocardium in dogs Two groups of dogs were subjected to a 15-minute period of regional myocardial ischemia by snaring the left anterior descending coronary artery proximal to its first diagonal branch. After release of the snare, the dogs were given either placebo (group 1: n = 7) or triiodothyronine (T3) therapy (group 2: n = 6). The dose of T3 given was 0.2 microgram/kg at 30-minute intervals to a total of six doses. Plasma free T3 level fell significantly during the ischemic period in both groups and continued to fall after reperfusion in group 1. In both groups, cardiac function deteriorated significantly during the period of ischemia and rapidly returned to control level after reperfusion. After 90 minutes of reperfusion, however, deterioration of left ventricular function was observed in group 1 and was significantly worse than in group 2, in which hemodynamic function was maintained and, in fact, improved to levels superior to control. It is suggested that T3 therapy may be worthy of trial in patients in whom reperfusion of the myocardium takes place after a relatively short ischemic period (the "stunned myocardium").
The cancer experience in the Framingham Heart Study cohort. The almost 40-year records of The Framingham Heart Study (FHS) cohort were reviewed to establish the cancer experience of this noninstitutionalized group of white subjects. Diagnoses were confirmed from pathology and laboratory reports and clinical notes. Age-specific incidence rates were compared with Connecticut Surveillance, Epidemiology, and End Results (SEER) data. Among the 5209 subjects, 1201 malignancies were confirmed. Median age at diagnosis was 69 for men and 65 for women. Lung, prostate, skin, and colon accounted for more than half of men's cancers; breast, colon, and skin made up half of the women's. FHS and Connecticut SEER rates matched closely, with the same primary tumor sites appearing commonly in both groups. Thus, the FHS cohort should provide a fair database for analysis of risk factors in cancer incidence, as it has done in cardiovascular diseases.
Interferons and collagen production. The immunoregulatory, antiviral, and antiproliferative agents known as the interferons have profound effects on collagen synthesis. Interferons alpha, beta, and gamma suppress collagen synthesis by dermal fibroblasts. In addition, interferon gamma (IFN-gamma) inhibits the constitutively increased collagen synthesis characteristic of fibroblasts derived from lesions of patients with scleroderma. IFN-gamma also inhibits collagen synthesis by myofibroblasts and synovial fibroblast-like cells. Inhibition of collagen synthesis by IFN-gamma is associated with a coordinate inhibition of transcription for types I and III collagen. In addition, IFN-gamma suppresses levels of procollagen mRNA and type II collagen synthesis in human articular chondrocytes. In vivo studies in mice have demonstrated that IFN-gamma inhibits the collagen synthesis associated with the fibrotic response to an implanted foreign body, bleomycin-induced pulmonary fibrosis, and the healing response to cutaneous thermal burns. In the latter case, while collagen content of the wound scar was decreased, hyaluronic acid was increased in mice receiving IFN-gamma compared to controls. This is in accord with in vitro studies showing that, while interferons alpha and beta decrease production of glycosaminoglycans, IFN-gamma increases production of glycosaminoglycans. Of interest, acute inflammation at sites of thermal injury, or when elicited by proinflammatory agents in separate experiments, also was suppressed in mice treated with IFN-gamma. The means by which IFN-gamma inhibits collagen synthesis involves transcriptional regulation. There is a single report that interferon alpha can decrease the size of a keloid of recent onset in a human patient. Because the interferons can inhibit collagen synthesis in vivo, further studies may be warranted to evaluate the usefulness of these agents in the treatment of disease states characterized by abnormal fibrotic responses as well as their potential for altering the healing response associated with particular therapeutic interventions.
Overexpression of normal and mutated forms of HRAS induces orthotopic bladder invasion in a human transitional cell carcinoma. Recent studies have shown that orthotopic (transurethral) transplantation of human bladder cancer cell lines into nude mice permits tumor growth that accurately reflects their clinical malignant status in the original host. Thus, such a system allows a unique opportunity to analyze the genetic events involved in the conversion of low-grade bladder cancer, the vast majority of which are curable, to the high-grade life-threatening form of the disease. Since 5-10% of transitional cell carcinomas (TCCs) have been shown to contain a mutated HRAS gene, and protein expression levels of all forms of HRAS have been correlated with TCC progression, we chose to study the contribution of the HRAS oncogene in bladder tumor progression. We evaluated the effects of transfection of normal or mutated HRAS genes into a human TCC, called RT-4, that behaves as a superficial noninvasive papillary tumor after transurethral orthotopic inoculation into athymic nude mice. We found that overexpression of either transfected normal or mutated HRAS genes converted RT-4 cells to express an invasive phenotype remarkably similar in nature to the clinical behavior of high-grade bladder carcinomas. These results suggest a role for overexpressed normal or mutated RAS genes in human bladder carcinoma progression, and highlight the importance of using orthotopic inoculation systems for evaluation of the contribution of oncogenes to malignant tumor progression.
Mapping chromosome band 11q23 in human acute leukemia with biotinylated probes: identification of 11q23 translocation breakpoints with a yeast artificial chromosome. Translocations involving chromosome 11, band q23, are frequent recurring abnormalities in human acute lymphoblastic and acute myeloid leukemia. We used 19 biotin-labeled probes derived from genes and anonymous cosmids for hybridization to metaphase chromosomes from leukemia cells that contained four translocations involving band 11q23: t(4;11)(q21;q23), t(6;11)(q27;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13). The location of the cosmid probes relative to the breakpoint in 11q23 was the same in all translocations. Of the cosmid clones containing known genes, CD3D was proximal and PBGD, THY1, SRPR, and ETS1 were distal to the breakpoint on 11q23. Hybridization of genomic DNA from a yeast clone containing yeast artificial chromosomes (YACs), that carry 320 kilobases (kb) of human DNA including CD3D and CD3G genes, showed that the YACs were split in all four translocations. These results indicate that the breakpoint at 11q23 in each of these translocations occurs within the 320 kb encompassed by these YACs; whether the breakpoint within the YACs is precisely the same in the different translocations is presently unknown.
Increased susceptibility to hypoxia of prolonged action potential duration in ventricular papillary muscles from diabetic rats. The action potential duration (APD) of ventricular muscles obtained from diabetic animals is reported to be prolonged. We studied the effect of varied periods of diabetes on APD prolongation using isolated ventricular papillary muscles from streptozocin-injected rats. We found that a diabetic period greater than 30 wk was necessary for the evolution of significant prolongation of APD. We then studied the effect of repeated hypoxia (PO2 40 mmHg) and normoxia (PO2 300 mmHg) on prolonged APD of diabetic muscles and compared the findings with those from control rats. Transmembrane potentials were recorded with conventional glass microelectrodes. Under normoxic conditions, the APDs of diabetic muscles were significantly prolonged, the maximum upstroke velocity of action potentials tended to be decreased, and the resting membrane potential was not changed significantly compared with controls. The first hypoxia (20 min) shortened the APD in both diabetic and control rats but more so in diabetic rats, thereby making the APD of diabetic rats virtually identical to the control rat APD during the hypoxia. On subsequent reoxygenation (30 min), these hypoxia-induced changes were almost recovered. The second hypoxia (20 min) produced more severe shortening of the APD in both muscle types, and the effect was again far greater in diabetic rats than controls, ending with a reversed sequence of APDs and the APD of diabetic muscles much shorter than the controls. Excessive shortening of APD in diabetic muscles during hypoxic conditions was speculated to be due to greater increases in the outward K+ current through ATP-regulated K+ channels that may be secondary to the more severe reduction of intracellular ATP concentrations in diabetic versus control hearts.
Nonspecific magnetic resonance appearance of renal oncocytomas: report of 3 cases and review of the literature. We report the magnetic resonance appearance of 3 cases of solitary renal oncocytomas. All lesions were of low to moderate signal intensity on T1-weighted images and became considerably brighter on the more heavily T2-weighted images. One lesion contained a large central area of cystic degeneration, while the other 2 were solid. A central stellate scar was present in the smaller of the 2 solid lesions. Our observations lend further support to earlier reports on the nonspecific magnetic resonance features of oncocytomas.
Oncogenes and suppressor genes: their involvement in colon cancer [editorial] Abnormalities in oncogenes, which are broadly classified into viral and cellular oncogenes, and suppressor genes appear critical for the development of colon cancer. Cellular oncogenes contribute to malignant transformation when they become activated by point mutation, translocation, amplification, or loss of regulator sequences. The properties of the oncoproteins, the proteins encoded by oncogenes which are essential for carcinogenesis, are unclear. Suppressor genes normally suppress the tumorigenic phenotype by keeping the growth of cells in check; it is their inactivation that contributes to malignant transformation. Development of colon cancer appears to take place by stepwise accumulation of multiple genetic alterations during the progression from normal colon to adenoma and carcinoma. Activation of ras, an early event in this sequence, is found in 50% of colon cancers; overexpression of c-myc is found in approximately 80%. Inactivation of suppressor genes, which occurs during later stages, is noted in greater than 70% of tumors. A current model of colonic tumorigenesis is presented.
Angiotensin converting enzyme inhibitors and quality of life. The term quality of life implies more than adverse effects that make treatment intolerable. It is not new but has only relatively recently become a parameter to be measured in patients treated for cardiovascular disease. Lessons can be learned from other conditions in which the Karnovsky Index and the Arthritis Impact Measurement Scale have been used. Several investigators have used questionnaires to assess quality of life during antihypertensive therapy. However, assessment of the effect of angiotensin converting enzyme (ACE) inhibition on quality of life has only been done recently. The largest and best known study, of 625 white men with mild hypertension, reported that patients given captopril showed a significant improvement after 6 months in general well-being, work performance, and those skills associated with cognitive function. No such improvement was found with methyldopa and there was significant worsening in measures associated with depression, sexual dysfunction, and life satisfaction. The propranolol group, while showing improvement in cognitive functioning and social participation, manifested worsening of sexual function and physical symptoms. Diuretic therapy had a greater negative impact on the quality of life of hypertensive patients than captopril, propranolol, or methyldopa alone. Whether these results will be seen in other patient populations, and the pharmacological basis for these results, remains to be determined. As newer agents become available (eg, beta-blockers with ancillary properties, calcium channel blockers with allegedly more selective actions on various vascular beds), comparative studies between these agents and ACE inhibitors old and new are awaited with interest.
Late potentials in progressive muscular dystrophy of the Duchenne type. This study describes the late potentials (LPs) obtained by signal-averaged electrocardiography (SAECG) in 66 patients with Duchenne's progressive muscular dystrophy (DMD). It also assesses the possible relationships between LPs and the severity of DMD, and the findings of two-dimensional echocardiography, as well as ventricular arrhythmias examined with the Holter system. SAECGs were performed with a Marquette MAC-1 unit. Based on Swinyard-Deaver's system of stages, ranging from the mildest, S1, to the most severe, S8, one patient each could be assigned to S2 and S4, 6 to S5, 20 to S6, 21 to S7, and 17 to S8. LPs were observed in 21 of the 66 patients (32%), including 3 of the 20 assigned to S6 (15%), 10 of the 21 in S7 (48%), and 8 of the 17 in S8 (47%). The total wall motion index evaluated by the method of Hegar was significantly greater in the patients with LPs (8.4 +/- 4.4) than in those without LPs (5.8 +/- 3.1) (p less than 0.05). The incidence of LPs was found to be higher in the dilated cardiomyopathy (DCM) type (8 of 12;67%) than in the normal type (9 of 41;22%) (p less than 0.01). The incidence of ventricular premature complexes (VPCs) was significantly higher in patients with LPs (13 of 21;62%) than in those without LPs (13 of 45;29%) (p less than 0.05). No sustained ventricular tachycardia (VT) was observed, although nonsustained VT was noted in three patients with LPs. The LPs in patients with DMD were thus associated with left ventricular dysfunction, and the presence of LPs might be correlated with the extent of myocardial derangement in DMD.
Outpatient sedation: an essential addition to gynecologic care for persons with mental retardation. Routine gynecologic care for persons with mental retardation may be difficult to provide, especially to those women who do not allow a pelvic examination to be performed. Of 275 women referred to a multidisciplinary clinic addressing the reproductive health concerns of mentally retarded women, 61 patients (22%) did not allow a gynecologic examination to be performed. The administration of ketamine alone, midazolam alone, or a combination of midazolam and ketamine allowed for the successful performance of a gynecologic examination in 81% of previously uncooperative women. No adverse effects of the medications were noted. We conclude that sedation of difficult-to-examine, mentally handicapped women can be safely performed in the outpatient setting, thus avoiding the need for general anesthesia and its inherent risks.
Thyroarytenoid muscle activity during hypoxia in awake lambs. It is generally accepted that hypoxia in early life results in active laryngeal braking of expiratory airflow via the recruitment of glottic adductor muscles. We examined the electromyogram expiratory activity of the thyroarytenoid muscle in seven 11- to 18-day-old awake nonsedated lambs exposed to an inspired O2 fraction of 0.08 for 18 min. The lambs breathed through a face mask and a pneumotachograph. During baseline prehypoxic breathing, the thyroarytenoid muscle was largely inactive in each awake lamb. Unexpectedly, no recruitment of the thyroarytenoid muscle was recorded during hypoxia in any of the seven lambs; simultaneous examination of the flow-volume curves revealed an absence of expiratory airflow braking. Also unexpectedly, marked expiratory activity of the thyroarytenoid muscle was recorded, with each expiration occurring within less than 10 s after the return to room air. The resulting delay of expiration was apparent in the flow-volume loops. Thus, in awake 11- to 18-day-old lambs, 1) active expiratory glottic adduction is absent during hypoxia and 2) a return from hypoxia to room air results in prolonged expiration as well as active glottic adduction that controls end-expiratory lung volume.
Axillosubclavian vein thrombosis produced by retrosternal thyroid. Several causes of axillosubclavian vein thrombosis have been described. Trauma to the subclavian vein by pacemaker wires or central venous lines as well as the so-called effort thrombosis have been recognized as frequently diagnosed precipitating factors. A patient is herein presented with thrombosis of the subclavian vein caused by a giant substernal thyroid compressing the innominate vein.
Cellular internalization, transport, and esterification of iodine-125-NP59 by MA-10 Leydig tumor cells. The present studies were directed toward understanding the cellular processing of the cholesterol analogue, NP59. NP59 readily entered MA-10 Leydig tumor cells. The cholesterol analogue entered the cells by binding to the plasma membrane and becoming internalized along with plasma membrane cholesterol. Internalized NP59 was readily esterified to NP59 ester. Transport of NP59 within the cell was indistinguishable from transport of cholesterol. Cholesterol and NP59 transport were under the control of cAMP, however, only cholesterol entered the mitochondria and was converted into progesterone. Thus, internalized NP59 could not be removed from the cell by conversion into steroid hormones. Esterified NP59 was metabolically inert and could not be converted back to free NP59 and free fatty acid. Since NP59 was not a substrate for the cholesteryl ester hydrolase, it became trapped in the cell as NP59 ester.
Induction of cytotoxicity of the renal hilar lymph nodes by pedal subcutaneous administration of interleukin-2 in patients with renal cancer. The authors attempted to increase the cytotoxicity of the renal hilar lymph nodes in ten patients with renal cell carcinoma by administration of recombinant interleukin-2 (IL-2) into the subcutaneous tissue of the instep. A total of 5000 to 21,000 units was given over 3 to 12 preoperative days. Mononuclear cells separated from the lymph nodes excised from the renal hilum at surgery served as the effector cells. Fresh autologous tumor cells and three cultured cell lines, K562, Raji, and ACHN, served as the target cells. Cytotoxicity was measured by a chromium-releasing assay. The results showed that the mononuclear cells from the lymph nodes of the patients given IL-2 became cytotoxic to all target cells. Surface markers of lymphocytes in the lymph nodes were unchanged. Peripheral blood lymphocytes showed increased cytotoxicity only against Raji cells. Adverse effects were mild or moderate and included local redness, high fever, liver dysfunction, and toxic erythema.
Effects of halothane on hypoxic pulmonary vasoconstriction in canine atelectasis. We studied the interactions of atelectasis and halothane on hypoxic pulmonary vasoconstriction using an isolated canine lobe. We divided pulmonary vascular resistance into arterial, venous, and middle segmental resistances by a vascular occlusion technique. We found that middle segmental resistance significantly increased (P less than 0.05) from 0.016 +/- 0.007 cm H2O.mL-1.min-1 during normoxic ventilation to 0.06 +/- 0.007 cm H2O.mL-1.min-1 during hypoxic ventilation. We then produced sublobar atelectasis by introducing 4.5-mm steel ball bearings into the lobar bronchus, which resulted in a significant increase (P less than 0.05) of middle segmental resistance to 0.046 +/- 0.014 cm H2O.mL-1.min-1 during normoxic ventilation and a further significant increase (P less than 0.05) to 0.084 +/- 0.02 cm H2O.mL-1.min-1 during hypoxic ventilation. Ventilation with 2.0% halothane but not 0.5% halothane prevented the increases in middle segmental resistance observed with either atelectasis or hypoxic ventilation. Values of arterial and venous segmental resistances were not similarly affected. We conclude that sublobar atelectasis increases pulmonary vascular resistance by stimulating hypoxic pulmonary vasoconstriction. Both halothane and hypoxia primarily act upon the middle vascular segment, but their effects are in opposite directions and, in the former instance, are concentration-dependent.