Immunoreactivity of lymphocytes from draining lymph nodes, peripheral blood and tumor infiltrates from oral cancer patients

Lymphocytes from metastatic (met) and nonmetastatic (non-met) regional lymph nodes, LNL peripheral blood (PBL) and tumor infiltrating lymphocytes (TIL) of patients with squamous cell carcinoma of the oral cavity and healthy donors were investigated for CD3, CD4, CD8 and HNK-1 phenotypes, Natural Killer (NK) cell Activity, Antibody Dependent Cellular Cytotoxicity (ADCC) and proliferative response to mitogen (PHA). Modulation of NK cytotoxicity with recombinant Interferon alpha (IFN-alpha) was also investigated in some cases. Lymphocytes from met and non-met lymph nodes showed no variation in the percentages of CD3+, CD4+ and CD8+ cells, when compared with each other and with PBL of oral cancer patients. TIL showed significantly less proportion of CD3+ and CD4+ cells. The percentage of HNK-1+ cells was significantly lower in LNL and TIL when compared to PBL of oral cancer patients. The mitogen responses of met and non-met LNL were comparable to each other and better than that of PBL from the same patients, while, TIL showed significant impairment in mitogen responses. The NK cytotoxicity and ADCC of PBL from oral cancer patients were comparable to healthy donors which could be augmented by rIFN alpha. LNL and TIL showed almost negligible NK and ADCC activities and NK activity could not be modulated by rIFN alpha. The results thus demonstrate that in oral cancer patients, lymphocytes from three compartments viz. PBL, LNL and TIL showed differential effector functions. The metastatic status of LN did not affect the immunoreactivity of LNL.     

Breast mass characterization using shear wave elastography and ultrasound

Purpose

To evaluate the role of SWE in characterizing breast masses and ascertain whether additional use of SWE to ultrasound for evaluating BI-RADS 3 and 4a masses could help reduce long-term follow-up and unnecessary biopsies of these suspicious breast masses.

Timing of operation in asymptomatic severe aortic stenosis

Calcific aortic stenosis is now the main cause of aortic stenosis in the majority of patients, due to declining incidence of rheumatic fever. Risk factors such as hyperlipidemia play an important role in the progression of aortic stenosis. According to the most recent American College of Cardiology/American Heart Association guidelines, peak velocity greater than 4 m/sec, a mean gradient of more than 40 mmHg and a valve area of less than 1.0 cm(2) is considered hemodynamically severe aortic stenosis. Aortic valve surgery promptly should be done in symptomatic patients due to dismal prognosis without operation. Features such as high aortic valve calcium and positive exercise test identify asymptomatic patients who would benefit from early aortic valve surgery. Due to improvement in surgical techniques and better prosthesis, aortic valve surgery can now be offered at low risk to a selected group of asymptomatic patients with severe aortic stenosis. Currently percutaneous aortic valves are used in very high-risk patients with severe symptomatic aortic stenosis. Their role may expand in the future, depending on the improvements in design and operator experience. Whether advances in molecular cardiology lead to novel therapies in preventing calcific aortic stenosis in the future remains to be seen.     

Radioimmunoassay for human prothrombin

I describe a radioimmunoassay for human prothrombin, with use of a double-antibody technique. Antiserum raised in rabbits was absorbed with Al(OH)3 and heated to 56 degrees C for 30 min. 125I-labeled prothrombin retaining more than 90% of its biological activity was prepared by the iodine monochloride method. The mean concentration of prothrombin in plasma of 12 normal individuals was 100 +/- 29.4 mg/L (2 SD). Prothrombin values were somewhat lower than those obtained by the Laurell electroimmunoassay or by two-stage biological assay of the same plasma, done the same day. The biological values were converted to protein on the basis of 1960 int. units/mg by comparison with the other two assays. The ability of activation fragments of human prothrombin to inhibit binding of labeled prothrombin to its antibody was evaluated by competitive radioimmunoassay. Although precipitin lines formed with undiluted antiserum against all the fragments tested (F-1, F-1.2, prethrombin-1, and thrombin), none of the fragments competed well with prothrombin, even in 10-fold molar excess. Evidently, the structural integrity of the prothrombin molecule is essential for its maximum binding to the antiserum, and antigenic sites are lost during its activation.     

Modulation of agonist binding to human dopamine receptor subtypes by L-prolyl-L-leucyl-glycinamide and a peptidomimetic analog

The present study was undertaken to investigate the role of the hypothalamic tripeptide L-prolyl-L-leucyl-glycinamide (PLG) and its conformationally constrained analog 3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA) in modulating agonist binding to human dopamine (DA) receptor subtypes using human neuroblastoma SH-SY5Y cells stably transfected with respective cDNAs. Both PLG and PAOPA enhanced agonist [3H]N-propylnorapomorphine (NPA) and [3H]quinpirole binding in a dose-dependent manner to the DA D2L,D2S, and D4 receptors. However, agonist binding to the D1 and D3 receptors and antagonist binding to the D2L receptors by PLG were not significantly affected. Scatchard analysis of [3H]NPA binding to membranes in the presence of PLG revealed a significant increase in affinity of the agonist binding sites for the D2L, D2S, and D4 receptors. Analysis of agonist/antagonist competition curves revealed that PLG and PAOPA increased the population and affinity of the high-affinity form of the D2L receptor and attenuated guanosine 5'-(beta,gamma-imido)-triphosphate-induced inhibition of high-affinity agonist binding sites for the DA D2L receptor. Furthermore, direct NPA binding with D2L cell membranes pretreated with suramin, a compound that can uncouple receptor/G protein complexes, and incubated with and without DA showed that both PLG and PAOPA had only increased agonist binding in membranes pretreated with both suramin and DA, suggesting that PLG requires the D2L receptor/G protein complex to increase agonist binding. These results suggest that PLG possibly modulates DA D2S, D2L, and D4 receptors in an allosteric manner and that the coupling of D2 receptors to the G protein is essential for this modulation to occur.     

Staging Systems for Newly Diagnosed Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplantation: The Revised International Staging System Shows the Most Differentiation between Groups

The Revised International Staging System (R-ISS) and the International Myeloma Working Group 2014 (IMWG 2014) are newer staging systems used to prognosticate multiple myeloma (MM) outcomes. We hypothesized that these would provide better prognostic differentiation for newly diagnosed multiple myeloma (MM) compared with ISS. We analyzed the Center for International Blood and Marrow Transplant Research database from 2008 to 2014 to compare the 3 systems (N?=?628) among newly diagnosed MM patients undergoing upfront autologous hematopoietic cell transplantation (AHCT). The median follow-up of survivors was 48 (range, 3 to 99) months. The R-ISS provided the greatest differentiation between survival curves for each stage (for overall survival [OS], the differentiation was 1.74 using the R-ISS, 1.58 using ISS, and 1.60 using the IMWG 2014) . Univariate analyses at 3 years for OS showed R-ISS I at 88% (95% confidence interval [CI], 83% to 93%), II at 75% (95% CI, 70% to 80%), and III at 56% (95% CI, 3% to 69%; P < .001). An integrated Brier score function demonstrated the R-ISS had the best prediction for PFS, though all systems had similar prediction for OS. Among available systems, the R-ISS is the most optimal among available prognostic tools for newly diagnosed MM undergoing AHCT. We recommend that serum lactate dehydrogenase and cytogenetic data be performed on every MM patient at diagnosis to allow accurate prognostication.     

Synchronous Hodgkin's disease and myelofibrosis terminating with granulocytic sarcoma and acute megakaryocytic leukemia

Our patient had stage IIIAI Hodgkin's disease with synchronous myelofibrosis and myeloid metaplasia. A slowly progressive myeloproliferative disease developed over 9 1/2 years and terminated in a painful osteolytic bone disease, spinal extradural granulocytic sarcoma and acute megakaryocytic leukemia. It is likely that this was a result of the myeloproliferative disease rather than a late complication from combination chemotherapy. Our case demonstrates the importance of a curative approach to Hodgkin's disease even in the face of a coexistent disease with a long or unknown natural history.     

Studies on the Mechanism of Oliguria in a Model of Unilateral Acute Renal Failure

To further evaluate the mechanism of the oliguria of acute renal failure, a model was utilized in which intense and prolonged vasoconstriction produced the unilateral cessation of urine flow. The radioactive microsphere method was used to measure total and regional blood flow before and after the intrarenal infusion of norepinephrine, 0.75 mug/kg/min, for 2 h in the dog. In the control kidney, renal blood flow increased 32% 48 h after norepinephrine in association with a fall in the fractional distribution of flow to the outer cortex. In the experimental kidney, total renal blood flow fell from 190 ml/min before norepinephrine to 116 ml/min at 48 h (P < 0.025) with a uniform reduction in cortical blood flow. After the administration of 10% body wt Ringer's solution, there was a marked redistribution of flow to inner cortical nephrons in both the control and experimental kidney. In addition, there was a marked increase in total blood flow in both kidneys. On the experimental side, flow rose to 235 ml/min, a value greater than in either the control period (P < 0.05) or at 48 h after norepinephrine (P < 0.001). However, in spite of this marked increase in blood flow, there was essentially no urine flow from the experimental kidney. In separate studies, the animals were prepared for micropuncture. In all studies, the surface tubules were collapsed, and there was no evidence of tubular obstruction or leakage of filtrate. Over 99% of the 15-muM spheres were extracted in one pass through the experimental kidney. An analysis of the forces affecting filtration suggested that an alteration in the ultrafiltration coefficient may be responsible, at least in part, for the anuria in this model. In this regard, transmission and scanning electron microscopy revealed a marked abnormality in the epithelial structure of the glomerulus. It is suggested that a decrease in glomerular capillary permeability may be present in this model of acute renal failure.     

Solitary plasmacytoma of the parotid gland

Extramedullary plasmacytoma involving the parotid gland is a rare occurrence. This report describes a case of solitary extramedullary plasmacytoma arising from the parotid gland of a 60-year-old woman. The importance of thorough follow up for these patients is stressed, as the possibility of multiple myeloma is higher in this group.