Desensitization of human breast-cancer cells by interferon-alpha

Continuous exposure of human breast cancer cells, MCF-7, to interferon-alpha (IFN) induces a state.of non-responsiveness termed as desensitization. mRNA 561 is transiently induced by IFN-alpha in MCF-7 cells, peak cytoplasmic levels are reached by six to twelve hours; the mRNA level declines steadily and is reduced to uninduced levels by forty eight hours. Induction of mRNA 561 was used as an index of responsiveness of cells to IFN-alpha and desensitization was characterized in MCF-7 cells and in MCF-7 cells transfected by the v-H-ras oncogene (MCF-7ras). The kinetics and degree of IFN-mediated induction of mRNA 561 was comparable in both the cell lines. Desensitization was observed in MCF-7 cells and not in MCF-7ras. It was a reversible event, requiring de novo protein synthesis as inclusion of cycloheximide inhibited desensitization. The cellular elements that mediate such a phenomena are elicited by IFNs during the initial phases of IFN action and may be polypeptides. The refractory period, the time after which MCF-7 cells become responsive, was determined to be five days. In conclusion, we demonstrate the use of mRNA 561 induction in evaluating desensitization. Inhibition of protein synthesis or transfection with ras blocks desensitization in MCF-7 cells.     

Evaluation of whole blood catalase estimation for diagnosis of malignancy

Whole blood catalase levels were estimated using a disc flotation method in 209 random patients with a wide variety of malignancies. Fifty patients had received no treatment, and the remainder, although having undergone prior therapy, had recurrent or metastatic disease at the time of the study. No relationship was found between the presence of cancer and catalase levels. A direct relationship was found for catalase with hemoglobin levels in both normal and patients' samples. Whole blood catalase is of no value in diagnosis and monitoring of cancer. The decreased catalase values found here and reported previously by others are the result of low hemoglobin levels found in many patients with cancer.     

Study of lymphatic metastatic patterns in gastric carcinoma according to tumor location

A total of 226 cases of advanced gastric cancer which occupied only one third of the stomach were analyzed in order to clarify whether and how lymphatic spread differed according to the tumor location and gross type of tumor. Out of the 226 patients, 45 cases had tumor in the upper third, 74 cases had it in the middle third, and 107 cases had it in the lower third of the stomach. The incidence of lymph node metastasis was found to be much higher for the tumors located in the lesser curvature (51.6%), greater curvature and posterior wall (54.4%), as compared to the tumors located in the anterior wall (28.0%). The tumors located in the upper third of the stomach did not show any metastasis in the N3 node, while the tumors located in the lower third of the stomach did not show any metastasis in the left cardial nodes, short gastric nodes, and the nodes along the left gastroepiploic vessels. Similarly, the tumors from the middle third of the stomach did not invade the left cardial nodes.     

Identification of a novel pulmonary oedema producing toxin from Indian red scorpion (Mesobuthus tamulus) venom.

The experiments were conducted to identify the toxin that produces pulmonary oedema in Mesobuthus tamulus (BT) envenomed animals. Crude BT venom was subjected to Sephadex gel filtration (G-75) and the fractions were screened for optical density (OD), neurotoxicity (prolongation of compound action potential in frog sciatic nerve) and lethality. All these parameters exhibited a peak between 54-94 ml eluates. Fractions of this peak were pooled (SP) and loaded on to carboxymethyl cellulose column. The column was then eluted with increasing buffer concentrations at constant pH and temperature. Eluates were screened for neurotoxicity and OD. Four peaks of neurotoxic activity (T1-T4) were detected. T2 and T3 were lethal whereas T1 and T4 were non-lethal. T2 exhibited mainly neurotoxicity and failed to augment phenyldiguanide (PDG)-induced reflex response or to produce pulmonary oedema. T3 was having minimal neurotoxic actions but augmented PDG-reflex and produced pulmonary oedema. The effects of T3 persisted even after dialysis with 8 kDa cut-off filter but not those of T2. The T3 effects resembled toxic manifestations of BT venom and were blocked by aprotinin pre-treatment. T3 demonstrated a band at approximately 100 kDa in SDS-PAGE. The results demonstrate the presence of a lethal, high molecular weight, pulmonary oedema producing toxin in BT venom.     

Nasal mucociliary clearance in health and disease

“Standard saccharine test is used to detect nasal mucociliary clearance time in healthy individuals both adults and children. The length of the nose was measured radiologically and with the help of a soft malleable rubber catheter. For healthy individuals, mean nasal mucociliary clearance lime is 8.2 minutes in children and 9.5 minutes in adults. The mean nasal mucociliary clearance rates were 11.1 mm/min for children and 12.7 mm/min for adults. Deviated nasal septum, chronic sinusitis, allergic rhinitis, atrophic rhinitis, chronic smokers and patients with recent nasal packings were taken as diseased conditions in adults, whereas children with adenoid hyperplasia were taken for the study. In all of these, nasal mucociliary clearance was significantly prolonged.”     

Pure Sertoli cell tumor of the ovary: A case report

Pure Sertoli cell tumors are an uncommon variant of rare ovarian Sertoli‐Leydig cell tumors. Due to nonspecific clinical and imaging features, diagnosis is often made after histopathological examination. The prognosis is excellent as most are detected in the early stages and surgical resection is often curative in most cases.     

Mutations responsible for the carbapenemase activity of SME-1

SME-1 is a carbapenemase, produced by Serratia marcescens organism and causes nosocomial infections such as in bloodstream, wounds, urinary tract, or respiratory tract infections. Treatment of such infections becomes very complex due its resistance towards penicillins, cephalosporins, monobactams, and carbapenems. Resistance to such antibiotics is of great medical concern. The misuse and overuse of these antibiotics result in the clinical mutation and production of novel β-lactamase enzymes such as SME-1, which show resistance to carbapenems. Class A contains most of the clinically significant extended spectrum of β-lactamase enzymes and carbapenemases. In this study, class A β-lactamase SME-1 sequence, structure, and binding were compared with naturally mutated class A β-lactamase enzymes and a wild-type TEM-1. This study was performed for revealing mutations, which could be responsible for the carbapenemase activity of SME-1. The dynamic characteristics of SME-1 enzymes manifest a different degree of conservation and variability, which confers them to possess carbapenemase activities. Met69Cys, Glu104Tyr, Tyr105His, Ala237Ser, and Gly238Cys mutations occur in SME-1 as compared to wild-type TEM-1. These mutated residues are present close to active site residues such as Ser70, Lys73, Ser130, Asn132, Glu166, and Asn170, which participate in the hydrolytic reaction of β-lactam antibiotics. Furthermore, these mutated residues demonstrate altered interactions with the β-lactam antibiotics (results in altered binding) and within themselves (results in active site structure alterations), which results in expanding the spectrum of activity of these enzymes. This study provides important insights into the structure and activity relationship of SME-1 enzymes. This is evident from the Ω-loop structure modification, which forms the wall of the active site and repositioning of residues involved in hydrolytic reactions, when present in the complex with meropenem in a stable state of MD simulation at 50 ns. Hence, Met69Cys, Glu104Tyr, Tyr105His, Ala237Ser, and Gly238Cys mutations could result in an altered active site structure, binding, and activity of SME-1 with meropenem and thus become resistantant against meropenem, which is a carbapenem.

Sequencing, molecular docking and dynamics, analysis of naturally mutated class A β-lactamase SME-1 was done to compared with 13 naturally mutated class A β-lactamase including SHV-1 and wild class A β-lactamase TEM-1.     

Cerebral hemodynamics in children with sickle cell disease in India: An observational cohort study

India has the second highest number of cases of sickle cell disease (SCD) and affects the most socioeconomically disadvantaged communities living in a horizontal belt from Gujarat to Odisha state. Despite high prevalence, information about cerebral hemodynamics among children with SCD in India remains scarcely described.We performed transcranial Doppler (TCD) to assess cerebral hemodynamics among Indian children with SCD and evaluated their association with clinical and hematological parameters.Children aged 3-18years, diagnosed with SCD living in Raipur in Chhattisgarh and Ahmedabad in Gujarat state were recruited. TCD was performed to obtain flow velocities from middle cerebral (MCA), intracranial internal carotid (ICA) and basilar artery. Associations were evaluated between timed-average-mean-maximum velocities (TAMMV) and various clinical and hematological parameters.Our prospective study included 62 consecutive children with known SCD. Mean ± SD age of the study population was 9.8 ± 3.9 years and 31 (50%) were male. Mean ± SD hemoglobin was 8.64 ± 1.34 Gm/dL while the mean HbSS ± SD was 70.25 ± 15.27%. While 6 (9.6%) children had suffered from stroke during previous 2 years, 7 (11%) demonstrated abnormal TAMMV. Higher HbSS level along with history of iron chelation therapy, blood transfusion and/or stroke showed a trend towards having higher TAMMV.Stroke and cerebral hemodynamic alterations are common among Indian children with SCD. Larger studies with detailed neuroimaging and genetic evaluations are needed for better understanding, characterization, risk stratification as well as optimization of the timing of blood transfusion to reduce physical disabilities among Indian children with SCD.