Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Immunostimulant Activity of Picroliv, the Iridoid Glycoside Fraction of Picrorhiza kurroa, and its Protective Action against Leishmania donovani Infection in Hamsters1

Picroliv, a standardised fraction from root and rhizome of Picrorhiza kurroa, consisting of iridoid glycosides and shown to be responsible for its hepatoprotective activity, was studied for immunostimulant activity. Oral administration of Picroliv (10 mg/kg x 7 days) in mice prior to immunization with sheep red blood cells (SRBC) resulted in a significant increase in haemagglutinating antibody (HA) titre, plaque forming cells (PFC), and delayed hypersensitivity (DTH) response to SRBC. Picroliv enhanced the non-specific immune response characterized by an increase in macrophage migration index (MMI), [14C]-glucosamine uptake, phagocytosis of [14C]-leucine labelled Escherichia coli, chemiluminescence of peritoneal macrophages, and higher uptake of [3H]-thymidine in the lymphocytes of treated mice. It also induced a high degree of protection in golden hamsters against challenge infection with Leishmania donovani promastigotes.     

Antileishmanial action of Tephrosia purpurea linn,extract and its fractions against experimental visceral leishmaniasis

Tephrosia purpurea (family: Fabaceae), which is used in traditional remedies for the treatment of febrile attacks, enlargement and obstruction of liver, spleen, and kidney, was found to have significant antileishmanial activity, and has been extensively fractionated to locate the abode of activity. A fraction (F062) obtained from N‐butanol extract of T. purpurea showed consistent antileishmanial activity at 50 mg/ kg × 5 days by oral route against Leishmania donovani infection in hamsters. Activity was further confirmed in a secondary model, i.e., Indian langur monkeys (Presbytis entellus). Thus, the fraction F062 from this plant possesses potential to produce significant antileishmanial activity by oral route without producing any toxic side effects. Drug. Dev. Res. 60:285–293, 2003. © 2003 Wiley‐Liss, Inc.     

Does Squatting Worsen Lower Limb Ischemia in Patients with Peripheral Arterial Disease?

Peripheral arterial disease (PAD) is an important cause of morbidity and mortality in the world affecting up to 20% in people over 70?years of age. The prevalence is increasing in India due to combined effects of increased life expectancy, increased tobacco smoking and increased prevalence of diabetes mellitus. The aim of the study was to examine the hypothesis whether squatting posture reduces blood flow to lower limbs resulting in worsening of symptoms of lower limb ischemia in patients with PAD. 10 patients with arterial disorders due to thromboangiitis obliterans (TAO), atherosclerosis and diabetic macro vascular disease were selected for patients and were compared with 10 healthy volunteers as controls. Clinical examination and duplex scan of posterior tibial artery (PTA) and dorsalis pedis artery (DPA) performed in standing and squatting position in a clinical environment. They were asked about symptoms of numbness, ischemic pain and the results were noted. Results were tabulated and analysed using Microsoft Excel?. Members in the control group complained of numbness of both the limbs after a period of 30?min on an average. In the patients group, members while squatting complained of numbness in the involved limb within 5?min. They complained of ischemic pain in the involved limb within 10?min and developed numbness in the opposite limb in within 15?min. Posterior tibial artery and dorsalis pedis artery pulsations disappeared for the entire duration of squatting in both groups as confirmed by duplex scanning. It may be recommended that patients with established peripheral vascular disease should avoid squatting position, even if it is for a very short period of time. It is desirable to advice such patients to use appropriate structures as supports which will allow them to work without squatting. This may also necessitate a change in occupation.     

Spectrum of hemoglobinopathies in Orissa, India

Five hundred and 20 cases (279 males; 241 females), referred for anemia, with a wide age range, from different parts of the state of Orissa, India, were investigated to evaluate the extent of the prevalence of hemoglobinopathies (sickle cell disorders and thalassemias) by analyzing the associated hemoglobin (Hb) profiles, Hb genotypes, as well as the clinical and hematological parameters. We found sickle cell trait (Hb AS) in 131 cases (62 males; 69 females), homozygous sickle cell anemia in 49 cases (34 males; 15 females) and Hb S-beta thalassemia (S-beta-thal) in 17 cases (nine males; eight females). There were also 46 cases (32 males; 14 females) of beta-thal major, 103 cases (51 males; 52 females) of beta-thal trait, six cases (four males; two females) of Hb E trait [beta26(B8)Glu-->Lys; GAG-->AAG], and 17 cases (12 males; five females) of Hb E-beta-thal (E-beta-thal). A large proportion of these anomalies were found among the general caste people rather than among the tribal population which constitutes 22% of the total population in this state. Hb E was found mainly in higher castes like Khandayat and Karan, residing in the coastal region of Orissa. This study provides comprehensive data on the spectrum of hemoglobinopathies in this state.