Induction of capacitation in human spermatozoa in vitro by an endometrial sialic acid-binding protein

A Ca²⁺-dependent sialic acid-binding protein (SABP) of humanendometrium, which specifically bound to human sperm head plasmamembrane in vitro, was found to increase the percentage motilityand acrosome-reacted pattern of uncapacitated spermatozoa. Theprotein was synthesized in the endometrium and secreted intothe uterine fluid. This intra-uterine factor, which is apparentlyadvantageous in vitro in inducing human sperm capacitation,may play a significant role in promoting the postrelease maturationof ejaculated spermatozoa by enhancing ⁴⁵Ca uptake into spermatozoaby a pathway which is insensitive to calcium-channel blockers.However, the ⁴⁵Ca uptake could be enhanced on exposure to thedivalent cation ionophore A23187 and inhibited in the presenceof the calmodulin inhibitor trifluoperazine. The SABP also inducesan increase in intracellular Ca²⁺ in spermatozoa, as seen byFURA-2 AM studies. Furthermore, overlay studies show human SABPto be a Ca²⁺-binding protein. The data presented here suggestthat SABP induces invitro sperm capacitation and the subsequentacrosome reaction by increasing intracellular Ca²⁺ concentration.     

Large Scale Manufacturing of B43(Anti-CD19)-Genistein for Clinical Trials in Leukemia and Lymphoma

We have conjugated the murine monoclonal anti-CD 19 antibody B43 to the tyrosine kinase inhibitor genistein to construct an effective immunoconjugate against CD 19 antigen positive hematologic malignancies. The scaled-up production and purification of B43 antibody, genistein, and B43-Genistein immunoconjugate permitted the manufacturing of a highly purified clinical-grade B43-Genistein preparation. In clonogenic assays, B43-Genistein elicited selective and potent cytotoxicity against CD 19 antigen positive human leukemia cells. To our knowledge, this work represents the first effort of producing a clinical-grade genistein immunoconjugate for treatment of B-lineage leukemia and lymphoma.     

TCOF1 gene encodes a putative nucleolar phosphoprotein that exhibits mutations in Treacher Collins Syndrome throughout its coding region

Treacher Collins Syndrome (TCS) is the most common of the human mandibulofacial dysostosis disorders. Recently, a partial TCOF1 cDNA was identified and shown to contain mutations in TCS families. Here we present the entire exon/intron genomic structure and the complete coding sequence of TCOF1. TCOF1 encodes a low complexity protein of 1,411 amino acids, whose predicted protein structure reveals repeated motifs that mirror the organization of its exons. These motifs are shared with nucleolar trafficking proteins in other species and are predicted to be highly phosphorylated by casein kinase. Consistent with this, the full-length TCOF1 protein sequence also contains putative nuclear and nucleolar localization signals. Throughout the open reading frame, we detected an additional eight mutations in TCS families and several polymorphisms. We postulate that TCS results from defects in a nucleolar trafficking protein that is critically required during human craniofacial development.     

Guillain Barre syndrome as a manifestation of neurological melioidosis

Neurological melioidosis is a very rare and very few cases have been reported from India. Presentation is an extremely varied and as this disease is associated with high mortality, high index of suspicion is needed to diagnose and treat. In this context, we report a patient presenting as Guillain Barre syndrome evaluated as melioidosis.Key Words: Guillain Barre’ syndrome, infection, melioidosis     

Synthesis of primaquine glyco‐conjugates as potential tissue schizontocidal antimalarial agents

Primaquine ( PQ ) is the only drug used to prevent relapse of malaria due to P. vivax and P. ovale, by eradicating the dormant liver form of the parasite (hypnozoites). The side‐effects associated with PQ limits is uses in treatment of malaria. To overcome the premature oxidative deamination and to increase the life span of drug in the biological system, the novel glyco‐conjugates of PQ were synthesized by coupling of primaquine with hexoses in phosphate buffer. The saccharide part of the hybrid molecules thought to direct the drug to the liver, where hypnozoites resides. All the synthesized compounds were fully characterized and evaluated for their radical curative activities. The three compounds viz glucoside ( 15a ), galactoside ( 15b ) and mannoside ( 15c ) with high activity were tested for their activity in rhesus monkeys where the most active compound 15b showed twofold activity (100% radical curative activity at 1.92 mmol/kg) than the standard drug PQ diphosphate (3.861 mmol/kg). It is proposed that results from these studies may be advantageous to develop a new potent tissue schizonticide antimalarial compound.     

Local thermal injury elicits immediate dynamic behavioural responses by corneal Langerhans cells

Langerhans cells (LCs) represent a special subset of immature dendritic cells (DCs) that reside in epithelial tissues at the environmental interfaces. Although dynamic interactions of mature DCs with T cells have been visualized in lymph nodes, the cellular behaviours linked with the surveillance of tissues for pathogenic signals, an important function of immature DCs, remain unknown. To visualize LCs in situ, bone marrow cells from C57BL/6 mice expressing the enhanced green fluorescent protein (EGFP) transgene were transplanted into syngeneic wild-type recipients. Motile activities of EGFP(+) corneal LCs in intact organ cultures were then recorded by time lapse two-photon microscopy. At baseline, corneal LCs exhibited a unique motion, termed dendrite surveillance extension and retraction cycling habitude (dSEARCH), characterized by rhythmic extension and retraction of their dendritic processes through intercellular spaces between epithelial cells. Upon pinpoint injury produced by infrared laser, LCs showed augmented dSEARCH and amoeba-like lateral movement. Interleukin (IL)-1 receptor antagonist completely abrogated both injury-associated changes, suggesting roles for IL-1. In the absence of injury, exogenous IL-1 caused a transient increase in dSEARCH without provoking lateral migration, whereas tumour necrosis factor-alpha induced both changes. Our results demonstrate rapid cytokine-mediated behavioural responses by LCs to local tissue injury, providing new insights into the biology of LCs.     

Induction of a single dose of streptozotocin (50 mg) in rat model causes insulin resistance with type 2 diabetes mellitus

Streptozotocin (STZ) is a broad-spectrum antibiotic that is toxic to the insulin-producing beta cells of the pancreatic islets. STZ is currently used clinically for the treatment of metastatic islet cell carcinoma of the pancreas and the induction of diabetes mellitus (DM) in rodents. So far, there has been no previous research to show that STZ injection in rodents causes insulin resistance in type 2 diabetes mellitus (T2DM). The purpose of this study was to determine if rats (Sprague–Dawley) developed type 2 diabetes mellitus (insulin resistance) after 72 h of intraperitoneal administration of 50 mg/kg STZ. Rats with fasting blood glucose levels above 11.0 mM, 72 h post-STZ induction, were used. The body weight and plasma glucose levels were measured every week throughout the 60-day treatment period. The plasma, liver, kidney, pancreas, and smooth muscle cells were harvested for antioxidant, biochemical analysis, histology, and gene expression studies. The results revealed that STZ was able to destroy the pancreatic insulin-producing beta cell, as evidenced by an increase in plasma glucose level, insulin resistance, and oxidative stress. Biochemical investigation indicates that STZ can generate diabetes complications through hepatocellular damage, elevated HbA1c, kidney damage, hyperlipidemia, cardiovascular damage, and impairment of the insulin-signaling pathway.     

Electrophysiological and behavioural study of localisation in presence of noise

Objective: The ability to determine the location of the sound source is often important for effective communication. However, it is not clear how the localisation is affected by background noise. In the current study, localisation in quiet versus noise was evaluated in adults both behaviourally, and using MMN and P3b.

Design: The speech token/da/was presented in a multi-deviant oddball paradigm in quiet and in presence of speech babble at +5?dB SNR. The deviants were presented at locations that differed from the standard by 30°, 60° and 90°.

Study sample: Sixteen normal hearing adults between the age range of 18–35?years participated in the study.

Results: The results showed that participants were significantly faster and more accurate at identifying deviants presented at 60° and 90° as compared to 30°. Neither reaction times nor electrophysiological measures (MMN/P3b) were affected by the background noise. The deviance magnitude (30°, 60° and 90°) did not affect the MMN amplitude, but the smaller deviant (30°) generated P3b with smaller amplitude.

Conclusions: Under the stimulus paradigm and measures employed in this study, localisation ability as effectively sampled appeared resistant to speech babble interference.