Differences in glycosylation patterns of heat shock protein, gp96: implications for prostate cancer prevention

Heat shock protein gp96 induces a tumor-specific protective immunity in a variety of experimental tumor models. Because the primary sequences of the glycoprotein, gp96 are identical between tumor and normal tissues, the peptides associated with gp96 and/or the posttranslational modifications of gp96, determine its immunogenicity. Gp96-associated peptides constitute the antigenic repertoire of the source tissue; thus, purified gp96-peptide complexes have clinical significance as autologous cancer vaccines. However, the role of altered glycosylation and its contribution in the biological as well as immunologic activity of gp96 still remains uncharacterized. We examined the cancer-specific glycosylation patterns of gp96. To this end, monosaccharide compositions of gp96 were compared between normal rat prostate and two cancerous rat prostate tissues, nonmetastatic/androgen-dependent Dunning G and metastatic/androgen-independent MAT-LyLu, as well as two human nonmetastatic prostate cancer cell lines, androgen-dependent LnCaP and androgen-independent DU145. Marked differences were observed between the gp96 monosaccharide compositions of the normal and cancerous tissues. Furthermore, gp96 molecules from more aggressive cellular transformations were found to carry decreasing quantities of several monosaccharides as well as sum total content of neutral and amino sugars. We believe that the unique glycosylation patterns contribute to cellular phenotype and that the posttranslational modifications of gp96 may affect its functional attributes.     

Head and neck squamous cell carcinoma: the role of post-operative adjuvant radiotherapy

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the leading cancers in India. Since a large majority present in loco-regionally advanced stages, surgery followed by adjuvant post-operative radiotherapy (PORT) has been the mainstay of treatment for resectable HNSCC. AIM: To identify clinico-pathologic factors that could have an impact on outcome in HNSCC in the postoperative setting. MATERIALS AND METHODS: A retrospective review of 348 previously untreated patients with HNSCC who received PORT following curative surgery. The outcome measures were local control, loco-regional control, and disease free survival (DFS). RESULTS: With a median follow-up of 36 months (range: 2-127 months) for surviving patients, the 5-year local control, loco-regional control, and DFS was 79%, 63%, and 56%, respectively for all patients. On univariate analysis, site of primary was an independent prognostic factor for all the outcome measures (P = 0.005, 0.02, and 0.04, respectively) with oral cavity lesions faring the worst. Peri-nodal extension (PNE) affected loco-regional control (P = 0.002) and DFS (P = 0.0005), but was not predictive for local control (P = 0.9852). Cut margin positivity predicted for inferior local control alone (P = 0.03), the significance of which was lost on multivariate analysis. Cox regression analysis however confirmed the significance of primary site and PNE as independent prognostic factors. CONCLUSION: Primary site and PNE are independent factors predicting outcome in the postoperative radiotherapeutic management of HNSCC.     

Design and synthesis of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease inhibitors

Design, synthesis, and biological evaluation of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease (SARS-3CLpro) inhibitors for severe acute respiratory syndrome coronavirus (SARS-CoV) are described. These inhibitors exhibited antiviral activity against SARS-CoV in infected cells in the micromolar range. An X-ray crystal structure of our lead inhibitor (4) bound to SARS-3CLpro provided important drug-design templates for the design of small-molecule inhibitors.     

Effectiveness of emergency argon laser retinopexy performed by trainee doctors

OBJECTIVE: To report the outcomes following treatment of retinal tears with argon laser photocoagulation by trainee doctors as an emergency procedure. METHODS: Retrospective, case note analysis of 100 consecutive patients treated between August 2000 and December 2002 at a tertiary referral hospital. RESULTS: The case notes of 100 consecutive patients (41 male, 59 female) with a mean age of 57.5 years were reviewed. Out of these 90 were symptomatic. The follow-up period ranged from 1 week to 8 months. All patients had argon laser retinopexy in the Emergency department. The on-call Registrar performed the procedure on 94 patients, and Senior House Officers performed the other six. A total of 98 procedures were performed on the slit lamp and two by laser indirect ophthalmoscope. In all, 24 patients needed further treatment with either indirect laser, cryotherapy, or surgery. At the last follow-up, all the patients had anatomically attached retinas. CONCLUSION: A significant proportion of patients (24%) undergoing laser retinopexy in the emergency department needed further treatment. The relative inexperience in using the indirect laser, together with its unavailability in the Emergency department, may be the contributory factors. There seems to be scope for supervised training in using the laser indirect ophthalmoscope for the trainees in the Ophthalmic Emergency department.     

Attenuation of hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats by aqueous extract of seed of Tamarindus indica

Streptozotocin (STZ)-induced diabetic rats were divided into mild diabetic (MD) and severe diabetic (SD) on the basis of fasting blood glucose (FBG) levels. Diabetes was confirmed here by intravenous glucose tolerance test (GTT), biochemical assay of glycogen content in liver and skeletal muscle, glucose-6-phosphatase activity in liver, and serum insulin levels. Hyperlipidemia developed in these experimental diabetic rats was assessed by quantification of total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc) and triglyceride (TG) in serum. Aqueous extract of seed of Tamarindus indica was given to MD and SD rats at the dose of 80 mg and 120 mg/0.5 ml distilled water/100 g body weight/d respectively for 14 d. Significant attenuation of hyperglycemia was indicated by measuring FBG, glycogen level and glucose-6-phosphatase activity along with monitoring of intravenous GTT and serum insulin level. Similarly, correction of hyperlipidemia in diabetic rats after this extract supplementation was confirmed by significant reduction in the levels of above-mentioned hyperlipidemic indicators. Intravenous GTT was performed that highlights the antidiabetic action of this extract is not due to its effect on the intestinal rate of glucose absorption but may be due to modulation of intracellular glucose utilization in target organs. This study focus the efficacy of this extract for the management of experimental diabetes in rat model which may shed some light on the scientific basis of ancient herbal therapy in this line using this seed.     

A novel Ser123Pro substitution in the MIDAS domain of integrin 3 associated with variant Glanzmann's thrombasthenia in an Indian patient

We report a novel 465T-->C (S123P) mutation in exon 3 of the GPIIIalpha gene in a patient with type III or variant Glanzmann's thrombasthenia (GT). Though this mutation did not affect fibrinogen binding to GPIIb-IIIalpha in activated platelets, it interfered with the platelet aggregation in a manner similar to GT.     

Collagen scaffolds derived from fresh water fish origin and their biocompatibility

Collagen, a major component of native extracellular matrix, has diverse biomedical applications. However, its application is limited due to lack of cost-effective production and risk of disease transmission from bovine sources currently utilized. This study describes fabrication and characterization of nano/micro fibrous scaffolds utilizing collagen extracted from fresh water fish origin. This is the first time collagen extracted from fresh water fish origin was studied for their biocompatibility and immunogenicity. The nano/micro fibrous collagen scaffolds were fabricated through self-assembly owing to its amphiphilic nature and were subsequently cross-linked. In vitro degradation study revealed higher stability of the cross-linked scaffolds with only ~50% reduction of mass in 30 days, while the uncross-linked one degraded completely in 4 days. Further, minimal inflammatory response was observed when collagen solution was injected in mice with or without adjuvant, without significant dilution of sera. The fish collagen scaffolds exhibited considerable cell viability and were comparable with that of bovine collagen. SEM and fluorescence microscopic analysis revealed significant proliferation rate of cells on the scaffolds and within 5 days the cells were fully confluent. These findings indicated that fish collagen scaffolds derived from fresh water origin were highly biocompatible in nature.     

Anti-protective antigen IgG enzyme-linked immunosorbent assay for diagnosis of cutaneous anthrax in India

Anthrax caused by Bacillus anthracis is a public health problem in several developing countries whose main source of income is farming. Anthrax is a disease of herbivorous animals, and humans can be infected by handling infected animals or contaminated animal products. Specific diagnostic tests are unavailable in India for the detection and confirmation of cutaneous anthrax in humans. Here, we describe the development of an enzyme-linked immunosorbent assay (ELISA) for detection of serum antibodies against Bacillus anthracis protective antigen in the Indian population. A total of 405 serum samples collected from different groups were tested by the developed ELISA. The assay provided a specificity of 99.41% (95% confidence interval [CI], 97.89 to 99.93) and a sensitivity of 100% (CI, 94.4 to 100) using a cutoff value of 0.29 ELISA unit (EU). The positive predictive value (PPV) and negative predictive value (NPV) of the assay were 97% and 100%, respectively. The efficiency and J index for the reliability of the assay were 99.5% and 0.994, respectively. The assay can be a very useful tool for surveillance as well as for diagnosis of cutaneous anthrax cases in India.     

Herbicide poisoning: A diagnostic challenge

Despite widespread availability, reports of herbicide poisoning from India are not common. Diagnosis is often difficult in the absence of proper history, non-specific clinical features and lack of diagnostic tests. A case of Paraquat poisoning is reported where diagnosis could be established only after the recovery of the patient. The literature is reviewed.     

Coinfection of Leptomonas seymouri and Leishmania donovani in Indian leishmaniasis

Leishmania donovani is considered the causative organism of visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). Testing of 4/29 DNA samples from VL and PKDL patients as well as 2/7 field isolates showed an aberrant internal transcribed spacer 1 (ITS1) restriction fragment length polymorphism (RFLP) pattern, which upon sequencing strongly matched Leptomonas seymouri, thus confirming its presence in Indian leishmaniasis.