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Biomedical subjects

M S Deshpande

Publications and source records attributed to M S Deshpande.

At least 19 recordsLinked to original sources
PubMed2006

Split therapy: planned neck dissection followed by definitive radiotherapy for a T1, T2 pharyngolaryngeal primary cancer with operable N2, N3 nodal metastases--a prospective study.

BACKGROUND: The management of patients with a small pharyngolaryngeal cancer (T1 and T2) with large nodal metastases is a subject of debate. We present data on the feasibility and outcome of treating these patients with surgery for the nodal metastases followed by definitive radiotherapy. METHODS: Prospective study of 59 patients of small pharyngolaryngeal primary squamous carcinomas with operable (N2/N3) nodal metastasis treated with neck dissection followed by radiotherapy. RESULTS: Complete nodal clearance was achieved in 54 (90%). The mean nodal size was 4 cm and extranodal extension was seen in 88% of patients in the study group. There were no significant postoperative complications. Median interval between surgery and radiotherapy was 23 days. Forty-nine patients (83%) started their RT within 6 weeks of surgery. With a median follow-up of 25 months, the disease free and overall survival was 54% and 60% (5 years). CONCLUSION: The management of patients with a radiocurable pharyngolaryngeal primary with large nodes by this approach is a feasible option with adequate control and survival.

Adult↗
PubMed2005

Mannheimia (Pasteurella) haemolytica leukotoxin binding domain lies within amino acids 1 to 291 of bovine CD18.

Previously, we identified bovine CD18 as the receptor for leukotoxin secreted by Mannheimia (Pasteurella) haemolytica. In this study, we constructed bovine-murine CD18 chimeras to locate the leukotoxin binding domain on CD18. Leukotoxin specifically lysed transfectants expressing bovine CD18 fragment encompassing amino acids 1 to 291, indicating that leukotoxin binding domain lies within amino acids 1 to 291 of bovine CD18.

Animals↗
PubMed2005

Simultaneous reconstruction of large skin and mucosal defect following head and neck surgery with a single skin paddle pectoralis major myocutaneous flap.

The pectoralis major myocutaneous (PMMC) flap is commonly used for head and neck reconstruction especially in impoverished nations. PMMC is a sturdy pedicled flap with relatively fewer complications, the learning curve is short and no specialized training in microvascular surgery is needed in order to use this flap. In a defect that requires a large skin and mucosal lining the authors routinely use either a bi-paddle PMMC or a combination of PMMC (for the mucosal lining) and a delto-pectoral flap (for the skin defect). It is indisputable that free tissue transfer is a better way of reconstruction for the majority of most such defects. Unfortunately, not all patients can be offered this form of reconstruction due to the cost, time, expertise and infrastructural constraints in high volume centres such as ours. Bi-paddling of PMMC is hazardous in obese males and most female patients. In such patients the skin defect is reconstructed usually by the delto-pectoral (DP) flap but this, for obvious reasons, is less welcomed by the patients. The authors suggest a technique wherein mucosal lining is created by the myofascial lining (inner surface) of the flap and the skin defect is reconstructed by the skin paddle of the single paddle PMMC. It should be considered wherever a DP flap is unacceptable, or bi-paddling or free tissue transfer is not possible.

Female↗
PubMed2004

Marginal mandibulectomy for lateral sulcus tumours.

OBJECTIVE: To report a retrospective series of marginal mandibulectomy for cancers of oral cavity, with special reference to squamous cancers of gingival buccal complex. METHODS: Retrospective record review of 107 patients who underwent marginal mandibulectomy between 1994 and 2001. RESULTS: Eighty-three marginal mandibulectomies were done for gingivo-buccal complex cancers. Local failure rate was 16%. The 2-year and 5-year disease free survival rates were 69 and 60%, respectively. The local recurrence free survival at the end of 2 and 5 years were 79 and 70%, respectively. CONCLUSION: In carefully selected patients, marginal mandibulectomy is an oncologically safe procedure to achieve good local control.

Carcinoma, Squamous Cell↗
PubMed2004

Upfront submandibular salivary gland transfer in pharyngeal cancers.

Head and neck irradiation results in salivary dysfunction and subsequent xerostomia. Twenty two patients with squamous cancer of oropharynx or hypopharynx underwent contralateral submandibular salivary gland transfer (SMSGT) to submental triangle to shield it from subsequent radiotherapy. Resting salivary outputs of transferred and untransferred gland (control) were measured before and after SMSGT and following radiotherapy, by cannulating individual submandibular duct. They were compared by paired samples t-test. Following radiation therapy transferred gland retained 73% and untransferred gland (control) retained 27% of baseline salivary output. This significant difference in post-radiation salivary outputs suggests preservation of function of transferred salivary gland.

Carcinoma, Squamous Cell↗
PubMed2003

Metastatic adenocarcinoma in testis presenting as a testicular mass--a case report and review of literature.

Testicular metastasis presenting as a testicular mass is an extremely rare condition. There are only nine previously reported cases where testicular mass was the first clinical manifestation of underlying malignancy. Here we report a case of metastatic mucin secreting adenocarcinoma in testis presenting as a testicular mass with unknown primary. We have given a brief review of literature about the spread of tumor to testes.

Adenocarcinoma, Mucinous↗
PubMed2002

Bovine CD18 is necessary and sufficient to mediate Mannheimia (Pasteurella) haemolytica leukotoxin-induced cytolysis.

Leukotoxin (Lkt) secreted by Mannheimia (Pasteurella) haemolytica is an RTX toxin which is specific for ruminant leukocytes. Lkt binds to beta(2) integrins on the surface of bovine leukocytes. beta(2) integrins have a common beta subunit, CD18, that associates with three distinct alpha chains, CD11a, CD11b, and CD11c, to give rise to three different beta(2) integrins, CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1), and CD11c/CD18 (CR4), respectively. Our earlier studies revealed that Lkt binds to all three beta(2) integrins, suggesting that the common beta subunit, CD18, may be the receptor for Lkt. In order to unequivocally elucidate the role of bovine CD18 as a receptor for Lkt, a murine cell line nonsusceptible to Lkt (P815) was transfected with cDNA for bovine CD18. One of the transfectants, 2B2, stably expressed bovine CD18 on the cell surface. The 2B2 transfectant was effectively lysed by Lkt in a concentration-dependent manner, whereas the P815 parent cells were not. Immunoprecipitation of cell surface proteins of 2B2 with monoclonal antibodies specific for bovine CD18 or murine CD11a suggested that bovine CD18 was expressed on the cell surface of 2B2 as a heterodimer with murine CD11a. Expression of bovine CD18 and the Lkt-induced cytotoxicity of 2B2 cells were compared with those of bovine polymorphonuclear neutrophils and lymphocytes. There was a strong correlation between cell surface expression of bovine CD18 and percent cytotoxicity induced by Lkt. These results indicate that bovine CD18 is necessary and sufficient to mediate Lkt-induced cytolysis of target cells.

Animals↗
PubMed2001

An approach to the identification of potent inhibitors of influenza virus fusion using parallel synthesis methodology.

Structure-activity studies associated with the salicylic acid-derived inhibitor of influenza fusion, BMY-27709, were examined using a parallel synthesis approach. This SAR survey led to the discovery of potent influenza inhibitory activity in a series of aromatic amides and thioamides derived from 1,3,3-trimethyl-5-hydroxycyclohexylmethylamine. Select compounds were characterized as inhibitors of the H1 subtype of influenza A viruses that act by preventing the pH-induced fusion process, thereby blocking viral entry into host cells. In a plaque-reduction assay, the most potent inhibitors displayed EC(50) values of 0.02-0.14 microg/mL.

Amines↗
PubMed2001

Heat shock protein-peptide complexes elicit cytotoxic T-lymphocyte and antibody responses specific for bovine herpesvirus 1.

Epitope-based vaccines offer a promising alternative to modified live vaccines against viruses such as herpesviruses which give rise to latent infections, and induce immunosuppression. The success of this approach depends on the ability to direct the CTL epitopes to the MHC class I antigen presentation pathway. The objective of this study was to evaluate the potential of the heat shock protein gp96 in this regard. A group of BALB/c mice was injected with three murine CTL epitope peptides of bovine herpesvirus 1 (BHV-1) complexed in vitro with bovine gp96 (gp96-peptides). Three other groups were injected with either the peptides alone, gp96 alone, or the peptides complexed with BSA. CTLs from mice immunized with gp96-peptides specifically lysed the peptide-pulsed syngeneic targets, as well as BHV-1-infected targets. CTLs from the other three groups did not lyse these targets. To further evaluate the utility of this approach, groups of BALB/c mice were immunized with gp96 isolated from a syngeneic cell-line transduced with BHV-1 glycoprotein D (BC-gD). Mice immunized with gp96 from BC-gD developed CTLs, as well as Abs specific for BHV-1 gD. Furthermore, in vitro stimulation of naive bovine PBMCs with gp96 from BC-gD resulted in CTLs specific for BHV-1. These results demonstrate the feasibility of using gp96-peptide complexes isolated from cells expressing BHV-1 proteins to induce CTL and Ab responses against BHV-1, without the prior knowledge of the CTL and Ab epitope sequences.

Amino Acid Sequence↗
PubMed2001

Core needle biopsy for bone tumours.

INTRODUCTION: Percutaneous core biopsy of bone lesions provides early and definitive diagnosis and guides decisions on management. It is an inexpensive examination technique and has negligible complication rates. METHODS: We performed a prospective study of 136 patients who underwent core biopsies for bone lesions over an 18-month period. A Jamshidi (J) needle was used to obtain a core of tissue and specimens were sent for histopathological examination. Biopsy results were analysed for adequacy, ability to yield diagnostic information and for accuracy of diagnosis. RESULTS: The mean age of patients was 27.5 years with a range of 3-72 years. There were 84 males and 52 females in the study. Histopathological diagnosis was obtained in 121 (89%) patients. The specimen was non-diagnostic in 15 patients. Fourteen patients required two attempts and two patients required three attempts at biopsy. Sixty-two of 64 patients (96.9%) who had a confirmed final diagnosis had an accurate J-needle histopathological diagnosis. None of the patients had any major complications. DISCUSSION: Core needle biopsy is an important tool in the evaluation of bone lesions. It is a safe, reliable and accurate procedure and yields diagnostic information in a high proportion of patients. It has several advantages over an open bone biopsy.

Adolescent↗
PubMed2000

4-Thiazolidinones: novel inhibitors of the bacterial enzyme MurB.

4-Thiazolidinones were synthesized and evaluated for their ability to inhibit the bacterial enzyme MurB. Selected 4-thiazolidinones displayed activity against the enzyme in vitro. This activity, coupled with the design principles of the thiazolidinones, supports the postulate that 4-thiazolidinones may be recognized as diphosphate mimics by a biological selector.

Bacteria↗
PubMed1999

Bovine lymphocyte antigen-A11--specific peptide motif as a means to identify cytotoxic T-lymphocyte epitopes of bovine herpesvirus 1.

Major histocompatibility complex (MHC) class I molecules present 8- to 10-mer viral peptides to antiviral cytotoxic T lymphocytes (CTLs). Identification of the allele-specific peptide motifs (ASPMs) of class I molecules enables the prediction of potential CTL epitopes of a virus from its protein sequences. Based on the bovine herpesvirus 1 (BHV-1) protein sequences that conform to the BoLA-A11 ASPM that we identified previously, potential CTL epitopes of BHV-1 were synthesized for use in cytotoxicity assays with CTLs from BHV-1-immunized calves. A peptide binding assay used to select the peptides that are most likely to be CTL epitopes categorized the peptides into groups of high, intermediate, and low binding capacity. Synthetic peptides stimulated lymphocytes from BHV-1-immunized calves to secrete interferon-gamma. Groups of peptides from the major glycoproteins of BHV-1 restimulated CTLs in vitro and sensitized targets for lysis by means of restimulated bulk CTLs.

Animals↗
PubMed1999

A novel cleavage protocol for use with Rf-encoded split pool synthesis technology: product cleavage and collection in standard 96 well format.

A novel protocol which employs commercially available, standard tools and hardware has been developed. This protocol allows for cleavage and collection of IRORI Microkan products in 96 well plate format. Typically, 640 compounds can be cleaved in a 4 hour time period using approximately 3 square feet of space. This protocol has been used successfully for the liberation of thousands of individual compounds, in single compound per well format from the solid phase. Additionally, this protocol is the first example of making IRORI Microkan technology directly compatible with standard 96 position deep well blocks.

Equipment and Supplies↗
PubMed1999

Recent advances in the solid phase synthesis of drug-like heterocyclic small molecules.

Phage display is a biological system which facilitates the cloning and rapid selection of peptides from large combinatorial libraries. In compa-rison to the chemical combinatorial approach, the advantages of phage display lie in its simplicity and replicability. While phage display has many diverse applications, this review will focus on the use of phage peptide libraries to discover epitopes recognised by monoclonal antibodies. As monoclonal antibodies are useful tools for the detection of proteins and for the investigation of molecular interactions, the identification of their epitopes will serve to elucidate the structure and function of proteins, as well as aid in the discovery of new drugs and the development of vaccines.

Drug Design↗
PubMed1998

Transition-metal-mediated reactions in combinatorial synthesis.

Transition-metal-mediated reactions have played an important role in expanding the scope of combinatorial chemistry from synthesis of peptidic libraries to synthesis of nonoligomeric, small-molecule libraries. Versatile reactions such as heteroannulations, olefin metathesis and dipolar cycloadditions are used for preparation of libraries of historical, as well as novel, pharmacophores. Transition-metal-mediated reactions have also been used strategically to provide traceless linkers' in solid-phase synthesis.

Alkenes↗
PubMed1992

Mapping the binding site of tissue kallikrein: preparation and testing of all possible substrate analog inhibitors homologous with the sequence of kininogen between Ser386 and Gln392.

Programs aimed at converting peptide inhibitors of proteolytic enzymes into more traditional drug structures require an understanding of the role played by the individual amino acid residues in the inhibitor. To this end, all possible substrate analogues occurring within the sequence Ser386-Pro-Phe-Arg-Ser-Val-Gln392 from bovine kininogen were synthesized and tested as inhibitors of tissue kallikrein (EC 3.4.21.35, beta-PPK). Of the 21 sequences which can be formed from the heptapeptide, 11 have inhibitory constants which could be measured in the chromogenic assay employed in these studies. No dipeptide and only one tripeptide, Ac-Phe-Arg-Ser-NH2 (Ki = 718 microM), measurably inhibits the enzyme. All longer peptides inhibit beta-PPK. The heptapeptide Ac-Ser-Pro-Phe-Arg-Ser-Val-Gln-NH2 is the most effective inhibitor in this series (Ki = 101 microM). Each amino acid residue in the sequence appears to alter binding in a relatively independent manner. The N-terminal seryl residue (P4) and the prolyl residue (P3) slightly improve the Ki of the various inhibitors. The phenylalanyl residue at P2 appears to have a more pronounced effect on Ki. The arginyl residue at P1 and the seryl residue at P1' appear to be the most important residues in the inhibitory sequence. They contribute approximately one-third and one-fourth of the binding energy to the interaction between the substrate analogues and beta-PPK, respectively. The valyl residue at P2', and the C-terminal glutaminyl residue improve Ki of each of the peptides tested. Almost 80% of the binding energy of the substrate analogue inhibitors comes from the core sequence Phe-Arg-Ser which occurs between P2 and P1'. Molecular models developed from the Chen-Bode coordinates of the aprotinin-beta-PPK complex have been used to interpret the results of these studies.

Amino Acid Sequence↗
PubMed1992

A systematic approach for determining minimum inhibitory sequence and contribution of individual residues in binding of kininogen fragments to tissue kallikrein.

A systematic approach to evaluate the contribution of individual residues occurring within the sequence Ser386-Pro-Phe-Arg-Ser-Val-Gln392 from bovine kininogen towards binding to tissue kallikrein is developed. Of the 21 sequences which can be formed, no dipeptide and only one tripeptide measurably inhibits the enzyme. Almost 80% of the binding energy of the substrate analogue inhibitors comes from the core sequence Phe-Arg-Ser which occurs between P2 and P1'. Molecular models developed from the Chen-Bode coordinates of the aprotinin--beta-PPK complex have been used to interpret the results of these studies.

Amino Acid Sequence↗