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Biomedical subjects

B Chandrasekhar

Publications and source records attributed to B Chandrasekhar.

17 recordsLinked to original sources
PubMed2000

A novel nonphagocytic mechanism of erythrocyte destruction involving direct cell-mediated cytotoxicity.

The number of erythrocytes fell when co-cultured with cell preparations derived from mouse spleen, thymus, bone marrow, or peritoneal exudate (PE) cells. Erythrocyte-depletion activities (EDA) of different leukocyte preparations were in the order PE > spleen > thymus > bone marrow. Adherent, nonadherent, T-depleted, and T-enriched cell subpopulations had comparable EDA. Spleen cells from athymic nude mice, however, lacked significant EDA. In addition, EDA was boosted by Concanavalin A (Con A) but not by lipopolysaccharide, indicating that T cells may play a crucial role in inducing EDA in spleen cells. Paraformaldehyde-fixed spleen or PE cells, as well as membrane preparations isolated from spleen cells, efficiently lysed erythrocytes. Erythrocyte ghost membranes inhibited erythrocyte lysis by control or paraformaldehyde-fixed spleen cells. Treatment with hamster anti-mouse Fas or anti-mouse tumor necrosis factor receptor (TNFR) antibody could opsonize erythrocytes for faster depletion by spleen cells, suggesting an expression of Fas and TNFR on erythrocytes. TNF alpha could lyse erythrocytes in a dose-dependent fashion. Additionally, enhanced spleen cell EDA induced in response to succenyl Con-A could be blocked by anti-TNF alpha antibodies. Our results provide evidence for a direct cell-mediated cytotoxicity (CMC) of erythrocytes by leukocytes. A role of molecules of Fas and the TNF family in CMC of erythrocytes has also been suggested. Further work is needed to understand if, and to what extent, CMC of erythrocytes contributes to erythrocyte destruction in vivo and to determine its patho-physiological significance.

Animals↗
PubMed1999

Salvage and reconstruction of complex post-extirpative knee wounds: a successful surgical protocol.

Six patients with massive post-extirpative wounds of the knee, all of whom had received adjuvant therapy, underwent wound closure and limb salvage via free-tissue transfer in all but one case. No instance of delayed wound healing requiring surgery occurred among the patients reconstructed by microsurgical tissue transfer. Five of the six patients are presently ambulating on the salvaged extremity. A protocol for management of these complex wounds is presented.

Amputation, Surgical↗
PubMed1996

Evidence for cell-surface association between fusin and the CD4-gp120 complex in human cell lines.

Accessory cell-surface molecules involved in the entry of human immunodeficiency virus-type 1 into cells have recently been identified and shown to belong to the family of chemokine receptors. Treatment of human cell lines with soluble monomeric gp120 at 37 degrees C induced an association between the surface CD4-gp120 complex and a 45-kilodalton protein, which can be down-modulated by the phorbol ester phorbol 12-myristate 13-acetate. The three proteins were coprecipitated from the cell membranes with antibodies to CD4 or to gp120. The 45-kilodalton protein comigrated with fusin on sodium dodecyl sulfate gels and reacted with rabbit antisera to fusin in protein immunoblots. No 45-kilodalton protein could be coprecipitated from similarly treated nonhuman cells. However, infection of 3T3.CD4.401 cells with vaccinia-fusin recombinant virus (vCBYF1), followed by gp120 treatment, resulted in coprecipitation of fusin and CD4.401 molecules from their membranes. Together these data provide evidence for physical association between fusin and the CD4-gp120 complex on cell membranes.

3T3 Cells↗
PubMed1995

Inhibitory cyclic analogues and chlorambucil derivatives of bombesin-like peptides.

Analogues of the amphibian neuropeptide, bombesin, and of the mammalian homologue, gastrin-releasing peptide, have been synthesized and their biological activity studied in small cell lung carcinoma and rat pancreatic acinar cells. The compounds are truncated sequences of the active tetradecapeptide BN(1-14) or GRP(20-27). Peptides were cyclized between position 5 or 7 and the carboxyl end of the des-Met14 fragment with D and L Ala11 and Lys5 substitutions, as well as various N-terminal groups attached. The smallest cyclic peptide, BN(7-13), bound to SCLC membranes with microM potency and inhibited BN stimulation of intracellular Ca++ levels. The most potent inhibitor is N-chloroambucil-[His7,D-Ala11]BN(7-13)ethyl ester, which antagonized BN function in SCLC and acinar cells with nM potency and also inhibited clonal growth of carcinoma cell lines.

Amino Acid Sequence↗
PubMed1995

Surgical treatment of complications 45 years after extraperiosteal pneumonolysis and plombage using acrylic resin balls for cavitary pulmonary tuberculosis.

An infected axillary sinus tract discharged balls made of an acrylic resin consisting essentially of polymerized methyl methacrylate (Lucite) 45 years following performance of an extraperiosteal pneumonolysis and Lucite ball plombage for collapse therapy of right upper lobe cavitary tuberculosis. Surgical extraction of the balls was performed, followed by a partial decortication of the lung and intrathoracic transposition of a pectoralis major muscle flap to fill the residual pleural space. Primary healing was attained, and the patient is well 1 1/2 years after surgery.

Axilla↗
PubMed1993

The extended deep inferior epigastric pedicle flap for lower extremity reconstruction.

Large soft-tissue defects of the lower extremity can present a challenging reconstructive problem. The extended deep inferior epigastric pedicle flap is a versatile and reliable flap that can be used for the coverage of complex lower extremity soft-tissue defects as far distal as the knee. We reviewed our 5-year experience with 20 consecutive extended deep inferior epigastric pedicle flaps used to cover lower extremity defects. All wounds, including 4 soft-tissue defects of the knee, were successfully covered. Two minor complications occurred. Flap anatomy, surgical approach, and new refinements in flap design are presented. The indications for the flap and its role in ablative tumor surgery are discussed. This flap has proved to be versatile, easy to raise, and extremely hardy. The ample skin island with its large arc of rotation is well vascularized, healing well even in irradiated wounds, and the flap tolerates both postoperative pressure and radiation.

Adult↗
PubMed1993

Coverage strategies in total joint replacement.

The strategy for soft-tissue management following total joint arthroplasty begins with prevention. The medical status of the patient is optimized preoperatively. Meticulous surgical technique with liberalized indication for flap closure primarily will reduce soft-tissue failures. Early identification and aggressive team management of complications are critical to decrease long-term morbidity and to obtain a good functional result.

Adult↗
PubMed1992

CD4(81-92)-based peptide derivatives. Structural requirements for blockade of HIV infection, blockade of HIV-induced syncytium formation, and virostatic activity in vitro.

CD4(81-92) peptide block human immunodeficiency virus (HIV) infection, virus-induced cell fusion, and antigen production by HIV-1-infected cells when derivatized on specific amino acid residues. An extensive series of structural variants of 1,4,5-tribenzyl-10-acetyl-CD4(81-92) were tested as anti-viral agents in an attempt to define the sequence and derivatization requirements for antiviral activity, and to maximize potency and stability for use as potential therapeutic agents. Alteration of the primary amino acid sequence of the stem compound 1,4,5-tribenzyl-CD4(81-92) diminished or abolished in parallel all three indices of anti-viral activity in a series of altered sequence compounds. Replacement of d- for l-amino acid residues at positions 1, 2, 3, 4, 5, or 6 but not position 10 decreased anti-viral potency, again with parallel effects on infection, synctium formation, and virostatic activity. Omission of the glutamine residue at position 9 did not affect anti-viral potency, while removal of the glutamic acids at position 11 and 12 resulted in virtually complete loss of biological activity. Changes in the derivatization pattern of the CD4(81-92) peptide backbone also affected anti-viral potency and efficacy. Optimal activity was obtained with benzyl residues at positions 1, 4, and 5, whereas the 1,4,7-tribenzyl-CD4(81-92) compound was without activity in all assays tested. Replacement of one of the benzyl groups with an acetamidomethyl moiety resulted in complete loss of biological activity. The previously reported (Nara et al., Proc Natl Acad Sci USA 86: 7139-7143, 1989) virostatic activity of 1,4,5-tribenzyl-10-acetyl-CD4(81-92) (peptide #18) is apparently due to acetylation, since the desacetyl stem compound shows much less virostatic activity while still possessing full anti-infective and anti-syncytial activity, and acetylation of the N-terminus rather than the lysine of 1,4,5-tribenzyl-CD4(81-92) yields a virostatic compound equipotent to peptide #18. Cyclization of the tribenzyl peptide to further conformationally restrict the molecule resulted in a compound with anti-infection, anti-syncytial, and virostatic activity at submicromolar concentrations.

Amino Acid Sequence↗
PubMed1992

Extended indications for functional limb-sparing surgery in extremity sarcoma using complex reconstruction.

From 1980 to 1991, 29 patients underwent complex reconstruction following extremity sarcoma resection. Soft tissue was the site of origin in 15 patients (52%) and bone was the site of origin in 14 patients (48%), with 20 sarcomas (69%) in the lower extremity. Resection consisted of the following procedures: extended anatomical soft-tissue resections (21 patients [72%]), bone resections (18 patients [62%]), and joint resections (14 patients [48%]). Reconstruction involved the following: myocutaneous flaps (20 patients [69%]), joint prosthesis (eight patients [28%]), and bone reconstruction (15 patients [52%]). There was no surgical mortality; one patient required an amputation owing to surgical complications. The site of the first failure was local (four [31%] of 13 patients), lung (five patients [38%]), others (four patients [31%]). At a median follow-up of 23 months, 18 patients (62%) had no evidence of disease, 27 (93%) had no local disease, 21 (72%) had good extremity function, three (10%) had major disabilities, and five (17%) underwent amputations. Local control improved when the margin of resection was larger than 10 mm. Disease-free survival was 67% at 3 years. Overall survival was 51% at 5 years. Tumor size was an independent predictor of overall survival. Local recurrence did not affect overall survival.

Adult↗
PubMed1990

Parascapular free flaps for head and neck reconstruction.

We report our experience with single-stage, primary reconstruction of the head and neck in 29 consecutive patients using parascapular free flaps. The commonest indications were for craniofacial defects (9), oropharyngeal soft tissue defects (10), and combined mandibular and soft tissue losses (4). Ablative surgery was performed for squamous carcinoma (22), melanoma (2), and malignant fibrous histiocytoma (2). Seven patients died of recurrent disease during a 3 1/2 year follow-up. Seven patients are alive with recurrence. Flap complications included total loss (2) due to unsalvageable microvascular thrombosis, wound breakdown with oropharyngeal fistula (2), mandibular osteomyelitis (1), trismus (2), neck contracture (1), and donor site wound dehiscence (1). The overall success of this reconstruction was 93%. Primary wound healing was the general rule with lower morbidity than with other reconstructive techniques. The flap is thin, pliable, and conforms well to three-dimensional defects. The lateral border of the scapula can be incorporated on the same vascular pedicle for single-stage mandibular reconstruction. No muscle is sacrificed, and the posterior donor defect is an added advantage. The parascapular flap is our first choice for reconstruction of major defects in the head and neck.

Adult↗
PubMed1989

Preparative reversed-phase high-performance liquid chromatography in the synthesis of viscosin, a cyclic depsipeptide.

The importance of peptides in biochemical research and the facility with which they can be prepared by solid-phase techniques highlights the need for continuing research in the chromatographic purification of these molecules on a preparative scale. In this regard, synthesis of the cyclic depsipeptide antibiotic, viscosin, has provided the opportunity to demonstrate the use of radial compression cartridge technology in the reversed-phase purification of three key peptide intermediates on a scale of several hundred milligrams. Superior resolution of linear and cyclic peptide mixtures on a Bondapak C18 radial compression cartridge by using an aqueous acetonitrile solvent system containing 0.1% trifluoroacetic acid contributed significantly to the first total synthesis of viscosin, and demonstrates the applicability of this system to the purification of peptide mixtures.

Amino Acid Sequence↗
PubMed1988

The external oblique myocutaneous flap for extended hemipelvectomy reconstruction.

This article documents the first case report of an extended hemipelvectomy defect closure using an ipsilateral external oblique myocutaneous flap. When a hemipelvectomy usually is performed for soft tissue tumor ablation, an anterior or posterior flap can be preserved for immediate coverage of vital structures. When these flaps are also resected to obtain clear tumor margins, closure becomes difficult. In our patient, although the rectus myocutaneous flap was a next logical choice, prior surgical scars precluded it use. The external oblique flap was successfully rotated and solved a difficult problem. This flap should be considered when the rectus abdominis myocutaneous flap is unavailable for extended hemipelvectomy closures.

Abdomen↗
PubMed1988

The inferior trapezius musculocutaneous flap in head and neck reconstruction.

The trapezius musculocutaneous flap based on the descending branch of the transverse cervical vessels has been used to reconstruct a variety of large and complex defects in the head and neck region. Forty-three flaps were performed in 41 patients over a period of 26 months. Excellent reconstruction was achieved in 37 patients. Six total and nine partial flap failures were noted. There were 8 deaths during this time, 2 attributable directly to flap failure. Patient positioning during surgery and the tedious dissection are disadvantageous. The advantages of this flap are its thinness, long reach, and a posterior donor defect. These attributes are ideally suited for certain complex reconstructive endeavors in the head and neck.

Adolescent↗
PubMed1988

Forehead expansion and total nasal reconstruction.

Forehead flaps are the method of choice for total nasal reconstruction. However, if adequate skin is unavailable, tissue expansion of this donor site for subtotal nasal reconstruction seems logical, as has been described elsewhere. The literature, however, appears devoid of reports of using this technique when all the nasal structures are absent. We report on 3 patients for whom expanded forehead flaps provided poor long-term results because of late shrinkage.

Adult↗
PubMed1987

On the possible mechanism of recognition of DNA base sequence by steroid hormones.

Geometry of the complex of a steroid hormone, dexamethasone, with a hexanucleotide sequence from the glucocorticoid responsive element d(TGTTCT)2, is optimised here using computer aided geometry simulation with an energy minimization technique. We have also optimised its geometries with genetically modified and arbitrarily chosen DNA sequences. The drug molecule is considered to have both intercalative as well as non-intercalative binding. Comparison of energetics and stereochemical aspects, as well as the H-bonding scheme, is used here to bring out salient features about the mechanism of DNA sequence recognition by steroid hormones.

Base Sequence↗
PubMed1986

Clinical applications of the extended deep inferior epigastric flap.

The extended deep inferior epigastric flap, described by Taylor et al. in 1983, consists of the lower portion of the rectus abdominis muscle and a superolateral fasciocutaneous extension based on the periumbilical perforators. We have used this flap four times to close large defects of the abdomen, groin, and thigh and twice as a free flap to close wounds of the head and leg. There were no ischemic complications, and there was uncomplicated wound healing in the recipient and in the donor wounds. We recommend this highly versatile and reliable flap as one to be considered early in planning the closure of large wounds.

Abdomen↗