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Biomedical subjects

Ganesh Shanmugam

Publications and source records attributed to Ganesh Shanmugam.

At least 19 recordsLinked to original sources

Structures of intact glycoproteins from vibrational circular dichroism.

Vibrational circular dichroism (VCD) spectra for the glycoproteins alpha1-acid glycoprotein (AGP) and bovine submaxillary mucin (BSM), have been measured in D2O solutions and for the films prepared from aqueous (H2O) buffer solutions in the 1800 to 900 cm(-1) region. The solution VCD results revealed that AGP has beta-sheet structure, along with a significant amount of alpha-helix as evidenced from a W pattern in the amide I region. The VCD of BSM solution suggested a polyproline II type structure, characterized by the appearance of strong negative couplet in the amide I region. The film VCD results on AGP and BSM suggested that the secondary structures of polypeptide fold in the film state are similar to those in the solution. The absence of any significant film VCD in the low frequency region (1200-900 cm(-1)), suggested that the dominant linkage for carbohydrate residues is likely to be a beta linkage. VCD spectroscopy gains importance in the secondary structural analysis of polypeptide fold in glycoproteins due to the absence of interfering VCD from the carbohydrate residues in the conformationally sensitive amide I region. Also, film VCD studies permit measurements in the low wavenumber region (1200-900 cm(-1)) that reveal the dominant type of linkage for carbohydrate residues. Such clear structural information is unlike that from ECD, where ECD bands of acylated amino sugar residues interfere with those of polypeptide backbone in the conformationally sensitive far-UV region.

Circular Dichroism↗

Primary cardiac sarcoma.

Primary malignant lesions of the heart are rare. Although myxomas have been extensively described, there is a paucity of large studies on non-myxomatous cardiac tumours. On the other hand, there are several case reports on specific histopathological variants, in small numbers. Consequently there exists no consensus on therapeutic modalities for cardiac sarcomas. The prognosis for these lesions remains dismal, despite the enhanced diagnostic ability of newer technology. The reasons for the dismal prognosis are (1) the advanced tumour stage at presentation, (2) non-specific symptomatolgy, (3) insufficient awareness of these lesions, due to their rarity, (4) delayed diagnosis and/or misdiagnosis, which leads to (5) advanced tumour stage at presentation. Thus a vicious cycle is created. This article addresses these issues, deals with the surgically relevant modes of presentation, rather than the histopathology, and reviews the diagnosis and management options for the various sarcomas, categorized by the site and extent of cardiac involvement. Clinicians should be familiar with the presentation of these tumours and have a high index of suspicion, since the potential for long-term survival following resection does exist. Wide surgical resection remains the cornerstone of sarcoma therapy. Complete characterization of tumour extent using echocardiography and CT/MRI is mandatory to achieve this goal. Radical resections such as 'bench surgery' and transplantation may reduce local recurrence, but the risk of metastatic disease remains. The clinical experience with such approaches is limited. The role of adjuvant therapy is not yet established. In no other field of cardiac surgery would a multidisciplinary approach be more useful, in achieving cure or long-term palliation.

Diagnosis, Differential↗

Adult dysphagia associated with type B double aortic arch.

Esophageal compression secondary to a double aortic arch is rare in adults due to its propensity to cause severe symptoms in infancy or childhood. We report four adult patients with dysphagia associated with a double aortic arch. Chromosome analysis in one of these patients revealed a balanced translocation between chromosomes 4 and 18 - this has not been previously reported. Surgical division is indicated in all symptomatic patients and provides excellent operative results.

Adult↗

Effect of D-amino acids at Asp23 and Ser26 residues on the conformational preference of Abeta20-29 peptides.

The effects of d-amino acids at Asp(23) and Ser(26) residues on the conformational preference of beta-amyloid (Abeta) peptide fragment (Abeta(20-29)) have been studied using different spectroscopic techniques, namely vibrational circular dichroism (VCD), vibrational absorption, and electronic circular dichroism. To study the structure of the Abeta(20-29), [d-Asp(23)]Abeta(20-29), and [d-Ser(26)]Abeta(20-29) peptides under different conditions, the spectra were measured in 10mM acetate buffer (pH 3) and in 2,2,2-trifluoroethanol (TFE). The spectroscopic results indicated that at pH 3, Abeta(20-29) peptide takes random coil with beta-turn structure, while [d-Ser(26)]Abeta(20-29) peptide adopts significant amount of polyproline II (PPII) type structure along with beta-turn contribution and d-Asp-substituted peptide ([d-Asp(23)]Abeta(20-29)) adopts predominantly PPII type structure. The increased propensity for PPII conformation upon d-amino acid substitution, in acidic medium, has important biological implications. In TFE, Abeta(20-29), [d-Asp(23)]Abeta(20-29), and [d-Ser(26)]Abeta(20-29) peptides adopt 3(10)-helix, alpha-helix, and random coil with some beta-turn structures, respectively. The VCD data obtained for the Abeta peptide films suggested that the secondary structures for the peptide films are not the same as those for corresponding solution and are also different among the Abeta peptides studied here. This observation suggests that dehydration can have a significant influence on the structural preferences of these peptides.

Amino Acid Sequence↗

Aortic valve replacement following previous coronary surgery.

Aortic valve replacement following previous coronary surgery is associated with high risk. Major intraoperative problems include those associated with reentry, damage to the left internal mammary artery and myocardial protection. These factors influence operative results and eventual outcome to a large extent. The available evidence largely consists of retrospective series and case reports, with their own institutional bias, and it has been difficult to make specific recommendations on the basis of this evidence. However the article reviews the various surgical options available to manage this difficult subset of patients and discusses their pros and cons.

Aortic Valve Stenosis↗

Vasoplegic syndrome--the role of methylene blue.

Vasoplegic syndrome is a recognized complication following cardiac surgery using cardiopulmonary bypass and is associated with increased morbidity and mortality. In several patients profound post-operative vasodilatation does not respond to conventional vasoconstrictor therapy. Methylene blue has been advocated as an adjunct to conventional vasoconstrictors in such situations. There is limited data pertaining to the use of methylene blue and a number of reports have been anecdotal observations. This article reviews the incidence and problems associated with the vasoplegic syndrome, the mechanism of action of methylene blue, its effects and adverse reactions and the literature supporting its intra-operative and post-operative use. In cases where first-line therapy fails, the use of methylene blue seems to be a potent approach to refractory vasoplegia. The early use of methylene blue may halt the progression of low systemic vascular resistance even in patients responsive to norepinephrine and mitigate the need for prolonged vasoconstrictor use. However, dosing regimens and protocols need to be clearly defined before widespread routine use. Whether methylene blue should be the first line of therapy in patients with vasoplegia is a matter of debate, and there is inadequate evidence to support its use as a first line drug. More scientific evidence is needed to define the role of MB in the treatment of catecholamine refractory vasoplegia.

Cardiopulmonary Bypass↗

The structure of antimicrobial pexiganan peptide in solution probed by Fourier transform infrared absorption, vibrational circular dichroism, and electronic circular dichroism spectroscopy.

Pexiganan (Gly-Ile-Gly-Lys-Phe-Leu-Lys-Lys-Ala-Lys-Lys-Phe-Gly-Lys-Ala-Phe-Val-Lys-Ile-Leu-Lys-Lys), a 22 amino acid peptide, is an analogue of the magainin family of antimicrobial peptides present in the skin of the African clawed frog. Conformational analysis of pexiganan was carried out in different solvent environments for the first time. Organic solvents, trifluoroethanol (TFE) and methanol, were used to study the secondary structural preferences of this peptide in the membrane-mimicking environments. In addition, aqueous (D2O) and dimethyl sulfoxide (DMSO) solutions were also investigated to study the role of hydrogen bonding involved in the secondary structure formation. Fourier transform infrared absorption, vibrational circular dichroism (VCD), and electronic circular dichroism (ECD) measurements were carried out under the same conditions to ascertain the conformational assignments in different solvents. All these spectroscopic measurements suggest that the pexiganan peptide has the tendency to adopt different structures in different environments. Pexiganan appears to adopt an alpha-helical conformation in TFE, a sheet-stabilized beta-turn structure in methanol, a random coil with beta-turn structure in D2O, and a solvated beta-turn structure in DMSO.

Antimicrobial Cationic Peptides↗

Anomalous left coronary artery, ventricular septal defect, and double aortic arch.

Anomalous origin of the left coronary artery from the pulmonary artery generally occurs in isolation. We report an infant diagnosed with double aortic arch and ventricular septal defect who was found to have an anomalous origin of the left coronary artery from the pulmonary artery at surgery. Successful ventricular septal defect repair, division of the arch, and aortic reimplantation of the left coronary artery was performed. This article describes a combination of lesions previously not described, highlights the altered presentation when multiple lesions coexist, discusses the propensity to miss the anomalous coronary, and reviews the literature that demonstrates the consequences of overlooking this defect.

Aorta, Thoracic↗

Congenital lung malformations--antenatal and postnatal evaluation and management.

We reviewed our institutional experience with pulmonary resection for congenital bronchopulmonary malformations and analysed the management and outcome of pregnancies with a prenatal diagnosis of congenital lung malformations. Between January 1993 and December 2003, 31 patients underwent evaluation and pulmonary resection for bronchopulmonary malformations. Common clinical presentations were respiratory distress (9), respiratory infections/pneumonias (22), and dyspnoea (9). Diagnostic modalities included chest radiography, CT scan (22), MRI scan (7), arteriography (1), and bronchoscopy (5). There were 13 congenital cystic adenomatoid malformations (CCAM), six pulmonary sequestrations, three bronchogenic cysts, and nine congenital lobar emphysemas (CLE). Fifteen patients who underwent resection were diagnosed by antenatal ultrasound. No foetus had hydrops or associated malformations. No pregnancy was terminated. There was no foetal demise. Regression of the sonographic appearance was observed in six cases. Amniotic puncture was required for hydramnios in three cases. Eight emergency resections were performed (CCAM 4; CLE 3; Bronchogenic cyst 1). Surgical procedures included 24 lobectomies, one right middle lobectomy with a wedge resection of the right lower lobe, one completion right lower lobectomy, four sequestrectomies, one mediastinal mass excision and one wedge resection for a bronchogenic cyst. There were no deaths. Postoperative complications included: persistent air leak (n=2; one requiring completion lobectomy) and pneumothorax (1). Persistent mild symptoms were present in five patients, at long-term follow-up. Congenital cystic adenomatoid malformation and congenital lobar emphysema were the commonest congenital anomalies. Congenital lung malformations are increasingly diagnosed antenatally, sometimes necessitating emergent surgical resection. The natural history is variable. All infants with a prenatal diagnosis require postnatal evaluation. Patients should be evaluated for associated disorders. The presence of mass effects is an indication for therapeutic decompression. The risk of pulmonary compression, infection and malignant degeneration makes resection imperative, even in asymptomatic patients. Lobectomy is the procedure of choice, is well tolerated, and leads to excellent outcomes.

Bronchial Diseases↗