Effect of introducing aib in a designed helical inhibitor of hdm2-p53 interaction: A molecular dynamics study.

Although p53 is an intrinsically disordered protein, upon binding to Hdm2, a short stretch (residues 19-25) comprising the binding epitope assumes a helical backbone. Because the allowed conformational space of α-aminoisobutyric acid (Aib) is restricted to only the helical basin, Aib-containing helical mimics of p53 (binding epitope) are expected to inhibit interaction between p53 and Hdm2 with a much stronger affinity than the wild type p53 peptide (binding epitope), due to the entropic advantage associated with Aib. However, the IC50 values for the disruption of p53-Hdm2 interaction by Aib-p53 peptides and wild type p53 peptide were found to be comparable (J. Peptide Res. 2002, 60:88-94). To understand why incorporation of Aib didn't substantially increase Hdm2 affinity of Aib-p53 peptides, a series of molecular dynamics simulations were performed. It was found that despite stabilizing a helical backbone in the unbound state, the Aib residues in Aib-p53 peptide arrested two functionally important side-chains (F19 and W23) in non-productive conformations, resulting in relative side-chain orientations of the binding triad F19-W23-L26 incompatible with the bound conformation. Therefore, although a Aib-induced pre-formed helical peptide backbone in the unbound state is expected to favor binding, the locked side-chain orientations of the binding triad in non-productive modes would disfavor binding. This study shows that when using Aib to design functionally important helical peptides, care must be taken to consider potential interactions between side-chains of neighboring residues and Aib in the unbound state.

Direct evidence for CH···π interaction mediated stabilization of Pro-cisPro bond in peptides with Pro-Pro-aromatic motifs.

Although weak interactions play subtle but important roles in dictating protein structures, their experimental detection is nontrivial. From NOE experiments we provide direct evidence for the presence of CH···π interaction, operational between the C(α)-H of the first Pro and the aromatic (Aro) side chain of Xaa, in a peptide series with the general sequence Ac-Pro-Pro-Xaa-NH(2). Indirect evidence of CH···π interaction is provided from ring current-induced upfield displacement of Pro(1) C(α)-H chemical shifts and restriction of side-chain (χ1) rotation of Xaa. A consequence of this interaction is the enhanced stability of the Pro-cisPro conformer in Ac-Pro-Pro-Xaa-NH(2) when Xaa is aromatic. The free energies associated with trans to cis transformation of the Pro-Pro moiety are 0.35, 0.59, 0.64, and 0.82 kcal/mol when Xaa is Tyr, Trp, Phe, and His (pH of 8.4), respectively. In comparison, the corresponding free energy is ∼1.55 kcal/mol when Xaa is nonaromatic. The observed population of Pro-cisPro-His and the pH-induced perturbation of electron density of the His side chain were correlated, providing further evidence for a direct role of CH···π interaction in modulating the stability of Pro-cisPro population in Ac-Pro-Pro-Aro-NH(2). Our study establishes Pro-Pro-Aro to be a new sequence motif that can stabilize Pro-cisPro peptide bonds. This study not only identifies a new structurally biased sequence motif but also directly demonstrates the role played by CH···π interactions in subtly altering conformational preferences of three-residue peptide sequences with implications on the role played by cis-peptide bonds in unfolded proteins.

Basal cell carcinoma-clinico-pathological study in Eastern India in correlation with different risk factors.

Objectives: To study the histological variants and mimickers of basal cell carcinoma (BCC) alongwith different risk factors among a group of patients from eastern India. Methods: The specimen for the study was sent by the dermatology department for histopathology after skin biopsy. Results: Out of 42 patients, 15 patients studied were males and the rest of the cases were females. The male to female ratio was 0.55:1. Maximum (15 cases) cases were in the age group of 50-59 years. Apart from sunlight, chronic arsenic exposure is an important risk factor of BCC. Basal cell hyperplasia and squamous cell carcinoma are the histological differential diagnosis of nodular BCC and basosquamous BCC. Conclusion: BCC is a disease of the older age group and with female preponderance in our study. Nodular basal cell carcinoma was the most common histologic type of basal cell carcinoma. The face was the most common site for BCC followed by the scalp. UV radiations and Arsenic do play role in the pathogenesis of BCC. CD10 helps differentiate superficial BCC from basal cell hyperplasia.

Conformational preferences of a short Aib/Ala-based water-soluble peptide as a function of temperature.

The amino acid Aib predisposes a peptide to be helical with context-dependent preference for either 3(10)- or alpha- or a mixed helical conformation. Short peptides also show an inherent tendency to be unfolded. To characterize helical and unfolded states adopted by water-soluble Aib-containing peptides, the conformational preference of Ac-Ala-Aib-Ala-Lys-Ala-Aib-Lys-Ala-Lys-Ala-Aib-Tyr-NH(2) was determined by CD, NMR and MD simulations as a function of temperature. Temperature-dependent CD data indicated the contribution of two major components, each an admixture of helical and extended/polyproline II structures. Both right- and left-handed helical conformations were detected from deconvolution of CD data and (13)C NMR experiments. The presence of a helical backbone, more pronounced at the N-terminal, and a temperature-induced shift in alpha-helix/3(10)-helix equilibrium, more pronounced at the C-terminal, emerged from NMR data. Starting from polyproline II, the N-terminal of the peptide folded into a helical backbone in MD simulations within 5 ns at 60 degrees C. Longer simulations showed a mixed-helical backbone to be stable over the entire peptide at 5 degrees C while at 60 degrees C the mixed-helix was either stable at the N-terminus or occurred in short stretches through out the peptide, along with a significant population of polyproline II. Our results point towards conformational heterogeneity of water-soluble Aib-based peptide helices and the associated subtleties. The problem of analyzing CD and NMR data of both left- and right-handed helices are discussed, especially the validity of the ellipticity ratio [theta](222)/[theta](207), as a reporter of alpha-/3(10)- population ratio, in right- and left-handed helical mixtures.

Disseminated Cryptococcosis in an Immunocompetent Child.

A case of disseminated cryptococcus infection in an immunocompetent host is described. The present case attests to the importance of using a cautious approach for the diagnosis of granulomatous lymphadenitis. The patient was initially misdiagnosed and treated as disseminated tuberculosis. Later the patient developed visual loss and skin lesions. Periodic Acid Schiff stained sections of lymph node biopsy and cerebrospinal fluid culture established the diagnosis.

CD8-positive Mycosis Fungoides Masquerading as Pyoderma Gangrenosum.

Mycosis fungoides (MF), a primary cutaneous T-cell lymphoma, accounts for <1% of non-Hodgkin lymphomas. The diagnosis of classic MF is based on a constellation of typical clinical presentation, histopathology, immunohistochemistry, and T-cell monoclonality detected by molecular studies. Rarely, atypical clinical presentation may occur. The typical immunohistochemical phenotype is, CD2 +ve, CD3 +ve, CD5 +ve, CD4 +ve, and CD8 - ve. Here, we report a rare case of CD8 +ve MF in a 43-year-male patient who was clinically diagnosed as pyoderma gangrenosum initially. The atypical presentation and rarity of such case have prompted this report.

Primary pulmonary synovial sarcoma: A case report and review of literature.

Primary pulmonary synovial sarcoma is a very rare, but highly aggressive tumor. Metastatic pulmonary sarcoma due to hematogenous dissemination is much more common. Hence why in any case of pulmonary sarcoma, whole body survey is necessary to exclude a primary tumor elsewhere. No clinical or radiological presentations are specific for pulmonary sarcoma hence; it is often confused with bronchogenic carcinoma. On the other hand, image-guided fine needle aspiration cytology (FNAC) is very much helpful in diagnosis of bronchogenic carcinoma, whereas, it may be inclusive in cases pulmonary sarcomas including primary synovial sarcoma, especially in cases of huge pulmonary masses. So why image-guided tru-cut core biopsy or open lung biopsy and their histopathological examination, supplemented by immunohistochemistry are preferable for the tissue diagnosis of pulmonary synovial sarcoma, although FNAC and immunocytochemistry may be used for the diagnosis. Surgical resection is treatment of choice, if it is not possible, palliative chemotherapy may be an option. Here, we report a rare case of primary synovial sarcoma which occupied almost whole of the right hemithorax in a 60-year-old male farmer.

Ganglioneuroblastoma: Unusual presentation as a pleural mass mimicking mesothelioma.

Ganglioneuroblastoma (GNB) is a rare peripheral neuroblastic tumor that is derived from developing neuronal cells of the sympathetic nervous system, and usually occurs in young children. We present a case of GNB occurring as pleural mass in a 2-year-old boy, which led to diagnostic confusion. On fine-needle aspiration cytology (FNAC), it was misinterpreted as mesothelioma. He underwent thoracotomy with excision of the mass. Histopathological findings showed features of a biphasic tumor suggestive of mesothelioma. Immunohistochemistry (IHC) performed for mesothelioma markers were inconclusive. On review of the histology slides, GNB was considered, which was subsequently proven by IHC. The rarity of this tumor, along with its nearly restricted occurrence at a young age, necessitates a strong suspicion in patients presenting with a symptomatic intrathoracic mass.

Cervical intramural pregnancy: Report of a rare case.

Cervical pregnancy is an extremely rare condition of ectopic pregnancy with potential grave consequences if not diagnosed and treated early. A case of intramural pregnancy in the cervix is being reported for its rarity. Early diagnosis is imperative to preserve fertility, otherwise if the pregnancy is disturbed, it may precipitate massive haemorrhage, which may require hysterectomy to save the patient.

Squamous cell carcinoma of lung metastasizinig in breast.

Metastasis in breast from extra-mammary malignancy is rare and lung is the third most common primary site when such a metastasis occurs. Small cell carcinoma and adenocarcinoma are two histological varieties of lung carcinoma that may metastasize to breast and squamous cell type is very rare. Here we report a case of squamous cell carcinoma of lung that metastasized in the breast and mimicked primary breast carcinoma.

Encapsulated follicular variant papillary thyroid carcinoma: problems in histological diagnosis.

Thyroid neoplasms are the commonest endocrine neoplasms and account for the most number of thyroidectomies done. Encapsulated thyroid lesions are being encountered more commonly in thyroidectomy specimens in recent time. The present study was undertaken to analyse the incidence of thyroid malignancies with a changing pattern and to discuss the difficulties encountered in histopathological interpretation of encapsulated neoplastic lesions of follicular cell origin. It is a retrospective study done in the department of pathology, NRS Medical College, Kolkata. Data of all the thyroidectomy specimens examined over last four years (August 2006 to July 2010) were retrieved and slides were reviewed. All slides of thyroid lesion received in the department of pathology, NRS Medical College for review were also included in this study. Frequency distribution study was done with the sample analysed. Follicular variant of papillary carcinoma was the commonest type of thyroid malignancy, on review, with the encapsulated sub-variant exceeding the diffuse type. This variant is a diagnostic challenge because it has to be differentiated from other encapsulated follicular thyroid lesions, especially follicular adenoma. The data analysis, results and problems in the diagnostic protocols are discussed in this study along with review of literature. Reclassification of thyroid tumour may be warranted in future with this background.

Colorectal carcinoma in a ten-year-old girl: a case report.

Colorectal carcinoma is very rare in childhood. In this case report, we depict a ten-year-old girl who presented with features of intestinal obstruction which turned out to be due to poorly differentiated mucin secreting adenocarcinoma of descending colon. Only increased awareness of this malignancy in this age-group and a high index of suspicion can help when a child complains of persistent pain of abdomen, altered bowel habits or rectal bleeding, and may provide diagnosis at an earlier stage, thereby improving the prognosis.

Hemangioendothelioma of soft tissue: Cytological dilemma in two cases at unusual sites.

Hemangioendothelioma is a rare vascular tumor of intermediate malignancy. Cytologically, it can simulate a non-vascular malignant tumor. We report two cases of this tumor, which were misdiagnosed at cytology. In the first case, a 27-year-old man presented with an anterior abdominal wall tumor. Fine needle aspiration cytology (FNAC) of the tumor showed polygonal cells with vacuolated cytoplasm in clusters having moderate nuclear atypia in a background of necrosis. A diagnosis of metastatic carcinoma was made. The histological examination showed features of epithelioid hemangioendothelioma. In the second case, a 13-year-old female child presented with unilateral enlargement of the right tonsil. At ultrasound-guided FNAC, a diagnosis of, 'small round cell tumor, could be consistent with alveolar rhabdomyosarcoma,' was made. The histological examination showed features of papillary intralymphatic angioendothelioma (Dabska's tumor). We conclude that epithelioid hemangioendothelioma should be considered in the differential diagnosis of metastatic carcinoma and small round cell tumor even at unusual sites.

Hepatoblastoma in the neonatal period: An unusual presentation.

Hepatoblastoma (HBL) is a rare primary malignant liver tumor affecting mainly pediatric patients in the age group 6 months to 3 years. Presentation of HBL in the neonatal period is rare. HBL can be diagnosed on cytology along with subtyping. Estimation of serum alpha-fetoprotein (AFP) is essential as a tumor marker. Fetal type HBL usually shows high AFP level. In this report, diagnosis of HBL in a 10-day-old baby with low serum AFP is being described for its unusual presentation.

Perineal accessory scrotum with congenital lipoma: a rare case report.

A case of accessory scrotum in a 1-year-old boy is reported because of its rarity. A boy presented with a tumor mass attached with scrotum-like skin on its tip in the right side of perineum between the scrotum and anus. Both testes had descended into the scrotum. There was no other urological anomaly. Histological findings of the tumor indicated perineal lipoma, and the scrotum-like portion accessory scrotum. An overview of sequences during the normal development of male external genitalia has been provided and the deranged mechanism resulting in this anomaly has been reviewed with hypothesis regarding etiology of accessory scrotum.

Heteropagus twins-a tale of two cases.

Heteropagus twinning is a rare occurrence. Parasitic and asymmetric conjoined twins are rarer anomalies of monochorionic monoamniotic twins; which consist of an incomplete twin attached to the fully developed body of the co-twin. We present here two such cases of Heteropagus twinning.

Infratemporal fossa myoepithelial carcinoma--a rare case report.

INTRODUCTION: Myoepithelial tumours are rare clinicopathological identity. It has been found in parotid glands and salivary glands but never reported in infratemporal fossa or other sites of lateral skull base region. DISCUSSION: Unlike its benign counterpart, myoepithelial carcinoma is biologically very aggressive and prone to recur even after adequate therapy. CASE REPORT: Here, a rare case of myoepithelial carcinoma arising from infratemporal fossa has been described along with its treatment options and outcome.

Peripheral primitive neuroectodermal tumor of head-neck region: our experience.

To present four rare cases of peripheral primitive neuroectodermal tumors of different sites of head and neck region. Four cases of different age (range 8-40 years) and sex (three female, one male) with rare primitive neuroectodermal tumor of sinonasal region and neck are presented. Treatment options, biological behavior and prognostic outcome are discussed herewith. Two patients succumbed to the disease within four to six months of treatment; other two patients are still under follow-up depicting the aggressive nature of the tumor. Primitive neuroectodermal tumor belongs to the class of malignant round cell tumor. Immunohistochemistry plays a pivotal role in differentiating this tumor entity. Chemoradiation was tried, but local and systemic spread occurs early and holds poor prognosis. This case series is an attempt to describe the aggressive behavior of this rare tumor with high mortality.

Extragonadal teratomas presenting at birth and originating from 3 different sites--a report of 3 cases.

Three cases of extragonadal teratomas presented at birth and all the cases arisen from three separate sites are reported in the present study. A huge sacrococcygeal teratoma is being reported and the other two retroperitoneal and nasopharyngeal teratomas, are reported for the rarity of their location in neonatal period. Teratomas of all three babies were mature benign on histopathology and surgical removal sufficed as mode of treatment. No recurrence was noted on follow-up.