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Biomedical subjects

Prashant Sharma

Publications and source records attributed to Prashant Sharma.

At least 19 recordsLinked to original sources

Giant cell tumour (osteoclastoma) of the zygoma: an extremely unusual neoplasm.

We report an extremely rare case of a giant cell tumour of the zygomatic bone in a 36-year-old female. The tumour was excised with healthy margins. The patient is asymptomatic without any evidence of recurrence 14 months postoperatively. To our knowledge, this is only the third reported case of this tumour occurring in the zygomatic bone in the medical literature.

Adult↗

Parvovirus B-19 induced acute pure red cell aplasia in patients with chronic lymphocytic leukemia and neurofibromatosis type-1.

Parvovirus B19 induced pure red cell aplasia (PRCA) has been previously reported in a variety of settings. We present two cases, an adult patient with chronic lymphocytic leukemia (CLL) and a child with neurofibromatosis type-1 (NF-1), where the abrupt appearance of severe anemia raised ominous clinical suspicions. Evidence of recent parvovirus B19 infection in association with the selective erythroid precursor deficiency in marrow helped exclude other etiologies. We emphasize the importance of bearing this infectious agent in mind, even when there are associated disorders (such as CLL) that may independently cause PRCA. An association of NF-1 with acute PRCA has not been described in indexed English literature in the past.

Acute Disease↗

Semiclassical ordering in the large-N pyrochlore antiferromagnet.

We study the semiclassical limit of the Sp(N) generalization of the pyrochlore lattice Heisenberg antiferromagnet by expanding about the N --> infinity saddlepoint in powers of a generalized inverse spin. To leading order, we write down an effective Hamiltonian as a series in loops on the lattice. Using this as a formula for calculating the energy of any classical ground state, we perform Monte Carlo simulations and find a unique collinear ground state. This state is not a ground state of linear spin-wave theory, and can therefore not be a physical (N = 1) semiclassical ground state.

Journal Article↗

Ki-67 expression in cytologic scrapes from oral squamous cell carcinoma before and after 24 gray radiotherapy--a study on 43 patients.

OBJECTIVE: To study the Ki-67 labeling indices in surface scrape smears from patients with oral squamous cell carcinoma before and after 24 Gray radiotherapy. STUDY DESIGN: Forty three patients with histologically documented squamous cell carcinoma of the oral cavity were sampled by means of surface scrape smears prior to therapy and after receiving 24 Gray fractionated radiotherapy. These smears were stained for Ki-67 expression using the avidin biotin alkaline phosphatase technique. RESULTS: Ki-67 expression was seen in an extremely small number of cells. Only 10 tumors showed positive cells, and the labeling index in them varied from 0.1 % to 0.01 %. After 24 Gray irradiation, no case showed any Ki-67 positive cells. CONCLUSIONS: The overall yield of malignant cells in surface smears is low even prior to therapy and their number decreases further after irradiation. This, along with other factors including low concentration of proliferating cells on the surface of the lesion and obscuring inflammatory cells, anucleate squames, bacterial colonies and proteinaceous material could have accounted for the low labeling indices obtained. Radiation induced decline in proliferation has been described previously. The major conclusion, in balance, is that conventional oral scrape cytology may not be the optimal tool for immunocytochemical evaluation of proliferation in oral squamous cell cancer.

Adult↗

Mutation of SENP1/SuPr-2 reveals an essential role for desumoylation in mouse development.

The covalent modification of proteins by the small ubiquitin-like protein SUMO has been implicated in the regulation of numerous biological processes, including nucleocytoplasmic transport, genomic stability, and gene transcription. Sumoylation occurs by a multienzyme process similar to ubiquitination and, in Saccharomyces cerevisiae, is reversed by desumoylating enzymes encoded by the Ulp1 and Smt4/Ulp2 genes. The physiological importance of desumoylation has been revealed by mutations in either gene, which lead to nonoverlapping defects in cell cycle transition and meiosis. Several mammalian Ulp homologues have been identified, but, to date, nothing is known of the phenotypic effects of their loss of function. Here, we describe a random retroviral insertional mutation of one homolog, mouse SENP1/SuPr-2. The mutation causes increased steady-state levels of the sumoylated forms of a number of proteins and results in placental abnormalities incompatible with embryonic development. Our findings provide the first insight into the critical importance of regulating sumoylation in mammals.

Animals↗

Quantitative analysis of radiation-associated cellular changes in oral cancer and their correlations with histologic grade and clinical stage: a multivariate evaluation of 43 patients.

OBJECTIVE: To quantitate radiation-associated cytologic abnormalities in oral cancer cells and analyze their relationships with radiation dose, clinical stage and histologic grade. STUDY DESIGN: Forty-three oral cancer patients receiving 2 Gy of fractionated radiotherapy per day were enrolled. Scrape smears were taken from the tumor surface before treatment and serially after 6-, 12-, 18- and 24-Gy fractions. Counts were done after Giemsa staining for the number of tumor cells; micronucleated, nuclear budded, binucleated and multinucleated tumor cells; cells with abnormal nuclear chromatin and membrane; cells with cytoplasmic granulation and vacuolization; and histiocytic giant cells. The variation in these counts with increasing radiation dose was assessed and compared with the histologic grade and clinical stage. RESULTS: Before therapy, counts for 7 of 10 cytologic abnormalities were significantly different between the 3 histologic grades (Kruskal-Wallis test). With increasing radiation dose, only micronucleation and nuclear budding remained significantly different within the grades. Most cytologic features were not significantly different in early and advanced clinical stage cancers before or after irradiation (Mann-Whitney U test). CONCLUSION: Cellular changes do not show a relationship with clinical stage either before or after irradiation. However, they demonstrate a partial pretherapy correlation with histology. This relationship diminishes progressively with increasing radiation dose. Since micronucleation and nuclear budding remain significantly different between histologic grades even after 24 Gy of irradiation, they may be utilized as clinically practicable alternatives to biopsy at this stage and may be useful in further studies on cytologic prognostication of irradiated oral cancer.

Carcinoma, Squamous Cell↗

Ascorbate-mediated enhancement of reactive oxygen species generation from polymorphonuclear leukocytes: modulatory effect of nitric oxide.

Recent studies from our laboratory have demonstrated that ascorbate potentiated enzymatic synthesis of nitric oxide (NO) from polymorphonuclear leukocytes (PMNs). NO is known to modulate various function of PMNs such as chemotaxis, adherence, aggregation, and generation of reactive oxygen species (ROS). The role of ascorbate in the PMN phagocytosis, ROS generation, and apoptosis was thus evaluated in the present study. Ascorbate and its oxidized and cell-permeable analog, dehydroascorbate (DHA), did not affect the phagocytosis but enhanced ROS generation and apoptosis following treatment with Escherichia coli or arachidonic acid. A detailed investigation on the DHA-mediated response indicated that inhibitors of DHA uptake, reduced nicotinamide adenine dinucleotide phosphate oxidase, NO synthase, or ROS scavengers attenuated ROS generation. In DHA-treated cells, enhanced generation of peroxynitrite was also observed; thus, ascorbate-mediated ROS and reactive nitrogen species generation might mediate cytotoxicity toward the ingested microbes and subsequently, augmented PMN apoptosis. Results of the present study have helped in delineating the role of ascorbate in the modulation of NO-mediated ROS generation from PMNs.

Animals↗

Leiomyomatosis peritonealis disseminata with malignant change in a post-menopausal woman.

BACKGROUND: Leiomyomatosis peritonealis disseminata (LPD) is a rare condition characterized by multiple subperitoneal nodules of benign smooth muscle. The lesion usually occurs in women of childbearing age. CASE: A 55-year-old woman with a history of panhysterectomy 8 years ago presented with an abdominal lump. Ultrasonographic and peroperative finding of multiple omental nodules led to a clinical impression of disseminated malignancy. Only the largest nodule was excised, histopathology of which revealed a cellular leiomyoma. Seven months later, she developed an omental leiomyosarcoma. An omentectomy was done and the multiple smaller nodules were all confirmed to be composed of benign leiomyocytes. CONCLUSION: Malignant transformation in LPD in post-menopausal patients is an exceptional event that has been documented only twice previously in English literature.

Cell Transformation, Neoplastic↗

Mesoscopic effects in adiabatic spin pumping.

We show that temporal shape modulations (pumping) of a quantum dot in the presence of spin-orbital coupling lead to a finite dc spin current. Depending on the strength of the spin-orbit coupling, the spin current is polarized perpendicular to the plane of the two-dimensional electron gas, or has an arbitrary direction subject to mesoscopic fluctuations. We analyze the statistics of the spin and charge currents in the adiabatic limit for the full crossover from weak to strong spin-orbit coupling.

Journal Article↗

Role of ascorbate in the regulation of nitric oxide generation by polymorphonuclear leukocytes.

We have recently demonstrated that NO-mediated polymorphonuclear (PMN)-dependent inhibition of rat platelet aggregation is significantly enhanced in the presence of ascorbate. Consequently, the present study was undertaken to elucidate the underlying mechanisms involved in ascorbate-mediated potentiation of NO synthesis in PMNs. We observed that ascorbate or its oxidized product, dehydroascorbate (DHA), enhanced NOS activity, as measured by nitrite content, diaminofluorescein fluorescence or conversion of L-[3H]arginine to L-[3H]citrulline in rat, monkey, and human PMNs. The increase in NO generation following ascorbate treatment was due to the intracellular ascorbate as iodoacetamide-mediated inhibition of DHA to ascorbate conversion attenuated the DHA-mediated increase in NO synthesis. The augmentation of NOS activity in the PMN homogenate by tetrahydrobiopterin was significantly enhanced by ascorbate, while ascorbate alone did not influence the NOS activity. Ascorbate-mediated enhancement of NOS activity in the cultured PMNs was significantly reduced in the presence of biopterin synthesis inhibitors. Ascorbate, thus, seems to regulate the NOS activity in the PMNs through tetrahydrobiopterin.

Animals↗

Perineal nodule due to enterobiasis: an aspiration cytologic diagnosis.

Subcutaneous swelling due to Enterobious vermicularis infection is rare. Their presence in perineal subcutaneous tissue is unusual and a clinical curiosity. A case of subcutaneous nodule in the perineum due to E. vermicularis infection diagnosed on fine-needle aspiration is described. Tissue reaction was granulomatous with neutrophils and eosinophils. Lack of familiarity with the morphology of parasites or its eggs, degeneration, and inadequate sampling may make the diagnosis difficult. This case report provides the morphologic clues to cytopathologists toward rendering a diagnosis and alerts them to the possibility of parasitic infection in unusual locations.

Adult↗

NO synthesis and its regulation in the arachidonic-acid-stimulated rat polymorphonuclear leukocytes.

Nitric oxide (NO) synthesis and free radical generation from polymorphonuclear leukocytes (PMNs) play an important role in several pathological conditions. In the present study, regulation of NO synthesis has been investigated in the unstimulated and arachidonic-acid (AA)-stimulated rat PMNs. L-Citrulline formation or nitrite content was used as a marker of NO synthesis, while AA-induced free radical generation was assessed by flow cytometry using a dye, 2('),7(')-dichlorofluoreseindiacetate. L-Citrulline formation in the unstimulated PMNs increased in a time-dependent manner for up to 120 min. The increase was significantly less (25-55%) in AA-stimulated PMNs at all the time points. AA-induced free radical generation was maximum during the first 15 min followed by a time-dependent decrease. Interestingly, similar experiments under hyperoxic conditions did not exhibit any decrease in L-citrulline and nitrite formation after AA stimulation even though the free radical generation further increased. Scavenging or inhibition of free radicals by several types of interventions increased NO generation from AA-stimulated PMNs. The results of the present study suggest that the availability of oxygen, a common substrate for both NADPH oxidase and NOS, can inversely affect the synthesis of NO and PMNs seem to prefer oxygen utilization over NO synthesis for free radical generation.

Animals↗

Nitric oxide mediated modulation of free radical generation response in the rat polymorphonuclear leukocytes: a flowcytometric study.

Nitric oxide (NO) synthesis and free radical generation from polymorphonuclear leukocytes (PMNs) play an important role in several pathological conditions. It is therefore important to understand the regulatory mechanisms of free radical generation from PMNs. Flowcytometry can be used to assess generation of reactive oxygen and nitrogen species from PMNs by using fluorescent probes. In the present study regulation of NO synthesis in the control and lipopolysaccharide (LPS) treated rat PMNs has been investigated. Free radical generation was assessed by flow cytometry using a dye, 2'7'-dichlorodihydrofluorescein diacetate (DCFDA), dihydrorhodamine-123 (DHR) and 4,5-diaminofluorescein diacetate (DAF). Superoxide dismutase (SOD), and catalase significantly attenuated the arachidonic acid (AA, 1 x 10(-6) M) induced free radical generation, while 4-aminobenzoicacid hydrazide (ABH), myeloperoxidase (MPO) inhibitor had no significant effect. Intracellular and extracellular calcium levels also modulated FR generation. AA induced free radical generation from PMNs was also enhanced significantly after LPS treatment. NO synthase (NOS) inhibitors, aminoguanidine (AG) and 7-nitroindazole (NI) inhibited arachidonic acid induced free radical generation from LPS treated PMNs, while in control PMNs NOS inhibition had no effect. Augmentation of free radical generation from rat PMNs following LPS treatment seems to be regulated by NO.

Animals↗

Malignant fibrous histiocytoma of the chest wall masquerading as medullary breast carcinoma: a case report.

BACKGROUND: Cytologic diagnosis of malignant fibrous histiocytoma can be problematic, as these neoplasms are known to mimic multiple other conditions. CASE: A fine needle aspirate from a 60-year-old woman was diagnosed at 2 institutions as medullary carcinoma of the breast. The patient received neo-adjuvant chemoradiotherapy before the tumor war excised. Gross pathologic examination and histomorphology on routine staining were compatible with the cytologic diagnosis. The accurate diagnosis of pleomorphic-storiform-type malignant fibrous histiocytoma was a surprise and was established with immunocytochemical stains. In retrospect, it was thought that clinical and radiologic overlap, creating a high index of suspicion for a breast neoplasm and compounding the cytologic appearance of a medullary carcinoma with spindle cell metaplasia and syncytial cells, was responsible for the error. CONCLUSION: This case highlights a potential cytodiagnostic pitfall and the importance of establishing a definitive tissue diagnosis in the face of equivocal cytologic findings.

Antineoplastic Agents↗

Chronic wuchereriasis presenting as a vaginoperineal fistula: report of a case with aspiration cytologic diagnosis.

BACKGROUND: Filariasis is often an occult disease with myriad presentations. Cytology has an established role in diagnosing clinically unsuspected cases. CASE: A 20-year-old female presented with recurring perineal ulcers, vaginal discharge and inguinal lymphadenopathy. Radiology revealed a vaginoperineal fistula. Fine needle aspiration (FNA) of the ulcer bed and smears prepared from the ulcer discharge showed an adult, gravid, female filarial worm and unsheathed larvae. Similar microfilariae were also seen in FNA smears from inguinal lymph nodes. The atypical clinical presentation and unusual parasite morphology posed initial difficulties in characterization of the microfilarial species. CONCLUSION: This case report highlights the morphologic clues to the dif ferential diagnosis offilarial species on cytologic specimens. Chronic wuchereriasis presenting as a vaginoperineal fistula has not been reported previously.

Adult↗