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Biomedical subjects

Mahesh Kumar

Publications and source records attributed to Mahesh Kumar.

14 recordsLinked to original sources

Efficacy of inactivated vaccines against H5N1 avian influenza infection in ducks.

The current Asian H5N1 highly pathogenic avian influenza virus has spread over much of Asia and into Europe and Africa. As well as affecting village and commercial chicken operations in many South East Asian countries, it differs from past H5 avian influenza viruses in that it causes morbidity and mortalities in other domesticated birds, such as ducks and turkeys and in wild water birds. Effective vaccines that can prevent infection, as well as disease, and be used in a variety of avian species are needed for field use. In this report, a bivalent H5N9+H7N1 oil emulsion vaccine is compared, in ducks, to a monovalent H5N3 oil emulsion vaccine that has been derived by reverse genetics with an H5 from A/chicken/Vietnam/C58/04. While both vaccines protected against morbidity, the monovalent vaccine provided effective protection, with no evidence of shedding of the challenge virus and no serological response to the H5N1 challenge virus.

Animals↗

The immunogenicity and efficacy against H5N1 challenge of reverse genetics-derived H5N3 influenza vaccine in ducks and chickens.

H5N1 avian influenza viruses are continuing to spread in waterfowl in Eurasia and to threaten the health of avian and mammalian species. The possibility that highly pathogenic (HP) H5N1 avian influenza is now endemic in both domestic and migratory birds in Eurasia makes it unlikely that culling alone will control H5N1 influenza. Because ducks are not uniformly killed by HP H5N1 viruses, they are considered a major contributor to virus spread. Here, we describe a reverse genetics-derived high-growth H5N3 strain containing the modified H5 of A/chicken/Vietnam/C58/04, the N3 of A/duck/Germany/1215/73, and the internal genes of A/PR/8/34. One or two doses of inactivated oil emulsion vaccine containing 0.015 to 1.2 microg of HA protein provide highly efficacious protection against lethal H5N1 challenge in ducks; only the two dose regimen has so far been tested in chickens with high protective efficacy.

Animals↗

Inhibition of vascular endothelial growth factor (VEGF)-A causes a paradoxical increase in tumor blood flow and up-regulation of VEGF-D.

PURPOSE: Vascular endothelial growth factor (VEGF)-A is an important mediator of angiogenesis in almost all solid tumors. The aim of this study was to evaluate the effect of VEGF-A expression on tumor growth, perfusion, and chemotherapeutic efficacy in orthotopic 9L gliosarcomas. EXPERIMENTAL DESIGN: Stable 9L cell lines underexpressing and overexpressing VEGF-A were generated. Anatomic, susceptibility contrast, and continuous arterial spin-labeling magnetic resonance imaging were used to quantify the volume, blood volume, and blood flow of tumors orthotopically grown from these and wild-type 9L cells. Histologic, immunohistochemical, and quantitative reverse transcription-PCR analyses were also done on excised tumors. Finally, the effects of carmustine chemotherapy were also evaluated. RESULTS: Orthotopic tumors underexpressing VEGF-A had slower growth rates (increased median survival), greater blood flow, vessel density, and VEGF-D expression, but no statistical difference in blood volume and chemotherapeutic sensitivity, compared with tumors with wild-type levels of VEGF-A. Tumors overexpressing VEGF-A had faster growth rates, greater blood volume, vessel density, and blood flow but no statistical difference in VEGF-D expression and chemotherapeutic sensitivity compared with wild-type VEGF-A-expressing tumors. CONCLUSION: Blood volume and blood flow are independent and different biomarkers of tumor perfusion. Therefore, both should be measured when characterizing the efficacy of antiangiogenic therapies. Underexpression of VEGF-A does not result in complete inhibition of angiogenesis. Moreover, these tumors have a different perfusion phenotype, suggesting that angiogenesis is mediated by an alternative pathway. The results indicate that VEGF-D is a plausible alternative mediator of this angiogenesis.

Animals↗

Monitoring the therapeutic response of locally advanced breast cancer patients: sequential in vivo proton MR spectroscopy study.

PURPOSE: To evaluate the use of the water-to-fat (W-F) value obtained from in vivo proton ((1)H) MR spectroscopy (MRS) as a response indicator of cytologically confirmed patients with locally advanced breast cancer (LABC), and to monitor the therapeutic response of such patients to neoadjuvant chemotherapy (NACT). MATERIALS AND METHODS: Serial (1)H MR spectra were recorded both before and after the completion of chemotherapy in 33 LABC patients (with infiltrating ductal carcinoma (IDC)) at 1.5T. In addition, spectra from normal breast tissues of 28 healthy volunteers were recorded. RESULTS: Malignant breast tissues showed elevated W-F values compared to normal breast tissues of controls. Statistically significant higher pretherapy W-F value (P < 0.01) was observed in patients compared to controls. In patients who received NACT resulting in the reduction of the primary tumor size, the W-F value showed a decrease that was statistically significant (P < 0.01). Analysis of the MR data further indicates that the W-F value had no correlation with the menstrual status of the patients. A comparison of pretherapy W-F value with pretherapy tumor volume showed a fair correlation (P = 0.05), while the posttherapy W-F value showed no such correlation with the posttherapy tumor volume. CONCLUSION: This study demonstrates that simple, conventional in vivo (1)H MRS is a useful technique for monitoring the therapeutic response of breast cancer patients. The observed trend in the reduction of W-F value provides a noninvasive response indicator to monitor the clinical outcome of locally advanced breast cancer patients to NACT.

Analysis of Variance↗

Combined central retinal artery and vein occlusion secondary to systemic non-Hodgkin's lymphoma.

We report a rare case of low-grade systemic B-cell non-Hodgkin's lymphoma (NHL) causing central retinal artery and vein occlusion, which was the only manifestation of disease recurrence. A young man with resolved systemic NHL underwent fluorescein angiography, magnetic resonance imaging and computed tomography to investigate a severe unilateral visual loss. A combined vascular occlusion was observed in the right eye. Neuroimaging detected optic nerve infiltration; but no systemic/ central nervous system involvement was observed. The patient was treated with high-doses of corticosteroids and optic nerve irradiation. The optic neuropathy and vascular occlusion were resistant to treatment. The subsequent neovascular glaucoma was treated by panretinal photocoagulation, which relieved the pain, but vision was not recovered. No further recurrence was observed over the following year.

Adult↗

Structural transition in nanostructured Eu2O3 under high pressures.

We report here studies on the effect of high pressure on the structural properties of nano-sized Europium sesquioxide (Eu2O3) up to a pressure of about 16.4 GPa. At ambient conditions, the starting sample was found to be predominantly cubic type Eu2O3 or in Eu3+ state with a trace of Eu2+. The presence of Eu2+ state is assumed to be arising due to the non-stoichiometric Eu(1-x)O phase which is obtained from XPS studies by the deconvolution of the Eu 3d-core levels. The Raman studies at ambient show a strong peak at about 333 cm(-1), which is known to occur due to the Fg mode of cubic Eu2O3 and in a similar way, the XRD data shows major peaks corresponding to the cubic phase of Eu2O3. A Mao-Bell type diamond anvil cell (DAC) was used to generate high pressures for XRD and Raman spectroscopy studies. It was observed that the material undergoes a structural change from cubic to monoclinic structure with an on set transition pressure at around 2 GPa and completes at around 8 GPa. This has been inferred from the fact that above about 2.0 GPa pressure, Raman studies show the emergence of a new peak corresponding to the monoclinic phase which increases in intensity and shifts further with increase in pressure, while the XRD studies show that above about 2.0 GPa, the peaks corresponding to monoclinic phase emerge, which show a slight increase in preferred orientation as the pressure is increased. A detailed discussion has been provided to explain this fact.

Europium↗

Sodium magnetic resonance imaging of chemotherapeutic response in a rat glioma.

This study investigates the comparative changes in the sodium MRI signal and proton diffusion following treatment using a 9L rat glioma model to develop markers of earliest response to cancer therapy. Sodium MRI and proton diffusion mapping were performed on untreated (n = 5) and chemotherapy 1,3-bis(2-chloroethyl)-1-nitrosourea-treated rats (n = 5). Animals were scanned serially at 2- to 3-day intervals for up to 30 days following therapy. The time course of Na concentration in a tumor showed a dramatic increase in the treated brain tumor compared to the untreated tumor, which correlates in time with an increase in tumor water diffusion. The largest posttreatment increase in sodium signal occurred 7-9 days following treatment and correlated to the period of the greatest chemotherapy-induced cellular necrosis based on diffusion and histopathology. Both Na MRI and proton ADC mapping revealed early changes in tumor sodium content and cellularity. This study demonstrates the possibility of Na MRI to function as a biomarker for monitoring early tumor treatment and validates the use of monitoring changes in diffusion MRI values for assessing tumor cellularity.

Animals↗

Subclinical inflammation and soleus muscle intramyocellular lipids in healthy Asian Indian males.

OBJECTIVES: The relationship between C-reactive protein (CRP), a marker of subclinical inflammation, and intramyocellular lipid (IMCL) content, a novel correlate of insulin resistance, has not previously been investigated. METHOD AND DESIGN: We estimated IMCL content in soleus muscle in 30 healthy Asian Indian males using proton magnetic resonance spectroscopy ((1)H MRS), and correlated it with body mass index (BMI), measures of abdominal obesity, percentage of body fat (%BF), serum lipoproteins, fasting and post-oral glucose load serum insulin levels and other surrogate markers of insulin resistance. RESULTS: Soleus muscle IMCL content was significantly correlated with age (rho=0.64, P<0.001), BMI (rho=0.41, P<0.05), %BF (rho=.53, P<= 0.01), waist circumference (rho=0.45, P<0.05) and waist-to-hip circumference ratio (rho=0.58, P<0.01) but did not correlate significantly with insulin resistance measured by the homeostasis model assessment (HOMA-IR) or CRP levels. CRP levels did not correlate with the HOMA-IR value. CONCLUSIONS: Soleus muscle IMCL content correlated significantly with measures of generalized and abdominal obesity but not with insulin sensitivity or CRP levels in healthy Asian Indian males. Studies are needed in other ethnic groups to corroborate these data.

Asian People↗

Bioaccumulation properties of nickel-, cadmium-, and chromium-resistant mutants of Pseudomonas aeruginosa NBRI 4014 at alkaline pH.

Nickel-, cadmium-, and chromium-resistant mutants of Pseudomonas aeruginosa sp. NBRI 4014 are potent growth promontory strains. In the presence of metal(s), they have shown increased cell morphology and could accumulate nickel (2.0874 mM/g), cadmium (2.295 mM/g), and chromium (2.997 mM/g) at pH 9. However, chromium accumulation was maximum, but the toxicity levels of nickel, cadmium, and chromium was ranged from 90 to 504 microM of used metal(s). Bioaccumulation increases up to the fifth day at the highest used metal concentration and then became constant. This suggests their exploitation for detoxification and subsequently loaded biomass treatment for the recovery of accumulated metal(s).

Absorption↗

Proton magnetic resonance spectroscopy with a body coil in the diagnosis of carcinoma prostate.

We evaluate the feasibility of proton magnetic resonance spectroscopy ((1)H MRS) using a spine coil receiver (body coil) in the diagnosis of carcinoma prostate. Seventeen patients with biopsy-proven prostate carcinoma, five patients of benign prostatic hyperplasia (BPH) and five healthy young volunteers underwent (1)H MRS investigation. MRS was performed at 1.5 Tesla using a spine receiver coil for signal reception. In vivo citrate levels are reported as a ratio of citrate peak area to the sum of the areas of choline and creatine peak. MRS spectrum with good sensitivity and signal to noise (S/N) ratio was obtained in all 27 subjects. The citrate to creatine plus choline ratio was 0.31+/-0.25 in patients with cancer, 1.43+/-0.58 in BPH and 2.16+/-0.56 in controls. The difference in ratios between cancer and BPH and cancer and control was statistically significant ( p<0.01). Within the cancer group, there was a statistically significant decline in levels with higher-grade malignancy ( p<0.05). There were no complications of the procedure. There is a statistically significant decline in the ratio of citrate to choline plus creatine in the regions of cancer prostate when compared with BPH or normal control. The study demonstrates that MRS data can be reliably acquired using a spine coil receiver. MRS may also play a role in differentiating well-differentiated tumors from the anaplastic variety.

Adult↗

Metastasising clear cell odontogenic carcinoma: a case report and review of the literature.

Primary odontogenic carcinomas are rare and examples which have metastasised are even more uncommon. We describe the first reported case of a clear cell odontogenic carcinoma which metastasised to distant bones, namely the 5th lumbar vertebra and hip, 3 years after initial diagnosis. The initial incisional biopsy was thought to represent a calcifying epithelial odontogenic tumour, but in the subsequent resection the tumour showed a prominent clear cell component admixed with squamous cells showing peripheral palisading, widespread infiltration and necrosis indicating a malignant neoplasm. Radiologically guided biopsy revealed a metastatic lesion in L5 vertebrae and left hip, confirmed by immunohistochemistry. The metastatic lesion had similar appearances to the first biopsy, and diagnosis was confirmed by comparison of histological features, immunohistochemistry and exclusion of a second primary lesion by clinical examination and imaging. The diagnosis of clear cell odontogenic carcinoma is a difficult one to make. The behaviour of these tumours is unpredictable. This case confirms that clear cell odontogenic carcinomas have the potential for distant metastasis and require long-term follow up.

Adenocarcinoma, Clear Cell↗