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Biomedical subjects

H L Sharma

Publications and source records attributed to H L Sharma.

At least 37 records · Page 2Linked to original sources
PubMed1991

Radioimmuno positron emission tomography with monoclonal antibodies: a new approach to quantifying in vivo tumour concentration and biodistribution for radioimmunotherapy.

Radioimmunodetection of tumours with monoclonal antibodies is becoming an established procedure. Positron emission tomography (PET) shows better resolution than normal gamma camera single photon emission tomography and can provide more precise quantitative data. Thus, in the present study, these powerful methods have been combined to perform radioimmuno PET (RI-PET). Monoclonal antibodies directed against carcinoembryonic antigen (CEA) an IgG, its F(ab')2 and a mouse-human chimeric IgG derived from it were labelled with 124I, a positron-emitting radionuclide with a convenient physical half-life of four days. Mice, xenografted with a CEA-producing human colon carcinoma, were injected with the 124I-MAb and the tumours were visualized using PET. The concentrations of 124I in tumour and normal tissue were determined by both PET and direct radioactivity counting of the dissected animals, with very good agreement. To allow PET quantification, a procedure was established to account for the presence of radioactivity during the absorption correction measurement (transmission scan). Comparison of PET and tissue counting indicates that this novel combination of radioimmunolocalization and PET (RI-PET) will provide, in addition to more precise diagnosis, more accurate radiation dosimetry for radioimmunotherapy.

Animals↗
PubMed1990

Synthesis, characterization and anti-tumour testing of some platinum(II) amine complexes containing 1,1- and 1,2-cyclobutanedicarboxylate ligands.

A series of new platinum(II) amine complexes containing 1,1- and 1,2-cyclobutanedicarboxylate ligands, cis-[PtA2(1,1-CBDCA)] (A = RNH2, where R = C2H5, n-C3H7, n-C4H9, n-C5H11, n-C6H13, c-C3H5, c-C5H9, c-C6H11; A2 = ethylenediamine, 1,3-diaminopropane), cis-[PtA2(1,2-CBDCA)] (A = NH3, RNH2 where R = CH3, C2H5, n-C3H7, n-C4H9, c-C3H5) and trans-[Pt(NH3)2(1,1-CBDCAH)2] (CBDCA, CBDCAH = dianion and monoanion of the dicarboxylic acid, respectively) have been synthesized by an improved route. These complexes are stable in aqueous solution and show good aqueous solubility. The [Pt(c-C3H5NH2)2(1,1-CBDCA)] can be isolated in white, grey and blue forms. The grey and blue forms exhibit ESR signals analogous to the so-called platinum blues. The existence of the blue form in aqueous solution is time and temperature dependent. Several of the complexes have been tested against leukaemia L1210 in male BDF mice and activity appears to decrease with the increase in length of the aliphatic chain (or increase in size of the alicyclic ring) of the primary amine. The Yoshida lymphoscarcoma screen, usually insensitive to platinum drugs, was found to respond well to [Pt(n-C4H9NH2)2(1,1-CBDCA)] in 5-day subcutaneously implanted tumours in female Wistar rats.

Animals↗
PubMed1990

Thyroid imaging using positron emission tomography--a comparison with ultrasound imaging and conventional scintigraphy in thyrotoxicosis.

Forty-six comparative studies were performed on 41 patients with hyperthyroidism. Clinically these comprised two groups: those with Graves' disease, and those with multinodular goitre. All patients underwent an ultrasound examination and positron emission tomography (PET) using 124I, then gamma camera pinhole imaging following their 131I therapy administration. Although the 131I pinhole imaging was not performed for diagnostic purposes, there was good correlation (78% agreement) between it and 124I PET in determining relative lobe size. Hence either imaging modality could be used as an indicator of the relative radiation dose delivered to each thyroid lobe at a macroscopic level. In terms of gland morphology the PET images corresponded well to the high resolution ultrasound images (78% agreement), unlike the pinhole images which correlated poorly (only 28% agreement). The results showed that PET imaging gives better anatomical and physiological detail than 131I pinhole imaging. In 77% of cases where the pinhole image showed a uniform distribution of radioisotope, the improved spatial resolution of the PET images revealed non-homogeneous distribution indicating a non-uniform distribution of radiation dose. Since all dosimetry calculations are based on the assumption of uniform distribution of radioiodine, this non-uniformity could possibly have important consequences in the outcome of radioiodine therapy in thyrotoxicosis.

Adult↗
PubMed1990

Measurement of renal blood flow by 131I-labelled sodium iodohippurate imaging in a rat model of herpes encephalitis.

Renal blood flow was assessed qualitatively over a 30 min period in a rat model of herpes encephalitis by extra-renal scintigraphic imaging following the injection of 131I-labelled sodium iodohippurate. No significant differences were observed for renal blood flow in either kidney between (or within) infected and control groups. Our data suggest that kidney function is not compromised in this animal model of encephalitis. The results are discussed in the context of the development of a non-invasive protocol for the in vivo diagnosis of herpes encephalitis.

Animals↗
PubMed1990

Preparation and in vivo study of 124I-labelled monoclonal antibody H17E2 in a human tumour xenograft model. A prelude to positron emission tomography (PET).

Positron emission tomography (PET) is a powerful nuclear medicine technique which, unlike conventional gamma camera tomography, relies on the coincidental detection of the two 511 keV gamma photons produced from the annihilation of a single positron. Hence good spatial resolution and accurate quantitation may be achieved. 124I (t1/2 = 4 days), a positron-emitting isotope of iodine, was chosen for our initial PET studies because the techniques of antibody radio-iodination are well established. The murine monoclonal antibody H17E2 detecting placental alkaline phosphatase (PLAP) was radiolabelled using the Iodogen method. A specific activity of 2.3 microCi microgram-1 was achieved with a radiolabelling efficiency of 91%. Nude mice bearing subcutaneous HEp2 human tumour xenografts (a PLAP expressing cell-line) received 8.3 micrograms (18.8 microCi) of H17E2-124I by intraperitoneal injection. Animals were killed and dissected at 5 h, 1, 2, 3, and 7 days, and radioactivity was assessed in tumour and normal tissues. The half-life in the blood of H17E2-124I was 132 h as compared with 141 h for H17E2-131I. Activity in tumour rose to 4.26% injected dose g-1 by 48 h and remained at this level until day 7, giving a tumour:blood ratio of 0.78 at this time. The percentage injected dose g-1 in all tissues (with the exception of tumour) decreased with time giving tumour:tissue ratios greater than 1.00 from 24 h onwards in all cases except blood. In conclusion, tumour localization of H17E2-124I has been successfully achieved in this animal model. This demonstrates the feasibility of using tumour-associated monoclonal antibodies radiolabelled with a positron-emitting isotope for tumour localization studies.

Animals↗
PubMed1989

HM-PAO-imaging and herpes encephalitis.

Selective uptake of the cerebral blood-flow imaging agent 99mTc-hexamethylpropyleneamine oxime (HM-PAO) by Human Herpesvirus 1 (HSV-1) infected cells was investigated in vivo and in vitro. No specific uptake of HM-PAO was observed either in encephalitic rats (by brain scintigraphic imaging or by immunoperoxidase staining/autoradiography of brain sections) or in HSV-1 infected Vero cells.

Animals↗
PubMed1988

Specific neuro-radiological diagnosis of herpes encephalitis in an animal model.

The potential of utilizing a radio-labelled derivative of the antiviral drug (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU) for the specific, non-invasive, in vivo diagnosis of Herpes simplex virus encephalitis (HSVE) was investigated in a rat model of the disease. Following pharmacological disruption of the blood brain barrier radiolabelled IVDU was administered by intra-carotid injection. Brain radioactivity was compared between control and infected animals via gamma camera scintigraphy. After clearance of non-metabolized drug, markedly higher levels of activity were found in infected brain. Post-mortem studies of cryostat sections of brain examined by autoradiography and immunochemical staining showed the radioactivity selectively accumulated in areas of virus infection. These results indicate that radio-labelled derivatives of antiviral drugs may allow the specific neuro-radiological diagnosis of HSVE.

Animals↗
PubMed1988

Estimating the parameters of a Polya-Aeppli distribution.

"The paper provides expressions for the 'maximum likelihood equations' and the asymptotic variances and co-variance of the maximum likelihood estimators of the parameters in a Polya-Aeppli distribution provided that we have a knowledge of the number of groups with zero objects...the number of groups with one object...and the total number of groups.... The results are illustrated using an example involving demographic data [for India]." The focus is on the number and types of households.

Asia↗
PubMed1988

The behavior of autologous indium-114m-labeled lymphocytes in patients with lymphoid cell malignancy.

It has been shown that radioactive material can be localized to lymphocyte traffic areas using radiolabeled autologous lymphocytes and that 114mIn deposited in such a way in rats produces a lymphopoenia by establishing a selective internal irradiation of circulating lymphocytes. The study reported here was undertaken to investigate the feasibility of using this technique in patients with lymphoid cell malignancy. Up to 22.7 MBq was administered to seven patients with active non-Hodgkin's lymphoma involving the spleen and the behavior of the radioactive material was followed over subsequent months. Estimates of the activity in peripheral blood, bone marrow, excreta samples, and of the variation in the whole-body distribution were obtained. The administered radioactive material cleared rapidly from the blood, 85% being removed within the first 30 min. There was an almost immediate uptake of most of this by the spleen and liver with less than 5% of administered activity accumulating in the bone marrow. After 48 hr, the whole-body distribution changed only slowly and there was a regular decrease of the activity in the spleen. Excretion of radioactive material occurred via both the urine and feces and amounted to less than 1% of administered activity per day. This pharmacokinetic data was used to calculate radiation absorbed doses to various organs for a standard man. It is concluded that this represents a feasible technique for the targeting of radioactive material for the treatment of lymphoid malignancy.

Adult↗
PubMed1987

Factors influencing the sensitivity of two human bladder carcinoma cell lines to cis-diamminedichloroplatinum(II).

A two-fold difference in sensitivity to cis-diamminedichloroplatinum(II) (cisplatin), as judged by colony forming assays, has been demonstrated in two human bladder carcinoma continuous cell lines. Approximately twice as many DNA-DNA interstrand cross-links (ISL) and a 2-fold greater inhibition of DNA synthesis occurred in the more sensitive T24 cell line than in the RT112 cell line after exposure to the same concentrations of cisplatin. Equitoxic concentrations of cisplatin resulted in similar extents of ISL and inhibition of DNA synthesis in both cell lines. Although drug uptake was identical, twice as much cisplatin was bound to the DNA of T24 cells than RT112 cells. However after equitoxic concentrations of cisplatin the DNA from both cell lines was platinated to a similar extent. In addition, levels of glutathione (GSH), glutathione reductase (GR) and total glutathione-S-transferases (GST) were higher in the less sensitive RT112 cell line.

Biological Transport↗
PubMed1987

Assessment of gastric emptying using gamma scintigraphy.

Gamma scintigraphy was used to measure the gastric emptying rates of three test meals in human volunteers. Emptying rates were determined for solid and liquid materials alone, and for liquid in the presence of solid material. It was shown that the emptying of solids from the stomach was significantly slower than that of liquid, whether liquid alone or liquid in the presence of solid material. It was concluded from these results that, in the case of a solid test meal from which radio-label could be eluted, the free label would empty considerably faster than the remaining solid material. The emptying rate observed scintigraphically would not, therefore, be a true estimate of the solid emptying rate.

Contrast Media↗
PubMed1987

A probability distribution for out-migration.

"Under certain simplifying assumptions, an inflated generalized Poisson distribution has been proposed to study the trends for out-migration. This distribution has been fitted to data estimating the parameters by (i) method of moments and (ii) maximum likelihood method....Asymptotic expressions for variance and covariance of the maximum likelihood estimates are obtained." The method is tested using data from the Rural Development and Population Growth survey undertaken in Varanasi, India, in 1978.

Asia↗