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Biomedical subjects

V L Kubic

Publications and source records attributed to V L Kubic.

14 recordsLinked to original sources
PubMed1996

Posttransplant T-cell lymphoproliferative disorders--an aggressive, late complication of solid-organ transplantation.

T-cell non-Hodgkin's lymphomas are an uncommon occurrence after solid-organ transplantation. We describe a morphologically and immunophenotypically distinct group of T-cell lymphoproliferative disorders that occurred late in the course of six patients with solid-organ transplants. The patients ranged in age from 31 to 56 years (median, 43). Three were male; all were splenectomized. The interval from transplant to the diagnosis of lymphoma ranged from 4 to 26 years (median, 15). Symptoms at presentation were related to sites of involvement. Pulmonary, marrow, and CNS involvement were present in five, four, and one case, respectively. No patient had lymphadenopathy. Five patients had an elevated lactate dehydrogenase level (range, 226 to 4,880 IU/L; median, 1,220 IU/L). Five of six patients had a leukoerythroblastic reaction. All cases had large-cell histology and frequently contained cytoplasmic granules. Those cases tested expressed CD2, CD3, and CD8 and were negative for B-cell antigens. T-cell receptor beta- and gamma-chain genes were clonally rearranged in three of three and one of three cases, respectively. All T-cell posttransplant lymphoproliferative disorders (T-PTLDs) studied were negative for Epstein-Barr virus (EBV), human T-cell leukemia/lymphoma virus type 1 (HTLV-1), human T-cell leukemia/lymphoma virus type 2 (HTLV-2), and human herpes virus type 8 (HHV-8) genomes. Treatment with acyclovir (three patients) or chemotherapy (three patients) resulted in two responses. All patients had an aggressive course, with a median survival duration of 5 weeks. In conclusion, a clinically aggressive T-PTLD may be a late complication of solid-organ transplantation and does not appear to be related to EBV, HTLV-1, HTLV-2, or HHV-8 infection.

Adult↗
PubMed1991

The morphologic and immunophenotypic assessment of the lymphocytosis accompanying Bordetella pertussis infection.

Bordetella pertussis (Bp) infection in infants and young children can be associated with a significant increase in small lymphocytes with convoluted and cleaved nuclei (SLCCN) in the peripheral blood (PB). Buffy coat smears were studied that were prepared from the PB of 11 children with documented Bp infection, whose ages ranged from one month to four years. The white blood cell count ranged from 8.4 to 72.9 X 10(9)/L, with a mean of 28.6 X 10(9)/L. In all cases, the percentage of PB lymphocytes was in the normal range; the absolute lymphocyte count ranged from 6.5 to 54.8 X 10(9)/L, with a mean of 20.3 X 10(9)/L. SLCCN represented 12-56% of the lymphocyte population. B and T lymphocytes, identified with monoclonal antibodies with the use of an immunoalkaline phosphatase method, accounted for a mean of 21% and 53%, respectively, of the total nucleated cells (TNCs) on buffy coat smears. The T-helper and T-suppressor subsets represented 38% and 16% of the TNCs, respectively, resulting in a CD4-CD8 ratio of 2.4. Most SLCCN were of the T-helper phenotype; SLCCN of the T-suppressor subset and, rarely, of the B-cell type also were identified. These observations document that the lymphocytosis associated with Bp infection in infants and young children is characterized by the presence of morphologically abnormal cells that are predominantly CD4 positive and appear to represent an expansion of an immunophenotypically normal lymphocyte population.

Antigens, CD↗
PubMed1990

Comparison of in situ hybridization and immunohistochemistry for detection of cytomegalovirus and herpes simplex virus.

In situ hybridization (ISH) and immunohistochemistry (IHC) were compared for detection of cytomegalovirus (CMV) and herpes simplex virus (HSV) in routinely processed tissue. Fifty-four formalin-fixed paraffin-embedded tissue samples infected with CMV (36 tissues) or HSV (18 tissues) from 30 autopsies were studied. All tissues had either positive viral cultures (38 of 54) or characteristic viral inclusions on hematoxylin and eosin examination (39 of 54). The tissues examined included lung (28), liver (nine), kidney (five), heart (three), adrenal (two), spleen (two), and thymus, pancreas, appendix, esophagus, and duodenum (one each). Studies by ISH were performed with two detection systems, using biotinylated probes to CMV and HSV (Enzo Biochem, New York, NY). Using ISH with an alkaline phosphatase detection system, infected cells were detected in 33 of 54 tissues (CMV: 23 of 36, HSV: 10 of 18). Using ISH with a peroxidase detection system, infected cells were identified in 30 of 54 tissues (CMV: 22 of 36, HSV: eight of 18). With IHC, antibodies to CMV and HSV stained the infected cells in 34 of 54 tissues (CMV: 24 of 36, HSV: 10 of 18). All infections detected with ISH were also detected with IHC. We conclude that these techniques for ISH and IHC are equally effective for detecting CMV and HSV in paraffin sections. The results of both techniques correlate better with viral inclusions than with culture results. The ISH stains are more difficult to prepare and in some cases are more difficult to interpret. Therefore, IHC may be preferable to ISH for detecting CMV and HSV in routine diagnostic work.

Cytomegalovirus↗
PubMed1989

Immunohistochemical evaluation of neoplasms in bone marrow biopsies using monoclonal antibodies reactive in paraffin-embedded tissue.

A panel of commercially available monoclonal antibodies (MoAbs) including LN1, LN2, MB2, L26, Leu M1, UCHL1, MT1 and L60 was used to evaluate a diverse group of neoplastic processes in 256 Zenker's-fixed, decalcified, paraffin-embedded bone marrow biopsies using the ABC immunoperoxidase technique. LN2 and MB2 were useful in delineating the extent of B-cell lymphoproliferative processes and in identifying interstitial patterns of involvement. The combined application of LN2, MB2 and UCHL1 had utility in differentiating B-cell from T-cell lymphoproliferative processes; in no instance was reactivity with LN2 observed in T-cell processes. The combined application of these three MoAbs was also used in differentiating benign reactive lymphoid aggregates from focal malignant B-cell proliferations. LN2 exhibited positivity with the Reed-Sternberg cells (RSC) of Hodgkin's Disease (HD) and significantly aided in the identification of these cells. Staining of RSC with Leu M1 was inconsistent and was observed in only 50% of cases of HD. Use of the entire panel of MoAbs together with more recently available reagents such as Cathepsin G, MAC 387 and neutrophil elastase was essential in optimally evaluating a particular lesion; none of these MoAbs used singly reliably differentiated myeloid from lymphoid, hematopoietic from metastatic, or reactive from malignant processes.

Antibodies, Monoclonal↗
PubMed1981

Mechanism of the microsomal reduction of carbon tetrachloride and halothane.

The source of the hydrogen atoms in reduced metabolites of carbon tetrachloride and halothane has been studied. This was approached by measuring deuterium incorporation into chloroform and 2-chloro-1,1,1-trifluoroethane formed as microsomal metabolites of carbon tetrachloride and halothane, respectively, in a medium enriched in deuterium oxide. GC/MS analysis showed no deuterium enrichment of chloroform when hepatic microsomal fractions from control rats were used; however, small increases in enrichment were seen when microsomes from phenobarbital or benzpyrene-treated rats were employed. no detectable deuterium incorporation into 2-chloro-1,1,1-trifluoroethane was observed. These results suggest that carbanions are not formed as major intermediates and suggest that one-electron transfer reactions predominate in the reductive metabolism of carbon tetrachloride and halothane.

Animals↗
PubMed1980

Halogenated methanes: metabolism and toxicity.

Dihalomethanes are metabolized to carbon monoxide (CO) both in vivo and in vitro. The reaction is catalyzed by the hepatic microsomal cytochrome P-450 dependent mixed function oxidase system. Reaction mechanism studies suggest an initial oxygen insertion reaction followed by rearrangement to a formyl halide intermediate, which in turn decomposes to yield CO. In vitro studies show that [14C]dichloromethane becomes covalently bound to both microsomal protein and lipid. The similar characteristics of metabolism to CO and covalent suggest that a common intermediate, perhaps the formyl halide, may be involved. Dihalomethanes are also metabolized for formaldehyde, formic acid, and inorganic halide. A glutathione transferase located in hepatic cytosol fractions appears to be involved. Reaction mechanism studies suggest that a S-hydroxymethyl glutathione intermediate may yield formaldehyde or be diverted via formaldehyde dehydrogenase/S-formyl glutathione hydrolase to yield formic acid. Haloforms are also metabolized to carbon monoxide both in vivo and in vitro by a hepatic microsomal cytochrome P-450 dependent mixed function oxidase system. In vitro, this reaction is markedly stimulated by sulfhydryl compounds. Reaction mechanism studies suggest an initial oxygen insertion reaction followed by rearrangement to a dihalocarbonyl intermediate, which in turn reacts with sulfhydryl reagents to yield a thiol-S-formyl halide. Subsequent attack by other sulfhydryl compounds would result in the formation of CO and a disulfide.

Biotransformation↗
PubMedDate not supplied

Metabolism of haloforms to carbon monoxide. I. In vitro studies.

Trihalomethanes (haloforms) were metabolized to carbon monoxide by a rat liver microsomal fraction requiring both NADPH and molecular oxygen for maximal activity. GSH alone did not serve as a cofactor; however, GSH in the presence of NADPH and oxygen produced an 8-fold increase in the metabolism of bromoform to CO. Similar results were obtained with other sulfhydryl compounds. The biotransformation of bromoform to CO was characterized with respect to time course, microsomal protein concentration, pH and temperature. The metabolism of haloforms to CO followed the halide order; thus, iodoform yielded the greatest amount of CO, whereas chloroform yielded the smallest amount. A KM of 6.78 +/- 2.71 mM was established for bromoform and the Vmax was 1.09 +/- 0.19 nmol of CO per mg of microsomal protein per min. The energy of activation for this reaction was 6.5 +/- 0.18 kcal/mol. Cytochrome P-450 was found to bind bromoform to produce a type I binding spectrum. Treatment of rats with phenobarbital or 3-methylcholanthrene increased the rate of conversion of bromoform to CO. Cobaltous chloride treatment of rats or storage of microsomal preparations at 4 degrees C reduced the rate of formation of CO from bromoform. SKF 525-A inhibited the conversion of bromoform to CO. These results suggest that haloforms are metabolized to CO via a cytochrome P-450-dependent mixed-function oxidase system.

Anaerobiosis↗
PubMedDate not supplied

Metabolism of dihalomethanes to carbon monoxide. II. In vitro studies.

Dibromomethane was metabolized to carbon monoxide and inorganic bromide by a rat liver microsomal fraction requiring both NADPH and molecular oxygen. This biotransformation was characterized with respect to time course, microsomal protein concentration, pH, and temperature. The metabolism of dihalomethanes to carbon monoxide followed the halide order; thus, diiodomethane yielded the greatest amount of carbon monoxide, whereas dichloromethane yielded the smallest amount. A KM of approximately 16 mM was established for dibromomethane while the Vmax was found to be about 8 nmol of CO per mg of microsomal protein per min. Cytochrome P-450 was found to bind dibromomethane to produce a type I binding spectrum. Pretreatment with phenobarbital increased both microsomal cytochrome P-450 levels and the rate of conversion of dibromomethane to carbon monoxide. Pretreatment with cobaltous chloride or storage of microsomal preparations at 4 degrees C resulted in parallel reductions of both cytochrome P-450 levels and the rate of formation of carbon monoxide from dibromomethane. SKF 525-A, ethylmorphine, and hexobarbital inhibited the conversion of dibromomethane to carbon monoxide. Microsomal preparations from rat lung metabolized this substrate at about 18% of the rate found in liver microsomes. The requirement for both NADPH and molecular oxygen, the inhibitory effects of SKF 525-A, ethylmorphine, and hexobarbital on the production of carbon monoxide from dibromomethane, and the correlation established between microsomal cytochrome P-450 levels and the rate of metabolism of dihalomethanes to carbon monoxide after treatments that alter the cytochrome to P-450 content suggest that these compounds are metabolized to carbon monoxide via a cytochrome P-450-dependent system.

Animals↗
PubMedDate not supplied

Metabolism of halogenated methanes and macromolecular binding.

Dihalomethanes are metabolized to carbon monoxide both in vivo and in vitro. The reaction is catalyzed by a hepatic microsomal cytochrome P-450 dependent mixed function oxidase system. Bioorganic mechanism studies suggest an initial oxygen insertion reaction followed by rearrangement to a formyl halide intermediate which in turn decomposes to yield carbon monoxide. In vitro studies show that 14C-dichloromethane becomes covalently bound to both microsomal protein and lipid. The similar characteristics of metabolism to carbon monoxide and covalent binding suggests that a common intermediate, perhaps the formyl halide, may be involved. Dihalomethanes are also metabolized to formaldehyde, formic acid, and inorganic halide. A glutathione transferase, located in hepatic cytosol fractions, appears to be involved. Reaction mechanism studies suggest that a S-hydroxymethyl glutathione intermediate may yield formaldehyde or be diverted via formaldehyde dehydrogenase/S-formyl glutathione hydrolase to yield formic acid. Haloforms are also metabolized in vitro to carbon monoxide by a hepatic microsomal cytochrome P-450 dependent mixed function oxidase system. This reaction is a markedly stimulated by sulfhydryl compounds.

Animals↗