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Biomedical subjects

J L Hess

Publications and source records attributed to J L Hess.

At least 37 records · Page 2Linked to original sources

Defects in yolk sac hematopoiesis in Mll-null embryos.

Translocations involving the mixed lineage leukemia gene (MLL), the human homolog of the Drosophila gene trithorax, are one of the most common genetic alterations in human acute leukemias. Each translocation involving MLL results in loss of one functional copy of MLL and the generation of a chimeric fusion protein with potential dominant negative or neomorphic activity. Mll is a positive regulator of Hox genes, which have been implicated in both axial skeleton patterning and hematopoietic development. Previous studies indicated that Hox gene expression is altered in Mll heterozygous (+/-) and homozygous (-/-) deficient mice. To study the role of Mll in hematopoiesis and to obtain insights into leukemogenesis, we have examined the effects of haplo-insufficiency or absence of Mll by in vitro differentiation of Mll +/+, +/-, and -/- yolk sac progenitor cells. Mll -/- colonies were fewer in number, took longer to develop, and contained fewer cells than their wild-type and heterozygous counterparts. Formation of colony-forming unit-granulocyte, erythroid, macrophage, megakaryocyte (CFU-GEMM), colony-forming unit-macrophage (CFU-M), and burst-forming unit-erythroid (BFU-E) was markedly decreased in Mll -/- cultures, while numbers of colony-forming unit-erythroid (CFU-E), colony-forming unit-granulocyte (CFU-G), and colony-forming unit-granulocyte macrophage (CFU-GM) were essentially unaffected. Despite the decreased numbers of colonies present, Mll -/- cultures showed all cell types without morphologic evidence of maturation arrest. These studies indicate that Mll is required for normal numbers of hematopoietic progenitors and their proper differentiation, especially along the myeloid and macrophage pathways.

Animals↗

Free amino acids reflect impact of selenite-dependent stress on primary metabolism in rat lens.

PURPOSE: A decrease in phase separation temperature, prior to nuclear cataract, has been correlated with elevated free amino acid content. Hence, we determined how selenite-induced stress alters free amino acid pools in the rat lens, following a single subcutaneous dose of sodium selenite (30 nmol g-1 body weight) in 10- to 14-day-old Sprague Dawley rats. RESULT: Oxidative stress was evident in lenses 24 h after rats were treated with selenite. Glutathione content was decreased by 60% in the lens cortex and nucleus; the flux of glucose through the pentose phosphate pathway was increased; and glycerol-3-phosphate content was elevated. Amino acid transport, evaluated as 14C-cycloleucine uptake, was not altered, although 14C-glutamine was oxidized at a slower rate. Lenses from treated animals displayed, among the free amino acids, increased glutamine, proline, serine, glycine and the branched chain amino acids, while aspartate, glutamate, and taurine were less. CONCLUSIONS: A systemic delivery of sodium selenite caused oxidative stress in the rat lens. Direct effects on primary metabolism altered free amino acid pools that may contribute to transient and permanent changes in lens transparency.

Amino Acids↗

Malignant hematopoietic breast tumors.

Hematopoietic neoplasms involving the breast, although less common than breast carcinoma, are often clinically indistinguishable from other breast tumors. Microscopically, these tumors can mimic primary carcinoma of the breast, especially in limited material such as needle biopsy specimens. Forty-five hematopoietic breast neoplasms including 21 primary non-Hodgkin's lymphomas (NHLs), 19 secondary NHLs, 1 undetermined NHL, 1 lesion secondary to Hodgkin's disease, and 3 granulocytic sarcomas were reviewed with regard to histologic subtype, morphologic features, and immunophenotype. The median age of patients at presentation was 67 years for those with primary NHLs and 61 years for those with secondary NHLs. The majority of lymphomas were intermediate or high grade. Diffuse large cell type was by far the most common histologic subtype. No lymphomas resembling lymphomas of mucosa-associated lymphoid tissue were identified in this series, suggesting that such lymphomas are rare in breast compared with other sites such as the gastrointestinal tract and lung. Four primary NHLs, 2 secondary NHLs, and 1 granulocytic sarcoma were initially misdiagnosed as carcinomas; three patients underwent radical mastectomy, and at least three other patients nearly received surgical treatment. One primary anaplastic large cell lymphoma of B-cell origin was identified that closely resembled poorly differentiated ductal carcinoma. "Single file" or targetoid patterns with extensive sclerosis mimicking invasive lobular carcinoma was common in lymphomas and was seen in one of the granulocytic sarcomas. In addition, two breast lymphomas, one of B-cell phenotype and the other of T-cell phenotype, showed frequent signet ring cells, which potentially could be confused with lobular carcinoma. Despite a number of recent articles on lymphomas of the breast, it appears that these tumors continue to be confused with carcinomas. Histologic features suggestive of lymphomatous involvement include absence of in situ carcinoma, frequent individual karyorrhectic cells, lymphoepithelial lesions, and cellular discohesiveness.

Adult↗

Juvenile chronic myelogenous leukemia.

Juvenile chronic myelogenous leukemia (JCML) is an aggressive myeloproliferative disorder of childhood that differs both clinically and pathologically from adult type, Philadelphia chromosome positive chronic myelogenous leukemia, and from the other myeloproliferative disorders that are more common in adulthood. The disease can have widely varying clinical presentations and shares many features with the monosomy 7 syndrome and chronic myelomonocytic leukemia. With no specific marker chromosome, establishing the diagnosis can be difficult, and relies on a constellation of clinical, pathologic, and laboratory findings. This article discusses the differential diagnosis of JCML with an emphasis on the pathologic findings and laboratory data that are particularly important for confirming the diagnosis. The sensitivity, specificity, and clinical utility of cell culture colony assays are reviewed. Finally, current knowledge of the biology of JCML and some of the controversies regarding this disease are discussed.

Biopsy, Needle↗

Precataractous changes affect lens transparency in the selenite cataract.

Selenite treatment of the preweanling rat stabilized the transparency of the lens nucleus to decreasing temperature. Hence, we compared properties of the cortex and nucleus from lenses of selenite-treated and age-matched control rats. A subcutaneous dose of 30 nmol Na2SeO3/g body weight was administered to 10- to 13-day-old Sprague-Dawley rats. Uninjected, age-matched littermates served as controls. As required, lenses were frozen in liquid N2 and separated into nuclear and cortical-epithelial fractions. Transparency of solutions of lens proteins (90-100 mg per ml) was monitored from 30 to 2 degrees C as percent transmittance (%T) at 490 nm. The critical phase separation temperature, Tc, was the temperature at 80%T. Protein associations were monitored with gel filtration chromatography. The nuclear 'cold cataract', in intact lenses, formed at similar temperatures at 14 and 15 days of age, but at a significantly lower temperature when the lenses were from a selenite-treated rat. The Tc, however, was greater by 1.5-2 degrees C for solutions of proteins isolated from whole lenses or lens nuclei from rats 24 and 48 h after treatment with selenite. Further, less gamma-crystallin was associated with the alpha-crystallin fraction in extracts from the nucleus of lenses from treated rats. Altered phase separation properties occurred as an early event in the etiology of selenite cataract. The different in vivo and in vitro responses to temperature indicated that properties of lens crystallins do not solely establish transparency in the intact lens.

Animals↗

Blastic transformation of mantle cell lymphoma.

In contrast to chronic lymphocytic lymphoma and low-grade follicular lymphomas, mantle cell lymphoma, formerly known as intermediate lymphocytic lymphoma, rarely transforms histologically into large cell lymphoma. Because of its rarity, little information is available on the prognostic or therapeutic implications of histologic transformation of mantle cell lymphoma to a "blastic" form. Here we report a case of a 68-year-old man whose mantle cell lymphoma transformed into a high-grade lymphoma with blastic cytology, which was associated with an extremely rapid clinical course. Flow cytometric analysis revealed the immunophenotype of the original lymphoma, which had typical mantle cell morphology, and the subsequent bone marrow aspirate was virtually identical, as was the immunophenotype of the small cells versus the blastic cells in the subsequent specimen. The rapid clinical course in the patient reported here is similar to that of other rare cases reported and suggests that mantle cell lymphoma in blastic transformation appears to be a very aggressive lymphoma with a clinical course similar to that of other low-grade lymphomas in histologic transformation.

Aged↗

Altered Hox expression and segmental identity in Mll-mutant mice.

The mixed-lineage leukaemia gene (MLL/HRX/ALL-1) is disrupted by chromosomal translocation in human acute leukaemias that often display mixed lymphoid-myeloid phenotypes and present in infancy. MLL possesses a highly conserved SET domain also found in Drosophila trithorax (trx) and Polycomb group (Pc-G) genes, which are known to regulate homeotic genes (HOM-C) in a positive or negative fashion, respectively. Mll was targeted in mice by homologous recombination in embryonic stem (ES) cells to assess its role in pattern development. Mll heterozygous (+/-) mice had retarded growth, displayed haematopoietic abnormalities, and demonstrated bidirectional homeotic transformations of the axial skeleton as well as sternal malformations. Mll deficiency (-/-) was embryonic lethal. Anterior boundaries of Hoxa-7 and Hoxc-9 expression were shifted posteriorly in Mll +/- embryos, but their expression was abolished in Mll -/- embryos. Thus Mll is required for proper segment identity in mammals, displays haplo-insufficiency, and positively regulates Hox gene expression.

Animals↗

Peripheral T-cell lymphoma in lckpr-bcl-2 transgenic mice.

t(14;18) is the most common translocation in human lymphoid malignancy and results in bcl-2 overexpression. Bcl-2 blocks apoptosis and constitutes the initial member of a new category of oncogenes, ie, regulators of cell death. Bcl-2-Ig transgenic mice develop follicular hyperplasia and progress to malignant B-cell lymphoma. To assess the oncogenic potential of bcl-2 in the T-cell lineage, a cohort of 68 lckpr-bcl-2 transgenic mice and 56 control littermates were monitored for signs of malignancy over a 24-month period. Eighteen (26%) lckpr-bcl-2 mice developed diffuse, predominantly large-cell lymphomas at a mean age of 18 months. In contrast, only one nontransgenic control mouse developed lymphoma. CD3 surface expression and clonal T-cell receptor beta rearrangements support the T-lineage classification of these neoplasms. lckpr-bcl-2-enforced lymphomas are predominantly CD4+CD8-, consistent with a mature peripheral T-cell phenotype. These data provide support for the thesis that violation of homeostasis through the repression of cell death can be a primary mechanism of tumorigenesis in multiple lineages.

Animals↗

Cutaneous presentation of juvenile chronic myelogenous leukemia: a diagnostic and therapeutic dilemma.

Annular, erythematous, circinate plaques were the first manifestation of juvenile chronic myelogenous leukemia (JCML) in an otherwise healthy 2.5-year-old boy who had had these lesions since 6 months of age. The lesions showed an atypical hematopoietic infiltrate on biopsy. Biopsy of a bone marrow specimen and peripheral blood smear were normal six months before leukemic transformation. At 3 years of age the boy developed splenomegaly, thrombocytopenia, and petechiae, and a bone marrow aspirate and cell marker studies were regarded as consistent with, if not diagnostic of, JCML. Four previous cases of cutaneous leukemic infiltrate associated with JCML have been published. Our patient had recurring urticarial-like plaques for two years before the initial bone marrow finding of JCML. Given the poor prognosis and progressively evolving course of JCML, it may be appropriate to consider therapy before bone marrow changes, based on the presence of the cutaneous eruption with the appropriate findings on skin biopsy and an elevated fetal hemoglobin.

Child, Preschool↗

Causes of decreased phase transition temperature in selenite cataract model.

PURPOSE: Lenses from selenite-treated animals develop reversible "cold cataract" at a lower temperature than is required for lenses from age-matched control animals. This unexplained, stabilized phase transition is readily observed in intact lenses 36 to 48 hours after treatment and occurs in lenses before the appearance of the irreversible nuclear opacity observed 72 to 96 hours after treatment. The objective of this study was to investigate factors that may be responsible for this difference. METHODS: Preweanling rats were injected with sodium selenite. Lens extracellular water volume was measured using 14C-inulin. Free amino acids were analyzed using precolumn derivatization and high performance liquid chromatography. Soluble protein was isolated from lenses of control, and treated animals and temperature-dependent changes in light scattering were measured at 490 nm. RESULTS: Lens extracellular water was increased by the selenite treatment, with a concurrent 10% decrease in intracellular volume. Solutions of soluble protein from lenses of selenite-treated animals after postinjection hours 24 and 48 had higher critical phase transition temperatures (Tc) compared to similar proteins from control lenses. From 24 to 72 hours after injection, the free amino acid content of the lens increased 42%. Taurine levels were unchanged over the same period. The addition of 7 mM glycine and 7 mM proline to solutions of soluble protein (96 mg ml-1) decreased the phase transition temperature. Taurine (14 mM) had a similar effect. Combining taurine and the glycine plus proline solutions had an additive effect in lowering the Tc. CONCLUSIONS: Increases in free amino acid concentration occur in lenses in response to the stress imposed by a systemic dose of selenite. The altered polyion content in lenses from selenite-treated animals, before nuclear cataract formation, contributes to the greater thermal stability of transparency in these lenses, thus lowering the temperature at which "cold cataract" forms.

Amino Acids↗

Histopathologic grading of nodular sclerosis Hodgkin's disease. Lack of prognostic significance in 254 surgically staged patients.

BACKGROUND: The cellular composition of nodular sclerosis Hodgkin's disease (NS-HD) varies greatly from patient to patient. It is unclear whether subclassifying NS-HD based on cellular composition has prognostic value, because reported studies examining this issue have shown conflicting results. METHODS: The initial pathology slides of 254 surgically staged patients with NS-HD treated at the Joint Center for Radiation Therapy were reviewed and subclassified according to British National Lymphoma Investigation criteria. The median follow-up time was 123 months. RESULTS: A total of 211 patients were classified NS I histology (83%), and 43 patients were classified NS II (17%). There were no differences in the distribution of NS I/NS II patients by age, number of sites of disease, B symptoms, or extent of mediastinal disease. Patients with NS II disease were more likely to be male (P = 0.001), and to have pathologic Stage I-II disease (P = 0.07). The 15-year actuarial rates of disease-free survival were 77 and 80% for NS I and NS II patients, respectively (P = not significant). The 15-year overall survival rates were 87 and 93% for NS I and NS II, respectively (P = not significant). No differences were seen between NS I and NS II patients for overall or disease free survival when analyzed separately by pathologic stage or by initial treatment. Similarly, no differences between NS I and NS II patients were seen in the large subgroup of 155 pathologic stage IA-IIA patients treated with radiation therapy alone. When other histologic parameters were analyzed separately, no differences were seen in the frequency of relapse between the groups based on extent of necrosis, atypia, fibrosis, variant atypia, variant syncytia, eosinophilia, or number of mitoses. CONCLUSIONS: The histologic subclassification of Hodgkin's disease had no prognostic significance in this group of surgically staged, uniformly treated patients.

Adolescent↗

Photosynthetic inhibition and superoxide dismutase activity in soybean cultivars exposed to short-term ozone fumigations.

Net photosynthesis (Pn) and mean stomatal conductance (gs) of soybean (Glycine max (M.) L.) cvs 'Dare', 'Essex' and 'Williams 82' were inhibited by exposure to 200 nliters liter(-1) ozone (O(3)) for 4 h. Changes in gas exchange rates were not uniform over time, and a near steady state condition was attained after fumigation for 2 h. There was no recovery of Pn or gs for up to 2 h following termination of O(3) application. The cv 'Dare' was considered most sensitive to O(3) since, in this cultivar, gs was least responsive during the initial 2.5 h of fumigation and the estimated internal O(3) flux was about 10% greater than in the other cultivars. Polyacrylamide gel electrophoresis of soybean leaf extracts, followed by activity staining for superoxide dismutase (SOD), revealed the presence of numerous major and minor bands. Cynide sensitivity of several isoforms indicated the presence of both Cu-Zn and Mn SODs. In cv 'Essex', each metalloform accounted for 50% of the total SOD activity. No qualitative differences in SOD banding patterns were evident among the three soybean cultivars before or after O(3) treatment. Ozone fumigation for 4 h did not significantly alter SOD activity in any cultivar. The contribution of gs, as a flux limitation, and SOD activity are discussed as tolerance mechanisms to O(3) in soybean.

Journal Article↗

Intermediate lymphocytic lymphoma: clinical and pathologic features of a recently characterized subtype of non-Hodgkin's lymphoma.

PURPOSE: We present a comprehensive review of clinical, pathologic, molecular, and prognostic features and therapy of intermediate lymphocytic (mantle cell) lymphoma (ILL/MCL), a recently characterized subtype that represents 2% to 8% of non-Hodgkin's lymphomas (NHLs), but which has not been included in most classification schemes, including the International Working Formulation. DESIGN: The English-language literature encompassing the above aspects, published between 1977 and 1992, is critically reviewed. RESULTS AND CONCLUSION: ILL/MCL is a disease of proliferating B lymphocytes that is characterized by generalized lymphadenopathy and frequent, often extensive, involvement of the spleen, bone marrow, and gastrointestinal tract. The malignant cells usually express the markers CD5 and IgM with or without IgD, but not CD10, on the cell surface, and grow in one of two dominant histologic patterns: mantle zone and diffuse. The characteristic cytogenetic abnormality is a t(11;14)(q13;q32) translocation, which juxtaposes the bcl-1 locus on chromosome 11 with the immunoglobulin (Ig) heavy-chain locus on chromosome 14, and appears to result in dysregulated expression of the gene encoding cyclin D1. Median survival is in the range of 2 to 5 years. While responses to chemotherapy may be seen in up to half the patients, relapses are the rule, and longterm survival is uncommon. The optimal treatment remains undefined, although therapy may be deferred until there are symptoms or complications, at which time judicious administration of alkylating agents and glucocorticoids may result in effective palliation.

Humans↗

Selenite and Ca2+ homeostasis in the rat lens: effect on Ca-ATPase and passive Ca2+ transport.

Calcium permeability was significantly increased in lenses from rats 36 h following a single injection of a cataractogenic dose of sodium selenite (30 nmol/g body weight) and this permeability returned to control values by 72 h post-injection (PI). The greater Ca2+ permeability could be partially reversed by incubating lenses in medium containing 2 mM dithiothreitol (DTT). Estimations of Ca-ATPase activity revealed the greatest level occurred in the epithelial layer and that the nucleus had no detectable activity. By 48 h PI both Ca(2+)-pump activity and the Ca(2+)-dependent ATP hydrolytic activity were less compared to controls in membrane preparations from rat lenses. Only the hydrolytic activity could be partially restored by treatment with 5 mM DTT. Both permeability and active Ca2+ transport were affected by selenite in a manner that would lead to increased Ca2+ accumulation in lenses from rats treated with selenite. It is suggested that the oxidative damage that accompanies in vivo exposure to selenite could affect Ca2+ homeostasis in the lens by directly altering permeability and Ca-ATPase.

Animals↗

Lens GSH depletion and electrolyte changes preceding cataracts induced by buthionine sulfoximine in suckling mice.

Cataracts were induced in suckling mice by multiple injections of L-buthionine-S,R-sulfoximine (BSO), a specific inhibitor of GSH biosynthesis, starting on post-natal day 7. The earliest visible lens aberrations began approximately 2 days after t(o), following 99% depletion of lens GSH. Cataract development then proceeded through four stages within less than 24 hr. Elevated Na+ and Ca+ and decreased K+ were first detected in pre-cataractous (stage 0) lenses. During stage 0, lens Na+ and K+ levels displayed a significant inverse correlation; by contrast, Ca2+ levels were poorly correlated with those of Na+. The initial increase in Na+ exceeded the decrease in K+. This suggested the presence of osmotic stress prior to cataract stage 1 (developing floriform). Increased lens hydration was first apparent in stage 1, coincident with a marked elevation of Ca2+, further increase in Na+ and decrease in K+. These trends persisted in the stage 2 cataract (completed floriform). Subsequent changes in lens hydration and cation content during cataract stages 3 (degenerate floriform) and 4 (amorphous translucent) suggested substantial influx of extracellular fluid into the affected lenses. The BSO cataract may represent a useful in vivo model to study the functions of GSH in maintaining normal lens cation balance and transparency.

Animals↗

Biochemical changes and cataract formation in lenses from rats receiving multiple, low doses of sodium selenite.

Nuclear cataract formed in rat lens in response to a protocol of multiple, low doses of sodium selenite. Nuclear cataract occurred, in both Wistar and Sprague-Dawley rats, following five subcutaneous injections of selenite over an 8-day period with an accumulated dose of 40-50 nmol selenite g-1 body weight. Glutathione content decreased within the first 24 hr of treatment and remained at 60% of controls. Lipid peroxidation occurred in Wistar rats prior to nuclear cataract formation. A two to three-fold increase in calcium concentration and decreased protein content accompanied nuclear cataract development. Enzyme activities were measured for glutathione peroxidase, glutathione reductase, and glutathione S-transferase, and only the peroxidase activity remained constant through the period of cataract formation. This protocol resulted in nuclear cataracts similar in appearance to those observed with a single, acute dose of selenite. The opportunity to control the rate of selenite-dependent cataract formation allows further definition of precataractous events.

Animals↗

Purification of Multiple Forms of Glutathione Reductase from Pea (Pisum sativum L.) Seedlings and Enzyme Levels in Ozone-Fumigated Pea Leaves.

Glutathione reductase was purified from pea seedlings using a procedure that included 2',5'-ADP Sepharose, fast protein liquid chromatography (FPLC)-anion exchange, and FPLC-hydrophobic interaction chromatography. The purified glutathione reductase was resolved into six isoforms by chromatofocusing. The isoform eluting with an isoelectric point of 4.9 accounted for 18% of the total activity. The five isoforms with isoelectric points between 4.1 and 4.8 accounted for 82% of the activity. Purified glutathione reductase from isolated, intact chloroplasts also resolved into six isoforms after chromatofocusing. The isoform eluting at pH 4.9 constituted a minor fraction of the total activity. By comparing the chromatofocusing profile of the seedling extract with that of the chloroplast extract, we inferred that the least acidic isoform was extraplastidic and that the five isoforms eluting from pH 4.1 to 4.8 were plastidic. Both the plastidic (five isoforms were pooled) and extraplastidic glutathione reductases had a native molecular mass of 114 kD. The plastidic glutathione reductase is a homodimer with a subunit molecular mass of 55 kD. Both glutathione reductases had optimum activity at pH 7.8. The K(m) for the oxidized form of glutathione (GSSG) was 56.0 and 33.8 mum for plastidic and extraplastidic glutathione reductase, respectively, at 25 degrees C. The K(m) for NADPH was 4.8 and 4.0 mum for plastidic and extraplastidic isoforms, respectively. Antiserum raised against the plastidic glutathione reductase recognized a 55-kD polypeptide from purified antigen on western blots. In addition to the 55-kD polypeptide, another 36-kD polypeptide appeared on western blots of leaf crude extracts and the purified extraplastidic isoform. The lower molecular mass polypeptide might represent GSSG-independent enzyme activity observed on activity-staining gels of crude extracts or a protein that has an epitope similar to that in glutathione reductase. Fumigation with 75 nL L(-1) ozone for 4 h on 2 consecutive days had no significant effect on glutathione reductase activity in peas (Pisum sativum L.). However, immunoblotting showed a greater level of glutathione reductase protein in extracts from ozone-fumigated plants compared with that in control plants at the time when the target concentration was first reached, approximately 40 min from the start of the fumigation, and 4 h on the first day of fumigation.

Journal Article↗

Seasonal variation in the antioxidant system of eastern white pine needles : evidence for thermal dependence.

Antioxidant metabolites in eastern white pine (Pinus strobus L.) needles increased two- to fourfold from the summer to the winter season. Antioxidant enzymes in needle tissue increased between 2- and 122-fold during this same period. These seasonal changes were determined by monitoring ascorbate and glutathione concentrations and the activity of ascorbate peroxidase, glutathione reductase (GR), and superoxide dismutase. Levels of antioxidant metabolites and enzymes were observed always to be lowest during the summer, or active growing season, and highest during the winter, or dormant season. These data correlated well with the thermal kinetic window for purified GR obtained from summer needles. The minimum, apparent K(m,NADPH) for two isoforms of GR (GR(A) and GR(B)) occurred at 5 and 10 degrees C, respectively. The upper limit of the thermal kinetic window (200% of the minimum K(m)) for GR(A) and GR(B) was 20 and 25 degrees C, respectively, indicating that needle temperatures exceeding 25 degrees C may result in impairment of antioxidant metabolism. The needle content and kinetic properties of GR, the increased activities of other enzymes, and the high substrate concentrations observed during the winter are consistent with the protective function this pathway may provide against photooxidative, winter injury.

Journal Article↗