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Biomedical subjects

J M Rowe

Publications and source records attributed to J M Rowe.

At least 145 records · Page 8Linked to original sources

Variability of the erythropoietic response in autoimmune hemolytic anemia: analysis of 109 cases.

One hundred-nine cases of autoimmune hemolysis were reviewed to determine the frequency of reticulocytopenia, the state of the erythroid marrow in reticulocytopenic cases, and the course of reticulocyte production indices with time and glucocorticoid treatment. The mean hematocrit at presentation was 24 mL/dL, but 30% of cases had an initial hematocrit less than 20 mL/dL. Median reticulocyte percentage at diagnosis was 9%, and median reticulocyte production index was 2.8 times basal. Twenty percent of cases had an initial reticulocyte count less than 4%, and 37% had an initial reticulocyte production index less than 2.0 times basal. These reticulocytopenic patients were nearly evenly distributed between warm and cold antibody-mediated cases and between primary and secondary cases. Fifty-four percent of reticulocytopenic cases had a bone marrow examination during hospitalization. Three-fourths of these marrows showed erythroid hyperplasia, and erythroid hypoplasia was seen in only one case. Eighty-eight cases had serial reticulocyte measurements, and in only 15% of patients did the reticulocyte production index remain less than 2.0 times basal. Thus, in most cases, the initially low reticulocyte production index may represent a lag in marrow responsiveness to hemolytic stress. In cases with persistent reticulocytopenia, ineffective erythropoiesis is suggested by the frequency of marrow erythroid hyperplasia. In the cases that were initially reticulocytopenic and demonstrated an increase in reticulocyte production index, the magnitude of this increase was significantly greater in glucocorticoid-treated patients than in those not so treated, indicating that a glucocorticoid sensitive component exists in the marrow erythropoietic response to hemolysis. Awareness of the frequency of an initial reticulocytopenia in cases of autoimmune hemolysis may be important in initial diagnosis and treatment.

Anemia, Hemolytic, Autoimmune↗

Purification and characterization of a human pituitary growth factor.

A growth factor has been purified to homogeneity from human pituitary glands. The pituitary growth factor (PGF) is trypsin-sensitive and acid- and heat-labile and has a molecular weight of 18,000 and an isoelectric point of 7.5. PGF was purified by heparin and copper affinity chromatography followed by carboxymethylcellulose 52. The amino-terminal amino acid sequence of PGF was established as PALPEXGGXGA and is identical with that of basic fibroblast growth factor at the identified amino acid residues. PGF was mitogenic for rabbit fetal chondrocytes and bovine corneal endothelial cells in the range of 0.015-15 ng mL-1. Heparin alone at low concentrations (0.5 microgram mL-1) was found to be weakly mitogenic for rabbit fetal chondrocytes. In combination with PGF a marked increase in cell growth was observed, which was inhibited by protamine sulfate. These data demonstrate the presence of a potent mitogen in human pituitaries that is structurally related to basic fibroblast growth factor and synergizes with heparin to promote cell growth.

Animals↗

Translocation between chromosomes 1 and 9 in childhood acute lymphoblastic leukemia.

A case of a non-T, non-B acute lymphoblastic leukemia with a translocation between chromosomes #1 and #9 is described. The breakpoints in these chromosomes were determined to be at bands 1q23 and 9p22, respectively. The breakpoint in chromosome #1 was at the same site as that in a subgroup of acute lymphoblastic leukemia with t(1;19), and the breakpoint in #9 was the same as that in t(9;11)(p22;q23) in acute monoblastic leukemia. We discuss the possible association between these chromosome bands (1q23, 9p22, 11q23, and 19p13) and the morphologic features of the leukemic cells. The breakpoint in chromosome band 1q23 may be specifically associated with acute lymphoblastic leukemia.

Child↗

Secondary acute myeloblastic leukemia with a Ph translocation in a treated Wegener's granulomatosis.

Ph-positive acute myeloblastic leukemia (AML) developing in a treated case of Wegener's granulomatosis is reported. The patient was a 70-year-old white male who received cyclophosphamide (150 mg/day) starting in July 1978; in May 1984 the patient was diagnosed as having AML, following a diagnosis of myelodysplastic syndrome lasting 3 months. Cytogenetic study of bone marrow cells at the diagnosis of the myelodysplastic syndrome revealed a standard Ph translocation in addition to numerical chromosome changes [i.e., 45,XY, -5, -7, -8, +19, +mar/45,XY, -5, -7, -8, +19, +mar,t(9;22)(q34;q11]). The events in this case suggest a strong possibility of the Ph-positive AML being a secondary disease related to prior cyclophosphamide therapy.

Aged↗

Leukapheresis for control of chronic myelogenous leukemia during pregnancy.

Leukapheresis was used as the sole modality of treatment of a patient with chronic myelogenous leukemia (CML) during her pregnancy. The specific requirements for safe leukapheresis during pregnancy are discussed, and the literature describing the management of CML during pregnancy is reviewed. Leukapheresis may be the treatment of choice in selected pregnancy patients with CML since it avoids the potential teratogenic effects of chemotherapy or radiation therapy.

Adult↗

Purification and characterization of a human mammary tumor-derived growth factor.

A growth factor has been purified to homogeneity from human mammary tumors. The human mammary tumor-derived growth factor (h.MTGF) has a molecular weight of 16,000 and an isoelectric point of 8.0 and is sensitive to heat, trypsin digestion, acid, and reduction. h.MTGF was purified to homogeneity using carboxymethylcellulose 52, heparin-Sepharose, and copper-Sepharose affinity chromatography. The stimulation of proliferation in cultured rabbit fetal chondrocytes was used as the principal bioassay. Purified h.MTGF was also mitogenic for bovine corneal endothelial cells, human fibroblasts, and a human breast cancer cell line, T-47D. It is postulated that h.MTGF may play a role in the fibrovascular changes of malignant breast tumors and promote the autonomous growth of the neoplastic cell population.

Acids↗

Thrombotic thrombocytopenic purpura: recovery after splenectomy associated with persistence of abnormally large von Willebrand factor multimers.

A patient with thrombotic thrombocytopenic purpura (TTP) responded transiently to four courses of plasma exchange therapy, then subsequently had a sustained completed remission following splenectomy. The von Willebrand factor multimeric pattern during remission following each plasma exchange and during the entire postsplenectomy period showed abnormally large forms that were not present on presentation and with each clinical relapse. These findings support prior observations regarding the presence of abnormal von Willebrand factor multimers in relapsing TTP and suggest that the multimers contribute to platelet aggregation and the thrombotic lesions. The association of sustained remission and persistence of the abnormally large plasma multimers after splenectomy suggests that this response was not coincidental. This supports the concept that a subgroup of patients with TTP may exist in which the pathophysiology of disease is significantly modulated by the spleen and in which splenectomy may induce long-lasting remission.

Blood Coagulation Factors↗

Successful thrombolytic therapy in two patients with renal vein thrombosis.

Thrombolytic therapy was administered to two patients with angiographically documented renal vein thrombosis. One patient with bilateral thrombotic disease complicating membranous glomerulonephritis was treated with systemic streptokinase; the second patient had unilateral renal vein thrombosis associated with chronic pyelonephritis and was treated with streptokinase and urokinase administered directly into the involved vessel. Lysis of all thrombus material was demonstrated by follow-up renal venography and was associated with a gratifying improvement of clinical well-being and laboratory function. These cases demonstrate the feasibility of dissolving renal vein thrombi of presumed recent onset and suggest that rapid lysis of the thrombus accelerates functional and clinical recovery.

Drug Therapy, Combination↗

Hyperleukocytosis and leukostasis: common features of childhood chronic myelogenous leukemia.

Ten patients under 20 yr of age with the usual (adult) type of chronic myelogenous leukemia (CML) were seen at the University of Rochester Medical Center from 1970 to 1982. The mean white cell count in these 10 patients at presentation was 360,000/microliter, as compared to a mean of 137,000/microliter in 80 CML patients over 20 yr of age seen during the same time interval (p less than 0.02). Analyses of all 90 cases revealed a significant decrease in the average leukocyte count at presentation with increasing age. The childhood cases also had a significantly higher proportion of blood blasts, promyelocytes, and myelocytes than did the adult subjects (p less than 0.01). Signs of leukostasis were present in 12% of adult cases as compared to 60% of the 10 childhood cases, and in these 6 subjects, the mean white cell count was 510,000/microliter. In these 6 patients, leukapheresis and/or chemical therapy was initiated rapidly, and this was followed by complete resolution of the clinical signs of leukostasis. A review of the literature from 1960 to 1982 identified 61 childhood cases that were reported with the usual type of CML. In this group, the frequency of hyperleukocytosis and the distribution of white cell counts corresponded very closely to the 10 cases studied at the University of Rochester. Thus, the usual type of CML presenting in childhood differs from that of adults in that hyperleukocytosis, blood granulocyte immaturity, and leukostatic central nervous system, retinal, and respiratory signs are significantly more common and extreme and merit rapid cytoreductive treatment.

Adolescent↗

Clinical and laboratory features of the myeloid and lymphocytic leukemias.

This paper reviews the pertinent presenting features (clinical and laboratory) in the myeloid and lymphocytic leukemias, with emphasis on findings in the blood smear. Cell counts and their diagnostic significance are discussed. Data reported are derived from a study of patients seen at the University of Rochester Medical Center between 1970 and 1982.

Adolescent↗

Chondrocyte growth factor from the human pituitary gland.

Extracts of frozen human pituitaries were mitogenic in a fetal rabbit chondrocyte bioassay. In the presence of 10% fetal bovine serum, a 10-fold increase in chondrocyte cell number was observed upon addition of the pituitary factor to the culture medium. After gel filtration, the chondrocyte growth factor eluted with proteins of approximately 40,000 molecular weight. These fractions were pooled and purified further upon ion exchange chromatography using DEAE-cellulose. The most active fraction stimulated cell proliferation in a dose-dependent manner down to 10 ng/ml. The chondrocyte growth factor was trypsin- and heat-sensitive (100 degrees C, 10-15 min). Its isoelectric point (pI 7.9) was different from bovine brain and pituitary fibroblast growth factor (pI 4.8-5.8 and pI 9.5, respectively. Unlike the somatomedins and epidermal growth factor, it was acid-labile. Preparations of human growth hormone, prolactin, luteinizing hormone, and follicle-stimulating hormone, prolactin, luteinizing hormone, and follicle-stimulating hormone, as well as vasopressin and oxytocin, were inactive in the bioassay, demonstrating that the human pituitary contains a chondrocyte growth factor which appears to be distinct from these anterior and posterior pituitary hormones.

Animals↗

Hyperleukocytic leukemias: rheological, clinical, and therapeutic considerations.

A small proportion of patients with acute or chronic leukemia has an extraordinarily high blood leukocyte count. These high counts can result in a very high fractional volume of leukocytes (leukocrit), which is also a function of the mean leukocyte volume in different types of leukemia. Despite a high fractional volume of leukocytes, bulk viscosity of blood is usually not increased because a decrement in the fractional volume of erythrocytes accompanies the increase in leukocytes. Nevertheless, the excessive numbers of leukocytes present two major problems: first, they can seriously affect flow in the circulation of the lung, brain, and less often, other organs by obstructing microchannels or by forming aggregates and white thrombi in small veins. Moreover, leukemic blasts may compete for oxygen in the microcirculation and they may be invasive, damaging vessel walls. Second, their rapid destruction in response to cytotoxic drugs causes metabolic disturbances, especially uric acid accumulation, which can lead to obstructive uropathy.

Adolescent↗

The characterization of growth factor activity in human brain.

The purification of fibroblast growth factor from bovine brain has been reported (Gospodarowicz, D., Bialecki, H., and Greenberg, G. (1978) J. Biol. Chem. 253, 3736-3743). Westall et al. (Westall, F. C., Lennon, V. A., and Gospodarowicz, D. (1978) Proc. Natl. Acad. Sci. U. S. A. 75, 4675-4678) showed that bovine brain fibroblast growth factor was composed of three fragments derived by limited proteolysis from myelin basic protein. In the present study using similar purification methods, we isolated a fraction enriched in growth factor activity from human brain. The mitogenic activity could not be resolved from myelin basic protein by chromatographic procedures but, upon isoelectric focusing, the mitogen and myelin basic protein were readily dissociated. At least two potent growth factors (pI values 7.2 to 7.4 and 8.1 to 8.6) were identified. Studies of a relatively crude basic extract of human brain suggested that the brain may contain a number of growth factors.

Brain Chemistry↗

Attachment of particle-bound IgG and complement to human neutrophils.

The attachment of particle-bound IgG in a nonphagocytic system stimulates formation of a microfilament-rich, organelle-poor zone in the subjacent cytoplasm of human neutrophils. The attachment site is characterized by ruffling and invagination of the neutrophil membrane. Both IgG attachment and formation of the organelle-poor zone are inhibited by the microfilament inhibitor cytochalasin-B, but not by inhibitors of microtubules, such as colchicine or vinca alkaloids. In contrast, attachment of particle-bound complement is not inhibited by cytochalasin-B in doses known to disrupt actin filaments. There is no discernable change in the subjacent cytoplasm of the neutrophil in response to complement and the membrane attachment site is smooth, without ruffling or invagination. These studies disclose that both IgG-mediated attachment to neutrophils and its sequel, peripheral cytoplasmic reorganization, are mediated by cytochalasin-sensitive structures, possibly actin. Complement-mediated attachment to neutrophils is insensitive to high doses of cytochalasin, suggesting that actin integrity is not required.

Animals↗