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Biomedical subjects

J L Wolf

Publications and source records attributed to J L Wolf.

At least 37 records · Page 2Linked to original sources
PubMed1990

Intraluminal proteolytic activation plays an important role in replication of type 1 reovirus in the intestines of neonatal mice.

Oral inoculation of suckling mice with reovirus serotype 1 (strain Lang) results in the conversion of intact virions to intermediate subviral particles (ISVPs) in the intestinal lumen. Digestion of virus in vitro with chymotrypsin or trypsin reveals two distinct forms of ISVPs, while the predominant species of ISVPs found in the small intestinal lumen appears to be identical to the chymotrypsin product. The in vivo conversion of virions to ISVPs was blocked by pretreatment of mice with protease inhibitors, resulting in inefficient replication of reovirus in intestinal tissue. The early inhibition of viral replication in suckling mice pretreated with protease inhibitors was not observed when suckling mice were inoculated with ISVPs generated by in vitro digestion with either chymotrypsin or trypsin. However, replication was decreased during secondary rounds of replication in mice receiving repeated doses of protease inhibitors, suggesting that luminal proteolytic digestion is important in rendering progeny virions infectious in the gut.

Animals↗
PubMed1990

Pharmacologic characterization of the rabbit neutrophil receptor for platelet-activating factor.

The characteristics of receptors for platelet-activating factor (PAF) on rabbit neutrophils are investigated in this report. The presence of PAF-specific binding to rabbit neutrophils was confirmed using radiolabeled ligand binding assays and a rabbit peritoneal neutrophil membrane preparation. Binding of PAF to the neutrophil membranes was reversible and reached equilibrium within 30 min. Scatchard analysis of PAF-specific binding to the rabbit neutrophil membranes revealed a dissociation constant (Kd) for PAF of 0.41 +/- 0.045 nM and a Bmax of 0.32 +/- 0.11 pmol of PAF receptor/mg of protein. The order of potencies of PAF receptor antagonists to inhibit the binding of 3H-PAF to rabbit peritoneal neutrophil membranes was determined. For the competition assays, 100 micrograms of neutrophil or platelet membrane protein, 0.18 nM 3H-PAF, and varying amounts of PAF antagonist were incubated at room temperature for 1 hr. PAF receptor antagonists tested were ONO-6240, brotizolam, kadsurenone, WEB-2086, L-652-731, BN-52021, CV-3988, triazolam, alprazolam, and verapamil. The orders of potencies of these PAF receptor antagonists were similar for inhibition of 3H-PAF binding to rabbit peritoneal neutrophil and platelet membranes (correlation coefficient, r = 0.97). PAF had a significantly higher affinity for rabbit neutrophil membranes (Kd = 0.41 +/- 0.045 nM), as compared with its affinity for rabbit platelet membranes (Kd = 0.87 +/- 0.092 nM). In addition, sodium was found to inhibit 3H-PAF specific binding to rabbit platelet membranes and not to affect 3H-PAF binding to neutrophil membranes. These data indicate that, although PAF receptors on rabbit platelets and neutrophils exhibit similar orders of potencies of PAF receptor antagonists to inhibit the binding of 3H-PAF, the disparity in Kd of PAF for the receptors and the effect of NaCl on the binding of 3H-PAF reveal subtle differences between the cell types.

Animals↗
PubMed1988

Deficiency of protein 4.2 in erythrocytes from a patient with a Coombs negative hemolytic anemia. Evidence for a role of protein 4.2 in stabilizing ankyrin on the membrane.

A patient with a mild hemolytic anemia and osmotically fragile, spherocytic erythrocytes was studied. Analysis of the erythrocyte membrane proteins by SDS-PAGE revealed a deficiency of protein 4.2 (less than 0.10% of normal). The protein 4.2-deficient erythrocytes contained normal amounts of all other membrane proteins, although the amount of band 3 was slightly reduced and the amount of band 6 (G3PD) was slightly elevated. The spectrin content of these cells was normal, as measured by both SDS-PAGE and radioimmunoassay. Erythrocytes from the patient's biologic parents were hematologically normal and contained normal amounts of protein 4.2. Immunological analysis using affinity purified antibodies revealed that the patient's protein 4.2 was composed of equal amounts of a 74-kD and 72-kD protein doublet, whereas the normal protein was composed primarily of a 72-kD monomer. Proteolytic digestion studies using trypsin, alpha-chymotrypsin and papain demonstrated that the patient's protein 4.2 was similar but not identical to the normal protein. Binding studies showed that the protein 4.2-deficient membranes bound purified protein 4.2 to the same extent as normal membranes, suggesting that the membrane binding site(s) for the protein were normal. Depleting the protein 4.2-deficient membranes of spectrin and actin resulted in a loss of nearly two-thirds of the membrane ankyrin, whereas similar depletion of normal membranes resulted in no loss of ankyrin. Repletion of the protein 4.2-deficient membranes with purified protein 4.2 before spectrin-actin extraction partially prevented the loss of ankyrin. These results suggest that protein 4.2 may function to stabilize ankyrin on the erythrocyte membrane.

Adult↗
PubMed1988

Reovirus type I infection of small intestinal epithelium in suckling mice and its effect on M cells.

In 10-day-old mice, reovirus serotype I (reo I) selectively adheres to the apical surface of M cells and penetrates the intestinal epithelium via M cells overlying Peyer's patches before causing disseminated infection. Recently, reo I enteritis has been described in adult mice. We wished to determine if reo I enteritis also occurs in suckling mice and, if so, to determine which major epithelial cell types become infected and where the virus enters epithelial cells other than M cells. Transmission electron microscopy revealed that after oral inoculation of 10-day-old mice, peak infection of M cells preceded that of absorptive and undifferentiated crypt cells. The percentage of M cells in the dome epithelial cell population was reduced more than 4-fold between 4 and 72 hours after reo I inoculation compared with saline-inoculated mice. By 6 days after inoculation, reo I replication was no longer observed and there was a more than 2-fold increase in M cells overlying Peyer's patches domes of reo I-inoculated mice compared with saline controls. By 13 days, control and infected mice had similar percentages of M cells. When incubated with isolated intestinal epithelial sheets, reo I adhered selectively to and was endocytosed via the basal plasma membrane of absorptive cells. Thus, reo I initially penetrates the intestinal epithelium via the apical surface of M cells which become infected. Virions subsequently enter absorptive and crypt cells via their basal surfaces. During the first 3 days of enteritis, the M cell population becomes markedly depleted which may affect the permeability of the mucosal barrier to microorganisms and other antigens as well as influence the host immune response.

Animals↗
PubMed1987

Adherence to and penetration of the intestinal epithelium by reovirus type 1 in neonatal mice.

In 10-day-old suckling and adult mice, reovirus type 1 adheres selectively to and penetrates membranous epithelial (M) cells. To determine when M cells first appear, when they first transport reovirus, and if reovirus adheres to and is endocytosed by other epithelial cells in the first postnatal week, we examined neonatal mouse intestine by transmission electron microscopy after reovirus type 1 exposure. At 2 days M cells accounted for 0.9% of dome epithelial cells. By 9 days M cells had increased to 7.4%. Reovirus type 1 adherence to the surface of villus and dome epithelial cells showed marked variation in 2-6-day-old animals, but by 7 days only a few absorptive cell profiles had adherent reovirus. Adherence to greater than 50% of M-cell profiles occurred in all but 2 animals, but adherence to the majority of Peyer's patch absorptive cell profiles was present only in some 4- and 5-day-old animals. Adherence to a majority of undifferentiated cell profiles occurred in some animals at all ages. Membranous epithelial cells endocytosed reovirus at all ages but only at 2 days did rare villus and dome absorptive cells endocytose reovirus into the apical cytoplasm. Thus, adherence of reovirus to the apical surface of mucosal epithelial cells is nonselective in newborn mice but becomes more selective within the first postnatal week with adherence by day 7 to most M-cell profiles, to a substantial but variable number of undifferentiated cell profiles, but to few absorptive cell profiles.

Animals↗
PubMed1984

Outcome of bone marrow transplantation in patients with extramedullary involvement of acute leukemia.

Infiltration of extrahemopoietic tissue with leukemic cells was evaluated as a prognostic indicator in 18 patients with acute leukemia undergoing bone marrow transplantation. When compared to 107 patients who did not have extramedullary leukemia at any time prior to marrow grafting, the patients with leukemic invasion into organs outside the hemopoietic system had a significant increase of leukemic recurrence and a significant decrease in survival after marrow transplantation. Extramedullary leukemia may be a negative prognostic indicator for bone marrow transplantation candidates.

Acute Disease↗
PubMed1984

The membranous epithelial (M) cell and the mucosal immune system.

Membranous epithelial (M) cells are specialized epithelial cells overlying the subepithelial lymphoid follicles in the gastrointestinal and respiratory tracts. Antigens, including some viruses and bacteria, penetrate the mucosal barrier via the M cell, which endocytoses and transports antigens and microorganisms into the Peyer's patch or bronchial-associated lymphoid tissue. Here antigens may initiate an immune response and/or disseminate and induce disease. This review discusses the structure and function of the M cell, its role in macromolecular uptake, and its interaction with the immune system.

Animals↗
PubMed1983

The sigma 1 protein determines the extent of spread of reovirus from the gastrointestinal tract of mice.

After intragastric inoculation of adult mice, type 1 reovirus was initially concentrated in Peyer's patches over the first 4 hr after inoculation, then spread sequentially to the mesenteric lymph nodes and spleen. For type 3 reovirus, however, initial entry into Peyer's patches in adult mice was followed by loss of viral infectivity so that by 4 hr after inoculation virtually no infectious virus was detected in the intestine, and spread to extraintestinal tissues did not occur. In 10-day-old mice, type 3 was capable of spread to the mesenteric lymph nodes but not the spleen. Thus, as animals aged there was a greater restriction of the spread of type 3 from the intestine. Studies using a field isolate of type 3 reovirus that is resistant to intestinal proteases, and genetic studies utilizing type 1 x type 3 viral reassortants, revealed that the viral sigma 1 protein determined the capacity of reovirus to spread from the intestine in both adult and 10-day-old mice. Thus, the interaction of reovirus with host defense mechanisms, and the age-dependent restriction of spread of type 3 reovirus from the intestine are mediated by the viral sigma 1 protein.

Aging↗
PubMed1983

Successful second bone marrow transplantation in a patient with myositis ossificans progressiva and aplastic anemia.

Bone marrow transplantation has become the treatment of choice for patients with severe aplastic anemia who are fortunate enough to have allogeneic sibling donors. As patients have been transplanted earlier in the course of their disease, significant improvements have been obtained in long-term survival. However, in patients who have been sensitized by previous blood product transfusions, graft rejection continues to be a significant problem and second transplants when performed are frequently unsuccessful. This case report deals with a patient with myositis ossificans progressiva (MOP) who developed severe idiopathic aplastic anemia. He rejected his first graft after 160 days. However, he was successfully reingrafted with marrow from the same donor using a different conditioning regimen.

Anemia, Aplastic↗
PubMed1983

Determinants of reovirus interaction with the intestinal M cells and absorptive cells of murine intestine.

Reovirus type 1 penetrates the gastrointestinal tract in suckling mice via specialized epithelial cells, designated membranous cells, or M cells, located in the epithelium overlying Peyer's patches. We have examined whether the interaction of reovirus with murine mucosa of in situ closed ileal loops is influenced by mouse age or strain or reovirus serotype. Neither mouse age (suckling or adult), strain (C3H/HeJ or Balb/cJ), nor reovirus serotype (types 1 and 3) affected reovirus adherence to and transport through M cells. In all conditions, reovirions adhered to the M-cell surface and were transported across M cells in endocytic vesicles. The adherence to and endocytosis by M cells of type 1 reovirus and reassortants with the viral hemagglutinin of type 1 were selective in suckling mice; type 1 virus was not adherent to nor endocytosed by absorptive cells. In adult mice, type 1 reovirions adhered to the surface of a minority of absorptive cells but were never seen within absorptive cell cytoplasm. In contrast, type 3 reovirus and reassortants with the viral hemagglutinin of type 3 adhered to and were endocytosed not only by M cells but also by absorptive cells of suckling mice. Virions accumulated within lysosomelike bodies in absorptive cells but transport of virions across absorptive cells was not observed. These studies indicate that (a) adherence of reovirus to the apical surface of and transcellular transport by M cells is independent of viral serotype or viral surface proteins, (b) adherence of reovirus to and transcellular transport by M cells is independent of mouse age after 9 days and comparable in two mouse strains, and (c) adherence of reovirus to and their endocytosis by absorptive cells of suckling mice is determined by the viral hemagglutinin (sigma 1 protein).

Age Factors↗
PubMed1983

Bone marrow ablation followed by allogeneic marrow grafting during first complete remission of acute nonlymphocytic leukemia.

Of 33 patients who had undergone allogeneic bone marrow transplantation during first complete remission of acute nonlymphocytic leukemia, 21 patients have now been followed in continued complete remission for 6-64 mo (median greater than 18 mo) without maintenance chemotherapy. The median age of the surviving patients is 27 yr. Transplant-related complications occurring throughout the first year after marrow grafting were fatal in 7 patients, and leukemic recurrence led to the death of 5 patients. The actuarial long-term disease-free survival is 60% and the actuarial remission rate is 79%.

Bone Marrow↗
PubMed1983

Ineffectiveness of single-dose human antiserum to core glycolipid (E. coli J5) for prophylaxis of bacteremic, gram-negative infections in patients with prolonged neutropenia.

It has been recently established that serum from human volunteers immunized with E. coli J5 vaccine prevents death of patients with gram-negative shock. The present study addressed the question whether the prophylactic administration of a similar amount of J5 antiserum could protect neutropenic patients from acquiring gram-negative infections. One hundred patients, the majority of which had acute non-lymphoblastic (63%) and lymphoblastic (29%) leukemia, presented 109 episodes of neutropenia. Sixty of the 100 patients underwent bone marrow transplantation. All patients were given one unit of either pre-immune (control) or J5 antiserum serum from volunteers at the onset of neutropenia. When compared to control serum, J5 antiserum given prophylactically did not reduce the number of febrile days, the number of gram-negative bacteremic episodes, or death from these infections. This inability to demonstrate a beneficial effect of prophylaxis with a single unit of J5 antiserum in prolonged neutropenia may have several explanations that are discussed.

Adolescent↗
PubMed1982

Platelet transfusion therapy in an alloimmunized patient. The value of crossmatch procedures for donor selection.

A 51-year-old patient with acute myelogenous leukemia, who was alloimmunized to platelets, failed to show adequate platelet increments after receiving transfusions of HLA grade A-identical platelets. Only platelets from an HLA grade B-matching donor gave high increments. Several crossmatching procedures were used to select platelet donors. A correlation was seen between in vitro tests and in vivo response. HLA typing has limitations in the selection of platelet-compatible donors.

Adult↗
PubMed1982

Structural features of the rat small intestinal microvillus membrane in acute experimental diabetes.

Experimentally induced diabetes enhances the specific activity of several microvillus membrane proteins in the rat small intestine. The increase in the specific activity of sucrase-isomaltase has been shown by others to be due to an increase in enzyme protein, raising the possibility that diabetes induces a generalized increase in microvillus membrane proteins. Since intramembrane particles (IMPs) seen on freeze-fracture replicas of microvillus membranes are thought to represent integral membrane proteins, we compared microvillus IMP densities in diabetic rats with those in control rats. In addition, mucosal sucrase, maltase, and alkaline phosphatase specific activities were measured in all animals. Diabetic rats had significantly increased sucrase and maltase but not alkaline phosphatase specific activities compared with control rats. The density of microvillus IMPs on both the protoplasmic and extracellular fracture faces of undifferentiated crypt cells and villus absorptive cells was not increased in experimental diabetes. These data indicate that diabetes does not result in a generalized increase in microvillus membrane proteins. Thus the enhanced activity of microvillus membrane proteins in diabetes appears to be highly selective.

Acute Disease↗
PubMed1982

Reversal of acute ("malignant") myelosclerosis by allogeneic bone marrow transplantation.

A 28-yr-old woman with acute malignant myelosclerosis received, as primary treatment, ablative chemotherapy and total body radiation therapy followed by bone marrow transplantation from her histocompatible brother. The patient is now well more than 15 mo after bone marrow transplantation, with normal peripheral blood counts, a normal bone marrow, no evidence of graft-versus-host disease, and is on no therapy. In light of the poor results obtained with conventional chemotherapy in this disease, bone marrow transplantation may represent the treatment of choice for patients who have an appropriate donor.

Acute Disease↗