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Biomedical subjects

S B Krantz

Publications and source records attributed to S B Krantz.

At least 127 records · Page 7Linked to original sources
PubMed1979

Evidence that endotoxin is the cyclic 3':5'-GMP--promoting factor in erythropoietin preparations.

Since Ep preparations are contaminated with endotoxin, the possibility that the latter might be the factor in crude Ep which increases cGMP levels in rat fetal liver cells was examined. Endotoxin produced a striking elevation of cGMP in rat fetal liver cells without affecting cAMP levels or heme synthesis. Absorption with Limulus lysate of more than 99% of the endotoxin in a crude Ep preparation caused a parallel decrease in the cGMP-promoting activity without reduction of heme synthetic potency. It is concluded that endotoxin is the component of crude Ep which increases cGMP levels in rat fetal liver. The precise role of elevated cGMP in the action of endotoxin on cells and the universality of this effect remain to be determined.

Animals↗
PubMed1979

Friend virus production and heme synthesis in primary mouse spleen cell cultures.

A cell culture method has been developed in which spleen cells from Friend virus (FV) infected mice can be studied for virus production as well as erythroid differentiation. Primary spleen cell cultures from plethoric Balb/c mice were initiated at 24, 48 or 73 h after FV infection. These cells manifested a well-defined wave of heme synthesis at approximately 64, 48, or 23 h, respectively, of cell culture. Assays for spleen focus-forming virus (SFFV) and helper murine leukemia virus (MuLV-F) production in these cultures revealed that the peak rates of production of both viruses occurred at essentially the same time as the peaks of heme synthesis. The time at which the peaks of virus production and heme synthesis occurred in vitro was related to the time interval after infection (80-105 h) rather than the time at which the cells were placed in cell culture or the number of hours of cell culture. Medium change experiments suggested that the temporal relation between heme synthesis and virus production was an intrinsic feature of FVP infected cells in this in vitro system.

Animals↗
PubMed1979

Cimetidine-induced neutropenia: a possible dose-related phenomenon.

Neutropenia associated with high-dose cimetidine therapy developed in a patient in whom earlier therapy, as well as rechallenge with low-dose cimetidine, did not result in neutropenia. As other factors cannot be implicated, a dose-related toxicity of cimetidine appears likely. Although the mechanism of cimetidine-induced neutropenia is unknown, it may involve the previously demonstrated ability of histamine H2 receptor antagonists to block the histamine-induced initiation of DNA synthesis in bone marrow stem cells.

Adult↗
PubMed1979

Upper airway obstruction as a complication of oral anticoagulation therapy. Report of three cases.

While taking orally administered anticoagulants, three patients had hemorrhages into their retropharyngeal and submandibular spaces, suffering eventual acute airway obstruction. One of the patients died. Despite the life-threatening nature of this complication of anticoagulant therapy, the diagnosis was obscure and initially veiled in complaints of sore throat or hoarseness, suggesting infection. Thorough investigation of such complaints is necessary in patients receiving anticoagulation therapy. If a hematoma is discovered, the patient should be admitted to the hospital for close observation and prompt reversal of anticoagulation with plasma. Intubation or tracheostomy also may be required.

Airway Obstruction↗
PubMed1978

Studies on red-cell aplasia: IX. Ferrokinetics during remission of the disease.

Ferrokinetic studies and external organ measurements of radioiron were performed on five patients with pure red-cell aplasia (PRCA) in remission. One patient with PRCA in relapse was also studied. Of those in remission, one patient had erythroid hyperplasia and ineffective erythropoiesis after the remission occurred. This was indicated by a very short 59Fe clearance rate and reduced red-cell 59Fe incorporation, a marked increase of the erythron iron turnover over the fixed red-cell iron turnover, and a prolonged marrow transit time. These indices were normal three years later. Four patients had normal effective erythropoiesis while in remission. Two patients had an extended marrow distribution. These studies indicate that some cases of PRCA evolve into a state of ineffective erythropoiesis with erythroid hyperplasia. It is possible that in some patients, primary refractory anemia with ineffective erythropoiesis may be related to PRCA because of the evolution from one state into the other. Alternatively, a second pathologic process may have been acquired between the PRCA and normal hematopoiesis.

Adult↗
PubMed1978

Haemoglobin Vanderbilt (alpha2beta289Ser leads to Arg): a new haemoglobin with high oxygen affinity and compensatory erythrocytosis.

Haemolysates of family members from three generations, all of whom had polycythaemia, were analysed by polyacrylamide gel electrophoresis at pH 8.8. Two closely spaced major bands were observed, one of which corresponded to Hb A and the other to a new mutant designated Hb Vanderbilt. Whole blood from a heterozygote for Hb Vanderbilt was analysed for oxygen affinity which was found to be much higher than that of normal subjects. Haemoglobin Vanderbilt was separated from Hb A using anion exchange chromatography. Cation exchange chromatography yielded a variant beta chain from which a mutant peptide was identified with a structure corresponding to residues beta83--89 with a Ser leads to Arg replacement at position 89. The oxygen affinity of 'stripped' haemolysates from the heterozygote was found to be much less sensitive to added organic phosphates than haemolysates from normal subjects. In while blood, the decreased sensitivity to 2,3-diphosphoglycerate results in an increased oxygen affinity, thus explaining the clinical observations of tissue hypoxia and compensatory polycythaemia.

Aged↗
PubMed1978

Pure red cell aplasia.

Complete or near complete remission of acquired pure red cell aplasia, not associated with thymoma, occurred in response to prednisone (six occasions), prednisone and cyclophosphamide (twice), cyclophosphamide alone (once) and splenectomy (once). These results were observed in four patients and confirm the value of cyclophosphamide and possibly splenectomy in patients resistant to prednisone in acquired red cell aplasia. In two of these patients, bone marrow progression from a state of ineffective erythropoiesis with many red cell precursors to that of red cell aplasia was observed. This indicates that some acquired refractory anaemias characterized by ineffective erythropoiesis may have the same pathogenesis as acquired red cell aplasia. The absence of demonstrable antibodies active against erythroblasts may merely reflect the insensitivity of currently available techniques. However it is possible that non-humoral immune mechanisms may be involved in the production of some forms of acquired red cell aplasia responsive to immunosuppressive drugs.

Adult↗
PubMed1977

Splenic erythroid response to friend polycythemia virus: time course in vitro after infection in vivo.

When spleen cells removed from plethoric BALB/c mice shortly after infection with Friend polycythemia virus were cultured, they subsequently increased their rate of hemoglobin synthesis in vitro without the addition of the hormone erythropoietin. The increased 59Fe incorporation into hemoglobin in vitro was part of a well-defined single wave unlike the progressive increase in hemoglobin synthesis that occurs in vivo. The peak occurred within the same total time (85-105 hr after infection), irrespective of either the virus dose or time after infection when the cells were removed from the animal and cultured. However, the magnitude of the peak increased with an increase in either of these two variables. Medium change experiments indicated that the time during which the peak occurred was not artificially determined by depletion of some medium component or the accumulation of an inhibitor. This system may be useful in separating the early events of Friend virus infection from the late effects on erythroid differentiation.

Animals↗
PubMed1977

Gamma heavy chain disease--presenting as pancytopenia and splenomegaly.

A patient with gamma heavy chain disease (Franklin's disease) was discovered during evaluation for pancytopenia and splenomegaly. Lymphadenopathy, palatal edema, and infiltration of the bone marrow palatal edema, and infiltration of the bone marrow with abnormal cells were all absent. Serum and urine protein electrophoresis demonstrated a monoclonal protein migrating in the beta region. Immunoelectrophoresis showed that it reacted with antibodies against the Fc fragment of IgG heavy chains (gamma chains) but not with antibodies against kappa and lambda but not with antibodies against kappa and lambda light chains of Fab fragments. In the first year after detection of the disease, the patient had acute cholecystitis and disseminated herpes zoster. Sixteen months after diagnosis he died of overwhelming pneumonia caused by Pseudomonas aeruginosa and lebsiella neumoniae. A striking feature of his illness was his asymptomatic presentation, with pancytophenia and splenomegaly the only indication of this disease.

Cholecystitis↗
PubMed1977

Detection of cytotoxic antibody to erythroblasts.

A two-stage test of cytotoxicity for erythroblasts has been developed that is faster and more sensitive than a previous method. Release of 59Fe from erythroid precursors was used as an index of cytotoxic injury. Optimal release was obtained by pretreating the labeled marrow cells with 0.46M reduced glutathione (GSH) at pH 8.0 for 1 hour at 37 degrees C. The first-stage test plasmas or IgG globulins were incubated with the treated cells at 22 degrees C. for 1 hour and the second-stage source of complement was incubated with the cells for 1 hour at 37 degrees C. These changes permitted cytotoxic plasmas to be detected when they previously would not have been identified. Substitution of the GSH by trypsin or neuraminidase did not yield comparable results. Measurement of the cytotoxicity for GSH-treated cells by the trypan blue exclusion technique showed that the loss of exclusion of trypan blue by marrow erythroblasts increased with an increased release of 50Fe. No cytotoxicity was detected if complement was inactivated at 56 degrees C. The results observed with trypan blue and the occurence of cytotoxicity with the addition of IgG globulins and complement indicate that this system can be used to detect cytotoxic antibody to erythroblasts.

Animals↗
PubMed1976

Diagnosis and treatment of pure red cell aplasia.

Pure red cell aplasia is a selective aplasia of the marrow erythroid cells. Unlike aplastic anemia, the marrow has a normal cellularity and the patients generally have normal leukocyte and platelet blood counts. The congenital form of the disease occurs in the firlst 1 1/2 years of life and is often responsive to corticosteroids. The acquired form may be secondary to infections, drugs, chemicals, or hemolytic anemia (aplastic crisis). In these cases it is often acute and self-limited with cessation of the infection or drug ingestion. It may also be secondary to systemic lupus erythematosus, rheumatoid arthritis, acute severe renal failure, severe nutritional deficiency, or diverse neoplasms, and may remit with treatment of the primary condition. When a thymoma is present, it should be resected since a remission is produced in 29 per cent of these patients. The remaining patients have an acquired primary form of the disease that tends to be chronic and in some cases may have an immune pathogenesis. A cytotoxic immunoglobulin inhibitor of the marrow erythroid cells or erythropoietin has been described and these patients may respond to prednisone and/or to cytotoxic immunosuppressive drugs such as cyclophosphamide and 6-mercaptopurine. Pure red cell aplasia appears to be more common than the literature has revealed and has stimulated much investigation into an immune pathogenesis for marrow failure.

Acute Kidney Injury↗
PubMed1976

Studies on pure red cell aplasia. Maintenance therapy with immunosuppressive drugs.

Two patients with pure red cell aplasia, whose marrow cells were capable of increasing their rate of haem synthesis when incubated in vitro with erythropoietin concentrate, had a complete remission associated with the administration of cyclophosphamide and prednisone. Both patients relapsed when the drugs were withdrawn. The patients again went into remission when therapy was reinstituted. Maintenance of normal erythropoiesis was dependent on the continued administration of these drugs. This study provides additional evidence for a causal relationship between immunosuppressive therapy and the resumption of erythropoiesis in patients with this disease and demonstrates the value of this therapy for the maintenance of a remission.

Adult↗