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Biomedical subjects

H S Jacob

Publications and source records attributed to H S Jacob.

At least 163 records · Page 9Linked to original sources
PubMed1977

Randomized study of nandrolone therapy for anemias due to bone marrow failure.

A prospective, randomized, double-blind study was designed to determine the effectiveness and toxicity of nandrolone phenpropionate in the treatment of anemias due to bone marrow failure. Twenty-four patients were initially entered; 21 now may be evaluated: seven with aplastic anemia, six with myelofibrosis, and eight with refractory anemia. Six patients improved, but only three were taking nandrolone, the other three placebo. Response did not correlate with type of anemia. No serious drug toxicity was noted. One patient with myelofibrosis improved dramatically with placebo therapy alone, no longer requiring frequent transfusions because of a hemoglobin level increase from 5.4 to 15.8 gm/100 ml. We conclude that no substantial improvement of anemia due to marrow failure can be ascribed to nandrolone as given, and that clinical trials in these conditions should be controlled to exclude spontaneous remissions as a cause of apparent improvement.

Adult↗
PubMed1977

Acquired granulocyte abnormality during drug allergic reactions: possible role of complement activation.

A profound defect in granulocyte chemotaxis was documented in an otherwise healthy 21-yr-old man who failed to localize granulocytes to an area of cellulitis during an allergic reaction to cephalothin. During the period of drug allergy, characterized by urticaria, eosinophilia, and profound hypocomplementemia, in vitro migration of the patient's granulocytes in the Boyden chamber was markedly impaired. Although devoid of hemolytic complement activity, the patient's serum possessed supranormal chemotactic activity, even following heat inactivation, suggesting the presence of chemotactically active complement split products. Chemotactic function improved concomitantly with steroid therapy and normalization of serum complement levels, and was entirely normal following clinical recovery and cessation of steroid therapy. The chemotactic abnormality noted in the patient's cells was reproduced in normal granulocytes by preincubation either with patient serum or with cobra venom-activated fresh (but not heated) normal serum, suggesting that in vivo exposure of granulocytes to activated complement was responsible for the patient's abnormal chemotactic response. This mechanism may contribute to the increased infection propensity noted in other conditions characterized by in vivo complement activation, such as rheumatoid arthritis and systemic lupus erythematosis.

Adult↗
PubMed1977

Association of decreased membrane protein phosphorylation with red blood cell spherocytosis.

A close association between sphering of human red cells and deficient phosphorylation of their membrane proteins has been documented in three spearate situations. Red cells rendered spheroidal by exposure to: (1) elevated temperatures; (2) two sulfhydryl inhibitors (N-ethylmaleimide or paramercuribenzoate); or (3) in the genetic situation of hereditary spherocytosis--all manifest deficient phosphorylation of endogenous membrane proteins by ATP. In the two former cases, we have noted an exact association between the onset of red cell sphering (e.g., as temperatures rose above 48 degrees C or N-ethylmaleimide concentrations exceeded 2 mumoles/ml RBC) and the development of deficient ghost protein phosphorylation.

Adenosine Triphosphate↗
PubMed1977

Postsurgical granulocyte dysfunction: studies in healthy kidney donors.

In order to determine whether surgical trauma affects granulocyte function, we performed sequential studies of granulocyte phagocytic and bactericidal function, chemotaxis, and adherence on 25 otherwise healthy subjects undergoing donor nephrectomy for kidney transplantation. All values were normal prior to surgery, and bacterial killing and phagocytosis were unaffected by surgery. Granulocyte chemotaxis and adherence were significantly impaired immediately following surgery, returning to normal in 24 hr. Anesthesia alone did not affect chemotaxis. Generation of chemoattractants from postoperative plasma was normal, and inhibitors of chemotaxis could not be demonstrated, suggesting an intrinsic cellular defect. We suggest that these postoperative abnormalities of granulocyte chemotaxis and adherence may contribute to the high incidence of infectious complications following surgery.

Cell Adhesion↗
PubMed1976

Fragmentation haemolysis in patients with severe diabetic angiopathy.

Haemolytic anaemia associated with prominent red cell fragmentation is described in seven patients with long-standing diabetes mellitus. A common freature in the patients was severe microangiopathy as detected by retinal examination and microscopic examination of the kidneys. Renal or pancreatic islet malfunction per se is not involved in the haemolytic syndrome, since red cell abnormalities persisted in one patient for over a year following successful renal and pancreatic transplantation--this, despite the maintenance of normal renal and carbohydrate homeostasis. The kinetics of fragmentation was sutdied by tranfusing snormal type O cells into this type A patient. With reisolation of these cells by the Ashby-technique, rapid and porgressive red cell fragmentation was demonstrated by: (a) membrane lipid loss; (b) osmotic fragility increase; and (c) increase in mean cell haemoblobin concentration. This studies indicate that a red-cell-fragmentation haemolytic anaemia may occur in long-standing diabetes mellitus, related to the angiopathy of this disease and not to insulin deficiency or renal malfunction.

Adult↗
PubMed1976

Accelerated myeloblast destruction and abnormal lysosome disruption in cultured bone marrow: association with indolent acute myelogenous leukemia.

Despite no chemotherapy and a marrow morphologically typical of frank relapse, an acute myelogenous leukemia (AML) patient survived for nearly 1 yr. During this time she remained asymptomatic and maintained nearly normal levels of platelets and hemoglobin. Cytochemical and electron microscopic studies of her bone marrow in liquid culture revealed on several occasions a unique maturational sequence in that leukemic cells differentiated to form morphologically abnormal primary granules which appeared to rupture and cause cytolysis of these cells. In these cultures, blasts rapidly disappeared and were replaced by more mature granulocytes, in contrast to observations in cultures derived from five other patients with AML in relapse which showed persistently elevated blast counts with no evidence of maturation in vitro. These findings support the concept that in AML cell maturation is regularly impaired and in some cases also aberrant. In addition, the abnormal granule formation with autolysis of the leukemic cells observed in one patient may explain both the early cell death in vitro and this patient's relatively indolent clinical course. Similar in vitro studies may help predict atypical clinical courses in patients with AML and facilitate design of appropriate chemotherapy.

Adult↗
PubMed1976

Complement-mediated granulocyte dysfunction in paroxysmal nocturnal hemoglobinuria.

In paroxysmal nocturnal hemoglobinuria (PNH), infection, both viral and bacterial, disproportionate to the mild neutropenia seen in many such patients is responsible for significant morbidity. We report impaired granulocyte chemotaxis efficiency which may contribute to the problems induced by bacterial infections. PNH (but not normal) granulocytes, after exposure to very small concentrations of activated serum complement components, migrate poorly, as documented by their inhibited chemotaxis toward bacterial products or activated complement components in Boyden chambers. The granulocytes remain intact, excluding trypan blue, phagocytosing, and killing bacteria, despite this activated complement exposure. It is also suggested that this chemotactic defect may involve only a clone of cells, analogous to the clonal lysis of PNH erythrocytes; those few granulocytes capable of migration after exposure to activated complement contain normal quantities of leukocyte alkaline phosphatase (LAP), in contrast to the LAP deficiency of the overall PNH granulocyte population. Since bacterial infection may initiate or potentiate hemolysis, one of the major symptoms of the disease, these results could explain much of the morbidity of PNH.

Alkaline Phosphatase↗
PubMed1976

A possible role for cyclic nucleotides in the regulation of erythrocyte shape and permeability.

Erythrocytes treated with vinblastine or colchicine become spheroidal, more permeable to sodium, and of diminished deformability; upon reinjection they are rapidly sequestered and destroyed in the spleen. These deleterious effects are competitively inhibited by the cyclic nucleotides, guanosine 3',5'-monophosphate or adenosine 3',5'-monophosphate. The data suggest that cyclic nucleotides may be involved in normal erythrocyte shape and survival by interacting with membrane components that also react with vinblastine and colchicine. Similar interactions have been noted previously in diverse proliferating cells as well.

Cell Membrane Permeability↗
PubMed1976

Spinal cord disease in hereditary spherocytosis: report of two cases with a hypothesized common mechanism for neurologic and red cell abnormalities.

Two unrelated patients with hereditary spherocytosis developed idiopathic spinal cord dysfunction. This coincidence, combined with similar individual case reports in the older European literature, suggests that abnormalities may exist in constituents common to red cell membranes and nerve tissue. A similar conclusion has been proposed to explain red cell membrane abnormalities in some of the muscular dystrophies.

Aged↗
PubMed1975

Abnormal red cell metabolism in patients with chronic uremia: Nature of the defect and its persistence despite adequate hemodialysis.

A red cell metabolic abnormality, which diminishes the maximum activity of the pentose phosphate shunt, occurs in some uremic patients, even those adequately dialyzed with fluids prepared from distilled or charcoal-filtered water. Within individual patients the severity of this abnormality does not change even after 9 mo of consecutive hemodialyses. However, between patients it does correlate inversely with hematocrit. When erythrocytes from patients with the abnormality are stressed with oxidant compounds, such as ascorbate, erythrocyte glucose consumption and lactate formation are abnormally increased, while lactate/pyruvate ratios abnormally diminish. Concomitantly, red cell glycolytic intermediates, including fructose-1,6-diphosphate, glyceraldehyde-3-phosphate, 3-phosphoglycerate, phosphoenol pyruvate, and pyruvate, markedly accumulate. Surprisingly, no increase of 2-phosphoglycerate occurs, which suggests that inefficient phosphoglyceromutase activity underlies this perturbation of erythrocyte metabolism and its associated hemolytic process.

Ascorbic Acid↗