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Biomedical subjects

R Carmel

Publications and source records attributed to R Carmel.

At least 91 records · Page 5Linked to original sources
PubMed1984

Cyclic eosinophilic leukocytosis in eosinophilic leukemia with observations on transcobalamin I and eosinophils.

A patient with eosinophilic leukemia was noted to have spontaneous fluctuations in his eosinophil and total leukocyte counts over a 3-year period. The range of eosinophil counts observed was from 736/microliters to 401,400/microliters. Sharp fluctuations occurred whether chemotherapy was administered at the nadir or the peak of a cycle or was withheld. A shortening of the cycle length from 44 to 25 days, and a marked increase in amplitude of the cycle occurred in the terminal phase of his illness. Two additional observations merit mention. An abnormal alpha-2 globulin of 40,000 molecular weight was detected in his serum. In addition, cyclic fluctuations of serum transcobalamin I that accompanied his cyclic eosinophil counts were noted, and eosinophils were documented for the first time to be rich sources of this protein.

Adult↗
PubMed1984

Congenital pernicious anemia: report of seven patients, with studies of the extended family.

Seven children ages 1 1/2 to 12 years with congenital pernicious anemia were detected in an extended Mexican family. All affected children had megaloblastic anemia accompanied by low serum B12 and normal serum folate levels. Gastric fluid analysis in six patients revealed normal gastric acidity and absent intrinsic factor. Serum antibodies to intrinsic factor or parietal cells were also absent. Schilling tests performed in six of the seven patients yielded abnormal results. Of the three patients in whom gastric biopsy was done, two had normal histologic findings (including examination by electron microscopy) and one had mild atrophy. All patients responded rapidly to parenterally administered vitamin B12 therapy. In addition, 170 family members were screened for the defect with complete blood counts and serum B12 levels. Such screening detected pernicious anemia in two of the children, but no other abnormalities that could be attributed to pernicious anemia were found in other family members. Based on the family pedigree, autosomal recessive inheritance is likely. The variability of age of presentation in this family is noteworthy and suggests that expression may be modified by still undefined factors.

Anemia, Pernicious↗
PubMed1984

Simultaneous detection of membrane markers with monoclonal antibodies and peroxidatic activities in leukaemia: ultrastructural analysis using a new method of fixation preserving the platelet peroxidase.

Simultaneous detection of specific surface markers by immunogold and intracellular peroxidase activity was determined ultrastructurally in normal and leukaemic progenitors of platelets, erythrocytes and granulocytes. A new method of fixation was employed to preserve platelet peroxidase activity. Monoclonal antibodies to platelet glycoproteins labelled exclusively platelet peroxidase (PPO) positive cells, i.e. platelets, megakaryocytes and promegakaryoblasts (PMKB). In acute megakaryoblastic leukaemia, most PMKB possessed both markers while a few PMKB identified by PPO did not bind monoclonal antibodies. This result suggests that PPO appears earlier in maturation than platelet glycoproteins. Although all glycoproteins (GP) displayed fewer sites in PMKB than platelets, GP Ib was often observed in more mature megakaryocytes. Surface (glycophorin A) and intracytoplasmic markers including ferritin, intra-mitrochondrial iron and diffuse peroxidase activity due to haemoglobin of erythroid progenitors, appeared simultaneously. The number of glycophorin A sites increased with maturation. In leukaemia involving PMKB and proerythroblasts, the surface markers were coincident with the localization of peroxidase activity; glycophorin A was always absent from blasts which exhibited PPO activity localized in endoplasmic reticulum. Platelet glycoproteins were never expressed in any other cell lineage. The myeloid surface antigen was present on normal late neutrophilic promyelocytes after the cessation of myeloperoxidase synthesis. In some cases of M1 and M2 AML (FAB classification), labelling was identical to normal cells while in others the antigen appeared earlier than normal. Our findings show that the surface phenotype of blasts from non-lymphoid leukaemia and the intracellular peroxidase activity of a given cell type can be simultaneously demonstrated and analysed by electron microscopy.

Antibodies, Monoclonal↗
PubMed1984

Transcobalamin II in human seminal plasma.

Study of cobalamin-binding proteins revealed seminal plasma to be the most concentrated site of transcobalamin II in man. The next richest normal fluid, blood, has approximately one-tenth its concentration. Normal seminal unsaturated cobalamin-binding capacity averaged 15,030 +/- 7,290 pg/ml, of which 11,550 +/- 6,660 pg/ml was transcobalamin II. Transcobalamin II levels were markedly diminished in subjects lacking seminal vesicles (1520-1660 pg/ml), but not after vasectomy. This suggests that seminal vesicles are the chief source of this protein in semen. R binder concentration was increased in postvasectomy subjects (9,970 +/- 4,900 pg/ml vs. 2,980 +/- 1,370 pg/ml in normals) and varied in other patients. The endogenous cobalamin content of semen was only 88-699 pg/ml, and was carried largely by R binder rather than by transcobalamin II. The function of the unusually large seminal transcobalamin II pool in reproduction is unknown, but seems unlikely to be related solely to cobalamin transport needs, at least within the male reproductive tract itself.

Humans↗
PubMed1984

Hereditary transcobalamin II deficiency with subnormal serum cobalamin levels.

An infant with transcobalamin II deficiency had the unusual feature of a low serum cobalamin level. Moreover, the level did not rise greatly with cobalamin therapy. Clinically, the features of the infant's illness were unexceptional other than the somewhat delayed onset of symptoms at 3 1/2 months of age. In addition, the patient's impaired antibody response to specific antigen challenge was not completely corrected following cobalamin therapy, and this result contrasts with the findings in the only previous examination of this feature of the disorder. As in previous cases, the transcobalamin II deficiency was accompanied by findings in the serum of complexing of the patient's R binder and the relative prominence of a cobalamin-binding peak eluting at a molecular weight of approximately 70,000 on Sephadex G-200 gel chromatography. In addition, the total serum R binder (free and complexed) level was low. This case demonstrates that transcobalamin II deficiency should be considered in any infant with a low serum cobalamin level in the first few months of life.

Agammaglobulinemia↗
PubMed1984

Congenital transcobalamin II deficiency presenting atypically with a low serum cobalamin level: studies demonstrating the coexistence of a circulating transcobalamin I (R binder) complex.

A case of transcobalamin II deficiency with several unique features is described. The clinical presentation was typical, except for a slightly delayed age at presentation and the occurrence of apparent neurologic dysfunction from the beginning. The unusual biochemical feature was a low serum cobalamin level (97 pg/ml). Several cobalamin-binding protein abnormalities coexisted and antedated cobalamin therapy. Chief among these was the complexing of all serum R binder (transcobalamin I), leaving the patient with no detectable R binder. This defect appeared to be transient. Noteworthy, too, was a prominent binder of 70,000 mol wt that also carried the bulk of his serum cobalamin after therapy; it was prominent in his presumably heterozygous relatives too. The interrelationship between all these abnormalities is intriguing but unclear. The abnormality in transcobalamin II deficiency is clearly not limited solely to deficiency of transcobalamin II. It is also evident that this entity must now be considered in the differential diagnosis of low serum cobalamin levels in infancy.

Carrier Proteins↗
PubMed1983

R-binder deficiency. A clinically benign cause of cobalamin pseudodeficiency.

A patient with R-binder deficiency lacked this cobalamin-binding protein in serum, saliva, gastric juice, and leukocytes, as demonstrated by cobalamin-binding ability and radioimmunoassay. The patient's condition was first detected because of a low serum cobalamin (vitamin B12) level. His level of serum cobalamin, however, which was carried largely by transcobalamin II, was not as decreased as in the initial cases reported and was higher by some assays than by others. The demonstration of normal bone marrow morphological appearance and deoxyuridine suppression test findings, lack of attributable neurological dysfunction, and absence of methylmalonic aciduria make clear that deficiency of R binder, whose function is unknown, did not produce notable disturbance of cobalamin metabolism. This entity is probably not as rare as originally thought. It must be considered in the differential diagnosis of low serum cobalamin levels, even among elderly patients, whose conditions often tend to be automatically diagnosed as pernicious anemia.

Anemia, Pernicious↗
PubMed1983

An unusual case of autoimmune agranulocytosis with total absence of myeloid precursors: demonstration of diverse sources of R binder for cobalamin in plasma and secretions.

An unusual autoimmune agranulocytosis featured intense plasmacytosis, hyperglobulinemia, and total absence of myeloid precursors. Remission was induced with prednisone and cyclophosphamide on two separate occasions, producing reversal of all the above abnormalities. Anti-granulocyte antibodies were demonstrated in relapse by staphylococcal protein A assay. During agranulocytosis, levels of the R binder for cobalamin in the blood were greatly diminished (20-60 pg/mL unsaturated binding capacity). Moreover, the acquired R binder deficiency was accompanied by the previously undescribed phenomenon of a shift of endogenous serum cobalamin to transcobalamin II; only 10-19% of endogenous cobalamin was attached to R binder. In remission, unsaturated R binder rose to normal levels and R binder also carried 78-91% of endogenous cobalamin. This confirms that granulocytes are responsible for most of the circulating R binder in humans. In contrast, salivary R binder concentration was normal throughout the patient's course, indicating that secretory R binder is nongranulocytic in origin. These data establish that R binder has more than one source in humans.

Adult↗
PubMed1983

Gastric juice in congenital pernicious anemia contains no immunoreactive intrinsic factor molecule: study of three kindreds with variable ages at presentation, including a patient first diagnosed in adulthood.

The mechanism responsible for the isolated intrinsic factor deficiency in congenital pernicious anemia is unknown. A new second-antibody radioimmunoassay capable of recognizing intrinsic factor independent of the molecule's ability to bind added cobalamin was used to study six patients from three kindreds with this disorder. One of the patients was first diagnosed at age 23 because of unusual circumstances in her case; yet the other patients also demonstrated great age variability at presentation of this presumably congenital disorder, even within the same kindred. The radioimmunoassay failed to detect immunoreactive intrinsic factor in any of the six patients, suggesting that elaboration of an abnormal molecule was not the pathogenetic mechanism. An unexpected incidental finding, contrasting with this observation in congenital pernicious anemia, was immunologic evidence that a previously described patient with familial R binder deficiency clearly elaborated an abnormal R binder molecule.

Adolescent↗
PubMed1982

Subtle cobalamin malabsorption in a vegan patient: evolution into classic pernicious anemia with anti-intrinsic factor antibody.

Classic pernicious anemia with abnormal Schilling test results developed in a previously described vegan patient who had coexisting subtle cobalamin malabsorption (demonstrable by abnormal ovalbumin-cobalamin absorption test results but normal Schilling test results). This suggests that the ovalbumin-cobalamin absorption test or a modified version may serve as a prodromal phenomenon to identify patients at risk for developing pernicious anemia. The patient's transformation was also accompanied by the appearance of serum anti-intrinsic factor antibody. A modified assay retrospectively detected this antibody a year earlier than did the standard assay, indicating that such modification enhances the sensitivity of this useful test.

Anemia, Pernicious↗
PubMed1982

Variable presentation of thrombocytopenia in Graves' disease.

An association between thrombocytopenia and thyrotoxicosis has been reported but its mechanism is unclear. We describe five patients in whom thrombocytopenia accompanied Graves' disease. The thrombocytopenia resembled idiopathic thrombocytopenic purpura and responded to prednisone therapy in cases 1 and 2. In case 3, thrombocytopenia remitted with treatment of the thyrotoxicosis, while, in case 4, remission occurred despite persistent hyperthyroidism. In case 5, thrombocytopenia persisted despite correction of the hyperthyroidism but remained clinically insignificant. We conclude that there is a clear association between the two conditions but the clinical patterns of presentation and pathogenesis seem heterogenous. This variability must be considered during management.

Adult↗
PubMed1982

A new case of deficiency of the R binder for cobalamin, with observations on minor cobalamin-binding proteins in serum and saliva.

A patient presented at the age of 77 yr with a low serum cobalamin level. Subsequent study showed that he had persistently very low R binder (TC I) cobalamin-binding capacity in serum (less than 5 ng/liter versus 213 +/- 171 ng/liter in normal controls), and that almost all of his endogenous serum cobalamin was carried by TC II instead of TC I. His saliva also demonstrated virtually undetectable R binder (binding capacity of 31-38 ng/liter versus 41,690 +/- 23,820 ng/liter for control subjects). Unlike previous cases of R binder deficiency, he seemed to maintain normal serum cobalamin levels while receiving monthly cyanocobalamin injections. This and his normal serum unsaturated binding capacity were due to elevated TC II levels. TC II carried 72%-98% of his endogenous cobalamin, the rest being attached to minor binders. As incidental findings, the patient had a serum component of molecular weight of approximately 70,000 that carried 7%-8% of his endogenous cobalamin and also had small quantities of TC II demonstrable in his saliva. Both these heretofore unappreciated minor peaks were identifiable because of the lack of R binder. The patient's clinical presentation supports the conclusion that R binder deficiency is a benign disorder. Whether his mild hypersegmentation of neutrophils and neuropathy were related to the R binder deficiency or, more likely, arose from coexisting folate deficiency and alcohol abuse, the overall picture contrasts dramatically with the severe clinical sequelae of TC II deficiency.

Aged↗
PubMed1982

Abnormal deoxyuridine suppression test in congenital methylmalonic aciduria-homocystinuria without megaloblastic anemia: divergent biochemical and morphological bone marrow manifestations of disordered cobalamin metabolism in man.

We studied two brothers (J.R. and M.R.) with the cobalamin D variant of congenital methylmalonic aciduria-homocystinuria, whose previously reported lack of megaloblastic anemia conflicted with current concepts of cobalamin's role in DNA synthesis and the "methyltetrahydrofolate (MTHF) trap" hypothesis. Both subjects were indeed hematologically normal, although J.R. had a mean corpuscular volume of 96 fl. However, both demonstrated abnormalities in the deoxyuridine suppression test. J.R. had an abnormal suppression value of 21.0% (normal less than 10%) that was correctable by adding hydroxocobalamin or folic acid in vitro but not MTHF. M.R. had normal suppression (8.9%), but demonstrated worsening (18.6%) when MTHF was added. J.R.'s classical deoxyuridine suppression pattern of cobalamin deficiency thus supports the trap hypothesis. However, his lack of comparable morphological changes suggests that impaired de novo thymidylate synthesis and the trap hypothesis, though valid, may not fully account for the megaloblastic maturation accompanying cobalamin deficiency. Equally noteworthy was the deleterious effect of MTHF on M.R.'s marrow, suggesting its potential usefulness as an in vitro "stress test" for latent cobalamin abnormality.

Adolescent↗
PubMed1982

Clinical and subclinical thyroid disorders associated with pernicious anemia. Observations on abnormal thyroid-stimulating hormone levels and on a possible association of blood group O with hyperthyroidism.

of 162 patients with pernicious anemia whom we studies, 24.1% had clinical thyroid disease; 11.7% were hypothyroid and 8.6% were hyperthyroid. When abnormal serum thyroid-stimulating hormone (TSH) levels were also considered, thyroid disorders existed in 48.3% of 143 patients. Increased or decreased TSH levels as the sole dysfunction occurred in 14.7% and 6.3% of cases, respectively, and were often associated with thyroid antibodies. The high TSH group fits the picture of subclinical hypothyroidism. The nature of the low TSH group remains to be defined. We conclude that TSH screening in patients with pernicious anemia uncovers frequent abnormalities, which are superimposed on a higher coincidence of overt thyroid disease than previously described. Interestingly, also, eight of nine hyperthyroid patients and all seven patients with low TSH levels had blood type O, contrasting significantly with hypothyroid subjects, who more often had blood type A, and with patients without thyroid disorders.

ABO Blood-Group System↗
PubMed1981

Profiles of black and Latin-American patients having pernicious anemia. HLA antigens, lymphocytotoxic antibody, anti-parietal cell antibody serum gastrin levels, and ABO blood groups.

Because of the unusual presentation of pernicious anemia in many black women, a further characterization of this disease among the different racial groups was undertaken. The following were found. (1) Black women under the age of 50 years had a significantly lower prevalence of anti-parietal cell antibody than did "European" and Latin-American patients or even older black women. The disease in the younger black women resembles juvenile pernicious anemia in this respect. Blacks in general had a lower prevalence of anti-parietal cell antibody than did "Europeans" and Latin Americans, though the difference was not statistically significant. A particularly striking finding was that anti-parietal cell antibody occurred much less often than anti-intrinsic factor antibody among black patients. (2) An analysis of all published HLA data for patients of European origin indicated a weak association of pernicious anemia with HLA-B7. However, no antigen association among the black and Latin-American patients studied was found. HLA-DR typing, not previously reported even for whites, also showed no association. (3) Lymphocytotoxic antibody was equally increased in frequency in all racial groups. (4) Serum gastrin levels did not follow a racial pattern; however, women with pernicious anemia had much higher levels than did men. (5) Pernicious anemia was not associated with blood group A.

ABO Blood-Group System↗