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Biomedical subjects

M Lahav

Publications and source records attributed to M Lahav.

At least 19 recordsLinked to original sources

The role of crystal polarity in alpha-amino acid crystals for induced nucleation of ice.

The hydrophobic faces of single crystals of a series of pairs of racemic and chiral-resolved hydrophobic alpha-amino acids were used as a substrate, onto which water vapor has been cooled to freezing. The morphologies and molecular packing arrangements within each crystal pair are similar but only one of each pair exhibits a polar axis, parallel to the hydrophobic face exposed to water. Those crystals that have a polar axis induce a freezing point higher by 4 degrees to 5 degrees C than the corresponding crystals that do not have a polar axis. The results are interpreted in terms of an electric field mechanism that helps align the water molecules into ice-like clusters en route to crystallization.

Amino Acids

Life threatening hypophosphataemia in a patient with Philadelphia chromosome-positive chronic myelogenous leukaemia in acute blastic crisis.

Life-threatening hypophosphataemia developed in a 47 year old woman with blastic crisis of chronic myelogenous leukaemia. The patient's hospitalization was characterized by reciprocal relationship between her white cell count and the serum phosphorus levels. The patient did not demonstrate any of the usual causes of profound hypophosphataemia. The postulated mechanism of this patient's hypophosphataemia is uptake by the rapidly dividing leukaemic cells. To the best of our knowledge this is the first case in the English literature of hypophosphataemia associated with blast crisis of Philadelphia chromosome-positive chronic myelogenous leukaemia.

Blast Crisis

Intermittent administration of furosemide vs continuous infusion preceded by a loading dose for congestive heart failure.

Several reports have suggested that continuous intravenous administration of loop diuretics may be superior to intermittent administration. We performed a prospective randomized crossover study comparing intermittent intravenous administration (IA) of furosemide with continuous infusion following a single loading dose (LDCI) in nine patients with severe congestive heart failure. At the time of hospital admission, patients were randomly assigned to one of two treatment groups. One group (four patients) received an IV bolus injection of furosemide followed immediately by a continuous infusion for 48 h. The second group (five patients) was treated with three IV bolus injections a day for 48 h. Total doses of furosemide were equivalent in the two groups. After 48 h, each patient was crossed over to the other method and treated for an additional 48 h. LDCI produced significantly greater diuresis and natriuresis than IA (total urine output increased by 12 to 26 percent, total sodium excretion increased by 11 to 33 percent) (p less than 0.01). There were no significant differences in side effects between the two methods. These results indicate that LDCI may be a preferred method for administration of furosemide in patients with congestive heart failure.

Aged

Immunologic abnormalities associated with primary anetoderma.

BACKGROUND AND DESIGN: Primary anetoderma is a rare cutaneous elastolytic disorder, the etiopathogenesis of which has not yet been established. Six patients with primary anetoderma were studied in an attempt to assess the role of the immunologic system in the elastolytic process. The investigation included the medical history, physical examination, routine blood tests, specific tests for collagen diseases, prothrombin time, activated partial thromboplastin time, thyroxine, indirect immunofluorescence test, and skin biopsies for histopathologic study and direct immunofluorescence. RESULTS: Two of the patients presented with autoimmune disorders: the first had Graves' disease, lupus anticoagulant, and autoimmune hemolysis, and the second had systemic scleroderma. There were positive direct immunofluorescence findings in most of the patients. Furthermore, all of them were found to have serologic immunologic abnormalities, of which the most common was a positive antinuclear factor. CONCLUSIONS: These findings indicate that there is an immunologic involvement in primary anetoderma.

Adult

Primary anetoderma associated with a wide spectrum of autoimmune abnormalities.

Although the underlying pathologic mechanisms of primary anetoderma have not yet been identified, data suggest the participation of an immunologic mechanism in some cases. In a woman with clinical and histopathologic features of primary anetoderma (Jadassohn-Pellizzari type) of 30 years' duration, laboratory investigation disclosed positive antinuclear factor, hypocomplementemia, hypergammaglobulinemia, granular deposits of immunoreactants along the dermoepidermal junction, and fibrillar deposits in the papillary dermis. In addition, she was found to have autoimmune hemolysis and circulating lupus anticoagulant associated with recurrent deep-vein thrombosis and a history of Graves' disease (starting 5 years after onset of primary anetoderma). To our knowledge, none of the latter three autoimmune conditions has been previously associated with primary anetoderma.

Antibodies, Antinuclear

Image analysis of changes in drusen area.

Computerized image processing was used to analyze color fundus photographs of 11 patients (22 eyes) with macular drusen who were followed for more than 2 years (mean follow-up, 4.7 years). Significant changes over time (more than +/- 20% of baseline area) were measured in the surface area of macular drusen in 18 of 22 (82%) eyes. An increase in the drusen area was associated significantly with eyes with mostly hard drusen and an initially smaller drusen area; but a decrease was associated with eyes with mostly soft drusen and an initially larger drusen area (P less than 0.01). The mean absolute rate of change in the drusen area was more than twice as great in eyes with mostly soft drusen compared with those with mostly hard drusen (P less than 0.05). All eye pairs studied showed a concomitant increase or decrease in the drusen area.

Aged

Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test.

Adrenal response to iv administration of 1-24 ACTH (250 micrograms) was examined in normal volunteers under various conditions. The effect of basal cortisol levels was examined by performing the tests at 0800 h with and without pretreatment with dexamethasone. The effect of time of day was evaluated by performing the tests at 0800 h and at 1600 h, eliminating possible basal cortisol influence by pretreatment with dexamethasone. In the first set of tests, despite significantly different baseline levels, 30-min cortisol levels were not different (618 +/- 50 vs. 590 +/- 52 nmol/L). Afternoon cortisol levels in response to ACTH were found to be significantly higher than morning levels at 5 min (254 +/- 50 vs. 144 +/- 36 nmol/L, p less than 0.01) and at 15 min (541 +/- 61 vs. 433 +/- 52 nmol/L, p less than 0.02). This difference in response was no longer notable at 30 min (629 +/- 52 and 591 +/- 52 nmol/L). We tried also to determine the lowest ACTH dose which will elicit a maximal cortisol response. No difference was found in cortisol levels at 30 and 60 min in response to 250 and 5 micrograms 1-24 ACTH. Using 1 micrograms ACTH, the 30-min response did not differ from that to 250 micrograms (704 +/- 72 vs. 718 +/- 55 nmol/L, respectively). However, the 60-min response to 1 microgram was significantly lower (549 +/- 61 vs. 842 +/- 110 nmol/L, p less than 0.01). Using this low dose ACTH test (1 microgram, measuring 30-min cortisol level), we were able to develop a much more sensitive ACTH test, which enabled us to differentiate a subgroup of patients on long-term steroid treatment who responded normally to the regular 250 micrograms test, but had a reduced response to 1 microgram. The stability of 1-24 ACTH in saline solution, kept at 4 C, was checked. ACTH was found to be fully stable after 2 hs in a concentration of 5 micrograms/ml in glass tube and 0.5 micrograms/ml in plastic tube. It was also found to be fully stable, both immunologically and biologically, for 4 months, under these conditions. We conclude that the 30-min cortisol response to ACTH is constant, unrelated to basal cortisol level or time of day. It is therefore the best criterion for measuring adrenal response in the short ACTH test. The higher afternoon responses at 5 and 15 min suggest greater adrenal sensitivity in the afternoon, but further studies are needed to clarify this issue.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Effect of hemoglobin oxidation products on the stability of red cell membrane skeletons and the associations of skeletal proteins: correlation with a release of hemin.

Oxidative injury to hemoglobin (Hb) leads to formation of methemoglobin (MetHb), reversible hemichromes (rHCRs), and irreversible hemichromes (iHCRs). iHCRs precipitate and form Heinz bodies that attach to the red cell membrane causing injury that leads to hemolysis. The molecular mechanisms of this membrane damage have not been fully elucidated. We have studied the effect of Hb oxidation products on the mechanical stability of red cell membrane skeletons and the associations of membrane skeletal proteins. Hb and MetHb stabilized the isolated membrane skeletons, whereas further oxidation to rHCRs abolished this stabilizing effect. Crude iHCRs prepared by phenylhydrazine oxidation of Hb destabilized membrane skeletons by decreasing formation of the spectrin-protein 4.1-actin complex, the effect similar to that of pure hemin. Whereas virtually no hemin was released from Hb and MetHb, high concentrations of hemin were released from crude iHCR preparations. After removal of this hemin fraction by Dowex resin, the iHCRs lost their destabilizing effect. We conclude that as the oxidation of Hb proceeds, the stabilizing effect of Hb on the membrane skeleton is gradually lost and the deleterious effect increases. The destabilization of the red cell membrane skeleton in the presence of crude iHCR is caused by release of hemin, which lowers the stability of membrane skeleton by weakening the spectrin-protein 4.1-actin interaction.

Actins

Structural and functional heterogeneity of alpha spectrin mutations involving the spectrin heterodimer self-association site: relationships to hematologic expression of homozygous hereditary elliptocytosis and hereditary pyropoikilocytosis.

Defects involving alpha spectrin (Sp) are found in patients with hereditary elliptocytosis and a related disorder, hereditary pyropoikilocytosis (HPP). We have previously found that the severity of hemolysis was related to the total spectrin content of the cells and the percentage of unassembled dimeric Sp (SpD) in the membranes, which, in turn, reflected the amount of mutant Sp in the cell. However, no data are available comparing differences in the function of various alpha Sp mutations to clinical severity. We now report studies of nine homozygotes or double heterozygotes for four alpha Sp mutations: alpha 1/74, alpha 1/46, alpha 1/65, and alpha 1/61, whose red blood cells (RBCs) contained only the mutant Sp and no normal Sp. Sp alpha 1/74, Sp alpha 1/46, and alpha 1/65 homozygotes differed strikingly in the severity of hemolysis that correlated with the severity of mutant Sp dysfunction, as reflected by the fraction of unassembled SpD in the membranes and the self-association of mutant Sp on inside-out vesicles. Homozygotes for Sp alpha 1/74 had a very severe hemolytic anemia and their SpD were virtually incapable of self-association, whereas SpD alpha 1/46 were not as severely affected. The Sp alpha 1/65 homozygotes had a relatively mild hemolytic anemia and their SpD showed the least impairment of function. Ultrastructural examination of membrane skeletons from subjects whose SpD self-association was severely impaired showed gross skeletal disruption and loss of hexagonal structure. In striking contrast, the homozygote for the mildly dysfunctional Sp alpha 1/65 had only a moderate disruption of the skeleton. Some of the homozygous or doubly heterozygous subjects also exhibited a partial deficiency of Sp that correlated with a RBC morphology characteristic of HPP, namely, marked microspherocytosis with virtual absence of elliptocytes. These data demonstrate striking differences in the function and structure of various alpha Sp mutants that underlie differences in clinical expression.

Adolescent

Metastatic thyroid carcinoma masquerading as lacrimal gland tumor.

A 56-year-old woman presented with orbital signs and symptoms suggestive of lacrimal gland tumor. An excised biopsy specimen was obtained and showed glandular tissue, which could be confused with lacrimal gland acini. Closer microscopic examination and immunohistochemical studies revealed a metastatic tumor of thyroid gland origin. Initially, there was no identifiable nodule in the thyroid, but 3 months later a thyroid nodule was found by ultrasound and radioisotope scan. The histopathologic appearance of the thyroid nodule was similar to that found in the orbit. This case demonstrates the usefulness of immunohistochemistry in establishing a diagnosis when the microscopic appearance is inconclusive.

Adenocarcinoma

Regulation of heme synthesis in the regenerating rat liver.

This investigation shows that the regulation of heme synthesis in the regenerating rat liver does not differ from the regulation in the normal liver. The heme saturation of tryptophan pyrrolase was found to be low, indicating a reduced concentration of heme in the regulatory heme pool of the regenerating rat liver. As expected, ALAS in the mitochondrial fraction was found to be elevated. It was also shown that ALAS in the regenerating rat liver can be induced by the porphyrinogenic drugs AIA and DDC and that heme reduces its activity. The decrease observed in the activity of cytosolic ALAS might be due to impaired synthesis of the enzyme but does not affect the regulation of the heme biosynthetic pathway.

5-Aminolevulinate Synthetase

Steroid-responsive idiopathic cold agglutinin disease: a case report.

We report a case of idiopathic cold agglutinin disease (ICAD) that responded well to corticosteroid therapy, though generally these patients show no response to such therapy. The cold agglutinins in this patient were found to be of low titer (1:32) and wide thermal range (4-37 degrees C). Three patients with ICAD were previously reported, also responsive to corticosteroid therapy and having the same characteristics of their autoantibodies. are likely to respond to corticosteroid therapy and that a therapeutic trial with such agents is warranted in these patients.

Adrenal Cortex Hormones

Effect of exercise on salivary composition and cortisol in serum and saliva in man.

The effect of exercise on electrolytes and cortisol levels in serum and saliva was examined in 27 young, healthy male volunteers who performed graded submaximal cycle exercise for nine min at up to 85% of their age-predicted maximal heart rate. Seventeen men performed the Wingate anaerobic test for 30 s. A significant increase in pulse rate and systolic blood pressure and a decrease in diastolic blood pressure were found, and serum concentrations of Na+, K+, and lactate were significantly elevated immediately after exercise. A nonsignificant increase in saliva and serum cortisol levels was found. Significantly lowered salivary flow rate and elevated salivary K+, protein, and lactate concentrations were found within ten min after exercise. Salivary Mg2+ was significantly elevated after anaerobic exercise only.

Adult

Mechanism of the luteolytic action of prostaglandin F-2 alpha in the rat.

PGF-2 alpha suppresses the LH-induced accumulation of cyclic AMP in young and mature corpora lutea (CL) of pseudopregnant rats, with mature CL being more sensitive. Calcium ions, and later phospholipase C activation, are believed to mediate this effect. In isolated CL of 2 and 10 days of age, depletion of extracellular calcium, or addition of calmodulin inhibitors or of 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxy-benzoate (TMB-8), did not prevent the suppressive effect of PGF-2 alpha. Phorbol 12-myristate 13-acetate augmented, rather than inhibited, the LH-induced cAMP accumulation in young and mature CL. Polyphosphoinositide turnover was stimulated by PGF-2 alpha in young, but not in mature CL. The suppression by PGF-2 alpha of luteal cAMP is therefore apparently not mediated by phospholipase C activation but two phosphodiesterase inhibitors, 3-isobutyl-1-methylxanthine and Ro-20-1724, abolished the inhibitory effect of PGF-2 alpha.

1-Methyl-3-isobutylxanthine