Biomedical subjects
A Kahn
Publications and source records attributed to A Kahn.
Receptor-mediated chemotactic response of a macrophage cell line (J774) to thrombin.
Human alpha-thrombin, the procoagulant activation product of prothrombin, elicits chemotaxis in several macrophage-like continuous cell lines, most notably J774. Effective alpha-thrombin concentrations eliciting cell movement range from 10(-10) to 10(-6) M, with the optimal response occurring at about 10(-8) M. At the latter concentration, the response is equivalent, on a molar basis, to that observed with f-Met-Leu-Phe-OH, the positive control used in these experiments. Blockage of alpha-thrombin's active center with diisopropylfluorophosphate or by tryptic proteolysis of the procoagulant exosite (i.e., gamma-thrombin) does not decrease chemotactic activity. However, formation of enzymatically inactive complexes with AT3 or hirudin eliminates chemotactic potency. Competition chemotaxis assays, carried out by comparing the abilities of varying concentrations of test substances placed in the upper compartment of Boyden chambers to inhibit gradient-oriented movement of cells toward a fixed concentration of thrombin in the lower compartment, demonstrate that, although the modified forms of thrombin cross-compete, formylated peptide will not inhibit thrombin's chemotactic effects. Binding studies carried out using 125I-alpha-thrombin on paraformaldehyde-fixed J774 cells show a Kd of approximately 7.5 nM with an estimated 14,100-binding sites/cell. This Kd is in agreement with the optimal chemotactic thrombin dose (approximately 10 nM). On the basis of the competition chemotaxis assays and the radiolabeled thrombin-binding data, it is proposed that unique thrombin-specific chemotactic receptors exist on J774 cell membranes, and that these receptors are distinct from those mediating chemotaxis by agents such as formylated peptides.
Rubella immunization policies for health care personnel.
Rubella vaccination of children in the United States has resulted in a shift in the age of affected and susceptible individuals toward older age groups. In an effort to reduce the incidence of congenital rubella syndrome, the American Academy of Pediatrics and the Advisory Committee on Immunization Practices have recommended rubella vaccine for all male and female medical personnel who might contract and spread rubella to pregnant women. A survey of hospitals and outpatient practices in Little Rock, Arkansas, revealed extremely low compliance with the recommendation, suggesting the need for further education or legislation on rubella immunization for health care personnel.
[Sudden and unexplained infant death].
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Oculocardiac reflex in near miss for sudden infant death syndrome infants.
To gain insight into the role of the vagus nerve in sudden infant death syndrome (SIDS), 180 infants ranging in age from 1 to 66 weeks were examined with respect to cardiac response to ocular compression. There were 35 near-miss infants, 76 normal siblings of SIDS victims, and 69 normal control infants. Asystoles within the control group ranged from 0.3 to 1.8 seconds. Ten of 35 (28%) near-miss infants and 10/76 (13%) siblings had asystoles greater than 2.0 seconds when first tested. When statistically compared, the near-miss infants were significantly different from both the control infants and the siblings (Kruskal-Wallis procedure: P less than .01, and P less than .05, respectively). It is concluded that in the first year of life a significant number of near-miss infants have an exaggerated cardiac response to ocular compression. Furthermore, the presence of prolonged asystoles in certain siblings indicates that vagal hypersensitivity, as manifested by ocular compression, may be, in part, hereditary.
Genetic and epigenetic control of the pyruvate kinase isozymes in mammals.
In man, patients with hereditary red cell pyruvate kinase (PK) deficiency have their enzyme concomitantly affected in both red cells and liver (PK-L), such that red cell L' and liver L PK subunits appear to be encoded by the same structural gene. Very recently, a mutant M1 PK has been described in muscle from a special mouse strain in which the M2 PK was concomitantly modified. Thus, it has been suggested that the M1 and M2 PK subunits are also encoded by the same structural gene, a gene distinct from that encoding L' and L. In this paper, we show that synthesis of each of the four PK subunits is specified by a different specific mRNA. Two structural genes, but at least four different mRNAs seem therefore to control synthesis of the PK isozymes. Genetic and epigenetic mechanisms responsible for generation of this diversity at the RNA level are discussed. In addition to these mechanisms of PK diversity, some PK subunits can be modified by post-translational events. In red cells, for instance, cell aging is associated with a progressive, partial proteolysis of the C-terminal extremities of L' subunits, ultimately resulting in cleavage of the phosphorylatable site.
Molecular organization of human L' and L pyruvate kinases.
Extremities, peptide maps and phosphorylatable site localization of human erythrocyte L' and liver L pyruvate kinases (EC 2.7.1.40) were investigated. L' and L subunits seemed to have similar, blocked NH2 termini and differ in their sensitivity to carboxypeptidase A, that is to say in their C-terminal ends. After digestion by Staphylococcus aureus V8 protease, the phosphorylated sites of both L' and L subunits were located on those peptides which were different in L' and L, that is to say on the C-terminal sides. A mild proteolytic attack of the native tetrameric enzymes by trypsin partially degraded the phosphorylatable peptides without removing the phosphoserine residue; in the same conditions, chymotrypsin split off this phosphorylated residue and subtilisin totally degraded the phosphorylated peptides. From these results it appears, therefore, that age-dependent proteolytic degradation of L' subunits in old red cells involves the C-terminal side of the molecules, ultimately resulting in cleavage of the phosphorylated site. Since erythrocyte L' and liver L subunits are encoded by different species of messenger RNAs, our results indicate, in addition, that these messenger RNA species should differ by their 3' coding sequences.
Two different species of messenger RNAs specify synthesis of M1 and M2 pyruvate kinase subunits.
A study was performed to determine whether M1 and M2 pyruvate kinases were synthesized under the direction of one or two messenger RNAs. We compared M1 and M2 pyruvate kinases purified from fresh tissues with those neosynthesized under the direction of messenger RNAs from tissues synthesizing either M1 or M2. RNA was isolated from rat muscle, lung, spleen and kidney by ethanol precipitation in 7 M guanidium chloride, translated in rabbit reticulocyte system and newly-synthesized pyruvate kinase subunits were purified by microimmunoaffinity chromatography. Pyruvate kinase from fresh muscle and spleen was purified in one step by a similar process. Muscle and spleen RNA directed the synthesis of M subunits with molecular weights of approx. 61000 and 62000, respectively, the same as those of the corresponding fresh tissue monomers. In addition, peptide maps obtained by partial digestion of neosynthesized M1 and M2 with V8 protease from Staphylococcus aureus confirmed that these polypeptides were clearly different.
Cellulose acetate electrophoresis of protein kinases: detection of the active forms using various substrates.
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Cotranslation of L and L' pyruvate kinase messenger RNAs from human fetal liver.
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Characterization of messenger RNA for aldolase B in adult and fetal human liver.
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Home monitoring of infants considered at risk for the sudden infant death syndrome. Four years' experience (1977-1981).
From 1977 to 1981, 500 infants had been referred to evaluate their risk for the sudden infant death syndrome (SIDS). These included 186 infants who had presented an event (prolonged apnea, hypotonia, pallor or cyanosis) initiated while asleep, 133 siblings and 181 "controls". All-night polygraphic recordings were performed in all infants, and if indicated by the history of the infants, complementary clinical investigations were done. These procedures led to the identification of 50 infants considered at risk for SIDS (10% of all referrals): 30 near-misses for SIDS, 10 siblings and 10 infants with a minor incident during sleep but with abnormal polygraphic recordings. These 50 infants (group I) were monitored at home during sleep with the help of a cardiac and respiratory monitor. Eight infants not considered at risk were monitored similarly at the request of their parents (group II). Forty of the 50 infants in group I presented with repetitive sleep apneas and bradycardias, and required stimulation by their parents to regain normal cardiorespiratory rhythm. Twelve had to be resuscitated at least once for a life-threatening event. None of the infants in group II showed alarms during sleep. Monitoring could be discontinued after a mean length of 7.2 months for the infants in group I, 4.1 months in group II. It is concluded that if identified in time through adequate investigations, some infants may be protected against SIDS through home monitoring. This approach requires expensive and well trained teams, ready, at any time, to cope with the problems that may arise in the homes of the monitored infants.
Adjuvant chemotherapy in advanced head and neck cancer. An update.
Two courses of triple-agent chemotherapy were given to 47 patients with advanced head and neck cancer. All but one patient with a nasopharyngeal carcinoma had resectable stage III and IV squamous cell carcinoma. Eighty-eight percent of the patients responded to the chemotherapy with a 50 percent or greater decrease in tumor size. Forty-three patients underwent surgical resection and 19 were histologically upgraded to stage II or better (T less than 2 cm, N0). None of these 19 patients have relapsed, with follow-up ranging from 12 to 42 months. In 12 of the 47 patients, recurrent tumor developed within the first 18 months of follow-up.
Pyruvate kinases from human erythrocytes and liver.
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Molecular studies of liver aldolase B in hereditary fructose intolerance using blotting and immunological techniques.
Hereditary fructose intolerance is due to a deficiency of liver aldolase (aldolase B). Little is known about its molecular mechanisms. We have tried to demonstrate the presence of the molecule and have explored the possibility of genetic heterogeneity. Liver samples from fifteen cases of hereditary fructose intolerance due to aldolase B deficiency were studied by various electrophoretic techniques. After electrophoresis on polyacrylamide gels, proteins were electrophoretically transferred on to nitrocellulose filters. They were treated with specific antialdolase B antibodies, and then with radioiodinated protein A, followed by autoradiography. Investigations included: (a) sodium dodecyl sulphate electrophoresis, in order to detect the presence of immunologically reactive molecules and to estimate the subunit size; (b) attempts to discover charge anomalies of the native molecule and of its subunits, by the use of: Isoelectric focusing of the native enzyme. Isoelectric focusing and non-equilibrium pH gradient electrophoresis (NEPHGE) after dissociation in urea. The major results were the following: (1) In all cases a cross-reacting material was found, with a molecular subunit size of 38000, indistinguishable from that of controls. (2) Evidence for molecular heterogeneity of the disease was provided by two types of data: amount of apparent immunologically reactive protein, which varied from less than 3% to 100% of that of controls; and charge data, aldolase B from seven patients showing an increased negative charge and from one patient a normal charge.
Gene conversion in the shibirets locus of Drosophila melanogaster.
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Pyruvate kinase and phosphofructokinase isozymes in childhood cancers.
Pyruvate kinase and phosphofructokinase isozymic expression have been investigated in 62 childhood cancers by electrofocusing and immunoneutralization. Isozymic expression was roughly intermediate between that of the corresponding normal adult and fetal tissue. There were unique features distinguishing malignant from both adult and fetal tissues. In addition, phosphofructokinase and pyruvate kinase appeared to be excellent markers for nervous tissue and skeletal muscle differentiation. In neuroblastomas there was a close relationship between the differentiation level of tumors and their isozyme composition. The same phenomenon was observed in rhabdomyosarcomas and teratomas.