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Biomedical subjects

M Nathan

Publications and source records attributed to M Nathan.

At least 55 records · Page 3Linked to original sources

Generation of recombinant cytoplasmic domain of epidermal growth factor receptor with intrinsic protein tyrosine kinase activity.

We have generated a recombinant baculovirus using the high expression vector pVL941 containing the complementary DNA encoding the intracellular domain of the human epidermal growth factor receptor (EGFR-IC). Upon infection of Spodoptera frugiperda insect cells, protein tyrosine kinase-active EGFR-IC was produced. The expressed protein has a molecular weight of 61,000 and is specifically recognized by antibodies directed against peptides representing different regions of human EGFR-IC. Upon sonication of infected cells, EGFR-IC was detected in both the soluble and insoluble fractions of the cell lysate. About 20-50% of the expressed EGFR-IC was soluble. Metabolic labeling and protein analyses showed that EGFR-IC comprised 7% of newly synthesized proteins in the cytoplasmic lysate and 0.1-0.2% of the total soluble protein. We have used a three-step purification procedure (fast-Q-Sepharose and phenyl-Sepharose column chromatographies and 30% ammonium sulfate precipitation) to purify EGFR-IC to 85% purity with 15-20% recovery from the initial soluble lysate. A yield of 3-4 mg of purified EGFR-IC has been consistently produced from 20 roller bottles with 2-4 x 10(8) infected cells/bottle. The tyrosine kinase activity was retained through purification. The enzyme demonstrated much higher autophosphorylation activity in the presence of Mn2+ than Mg2+. Phosphopeptide mapping revealed the same autophosphorylation sites utilized by EGFR-IC as those identified in wild-type EGFR. EGFR-IC-catalyzed phosphorylation of either a synthetic peptide representing the major autophosphorylation site or angiotensin II showed that the baculovirus-expressed EGFR-IC exhibits similar enzymatic kinetic characteristics to the intact activated EGFR kinase.

Animals↗

The danger of an inadequate water intake during prolonged exercise. A novel concept re-visited.

To prevent thermal injuries during distance running, the American College of Sports Medicine proposes that between 0.83 and 1.65 l of water should be ingested each hour during prolonged exercise. Yet such high rates of fluid intake have been reported to cause water intoxication. To establish the freely-chosen rates of fluid intake during prolonged competitive exercise, we measured fluid intake during, body weight before and after, and rectal temperature after competition in a total of 102 runners and 91 canoeists competing in events lasting from 170-340 min. Fluid intakes during competition ranged from 0.29-0.62 l.h-1; rates of water loss ranged from 0.69-1.27 l.h-1 in the runners; values were lower in the canoeists. Mean post-race rectal temperatures ranged from 38.0-39.0 degrees C. There was no relationship between the degree of dehydration and post-race rectal temperature. We conclude that hyperthermia is uncommon in prolonged competitive events held in mild environmental conditions, and that exercise intensity, not the level of dehydration, is probably the most important factor determining the postexercise rectal temperature. During prolonged exercise in mild environmental conditions, a fluid intake of 0.5 l.h-1 will prevent significant dehydration in the majority of athletes.

Adolescent↗

Restrictiveness-permissiveness of their environment as perceived by kibbutz twins and singletons.

This research compares similarities and differences between kibbutz twins and singletons on individual perceptions of extent of restriction imposed by their fathers and mothers, teachers, caretakers and peers with regard to the children's choices, plans, and actual activities. During the past two years, the parents of all kibbutz twins in Israel of age 1 to 18 have been contacted. They provided background information about themselves and their twin children. In each kibbutz, two control singletons were selected of the same sex and age for each twin pair, yielding a "quartet". With the aid of a mapping sentence, questionnaires were constructed to help ascertain the child's role in life areas such as family, friendship, school, hobbies, work, amusement. Questionnaires with the same facet design are being administered to children (twin and singleton), mothers, fathers, teachers, and caretakers. In addition, each child is given a battery of tests--including the verbal WISC, Block Design, Raven Matrices, and Reading Comprehension. The children will be interviewed and tested in three successive years, beginning either in grade 4 or 5. Data will thus be obtained on changes in perception of permissiveness-restrictiveness and their relation to performance at ages 9 to 13. To date 9-year-olds in 14 kibbutzim have been interviewed. Analyses of responses to four questions are presented in this paper. The preliminary analyses indicate that twins and singletons have similar means and distributions with regard to the extent to which the children feel they are told what to do by either parent.

Adolescent↗

Physiological and biochemical measurements during a 4-day surf-ski marathon.

We studied competitors in the 1983 Texan Challenge surf-ski paddle marathon to determine the effects of 4 days prolonged paddling on sweat rates, rectal temperatures, renal function, serum glucose, free fatty acid, porphyrin and C-reactive protein levels and serum creatine kinase activity. Sweat rates during the race varied from 0.5 to 1.0 l/h, and peak rectal temperatures did not exceed 38 degrees C, even in the most dehydrated subjects. Renal function was unchanged during the race. Plasma renin activity remained low during the race but C-reactive protein levels and serum creatine kinase activity were elevated. Seventy per cent of the subjects had immediate post-exercise blood glucose levels below 3.9 mmol/l after the 1st and 4th days, and 27% had values below 3.0 mmol/l, one competitor requiring intravenous glucose therapy on the beach. Surf-ski paddling is therefore associated with low sweat rates, low levels of dehydration, low body temperature and unchanged renal function. The low post-exercise blood glucose levels indicate that competitors must eat high-carbohydrate diets for the duration of the event and must either eat carbohydrate-containing foods or drink concentrated carbohydrate solutions while paddling.

Blood Glucose↗

Prostaglandin E1 infusion in unstable angina: effects on anginal frequency and cardiac function.

Intermittent vasospasm and/or platelet aggregation may play an important role in producing transient coronary artery obstruction leading to an unstable ischemic syndrome. To determine whether intravenous infusion of prostaglandin E1 (PGE1) a known coronary vasodilator and inhibitor of platelet aggregation, produces salutary effects in unstable angina, we evaluated its effects in 19 patients with an unstable acute ischemic syndrome. PGE1 produced a significant decrease in the number of episodes of rest angina (p less than 0.001) and eliminated the need for intravenous nitroglycerin and morphine in 10 patients. These salutary clinical effects were associated with a significant (p less than 0.05) reduction in mean arterial pressure, mean pulmonary artery pressure, mean pulmonary capillary wedge pressure, and the double product, without a reduction in the endocardial perfusion gradient (aortic diastolic blood pressure--mean pulmonary capillary wedge pressure). Adverse effects were generally minor and easily controlled. Thus PGE1 infusion may be of value in the treatment of acute unstable ischemic syndromes.

Aged↗

Similarities in test scores and profiles of kibbutz twins and singletons.

Resemblances on five cognitive tests were compared in fifty quartets of school children. Each quartet consisted of a twin pair (MZ or DZ) and a matched singleton pair from the same kibbutz peer group. Similarities of MZs and DZs on test scores essentially replicate those reported previously in other studies. The median correlation for singleton control pairs is 0.29, as compared with that of 0.26 reported in the Texas Adoption Study for unrelated children raised in the same home. In the two spatial tests, control pairs were as similar as the DZ pairs. This suggests a more powerful influence on shared environment in aspects of perceptual performance. A new structural analysis (POSAC) of individual profiles of test scores is presented. Comparison of space diagrams of MZ, DZ, and singleton pair profiles shows systematic differences in structure among the three groups, in accordance with the predicted levels of genetic influences. Such structural differences transcend mere differences in size of correlation, and may give more stringent evidence for the respective roles of genetics and environment.

Adolescent↗

The incidence and nature of rugby injuries experienced at one school during the 1982 rugby season.

Schoolboy rugby injuries are a cause for concern in medical and non-medical circles, but few scientific investigations into their nature and frequency have been undertaken. We therefore decided to carry out a prospective study of the pattern of injuries occurring during one rugby season among boys in age groups ranging from under 10 to under 19 at one school, and to relate them to age, team level, time of season, position played and phase of play. Results showed that there are well-defined physical factors and conditions of play most likely to cause injury, and suggestions are made as to how these injuries could be minimized.

Adolescent↗

[Fibroma of the ureter].

Fibrous polyps are very rarely found benign tumors of the ureter. Therapy should consist local resection of the tumor carrying part of the ureter with reestablishment of ureteral continuity. The diagnosis can be suspected from clinical signs, urography and retrograde pyelography. One own case of unusual morphology of ureteral fibroma is presented.

Adult↗

Effects of acute and chronic minoxidil administration on rest and exercise hemodynamics and clinical status in patients with severe, chronic heart failure.

The effects of acute and chronic oral administration of the vasodilator minoxidil on hemodynamics, oxygen consumption, exercise performance, and clinical status were investigated in 10 patients with severe, chronic heart failure refractory to digitalis and diuretic therapy. The cardiac index was 1.99 +/- 0.38 liters/min/m2 at rest and 2.88 +/- 0.79 at symptom-limited maximal exercise on conventional therapy, compared with 2.64 +/- 0.33 liters/min/m2 at rest and 3.55 +/- 0.84 at maximal exercise after short-term minoxidil administration (p less than 0.02, control versus minoxidil at both rest and exercise). Stroke volume was increased after minoxidil treatment, without significant effect on heart rate. Systemic vascular resistance was decreased by minoxidil from 2,050 +/- 722 to 1,325 +/- 374 dynes . s/cm-5 at rest and from 1,500 +/- 830 to 1,206 +/- 589 dynes . s/cm-5 at maximal exercise (p = 0.01, control versus minoxidil). No significant effect was observed on left ventricular filling, right atrial, or mean pulmonary arterial pressure, but pulmonary vascular resistance decreased both at rest and on exercise (p less than 0.05). Maximal exercise oxygen consumption increased from 8.9 +/- 3.2 ml/kg/min on conventional therapy to 10.5 +/- 2.4 on minoxidil therapy (p less than 0.03), median maximal exercise work load increased from 25 to 50 W and medium exercise duration increased from 6.0 to 9.0 minutes. On chronic minoxidil administration all 5 patients who completed a scheduled 6 week follow-up showed symptomatic improvement. However, worsening edema developed in all patients, requiring increased diuretic dosage and close supervision. Symptoms of ischemic heart disease worsened in 2 of 10 patients. We tentatively conclude that minoxidil may be a useful vasoactive agent in the pharmacologic therapy of severe chronic heart failure.

Adult↗

Quantitative importance of non-skeletal-muscle sources of N tau-methylhistidine in urine.

Direct measurement of N tau-methylhistidine turnover in skeletal muscle, skin and gastrointestinal muscle indicates that these three tissues contribute only 24.9, 6.8 and 9.8% of the total urinary excretion. Measurement of the decay rate of radioactively labelled N tau-methylhistidine in urine indicates that skeletal muscle accounts for 74.5% of the urinary excretion and this is probably an overestimate. These results suggest that the common assumption, that N tau-methylhistidine in urine originates almost entirely from skeletal muscle, may be wrong.

Animals↗

Clinical experience with the Lillehei-Kaster valve prosthesis.

The Lillehei-Kaster valve was used in 215 patients over a 7-year period. The aortic valve was replaced in 81 of them. Hospital mortality was 21% (17 patients). Ten patients were lost to follow-up and long-term mortality was 5% (3 patients). The incidence of thromboembolism was 2.6 per 100 patient-years, and actuarial survival was 96% at 5 and 87% at 7 years. Mitral valve replacement was performed in 108 patients. Hospital mortality was 20% (22 patients), 24 patients were lost to follow-up, and long-term mortality was 13% (11 patients). The combined incidence of thromboembolism was 5.0 per 100 patient-years, and actuarial survival was 81% at 5 years and 75% at 7 years. In both groups, the majority of patients improved clinically. Fifteen patients had double-valve replacement, and 11 had coronary revascularization in addition to valve replacement.

Adolescent↗

Serum alkaline phosphatase phenotypes and secretor status in several Jewish populations in Israel.

The frequency of serum alkaline phospatase phenotypes and secretor trait is determined for Israeli Jews originating from three distinct geographical regions: Eastern and Central Europe (group I), North Africa (group II) and the Middle East (group III). The frequency of the Pp 2 serum alkaline phosphatase phenotype in each of the three groups were 33.56% (group I), 29.79% (group II) and 24.07% (group III). The average frequency for the three groups combined was 30.58%. The corresponding frequencies of the se gene in the three groups were 0.4765, 0.5149 and 0.5468, respectively, and the average frequency for the total number examined was 0.4978.

Adult↗

ABO-typing of ancient skeletons from Israel.

Sixty-eight ancient skeletons, unearthed at Jerusalem and En Gedi and, according to the archeological data belonging to Jewish residents of these places from about 1,600 to 2,000 years ago, were ABO-typed by means of the hemagglutination-inhibition test. The blood groups of 13 skeletons were undiagnosable and the remaining 55 showed the following distribution: 30.91% A-group, 14.54% B-group, 50.91% AB-group and 3.64% O-group. According to these findings, the population to which these skeletons belonged must have had a high frequency of genes IA and IB, and a low occurrence of O blood group and its related IO gene.

ABO Blood-Group System↗