Studies on obesity. III. effect of triiodothyronine (T3) on thyroglobulin autoantibodies in euthyroid obese subjects.

Effect of T3 therapy on tanned red cell agglutinating thyroglobulin (TRC-TG) antibodies in 10 obese subjects without apparent thyroid disease was investigated. Six other obese subjects without thyroid dysfunction and of approximately the same mean age who also had circulating TRC-TG antibodies served as control subjects and were untreated. In vitro thyroid tests (TSH, total and free T4) performed before T3 therapy, as well as clinical examination, showed thyroid function to be normal in all subjects, and there was no evidence of thyroiditis. TRC-TG antibodies were present in low to moderate titers of 40-1280 in control subjects as well as in subjects selected for T3 treatment. Therapy with T3 was started at 50 mug/day and gradually increased to a maximum of 250 mug/day, depending on clinical needs. T3-treated as well as untreated obese control subjects were all maintained on a high protein, low fat, low carbohydrate diet. Duration of T3 therapy varied from 2-8 mo, and in all but one T3-treated subject, TRC-TG antibodies completely disappeared. In the one exceptional case, TRC-TG antibody titer decreased from 1280 to 80 after 7 mo of therapy. In non-T3-treated obese control subjects, antibody titers remained at the same levels throughout the observation period, thereby indicating a lack of spontaneous regression of circulating immune response. Therapy with T3, by inhibiting TSH, may have caused regression of inapparent immunologic thyroid lesion, thus leading to the disappearance of circulating TRC antibodies; alternatively, T3 specifically may have accelerated catabolism of thyroid antibodies. The latter possibility is favored in the absence of clinical and laboratory evidence of thyroiditis in T3-treated subjects.


Control of calcium absorption: effect of sodium chloride loading and depletion.

In six out of eight patients with normal parathyroid function and in two subjects with hypoparathyroidism, sodium chloride loading was shown to increase calcium absorption as measured by the 47Ca absorption test. Although no significant change was seen in the renal and fecal excretion of calcium, a slight decrease in total serum calcium did occur with increased sodium intake. The change in calcium absorption was not accompanied by a detectable change in calcium balance. Therefore, a compensatory change in gastrointestinal calcium secretion must have occurred. Sodium intake has an effect on calcium in the gastrointestinal tract, which is independent of parathyroid hormone. Sodium intake should be considered when results of studies of calcium metabolism are compared.


Changing attitudes of medical teachers towards medical education.

If medical education is to improve, this is largely dependent upon the attitudes of clinical teachers towards their own teaching and their students' learning. The aims and objectives of our workshop method of medical teacher training therefore includes some in the affective domain. Based on the theory of cognitive dissonance the experience-linked practical problem solving approach of the workshop encourages behaviour change, presuming this to cause 'attitude change'. Testing by means of a specially constructed and validated Likert-type attitude scale shows that attitudes do improve significantly and consistently over the 5 days of our workshops. A follow-up study shows these effects to be maintained and taken back to the participants' own medical schools.


A comparative study of teachers' attitudes in the teaching of undergraduate medical students.

Senior staff of the departments of medicine, surgery and general practice in each medical school in the United Kingdom were asked to annotate the same case studies which had been prepared by medical students. Analysis of the annotations showed that general practitioners demanded much greater consideration by the student of the patient, his family and his environment, whereas physicians and surgeons tended to be more disease orientated. Nevertheless, expectations and attitudes of teachers in similar departments are remarkably diverse and this highlighted the potential role of the case study as an educational tool for staff and students alike. Many departments need to clarify the difference between undergraduate and postgraduate teaching objectives.


The organization of a postgraduate training course for medical advisers in the pharmaceutical industry.

A postgraduate training and education course for physicians working in the field of pharmaceutical medicine is described. The course proved welcome and acceptable to the participants and provided valuable experience for the organizers. The scientific content and information gained in organizing the course have been incorporated in the planning of a postgraduate diploma course in pharmaceutical medicine.


Preclinical students' views on knowing cancer diagnosis: a data-based class exercise.

One way of tackling the problems of demonstrating the relevance of psychology to medical practice as well as to medically-inexperienced preclinical students is to elicit their views on topical issues and present them with a comparison of their own data and any available in the medical literature. In a survey of preclinical students' views on being told their diagnosis and prognosis in the hypothetical case of cancer, high agreement in the proportions wanting to be or not to be told was found between the responses of students and a sample of cancer patients reported by Kelly & Friesen (1950). The exercise served to demonstrate that the 'to tell or not to tell' debate is one in which students can also be involved.


Instruction on death and dying for the medical student.

With instruction on death and dying beginning to be included in the curricula of many medical schools and the likelihood that this development will spread, it is timely to examine the best ways in which the subject can be taught. The most important need at this stage is the creation of objectives. Nine objectives have been briefly outlined which have either been reported on by teachers in the field or which seem to be pertinent to death education. The focus on objectives rests on the premise that the format and content of courses will follow largely from the goals that are selected. Questions of who should teach death and dying, when it should be taught and what format should be used, are discussed.


Migration of Baroda medical graduates, 1949--72.

1. The migration of doctors from Medical College, Baroda, is studied in detail. 2. From 1949 to 1972, 584 doctors migrated to other countries and only twenty-nine doctors have returned so far. The incidence of migration is to the extent of 39-75%. 3. Among those who migrated 77-7% have gone to U.S.A. and 11-7% have gone to the U.K. 4. Ninety-four women graduates out of 241 passed prior to 1971 are abroad.. 5. The majority migrate for better and more comfortable living conditions. A small number migrate for better research facilities and encouragement. Those who are denied the opportunity of a post-graduate training also migrate. 6. Migration of doctors, though universal, is disturbingly high in India and a major cause of concern to the government and the educationist.


Performance of women medical graduates from Medical College, Baroda, 1949--74.

Women account for 15% of the total admissions in medicine. 271 women have graduated from Medical College, Baroda in 25 years. The examination results are better in women than in men. Obstetrics and gynaecology is the most common speciality selected by women. Job satisfaction is found in 87% of women. Unmarried women account for 15%, 66% have married a doctor and 19% are married to non-medical spouse. Emigration is to the extent of 39%.


Married women doctors' training and re-employment schemes in the West Midlands Region, with particular reference to psychiatry.

The response of one region to the Department of Health and Social Security recommendations on re-employment of women doctors contained in H.M. 69(6) is described. In many specialities there has been an encouraging return of married women doctors to medical practice within the hospital service. In the field of psychiatry the experience in a local sub-regional training scheme suggests that graduates of a high calibre can be attracted back to this speciality on a part-time basis for training; the training has been acceptable for full qualification and the examination success rate is high; part-time appointments, including senior registrar and consultant posts, can be obtained; it would not appear that training need, in the first instance, be confined to those people working in a main teaching centre; the satisfactory resolution of any conflict between trainees' domestic and professional commitments is important, as is a flexible approach to the individual professional needs of the trainees. Such schemes appear to tap a valuable source of potential manpower which higherto has not been fully utilized.


Constructing a new course for undergraduate teaching of general practice.

This paper outlines in Part I the method used to analyse and re-define a set of educational objectives on which a new course of teaching of general practice in the later clinical years is based. Part II describes the course, the learning methods, behavioural attainments and the techniques of evaluation to be implemented. A year was spent on the exercise by a group which comprised the professorial head, consultant senior lecturer and a senior registrar tutor from the Department of General Practice, Queen's University, Belfast, and a consultant educationalist, a senior lecturer, Department of Education, of the same University.


General practice teaching--within the hospital.

A programme of integrated teaching by consultants and general practitioners is described. The teaching took place in the hospitals used for the purpose by the Medical Faculty of the University of Birmingham.


Fluid exchanges through capillary walls: a modification of the Starling hypothesis.

In textbooks of physiology it is usually stated that fluids are extravasated from the arterial ends of capillaries, because, there, the outward transmural pressure of the blood exceeds its net inward osmotic pressure. At the venous ends, however, the position is reversed. The fluids are, therefore, reabsorbed. Inthis paper it is argued that this is not a true picture of what must really happen. For, having once become equal there is no reason why the pressures should ever cease to be so. Instead, fluids are absorbed at exactly that rate which just keeps pace with falling hydraulic pressure, as the blood proceeds along the capillary loop. Moreover, the forces are indeed shown to be equal at the extreme venous ends of the capillaries. It is further argued that, though this mechanism might operate anywhere in the horizontal position, it could not possibly work in the feet of a standing man. For here the hydraulic blood pressure everywhere greatly exceeds the osmotic pressure of plasma proteins. An addition to Starling's hypothesis is therefore suggested to adapt it to dependent tissues. An experiment by which the validity of this addition might be tested is described.


Biological function of ascorbic acid and the pathogenesis of scurvy: a working hypothesis.

This communication advances the proposal that all the diverse manifestations of scurvy can be attributed to depolymerisation of ground substance glycosaminoglycans brought about by exposure to uninhibited cellular hyaluronidase. It suggests that ascorbic acid exerts its prime biological function indirectly by incorporation into a glycosaminoglycan residue to form the physiological hyaluronidase inhibitor. The therapeutic implications of this working hypothesis are briefly discussed.


Clinical method is all wrong.

Two models of diagnostic clinical behaviour are studied: the conventional in which data gathering precedes interpretation, and the sequential in which each item is evaluated as it is acquired and incorporated into decision making, usually of binary type. The second model is proposed as that more closely related to the reality of clinical practice and also as potentially more capable of exploiting intellectual resources and creating logistic economies.


Folate deficiency and neurological disorders in adults.

The restless legs syndrome could represent a folate responsive disorder in both patients with acquired-folate deficiency and those with familial symptomatology. Patients with acquired folate-deficiency could be divided into two subgroups. (i) those with minor neurological signs (restless legs syndrome, vibration sense impairment and tactile hypoesthesia in both legs with diminished ankle jerks and a prolonged or assymetrical Achilles-reflex time) and (ii) those with major neurological signs (subacute combined degeneration with or without neuropathies). In some of these patients the classical triad of the malabsorption syndrome is replaced by another triad, constipation, abnormal jejunal biopsy and abnormal d-xylose absorption. A low folic serum acid level could induce minor neuropsychiatric symptoms while an additional low CSF folate could induce major neurological symptoms in spite of the presence of a normal erythrocyte folate level and in the absence of frank anemia. Possible further studies are described.


Is there a protein ligase?

Results obtained from experiments dealing with mammalian, bacterial, phage and mitochondrial protein biosynthesis as well as certain enzymatically performed amino acid replacement studies on Kunitz trypsin inhibitor strongly suggest that protein ligation may be occuring in vivo. Amino acid substitution experiments prove the reversibility of endopeptidase reactions, and protein ligation is the reverse of endopeptidase reaction. These experiments are discussed in detail and the suggestion is made that ligation may also be useful in the repair of certain essential proteins which may become damaged.


A newly developed therapeutic surgical and cardiac intensive care monitor.

A computerized intensive care monitor patterned after a clinical system operating at the University of Alabama has been developed. The system, which has been operating in an intensive care unit since February 1973, is equipped with conventional bedside biomedical instrumentation, special-purpose devices, and keyboard/display terminals interfaced with a minicomputer. Measurement of vital parameters as well as the automatic infusion of blood controlled by the computer in a closed loop feedback mode is available. Communication with the computer via the bedside terminals permits the display and retrieval of clinical data, entry of blood gas measurements and pressure limits for blood infusion, the revision of measurement status, and the control of the computer in measuring cardiac output. The administration of blood and intravenous fluid may be achieved under computer or manual option.


Endocardial electrograms and pacemaker sensing.

Endocardial electrograms in 77 acute cases (at time of pacemaker implant) and 56 chronic cases (at time of pulse generator replacement, with electrodes in service for at least 6 months) were recorded. The peak-to-peak voltage and rate of rise, or slew rate, were compared acutely and chronically. Both parameters must simultaneously exceed given thresholds to trigger the sensing circuits of implantable pacemakers. The average chronic slew rate was half the average acute value. The maximum slew rate and voltage swing occur during the intrinsic deflection as a virtually straight line segment of the electrogram. The findings are consistent with the predictions of a mathematical model for genesis of the electrogram, and also with a model for explaining acute-to-chronic changes in stimulation current thresholds.


Hydrogen-induced microelectronic capacitor failure in pacemakers.

Ceramic chip capacitors used in hybrid microelectronics for cardiac pacemakers are usually highly reliable. However, under certain conditions of capacitor construction, capacitor materials, mounting techniques, and environmental conditions, high failure rates may occur. A specific example is presented in which a ceramic capacitor used in an implanted pacemaker delaminated and failed approximately 30 days after being implanted. The failed capacitor caused a pulse rate rise, but due to circuit design techniques, the rate increase was limited to an acceptable value. The capacitor that failed was from an isolated lot of capacitors that was manufactured using pure palladium plates. The circuit containing this capacitor was hermetically sealed within a titanium case by welding. During the welding, a small amount of hydrogen was released from the titanium which, over a period of 2 to 4 weeks, was absorbed by the palladium plates in the capacitor. By absorbing the hydrogen, the palladium plates exhibit a volumetric expansion of sufficient magnitude to crack and delaminate the capacitor to the point of failure. Subsequently, the recurrence of this failure mode has been avoided by using capacitors containing special palladium alloys that cannot absorb hydrogen. This phenomenon is of interest to pacemaker designers since mercury batteries used in conventional pacemakers generate large amounts of hydrogen and potentially may be responsible for complications when used in conjunction with capacitors containing palladium.


A diameter-independent blood flow measurement technique.

A phase difference technique for measuring true volume flow rate has been developed. The concept utilizes the phase difference from unequal transit times between bursts of ultrasonic energy transmitted simultaneously against and with the blood flow. A theoretical analysis reveals that the volume flow rate sensitivity (V/ml/sec) for a point crystal illumination pattern directed diagonally through the center of the vessel is a function of the inverse of the diameter. But an illumination pattern orientated perpendicularly to the vessel axis, which spans the entire diameter of the vessel, yields a volume flow rate sensitivity independent of the diameter. Line illumination, in contrast to point illumination, does not require the vessel diameter to be measured in order to establish the sensitivity factor, and a change in diameter does not alter the sensitivity factor. Line illumination has a considerable advantage when used on small vessels in which the ratio of wall thickness to the lumen diameter is large and is often variable.


Semi-invasive method for instantaneous and phasic measurement of arterial blood pressure.

A method for the instantaneous and phasic measurement of arterial blood pressure that eliminates the necessity of entry of the artery is described. This is accomplished with a miniature strain gauge transducer enclosed within a plastic cuff which is positioned around the artery. The device is suitable for monitoring arterial pressure in seriously ill patients and for chronic measurements of pressure in untrained and unanesthetized laboratory animals. The system was found to be stable, and recorded pressures were virtually identical to those measured intra-arterially with a catheter-tip micromanometer.


A prospective evaluation of open prefrontal leucotomy.

Forty-three patients received an open prefrontal leucotomy for severe and intractable psychiatric illnesses. As a result of the operation three patients died, three developed personality changes and one had repeated grand-mal seizures. Of the 40 patients followed up for six months, 57-5% showed marked improvement in their clinical state and 30-0% mild to moderate degrees of improvement whilst no patient's condition was considered to be worse. Significant improvement was obtained after operation in the mean scores on the Hamilton Anxiety Scale, the Hamilton Depression Scale, the Beck Depression Scale and the Neuroticism Scale of the Eysenck Personality Inventory. Extroversion, as measured by the Eysenck Personality Inventory, was significantly increased after operation. It is recommended that open prefrontal leucotomy procedures be replaced by the safer stereotactic or electrode implantation techniques and that all psychosurgery be confined to specialist units.


An analysis of 340 cases of syphilis diagnosed in the laboratory in six months in 1973.

Between July and December, 1973, 340 new cases of syphilis previously unknown to the laboratory were diagnosed on the results of serological tests. The male-female ratio was 2-5 : 1. Homosexually acquired infections accounted for 34-3% of cases of syphilis in males. The cases were grouped into primary, secondary, latent and late stages of syphilis according to history, clinical signs and serological test results. Cases in each stage were subdivided into age groups. Primary and secondary syphilis (that is, the early infectious stages) occurred in 56 males and 23 females under 29 years of age. In 41 of the males (73-2%) this infection was homosexually acquired. The figures from this analysis show similar trends to those available in the United Kingdom.


Radioimmunoassay as an improved method for measurement of serum levels of gentamicin.

A radioimmunoassay is described for the measurement of serum concentrations of gentamicin. This radioimmunoassay is more rapid, more specific and more accurate than microbiological assays. Knowledge of serum levels of gentamicin assists the clinician in regulating drug dosage to obtain an optimal therapeutic effect, and yet avoid toxic serum levels.


Vasectomy.

Fifty consecutive patients who underwent vasectomy were followed up over a period of two years, and were subjected to a questionnaire, and the results were analysed. The technique for vasectomy is described and a few modifications are suggested, so that there is a reasonable chance of reversing the operation if need be. Special emphasis has been placed on the poorly understood medicolegal implications of vasectomy.


Microsporum nanum infection in South Australia.

Two cases of human ringworm caused by the dermatophyte Microsporum nanum are reported from South Australia. M. nanum is the commonest cause of ringworm in pigs and is known to cause porcine infections in Australia. This report shows the value of mycological investigations in determining the possible source of such infections.


Finance and fertility: the effects of heavy taxation on the birth rate.

Increasing taxation since World War II has been a factor in reducing the marriage rate and consequently the birth rate in Australia, as a result of raising the cost of living indicated by the retail price index. Taxation has increased enormously though the population has not.


Methadone blockade in the treatment of opiate addiction: a follow-up study.

This paper describes methadone blockade treatment of 50 opiate addicts. At follow-up, 36 patients were traced and interviewed. Results show that 89% of the 36 patients cooperated with the treatment programme, 88% had no new criminal convictions and 75% remained drug-free, apart from taking methadone during the follow-up period (mean, 12-5 months). Five of the 36 patients were free of all drug addictions, including methadone.


Diabetes insipidus treated by DDAVP.

The symptomatic treatment of diabetes insipidus with pitressin is well known and very effective. The only problem concerns the type of pitressin to be used. In the past, pitressin snuff and various other intranasal instillations have been used, but these either have not been very effective, or have resulted in unpleasant side effects such as rhinitis. Until recently, the only effective form of the drug available in Australia has been pitressin tannate in oil. This often has to be given as a daily injection, which, like all intramuscular injections, is painful and, being in an oily base, is particularly likely to result in abscess formation. The recent introduction of 1-deamino-8-D-arginine-vasopressin (DDAVP), which can be simply instilled into the nostril, appears to present an advance in therapy.


A commercial weight-reducing organization: a critical analysis.

A statistical analysis of the records of a commercial weight-reducing organization shows weight loss rates higher than those achieved by non-commercial weight reduction organizations and most medical trials, with 25.9% of women losing more than 9kg and 22% reaching goal weights. A reducing diet, aided by financial incentives and supportive group pressures, is suggested as the basis for these results.


Gallbladder rupture, an isolated seat belt injury.

This report  describes a patient who suffered free intraperitoneal perforation of a previously normal gallbladder as an isolated abdominal injury from seat belt compression. It is postulated that a  prerequisite for such an injury is distension of the gallbladder with bile. Alcohol ingestion in the fasting state is likely to produce  such a situation.


Thrombosis-perspective on a major side effect of oral contraceptives.

Evidence from retrospective studies suggests that the risk of thrombosis is related to the dose of  oestrogen in oral contraceptives. Postoperative thrombosis is four  times more likely to occur if oral contraceptives containing oestrogen are used  before a major surgical procedure. Older women who smoke are at greater risk, especially when the surgery is performed during the winter months. It is recommended that barrier methods of contraception (condom or vaginal diaphragm) be employed during the six weeks before an elective major surgical procedure or that a progestogen-only pill be used in place of a combined or sequential oral contraceptive for this period of time.


Rural Greeks and illness: an anthropologist's viewpoint.

Traditionally, the ill in Greece are supported by kin and neighbors, who often provide diagnosis, medication and the social support required by an invalid. In Australia, the Greek patient is likely to be faced with impersonal efficiency rather than the highly personalized sympathy he is used to. The absence of supporting kin and friends may combine with lack of familiarity in the Australian system to make illness in Australia an extremely anxious experience, perhaps much more anxious than it should ever be.


Comparative results of an obesity clinic and a commercial weight-reducing organization.

Members of a commercial weight-reducing organization achieved, on average, almost double the weight loss of patients attending an obestiy clinic, where an extensive regime of drugs and other therapies was offered. It is suggested that medical expertise could be used to supplement the benefits for patients attending community groups, rather than in the individual treatment of obesity.


Hexachlorophene emulsions and antiseptic skin care of newborn infants.

This paper reviews 81,756 live births and 858 infant deaths occurring during the years 1959 to 1969. Sixty-three instances of central nervous system vacuolation are reported. Prematurity is shown to be a necessary prerequisite for central nervous system vacuolation to occur during routine antiseptic skin care of newborn infants with 3% hexachlorophene emulsions. Hyperbilirubinaemia is a contributory factor in such premature infants. Long-term clinical follow-up studies show that, should central nervous system vacuolation occur in premature infants, there is no resultant detriment to their immediate clinical progress and physical and neurological development. Normal newborn infants weighing more than 2,000 g do not develop such central nervous system vacuolation during routine antiseptic skin care. The writers conclude that there is no rationale for regulations to restrict the use of 3% hexachlorophene emulsions in routine antiseptic skin care of normal newborn infants and that the benefits of such use far outweigh any possible risks from central nervous system vacuolation.


Some problems in diagnosis and management of spinal tuberculosis.

In Victoria spinal tuberculosis is now rare in childhood. Some features of the disease in adults are described. A paravertebral abscess, although a late feature of the disease, is commonly present before a diagnosis is made. Antituberculosis drug therapy has greatly altered the pattern of healing of both the bone lesion and, in contrast to the era before chemotherapy, the healing of the abscess is no longer the dominant factor in the healing of the bone lesion. The controversy about radical surgery is discussed.


Causes and clinical aspects of postoperative recurrent peptic ulcer.

General practitioners as well as surgeons should be aware that there is a high recurrence rate after the "standard" operation (vagotomy and pyloroplasty) for duodenal ulcer. Recognition of recurrence is much delayed. The much lower recurrence rate, with similar morbidity and mortality rates, after vagotomy and antrectomy, make this the operation of choice at present. The high overall recurrence rate, the not inconsiderable operative morbidity and occasional mortality, and the high postoperative morbidity rate for peptic ulcer surgery indicate that such surgery is not to be undertaken without positive indications, such as the presence of complications. An operation undertaken solely because an ulcer recurs within, say, two years can no longer be justified.


[Self-inflicted injuries by injecting contaminated solutions through the chest wall (author's transl)].

In the case of three prisoners, we observed the results of their attempt to induce an infection of the pleura and lungs by injecting themselves through the chest wall with a contaminated substance in order that they might be transferred to a sanatorium. Traces of the solution they had administered, which among other substances contained faeces, were found in the chest wall, in the pleural and subphrenic area, in the lungs and in the liver. The self-inflicted injuries described, led in the case of one of the prisoners to his death following a subphrenic abscess, a necrosis and abscess of the liver, septic shock and respiratory insufficiency. The clinically recognizable results of the injection only set in after a period of latency of several days. In one case there were still traces of stool in the liver 24 days after its initial introduction.


[Folic acid absorption in tropical enteropathy (author's transl)].

Folic acid absoprtion was measured in 45 patients before and after folic acid treatment by means of a folate tolerance test in serum and red-blood-cell-folate. 10 healthy men recently returned from the tropics volunteered as controls. There is no significant difference in the folate-tolerance tests in serum. The difference is significant however in the red-blood-cell-folate, which is markedly lower with the patients before treatment and raises after folate-treatment to the normal value of the control group. As the transport of folic acid in the mucosa follows two steps it is taken that the disturbance is localized in the hydrolysis of polyglutamate to monoglutamate-folic acid.


[Haemolytic anaemia and acute renal failure associated with cephalothin and furosemide therapy (author's transl)].

A case report is presented of a 79 year old patient with a bilateral brochopneumonia. Four days after beginning the therapy with cephalothin and furosemide an acute renal failure appeared and six days later a haemolytic anaemia was observed. The modificated Coombs test was positive. The post mortem histiological examination of the kidneys revealed cloudy swelling, necrosis of tubuli, containing protein cylinders ("chromoproteid kidney").


[Hemorrhage caused by thrombocytopathies: new aspect of treatment (author's transl)].

Hemorrhage due to thrombocytopathies can in most cases be stopped by application of the homologous coagulation-active phospholipide complex Fibraccel, as shown in a study in which 78 patients suffering from various thrombocytopathies were checked. This effect is especially important in patients with immunothrombocytopathies which do not permit any thrombocyte substitution. Recalcification time and thromboelastogram should be normalised during Fibraccel treatment. In existing extravascular coagulation Fibraccel treatment is contraindicated, especially in cases of inadequate protection by heparin.


[Consumption coagulopathy in a case of cystic spleen (author's transl)].

A case of a 65-year old female patient is reported, dealing with consumption coagulopathy and secondary hyperfibrinolysis due to cystic spleen. Following treatment with heparin, antifibrinolytic agents and replacement of clotting factors prior to surgery, the patient attained a satisfactory condition to be operated on. After removal of the cystic spleen, which was interspersed with massive hemorrhages, blood coagulation returned to normal quickly and continuously. The pathogenesis of consumption coagulopathy in relation to cystic spleen is discussed and it is referred to the pathomechanism of similar blood disorders in hemangiomatous and cavernous lesions of Kasabach-Merritt-syndrome, Klippel-Trenaunay-syndrome and pachymeningeosis haemorrhagica interna.


[Investigations of the mode action of buformin using a 3H-labelled glucose in people with a healthy metabolism (author's transl)].

In a total of 13 volunteers the changes in carbohydrate metabolism was investigated after administration of prednisolone, of buformin, and of a combination of prednisolone and buformin using 3H-labelled glucose. Under steady-state-conditions the glucose-turnover was estimated. Although, the changes of glucose assimilation of labelled and unlabelled glucose was observed to see the magnitude of glucose utilisation and of gluconeogenesis. It was concluded that biguanides enhance the glucose utilisation. Depending on the glucose level at the same time the gluconeogenesis is stimulated or inhibited.


[Lactic acidosis and biguanid therapy (author's transl)].

Ten case histories of patients with lactic acidosis and biguanide therapy are presented. 6 patients received phenformin, 4 buformin. The symptomatology was characterized by somnolence or unconsciousness with hyperventilation, renal insufficiency, signs of infection occasionally with detection of gram negative rods and in later stages circulatory insufficiency with high central venous pressure. Glucose, insulin, bicarbonate, dialysis, antibiotics and katecholamines were the therapeutic measurements. It is the proposal of this communication to call attention again to the potential toxicity of biguanids which makes necessary the strict observation of contraindications.


[Metabolism of phenylbutazone in the liver (author's transl)].

The object of the investigation was to study the capacity of the liver to metabolize drugs under diversified conditions (cirrhosis, hepatitis, cholestasis in alcoholics, in diabetics as well as in eplieptics treated with barbiturates) as well as the possibility of inducing this function. To accomplish this we determined the half-life of Butazolidin. Only in cirrhotics it was shown that the capacity to metabolize Butazolidin was reduced. Induction with barbiturates increased hepatic captation of the drug but did not modify the biotransformation of the same. This is attributed to the development of a "hypoactive hypertrophy" of the reticuloendothelium.


[Studies on calcium absorption out of a calcium-vitamin-D-preparation using calcium-47 (author's transl)].

Calcium absorption in man was studied by means of labelling an ampoule of Frubiase Calcium forte with calcium-47. For comparative purpose a solution containing the same amount of calcium salts as the ampoule was labelled as well. Already 10 minutes after oral administration of Ca-47 in 10 ml of Frubiase Calcium forte radioactivity was statistically significant measurable in blood. At the same time there was no significant radioactivity demonstrable out of the calcium salt solution. Between 45 and 120 minutes following oral application of the isotope both groups showed a statistically significant difference concerning the measurable blood activity. The Frubiase Calcium forte values were always higher, especially one and two hours after administration of the radiocalcium (up to 40%). The levels at these times correlate well with the total calcium absorption. Measurements over the compact bone region of the ankle demonstrated significantly higher values of calcium-47 in case of Frubiase Calcium forte compared with the calcium salt solution. These findings indicate in the case of Frubiase Calcium forte a higher bone mineral accretion. There is a good direct proportionality between the amount of these values and the total calcium absorption.


[Body potassium and skinfold thickness in an isocaloric, fat-rich diet (author's transl)].

Nine partly weak overweighted sport students got a fat rich isocaloric diet (70% fat, 20% protein, 10% carbohydrates) for three weeks. Body weight, body potassium and skinfold thicknesses were measured. A constant loss of body weight was the result. Lean body mass and body fat decreased. It is supposed that protein is used for gluconeogenesis if carbohydrate reduction is nearly total.


[Sudden, unexpected death of infants and electromagnetic fields (author's transl)].

The examination of 337 cases of Sudden Infant Death Syndorme (SIDS) ro Crib Deaths in Philadelphia, Penn., USA, and 294 cases in Hamburg, Federal Republic of Germany, shows regional concentrations which are close to uncommon magnetic fields or stray electric currents in the ground. The risk in the cellar and first floor of houses is higher than in the other floors. Therefore a possible causal relationship between electromagnetic fields and SIDS cases must be considered and checked by on-site measurements, animal experiments, and by more research on magnetic fields as stressor for infants.


Neutrophil leukocyte reserves in lymphoreticular malignancies.

The marginal neutrophil leukocyte pool and the bone marrow neutrophil reserves were assessed in 43 patients with lymphoreticular malignancies, using epinephrine and steroid stimulation. Thirty-three patients were studied before staging, following splenectomy, before and after nodal irradiation and during remission induction chemotherapy. Ten patients in partial remission were studied after 12 month or more of chemotherapy. A neutrophil count of 1,500-2,500 cells/mm3 is not a sufficient guide for midifying the chemotherapy. The response to steroid stimulation may be a more dependable guide to evaluate the patient's potential risk for infection.


Combination chemotherapy with adramycin (NSC-123127) and dimethyl triazeno imidazole carboxamide (DTIC) (NSC-45388) in children with metastatic solid tumors.

Combination chemotherapy with adriamycin and DTIC was used in 102 evaluable patients under 15 years of age who had previously treated metastatic solid tumors. Responses, defined as 50% or more reduction in all tumor masses, occurred in 10 out of 27 patients with neuroblastoma, 3 out of 8 patients with Wilms tumor, 7 out 15 patients with Ewing sarcoma, 2 out of 6 patients with osteosarcoma, 5 out of 13 patients with rhabdomyosarcoma, and 15 out of 33 patients with miscellaneous tumors which included a patient who had a complete regression of an extensive juvenile angiofibroma. Response rate to combination chemotherapy with adriamycin and DTIC in patients with Ewing sarcoma was significantly superior to the response rate obtained with adriamycin alone in another Southwest Oncology Group Study. Major toxicity included nausea, vomiting, myelosuppression, high incidence of pneumocystis carinii pneumonia (5 patients) and congestive heart failure (4 patients). There was 7 drug-associated deaths due to sepsis (1), pneumocystis carinii pneumonia (4), and congestive heart failure (2).


Clinical studies of beta-thioguanine deoxyriboside alone and in combination with arabinosyl cytosine.

Beta-thioguanine deoxyriboside (betaTGdR) is a purine nucleoside derivative which was studied alone or in combination with arabinosyl cytosine (Ara-C) in patients with solid tumors and acute leukemia. No significant responses were observed in 22 patients with solid tumors. The response rate with betaTGdR alone in acute leukemia was 26% and in combination with Ara-C was 24%. Responses were generally of short duration. Toxicity included myelosuppression, nausea, stomatitis, hyperpigmentation, photosensitivity, and liver function abnormalities.


Phase II study of profiromycin vs mitomycin-C utilizing acute intermittent schedules.

A randomized prosective study of Mitomycin-C and its N-methyl derivative, Porfiromycin, was conducted. Thirty-two patients with disseminated gastrointestinal cancer or other disseminated abdominal adenocarcinoma were treated with Mitomycin-C; 31 patients received Porfiromycin. Both drugs were given by acute intermittent bolus schedule (Mitomucin-C , 22.5 mg/M2 or Porfiromycin, 75 mg/M2 every 6--8 weeks as a single bolus i.v. injection). Eleven patients (34%) who received Mitomycin-C entered into partial remission. In 10 of the 31 patients (32%) receiving Porfiromycin, partial remission occured. Analysis by tumor type demonstrated that in the Mitomycin-C treated group responses occured in 4 of 12 patients with colorectal carcinoma, in 4 of 9 with upper GI cancers, and in 3 of 11 with ovarian cancer. Correspondingly in Porfiromycin group responses occured in 2 of 12 colorectal carcinoma patients, in 3 of 7 upper GI cancer patients, and in 5 of 12 ovarian cancer patients. Both drugs produced significant myelosuppression; however, Porfiromycin toxicity appeared more cumulative. Further clinical trial of Mitomycin in an acute intermittent bolus schedule appears justified.


In vivo quantitation of lesion radioactivity using external counting methods.

Quantitative external counting methods for the in vivo determination of the activity uniformly distributed in an area of interest (lesion) have been developed. The theoretical work has been extended to include the effects of regions of differing attenuation coefficient and of non-target organ activity in the tissue surrounding the lesion. A clinical quantitative procedure utilizing a "calibrated" gamma camera and associated computer system is described. Studies including a bone substitute material in a water phantom confirmed the basic theoretical work.


Calculations of two-dimensional electric field and potential distributions aroun electrodes in conducting media.

Tumor cells can be killed by heating to 42.5degreesC. It is convenient to localize heating by passing electric current at 500 kHz through tissue between a pair of electrodes. It is desirable to determine, for a given electrode-tissue configuration, what the resulting field and, therefore, current distribution will be. A computer program FFEARS was used to calculate electric field and potential distributions in two dimensions for three simple cases.


Method for calculating dose when lung tissue lies in the treatment field.

The absorbed dose in lung and beyond lung as a result of increased lung transmission of x and gamma irradiation is described. The correction factor used to calculate the absorbed dose is a function of beam energy, field area, lung density, and lung and soft tissue depth. Agreement between measurements and calculations in the Alderson phantom is within 3%. An example of how this technique can be used is described.


Phase effects in diagnostic radiological images.

The effect of phase on the quality of diagnostic radiological images is investigated on a theoretical basis and with the use of the computer simulations. Phase effects are divided into two categories: linear phase shift and asymmetric phase shift. Using a model of the x-ray focal spot distribution composed of two Gaussian functions, it is shown that the phase transfer function (PTF) is generally a continuous nonlinear function of spatial frequency. The linear phase shift serves only to shift the location of the image. The asymmetric phase shift in the model studied tends to accompany an improvement in the modulation transfer function (MTF) in the midfrequency region while introducing "wows" into the image. Contrast reversals are shown to be inherent in line spread functions (LSFs) which do not necessarily include linear or asymmetric phase effects, i.e., they are the result of another phenomenon.


Intensity distribution, modulation transfer function, and the effective dimension of a line-focus x-ray focal spot.

The radiant intensity along the anode-cathode dimension of a line-focus x-ray focal spot tends to peak at the center and decrease gradually to zero at the edges. In recognition of this varying intensity, the ICRU has recommended that the anode-cathode dimension of the focal spot be reported as 0.7 times the dimension measured with a pinhole camera. In this paper more objective correction factors are developed. These correction factors are based upon comparison of calculated MTFs of focal spots with Gaussian and cosine intensity distributions with the MTF for focal spots with a uniform intensity distribution.


Calculated neutron dose rates and flux densities from implantable californium-252 point and line sources.

The results of neutron-transport flux-density and dose rate calculations for implantable Californium-252 point and line sources in essentially infinite tissue-equivalent material are presented. The point-source flux densities were obtained from a discrete ordinates calculation, and the point dose rates were established by multiplying the flux densities by their appropriate kerma factors. Line-source dose rates were evaluated by integrating the point dose rates over the length of the line source. Dose-rate data are given within a 20 X 20-cm region from the source center for source lengths of 1.5, 2, and 3 cm. The dose rates established by these calculations showed good agreement with an independent Monte Carlo calculation. Detailed point-source flux-density data as a function of energy and position are also given.


Real-time display of radiation field intensity distribution.

A real-time display system has been designed and tested for use with a radiation field monitor. The system uses only pulse and waveform generators, a multiplexer, and an oscilloscope. The display consists of either a three-dimensional representation of the field intensity distribution or a series of simultaneous profiles.


Mathematical model of conventional tomography.

A Fourier decomposition approach is used to study the imaging properties of conventional tomography. Spatial frequency response curves (MTFs) are calculated for both linear and axial transverse tomography. These curves depend on the product of the spatial frequency of the sinusoidal density variations in thin layers parallel to the tomographic plane and the distance between such layers and the tomographic plane. Based on the spatial frequency response curves, a quantitative definition of tomographic layer thickness is given. Furthermore, the spatial frequency response curves suggest that unattenuated low-frequency information from outside the tomographic layer limits the resolution in conventional tomograms and that high-pass spatial filtering of the image may substantially improve the diagnostic quality of tomographic images, particularly in the identification of boundaries.


Calculations of two-dimensional electric field and potential distributions around electrodes in conducting media.

Tumor cells can be killed by heating to 42.5 degrees C. It is convenient to localize heating by passing electric current at 500 kHz through tissue between a pair of electrodes. It is desirable to determine, for a given electrode-tissue configuration, what the resulting field and, therefore, current distribution will be. A computer program FFEARS was used to calculate electric field and potential distributions in two dimensions for three simple cases.


Genetic exchanges caused by ultraviolet photoproducts in phage lambda DNA molecules: the role of DNA replication.

Genetic recombination induced by structural damage in DNA molecules was investigated in E. coli K12 (lambda) lysogens infected with genetically marked phage lambda. Photoproducts were induced in the phage DNA before infection by exposing them either to 313 nm light in the presence of acetophenone or to 254 nm light. To test the role of the replication of the damaged phage DNA on the frequency of the induced recombination, both heteroimmune and homimmune crosses were performed. First, samples of a heteroimmune phage lambda imm434 P80 exposed to these treatments were allowed to infect cells lysogenic for prophage lambda cI857 P3. Phage DNA replication and maturation took place, and the resulting progeny phages were assayed for the frequency of P+ recombinants. Recombination was less frequent in infected cells exposed to visible light and in wild type cells able to perform excision repair than in excision-defective lysogens. Therefore, much of the induced recombination can be attributed to the pyrimidine dimers in the phage DNA, the only photoproducts known to be dissociated by photoreactivating enzyme. Second, in homoimmune crosses, samples of similarly treated homoimmune lambda P3 phages were allowed to infect lysogens carrying lambda cI857 P80. Replication of the phage DNA containing ultraviolet photoproducts was repressed by lambda immunity, and was further blocked by the lack of the P gene product needed for replication. The lysogens were purified and scored for both colony forming ability and for P+ recombinant prophages. The 254 nm photoproducts increased the frequency of recombination in these homimmune crosses, even though phage DNA replication was blocked. Irradiation with 313 nm light and acetophenone M, which produces dimers and unknown photoproducts, was not as effective per dimer as the 254 nm light. It is concluded from these results that certain unidentified 254 nm photoproducts can cause recombination even in the absence of DNA replication. They are not pyrimidine dimers, as they are not susceptible to excision repair or photoreactivation. In contrast, pyrimidine dimers appear to cause recombination only when the DNA containing them undergoes replication.


Genetic control of the cell division cycle in the fission yeast Schizosaccharomyces pombe.

Twenty seven recessive temperature sensitive mutants have been isolated in Schizosaccharomyces pombe which are unable to complete the cell division cycle at the restrictive temperature. These mutants define 14 unlinked genes which are involved in DNA synthesis, nuclear division and cell plate formation. The products from most of these genes complete their function just before the cell cycle event in which they are involved. Physiological characterisation of the mutants has shown that DNA synthesis and nuclear division form a cycle of mutually dependent events which can operate in the absence of cell plate formation. Cell plate formation itself is usually dependent upon the completion of nuclear division.


Arg-7 mutant X wild-type crosses in Chlamydomonas reinhardi: study of the enzyme produced in diploid strains.

The arg-7 locus is the structural gene for the argininosuccinate lyase (ASL). Interallelic complementation was previously found to occur between several mutants of the locus: this is indicative for the homomultimeric nature of ASL. Two complementing (arg-7-5 and arg-7-7) and two non-complementing (arg-7-1 and arg-7-6) mutants of the arg-7 locus were crossed to the pab-2 strain (which is wild-type for the arg-7 locus). In each cross, heterozygote phenotypically wild-type strains were isolated; their diploid pattern was demonstrated by various criteria: mating type, cell volume, nuclear size. The four heterozygotes were compared to the haploid wild-type and in some experiments, to the diploid strain arg-1 X pab-2 homozygous for the arg-7 locus. No difference was found in growth rate and in the Michaelis constant values for ASL. The specific activity of the enzyme produced in the heterozygotes was about 50 percent of the activity found in haploid or diploid wild-type. The heat sensitivity of ASL was also investigated in the different strains: two (containing the complementing mutations arg-7-5 and arg-7-7) of the four heterozygotes produce ASL varieties different from the wild-type enzyme as far as the thermolability is concerned. These results suggest that hybrid ASL can be formed by interaction between the products of wild-type and mutant genes. A clear dominance of the wild-type allele is expected only when the mutant allele has no product of the gene: this could be the case for arg-7-1 and arg-7-6.


Characterization of mutations in the penicillinase operon Staphylococcus aureus.

Mutant penicillinase plasmids, in which penicillinase synthesis is not inducible by penicillin or a penicillin analogue, were examined by biochemical and genetic analyses. In five of the six mutants tested, penicillinase synthesis could be induced by growth in the presence of 5-methyltryptophan. It is known that the tryptophan analogue 5-methyltryptophan is readily incorporated into protein by S. aureus and that staphylococcal penicillinase lacks tryptophan. 5-methyltryptophan seems to induce penicillinase synthesis in wild-type plasmids by becoming incorporated into the repressor and thereby inactivating the operator binding function of the penicillinase repressor. Therefore, induction of penicillinase synthesis in the mutant plasmids by 5-methyltryptophan strongly suggests that the noninducible phenotype of these five plasmids is due to a mutation that inactivates the effector binding site of the penicillinase repressor (i.e., the five mutant plasmids carry an iS genotype for the penicillinase repressor). This conclusion was supported by heterodiploid analysis. The mutant plasmid that did not respond to 5-methyltryptophan either produces an exceedingly low basal level of penicillinase or does not produce active enzyme. This plasmid seems to carry a mutation in the penicillinase structural gene or in the promoter for the structural gene. Thus, a genetic characterization of many mutations in the penicillinase operon can be accomplished easily and rapidly by biochemical analysis.


Non Xenopus-like DNA sequence organization in the Chironomus tentans genome.

We have examined the sequence organization of Chironomus tentans DNA by means of optical and hydroxyapatite renaturation kinetics of total DNA fragment sizes of 0.36, 2.6 and 13.5 kilobases (kb) as well as isolated middle repeat DNA at sizes of 0.36 and 13.5 kb. 90% of the DNA renatured as unique sequences of a genome of 0.20 pg with the balance of DNA renaturing as middle repetitive sequences present on averge 90 times per haploid genome. At a DNA fragment length of 13.5 kb, 35% of the DNA was trapped on the hydroxyapatite as middle repetiitive fraction. We concluded C. tentans DNA to have a mean repeat length of about 4.3 kb distributed throuth out at least 35% of the genome with an inter repeat spacing of at least 13.5 kb but possibly being distributed throughout the whole genome with an inter repeat spacing of 36 kb. This shows C. tentans DNA organization not to follow the most ubiquitous Xenopus model but to be similar to the organization of Drosophila melanogaster DNA.


Kinetics of hydrogen-deuterium exchange of tryptophan and tryptophan peptides in deutero-trifluoroacetic acid using proton magenetic resonance spectroscopy.

The methods which have been used for the observation and assignment of resonances in the NMR spectra of proteins are reviewed. One such method, the selective deuteration of the aromatic protons of tryptophyl residues, is studied by NMR spectroscopy in model compounds in this paper, and in proteins in the following paper. On the basis of a reassignment of the PMR spectrum of the aromatic protons of L-tryptophan, the relative rates of H-D exchange in deutero-trifluoracetic acid (d-TFA) are H-2 greater than H-5 greater than H-6 greater than H-4 approximately H-7. The energies of activation for the first order exchange of both the H-2 and H-5 protons is 12 k.cal.mol-1. The rate constant for exchange of the H-2 protons of tryptophyl residues in peptides is much greater than in the amino acid itself and 5-10 times that for exchange of the H-5 protons. This suggests that the method can be used to label tryptophyl residues in proteins rapidly and specifically.


The glycerophosphateacyltransferases and their function in the metabolism of fatty acids.

1. From different studies on the cellular localization, postional specificity, and regulatory properties of acyl-CoA: glycerophosphate acyltransferase (EC 2,3,1.15) AND ACYL-CoA: 1-ACYLGLYCEROPHOSPHATE ACYLTRANSFERASE (EC 2,3,1....) the following conclusions can be drawn: The glycerophosphate acyltransferase is localized in the endoplasmatic reticulum (microsomes) and in the outer membrane of the mitochondria of the animal cell. Its reaction product is 1-acylglycerophosphate (1-lysophosphatidic acid). The mitochondrial enzyme shows a high preference for saturated fatty acids while the microsomal enzyme is less specific (alternatively the microsomes contain more than one glycerophsophate acyltransferase). 2. The 1-acylglycerphosphate acyltransferase is localized in the endoplasmatic reticulum (microsomes) in the animal cell. Possibly a minor fraction of this enzyme is localized to the outer membrane of the mitochondria. This enzyme shows a strong preference for unsaturated fatty acids. 3. Both the microsomal and the mitochondrial dihydroxyacetonephosphate acyltransferase show similar fatty acid specificity as the corresponding glycerophosphate acyltransferases. It cannot be excluded that dihydroxy-acetonephosphate and glycerophosphate are acylated by the same enzymes. 4. The activity of the glycerophosphate acyltransferase(s) in the liver decreases in fasting or fat feeding and increases upon feeding of carbohydrate. The activity of carnitine palmityltransferase varies exacty opposit. These enzymes do not show dietary variations in heart and adipose tissue. 5. Under the otherwise identical conditions the rate of carnitine acylation in isolated mitochondria decreases more than the rate of glycerophosphate acylation when the concentration of palmityl-CoA is reduced. 6. In isolated liver cells (which has lost most of their carnitine) addition of carnitine increases the rate of fatty acid oxidation and decreases the rate of triglyceride formation. 7. Glycerol and fructose lower the rate of fatty acid oxidation, probably by lowering the levels of acyl-CoA and acyl-carnitine in the cells. 8. It is concluded that the relative activities of glycerophosphate acyltranse and carnitine palmityltransferase probably influence the fate of fatty acids in the cell.


The synthesis of alpha-amylase by rough and in vitro reconstituted rough endoplasmic reticulum derived from rat parotid gland.

The isolation of rough and smooth endoplasmic reticulum from rat parotid salivary gland is described. The rough membrane was stripped of its bound ribosomes using the KCl-puromycin method. Rough endoplasmic reticulum was reconstituted from stripped-rough membrane and polyribosomes. The reconstituted rough membrane resembled the native rough membrane in the following aspects: RNA/protein ratio, buoyant density in a continuous sucrose gradient and amino acid incorporation capacity. The in vitro synthesis of alpha-amylase by both rough and in vitro reconstituted rough membrane was demonstrated using SDS polyacrylamide gel electrophoresis. The reconstituted rough membrane could be restripped by KCl-puromycin. The in vitro synthesized alpha-amylase remained associated with the rough or the in vitro reconstituted rough membrane, even after these membranes were stripped of their bound ribosomes.


Binding of aminoacyl-tRNA to rat liver ribosomal proteins.

Rat liver ribosome treatment with ethanol and 1 M NH4Cl releases some 31-33 ribosomal proteins. This split protein fraction binds Phe-tRNA, Ac-Phe-tRNA, Met-tRNAM and f-Met-tRNAF in the absence of K+ and Mg++ ions. When the split protein fraction is passed through Sephadex G-100 only six proteins are retained in the column: S10, S14, S15, S19, L35, and L36. The aminoacyl-tRNA binding activity of this protein fraction retained in the Sephadex G-100 column is similar to that of the total split protein fraction, suggesting that the above six proteins, or only some of them, are involved in the binding reaction.


Distribution of globin genes in chicken reticulocyte chromatin fractionated on urografin gradients.

Buoyant density centrifugation in Urografin solutions resolved French Pressure Cell-sheared, and micrococcal nuclease-digested avian reticulocyte chromatin into a broad profile of two peaks. Hybridization experiments using a globin cDNA probe suggested minimal fractionation of transcriptionally active and inactive components with chromatin sheared at 6000 psi, while no evidence was obtained for any fractionation with chromatin sheared at lower or higher pressures, or with chromatin digested to various extents with micrococcal nuclease, despite a considerable spread of chromatin material across gradients.


Further studies on collagen mRNA: partial chemical characterization and polyadenylic acid sequence.

Collagen mRNA has already been purified and characterized by us. Its purity has now been enhanced by two different methods. Gel electrophoresis shows in either method, a single peak with the same mobility already reported: 1.05 X 10(6) daltons. Base composition analyses of collagen mRNA purified by either method were almost identical. Chemical analyses of the isolated polyadenylic acid stretch show that it is, 0.48 X 10(5) daltons-long, (about 140 nucleotides-long), contains 75% AMP, and is located at the 3' end of the polymer.


[mRNA fractions of mouse plasmacytoma cells].

The sedimentation characteristics of polysomal mRNA labelled in vitro by [5-3H]uridine and electrophoretic mobility of similar non-labelled mRNA of mouse plasmacytoma were studied. Rapidly labelled polysomal mRNA may be considered as mRNA on the basis of several independent but indirect tests. These mRNA's are localized in 18-6S region of sucrose gradient. Some part of radioactivity have been found in the ribosomal RNA. It was shown that there is 8-10 RNA fractions in sucrose gradient. The 16S and 12-14S fractions are isolated and partially purified by two- and three-fold centrifugation. Fractions homogenous in sucrose gradient were electrophoresed in PAAG-SDS and divided into several subfractions some of them being common for 16S and 12-14S. The number of non-crossover subfractions was about 2-3. Not less than 20 different main fractions of polysomal mRNA were determined in plasmacytoma cells on the basis of electrophoretic data.


[Kinetic patterns of reactions with immobilized enzymes in open systems].

For studying the properties of immobilized enzyme, a flow reactor is suggested which provides ideal mixing of the reaction components with the granules of immobilized enzyme. To elucidate the mechanism of the reaction and to determine the effective values of maximal rates and Michaelis constants, an analysis of formal kinetic relationships describing the behaviour of the reactor in the stationary and non-stationary regimes has been carried out. The non-stationary kinetics is analyzed both for the case of step-wise and continuous supply of the substrate. A number of equations has been evolved which describe the time dependences of the concentrations of the substrate and reaction products; relationships have been found allowing determination of maximal rates and Michaelis constants from experimental data.


Naturally occuring mutagens.

Naturally occurring mutagens have usually been discovered as a result of outbreaks of disease in agricultural livestock, or as a result of epidemiological studies of cancer of the liver in man. Subsequent work has then shown that the toxic agents responsible often have mutagenic properties. Examples are the pyrrolizidine alkaloids, cyasin, a range of mycotoxins produced by various fungi, and at least two unidentified toxic agents in bracken. Commonly the toxic agent itself does not show high biological activity, but after ingestion it is converted by metabolic processes into the active mutagen or carcinogen. Some of these toxic substances have been responsible for considerable losses of agricultural livestock and therefore are of economic significance. From the view-point of genetic hazards to man, the most significant compounds are probably the mycotoxins, e.g. aflatoxin, because of the common risk of fungal contamination of food, especially in tropical regions. No information is yet available on the effects of these mutagens on natural populations of animals. Plants containing the pyrrolizidine alkaloids are found in areas of Africa and the Middle East where plagues of the migratory locust occur. Although it is known that some of the alkaloids can induce chromosomal damage in grasshoppers, whether such damage ever becomes a significant factor under ecological conditions is not known. In some cases, insects have not only evolved resistance towards mutagenic alkaloids but have become dependent on them for certain purposes. The males of certain Danaid butterflies feed on plants containing pyrrolizidine alkaloids. After ingestion, the alkaloids are metabolised to dihydropyrrolizine derivatives, which are then secreted on special organs (hair pencils) and, following dissemination into the atmosphere, act as pheromones for the stimulation of mating behaviour.


Localized mutagenesis in Streptomyces coelicolor A3 (2).

Nutritional mutants (co-mutants) were scored among nitrosoguanidine-induced revertants of four mutations in Streptomyces coelicolor A3 (2). All co-mutations were due to mutations in genes linked to the revertant locus. The co-mutant loci were located in a region of about 20 map units around the revertant locus (co-mutation region). Revertants for different loci showed co-mutation patterns different from each other and from that of random nitrosoguanidine-induced forward mutations. Mutations appeared to be completely abolished outside the co-mutation region (mutation restriction).


[Study of ribonucleoprotein particles by the method of RNA chromatography on a column of nucleoprotein-celite].

A novel method of RNA fractionation based on a gradual release of the RNA molecules from ribonucleoprotein complexes has been used for the analysis of ribosomal and non-ribosomal complexes of rat liver cytoplasm. Adsorption of native ribonucleoproteins on a Celite column (occuring through only the protein moiety) followed by a consequent dissociation of RNP complexes brought about by various agents results in RNA fractionation in accordance with the tightness of the RNA-protein bonds. The cytoplasmic ribosomal and rapidly labelled non-ribosomal RNA species are separated into several fractions identified as 18S and 28S rRNA's, mRNA and messenger-like RNA. A relatively small fraction (about 10% of the total) of rRNA tenaciously bound to protein has been also revealed.


The radiosensitivities of lymphocytes from pig, sheep, goat and cow.

Dose-effect curves for X-irradiation in vitro were determined on cultured blood lymphocytes of four mammalian species-cow, goat, sheep and pig-having approximately the same number of chromosome arms, the same nuclear volume and the same DNA content. The data from cow, but not those from the other species, exhibited significant inhomogeneity between the experiments. On inspection the numerical yields appear not to differ greatly in the lower dose range. Evaluation of the parameters according to the quadratic law and the power law, however, demonstrate significant differences. Pig differs from the other species regardless of which presentation is chosen. For the power law a significant difference is also found between goat and sheep.


X-Ray-induced translocations in spermatoginia. II. Fractionation in mice.

The dose-response curve for reciprocal translocations induced by X-rays in spermatogonial stem cells, and observed in primary spermatocytes of mice, is "hump-shaped", with a maximum yield at about 600 R. To test the hypothesis that the decrease in yield with increasing dose above 600 R is a consequence of the different sensitivities of cells in different stages of the cell cycle to both cell killing and chromosome aberration induction, several fractionation experiments were carried out. A total  dose of 2800 R was given in repeated doses of 400 R, separated by 8-week intervals. The yield of translocations is that expected for additivity; for example, the yield at 1600 R is approximately equal to that for four separate 400-R doses. When a total dose (500 R) which gives a translocation yield on the ascending part of the dose-response curve is given as two equal fractions separated by intervals of 30, 90, or 150 min, the translocation yield decreases with increasing interval. However, when a total dose (1000 R) which would give a translocation yield on the descending part of the dose-response curve is given in two equal fractions separated by intervals of from 30 min to 6 weeks, the response is different; the translocation yield increases with intervals up to 18 h, then decreases with intervals up to 4 weeks, and finally increases again to a yield equal to additivity with an interval of 6 weeks. These changes in translocation yield with changes in interval between the two doses are explained in terms of the differential sensitivity of cells to killing and aberration induction in the different phases of the cell cycle, and by assuming that the cells surviving the first dose and repopulating the testis have different cycle characteristics from normal cells.


[Inhibition of Aspergillus clavatus intracellular RNA-ase by nucleotides and the components comprising them].

The constants of inhibition by the nucleotides and constituting components catalysed by intracellular "acid" (pHopt 4.7), non-specific RNAse from Asp. clavatus (EC 3.1.4.23) were determined.. All the nucleotides were found to be competitive inhibitors. The influence of composition and structure of the nucleotides on their interaction with the active site of RNAse is discussed.


The influence of serum components on the growth and mutation of Chinese hamster cells in medium containing 8-azaguanine.

Low concentrations (less than or equal 20 mug/ml) of 8-azaguanine are 1000 fold more toxic to V79 Chinese hamster cells in medium containing 10% dialyzed fetal calf serum than in medium containing 10% undialyzed serum. Serum enzyme activity that converts AG to nontoxic 8-azaxanthine degrades AG at the same rate, whether or not the serum is dialyzed. However, cytotoxicity results similar to those obtained with US were produced in medium containing DS and 2.5 mug of hypoxanthine (HX)/ml (DSH). Therefore, serum HX is considered to be responsible for the relatively low cytotoxicity of AG in medium containing US. Colonies that arose in medium containing AG were isolated and characterized. Those that remained resistant to AG (40 mug/ml) and sensitive to aminopterin in the presence of HX and thymidine (HAT) were considered mutants; non-mutants were sensitive to AG and resistant to HAT. Colonies isolated from medium containing DSH or US and low concentrations of AG were not mutants, but those from medium containing high concentrations (greater than or equal 30 mug/ml) of AG were mutants. Spontaneous and N-methyl-N-nitro-N-nitrosoguanidine induced mutants were detectable in medium containing DSH without replating the cells prior to adding AG (greater than or equal 30 mug/ml), but in order to detect MNNG induced mutations in medium containing DS replating was essential. In DS, the mutation frequency increased as an exponential function of the toxicity of MNNG, but remained two orders of magnitude lower than the induced mutation frequencies that occurred in DSH. HX, in DSH or US, produced profound effects, other than interference with AG toxicity, that distort the results of mutagenesis assays. To study mutation using AG resistance as the endpoint, it is essential to use dialyzed serum.


[Molecular organization of aggregated forms of chlorophyll and its analogs].

Infrared spectra (in the region of 1800-1600 cm-1) of aggregated protochlorophyll, chlorophyll a and b, bacterioviridin, protopheophytin, pheophytin a (in the solid films) with different absorption spectra were studied. The formation of various types of aggregates is due to the realization of different modes of intermolecular bonding. The mode of interaction depends upon the chemical structure of the pigment and upon the inclusion of low-molecular addenda into the structure of aggregates. The forms 677 nm of chlorophyll a and 658 nm of chlorophyll b appear when the coordination bonds between the keto groups of the cyclopentanone ring and central magnesium atom are formed. The longwave forms of chlorophyll a (745 nm) and chlorophyll b (675 nm, 725 nm) are formed when methanol molecules are involved in the intermolecular bonds. The coordination bonds between C=O and magnesium atom in the longwave aggregate of bacterioviridin (750 nm) are observed without participation of the low-molecular addenda, The formation of the protochlorophyl 635 nm form and aggregated forms of magnesium-free pigments occurs without participation of carbonyl groups probably by direct interaction between the eta-electron systems of molecules. The frequencies of carbonyl groups of the solid films in dioxane vapours causing absorption maxima at 690 nm (chlorophyll a) and 670 nm (chlorophyll b) are not shifted as compared to the dissolved pigments. Thipoints to the intermolecular interaction without participation of C=O groups.


Mutagenic mechanism of 5-bromodeoxyuridine in Chinese hamster cells.

Resistance to 6-thioguanine was induced by 5-bromodeoxyuridine (BUdR) in synchronous Chinese hamster cells. The yield of mutant colonies was not proportional to the amount of BUdR incorporated into DNA; thus mutants were not due to mispairing of BUdR with guanine during replication. Few mutants were induced until BUdR concentrations exceeded that of the intracellular thymidine triphosphate pool and mutant yield was depressed by addition of thymidine to the medium. These data suggest that BUdR exerts an allosteric effect on the DNA synthesizing system which renders it more error prone.


Radiation-induced chromosomal aberrations in human lymphocytes. I. Dependence on the dose of gamma-rays and an anomaly at low doses.

Cultures of human lymphocytes obtained from blood of healthy adult donors were irradiated with different doses of 60Co gamma-rays and the irradiated cells were analysed in metaphase 50 h after irradiation. The effect (total yield of aberrations of chromosome type, or total yield of exchange type aberrations) produced by the lowest dose (5 rad) appears to be statistically significant in a sample of 1500 cells. In the usual dose range (25-400 rad), both parabolic and linear-quadratic equations give a satisfactory fit of experimental data (dicetrics, fragments, or all aberrations of chromosome type). Low doses of gamma-rays, however, produced more aberrations than expected, if one extrapolates dose-effect curves from higher doses. Both relations should be considered, therefore, merely as empirical equations. Dicentrics show at low doses (10-30 rad) a plateau which appears to be statistically significant. Some indications are obtained that the total number of chromosome-type aberrations is a more reliable criterion of cytogenetic damage than the usually accepted yield of dicentrics and rings.


[Calculation of the conformation of stereo-regular, double-spiral polynucleotides].

By the step-by-step selection method energetically optimal conformation of double-stranded polynucleotides were calculated proceeding from the conformations of mono-and dinucleotides. These structures were found to belong to the families of DNA A and B forms. The dependence of six torsion angles of the polynucleotide chain on the glycosidic angle chi was investigated. As a result certain areas admitting of double-helix polynucleotides with sugar C3-endo with chi = -80 degrees were established.


Mutagenicity and toxicity of amitrole. II. Human lymphocyte culture tests.

Effects of amitrole (3-amino-1,2,4-triazole) on human leucocytes in culture were investigated. Amitrole interfered with lymphoblast transformation and inhibited cell growth in concentrations of 0.2% w/v and higher. Selected metaphases were examined for the presence of chromosome and chromatid aberrations. No clastogenic effects were observed.


Chromosome damage induced by semicarbazide in spermatocytes of a grasshopper.

Semicarbazide hydrochloride (0.1 M in glass-distilled water), on injection, showed mutagenic action on the spermatocyte chromosomes of the grasshopper, Spathosternum prasiniferum. Aberrations such as chromatid and chromosome breaks, translocations, fragments and bridges were encountered. The sex chromosome and the long autosomes were affected. Semicarbazide, perhaps, reacts with DNA and the chromosome in a way similar to that of hydroxylamine and hydrazines.


Evaluation of the mutagenic potential of cyclohexylamine on spermatogonia of the Chinese hamster.

In a cytogenetic study on the spermatogonia of Chinese hamster, cyclohexylamine (neutral sulphate) was evaluated for mutagenic effects in comparison with an untreated control group and a group treated with the mutagenic compound cyclophosphamide, by assessing spermatogonial metaphases of treated Chinese hamster for chromosomal structural changes. Each test group comprised 8 male hamsters selected at random. Approximately 100 metaphases from each animal were assessed. The doses were 5 X 150 mg cyclohexylamine sulphate (approx. 5 X 102 mg base) per kg body-weight orally, and 5 X 100 mg cyclophosphamide per kg body-weight orally. The individual doses were administered at intervals of 24 h. Preparations were made 24 h after the final treatment, essentially by the method of Hoo and Bowles [10]. Gaps, breaks, fragments, deletions and translocations were assessed as structural changes; frequencies were determined of the metaphases (a) with aberration(s) including gaps, (b)with aberration(s) less gaps and (c)with translocation(s). Aberrations occurred in the untreated negative control group (1.24% incl. gaps, 0.25% without gaps). Translocations were not seen in the untreated group. In the cyclochexylamine group, the frequencies of the aberrant metaphases were sometimes less than in the control group (0.87% including gaps, 0.37% without gaps). Statistically, the results were not significantly different from the control data. No translocations were seen after administration of cyclohexylamine. The positive cyclophosphamide control group clearly differed from the untreated control and from the cyclohexylamine group in the parameters (a) to (c); mainly, the results were highly significantly different from those obtained in the untreated control group. The frequencies of the aberrant metaphases were 3.41% including gaps and 1.99% without gaps. The frequency of the translocations was 0.71% (5 out of 704). Cyclohexylamine sulphate, administered 5 times at 150 mg/kg body-weight orally, had no mutagenic effect, whereas cyclophosphamide, adminstered 5 times at 100 mg/kg body-weight orally, had a chromosome-damaging effect on Chinese hamster spermatogonia.


Further studies on the histological cytological and cytogenetic effects of nogalamycin in mammals.

The histological, cytological and cytogenetic effects of nogalamycin were studied in rats, mice and cultured human leukocytes. Four standard test systems were used in the cytological studies: (1)analysis of spermatogonial cells, (2)cytological evaluation of bone marrow metaphase plates, (3)micronucleus test in polychromatic erythrocytes, and (4)determination of chromosomal aberrations in cultured human leukocytes. The results of the studies indicated that the types and frequenices of cytological errors induced by the drug were not significantly different from the concurrent control. The reduced incidence of fertile matings from 22 to 35 days after treatment is attributed to the cytostatic effect of nogalamycin (NM) on spermatogonia and spermatocytes. Subsidence of NM-induced inhibition of spermatogonium differentiation and spermatocyte maturation occurred 37 days post-treatment. Accordingly, fertile matings, which had reached a zero level by 23rd day, occurred 35 days after treatment, and reached the control level between 47 and 49 days post-treatment.


Effect of tetracycline on cultured mouse cells.

By use of an assay system in vitro with cultured FM3A cells from a C3H mouse mammary carcinoma, tetracycline hydrochloride was found to have the ability to induce an 8-azaguanine-resistant mutation. It is suggested that an assay system using mammalian cells for the detection of mutagenicity of certain substances having antimicrobial action is more practical than a system using bacteria. As other effects of tetracycline hydrochloride on FM3A cells, the damage on chromosomes and the inhibition of syntheses of protein and nucleic acids were demonstrated.


Immunoglobulin content in the bronchial washings of patients with benign and malignant pulmonary disease.

The bronchial washings of 58 patients with benign and neoplastic conditions involving the lungs were evaluated for immunoglobulin content. Levels in the washings from the diseased lung were compared with those from the normal contralateral lung. In normal patients and those with either bilateral inflammatory diseases or unilateral bronchiectasis or tuberculosis, the mean variation in igA/K and igG/K ratios between diseased and uninvolved lungs was minimal. In unilateral pneumonitis, however, igG/K was markedly elevated (P less than 0.01). Significant changes in the igA/K occurred on the affected side in patients with cancer. In the group with squamous-cell cancer. the mean elevation was 4.6 times that of contralateral lung (P less than 0.005), whereas with adenocarcinoma and undifferentiated carcinoma, the rise was 6.4 and 2.8 times, respecitvely (P less than 0.01 and P less than 0.01). Thus, carcinoma appears to alter local immunoglobulin production in the affected lung as compared to its normal counterpart. (N Engl J Med 295:694-698, 1976).


Implementing formative health planning under PL 93-641.

The National Health Planning and Resources Development Act of 1974 (PL 93-641) melds the Hill-Burton program, Regional Medical Program and Comprehensive Health Planning into a new network for health planning and resources development. Health-systems agencies will possess broader powers than predecessor agencies, particularly in the areas of regulation, control of federal funds, resources development and implementation. PL 93-641 thus offers the possibility of transforming the basic concept of health planning from reactive to "proactive." Successful legislative implementaion will require each health-systems agency to build local legitimacy, ensure constructive consumer/provider dialogue, and respond to state and national managerial requirements. Many questions about planning implementation, the role of subarea councils, agency co-ordination and local governance remain unresolved. The new health-planning network has the potential to assume the function of active system transformation, but will be critically dependent on adequate program budgeting to fulfill this promise. (N Engl J Med 295:698-703, 1976).


Treatment of idiopathic membranous nephropathy.

In a retrospective study of the effect of treatment in biopsy-proved idiopathic membranous nephropathy, 91 adults and 12 children were followed for periods up to 29 years after clinical onset (mean, 6.5 years). Forty-four were treated with corticosteroids, 15 with corticosteroids and immunosuppressants; 44 had no treatment and served as a control group. Clinical cure and improvement were significantly greater in the treated than in the nontreated group (P less than 0.01). The recurrence rate, occurrence of renal failure and probability of death were significantly greater in the nontreated group, although some of these patients eventually showed improvement. Prognosis was better in patients who responded to therapy. These data strongly suggest that steroid therapy is beneficial in patients with membranous nephropathy.


Chlorambucil treatment of frequently relapsing nephrotic syndrome.

Chlorambucil, in combination with prednisone, was compared with prednisone alone in a randomized controlled trial in 21 children with either steroid-dependent or frequently relapsing nephrotic syndrome to assess its effect on the duration of remission and the rate of relapse. All control patients treated with prednisone alone continued to relapse at the same rate, with all patients experiencing a return of proteinuria by seven months. Conversely, those who received the same prednisone therapy along with chlorambucil for six to 12 weeks remained in complete remission, without further medication, during 12 to 34 months of follow-up observation. Complications were minimal. Immediate side effects commonly reported with cyclophosphamide were not seen with chlorambucil. Comparison with published reports also suggests that remission induced by chlorambucil is more stable than that after cyclophosphamide. Chlorambucil appears to be of value in the frequently relapsing nephrotic patient, adding an effect that is unattainable with prednisone alone.


Effect of alcohol (ethanol) administration on sex-hormone metabolism in normal men.

To determine whether ethanol per se affects testosterone metabolism, alcohol was administered to normal male volunteers for periods up to four weeks, resulting in an initial dampening of the episodic bursts of testosterone secretion followed by decreases in both the mean plasma concentration and the production rate of testosterone. The volunteers received adequate nutrition and none lost weight during the study, which tended to exclude a nutritional disturbance as the cause of the decreased testosterone levels. The changes in plasma luteinizing hormone suggested both a central (hypothalamus-pituitary) and gonadal effect of alcohol. In addition, alcohol consumption increased the metabolic clearance rate of testosterone in most subjects studied, probably owing to the combined effects of a decreased plasma binding capacity for the androgen and increased hepatic testosterone A-ring reductase activity. These results indicate that alcohol markedly affects testosterone metabolism independently of cirrhosis or nutritional factors.


Septicemia and meningitis in children splenectomized for hodgkin's disease.

Retrospective evaluation of the occurrence of septicemia and meningitis in 200 children who had staging laparotomy iwth splenectomy for Hodgkin's disease revealed 20 episodes occurring in 18 children. Symptoms were usually fulminant; only 10 of these patients survived their episode. Infections occurred eight days to three years after splenectomy. Adolescents, as well as younger children, were affected; half were older than 10 years of age. Leukopenia was not a major factor in onset or survival since the average white-cell count was 12,000 in both survivors and children who died. Pneumonococcus accounted for 50 per cent, and streptococcus for 15 per cent of infections; there was one episode each of Haemophilus influenzae and meningococcus; in 25 per cent, no organism was isolated. Predominance of penicillin-sensitive organisms and high mortality suggest that penicillin prophylaxis and the protection offered by bacterial vaccines should be evaluated in children with Hodgkin's disease whose staging laparotomy includes splenectomy.


Intrahepatic cholestasis in childhood.

The apparent well-being of some children who as neonates were believed to have obstructive jaundice prompted us to study the clinical course, histologic features and possible etiologic factors in 17 children with cholestasis in the neonatal period. During a follow-up period of five months to 22 years, all had signs of chronic cholestasis, but only four died (two from nonhepatic causes); the others live remarkably normal lives. Serial hepatic biopsies in 11 showed a variety of initial lesions, which progressed to hypoplasia of the intrahepatic bile ducts, increasing portal fibrosis and eventual cirrhosis. Although evidence of possible viral infection was found in only 10 cases, a hepatitis, beginning either before or after birth, appears to be a likely original cause. The histologic changes seen may represent different stages of one process, starting as cholestasis with or without evidence of hepatitis and progressing to obliteration or failure of normal growth of the intrahepatic bile ducts.


Platelet coagulant activities and serum lipids in transient cerebral ischemia.

To determine whether platelets play a part in the pathogenesis of transient cerebrovascular ischemia, we studied 22 patients with transient ischemia, 18 control patients and 38 normal subjects. Platelet aggregation and [14C]-serotonin release by ADP, epinephrine and collagen were normal in all patients, as were plasma coagulation assays, except for shortened partial thromboplastin times in the patients with transient ischemia. Platelet coagulant activities concerned with initiation and early stages of intrinsic coagulation were increased two to three times in 12 patients with transient ischemic attacks with normal serum lipids and normal in the 10 others with Type IV hyperlipoproteinemia. These results indicate an association between platelet coagulant hyperactivity and transient ischemic attacks in a group of patients with normal serum lipids.


Gender of offspring after oral-contraceptive use.

We examined the sex of offspring born after oral-contraceptive use according to duration of contraceptive use and the interval between cessation of use and conception for 6109 live births. The overall proportion of male births (with 90 per cent confidence) falls between 0.491 and 0.512. These data exclude with high probability a shift in the sex distribution of the magnitude previously hypothesized, and are not consistent with even a moderate shift in sex distribution. Sex of offspring was not related to total duration of oral-contraceptive use, duration of use since any previous pregnancy or interval between termination of use and conception. It appears that oral contraceptives have no bearing on the sex of subsequent offspring.


Respiratory failure associated with familial depression of ventilatory response to hypoxia and hypercapnia.

Respiratory failure has been associated with depressed ventilatory responses to hypoxia or hypercapnia or both. The possibility that familial factors are responsible for decreased chemosensitivity prompted this study of a child with unexplained respiratory failure and normal lung function. We found his ventilatory response to hypoxia and hypercapnia to be virtually absent. Studies of six healthy immediate family members (parents and siblings) showed that hypoxic response, as measured by an index of the relation between ventilation and hypoxia (index A), was consistently reduced: 45 +/- 8.7 S.E.M. (normal, 127 +/- 8.7) (P less than 0.005). Response to hypercapnia, measured as the slope of the ventilatory response to hypercapnia, was lower than normal, averaging 0.95 +/- 0.16 liters per minute per millimeter of mercury (normal, 1.76 +/- 0.13) (P less than 0.01). The patient's respiratory failure seemed related to deficient ventilatory responses to hypoxia and hypercapnia. It seems likely that this depressed hypoxic response is of familial origin.


Strategies for financing national health insurance: who wins and who loses.

Two sources of funds are available to underwrite the costs of any national health-insurance plan: prepayments (premiums, payroll taxes and income taxes) and out-of-pocket payments (coinsurance and deductibles). The extent to which taxes rather than premiums are used to finance an insurance program will be the major determinant of how large a share of the costs of health care will be borne by higher-income groups. The extent to which coinsurance and deductible provisions are reduced or waived for low-income persons will have a less important, but still substantial, role in determining how the costs of a program are distributed. These financing principles, once understood, provide a basis for the design of health-insurance legislation that will achieve any pattern of income redistribution that may be desired.


Lipid oxidation. Part. 1. Effect of free carboxyl group on the decomposition of lipid hydroperoxide.

Hydroperoxido butyl oleate was decomposed by heating in excess palmitic acid at 60-120 degrees C. The decomposition followed the kinetics of a first order reaction with formation of both monomeric and oligomeric secondary products. The proportions of oligomers slightly increased with increasing reaction temperature and decreased with increasing concentration of hydroperoxide. The activation energy was 70.4 kJ/mol +/- 4.7 kJ/mol. The decomposition of hydroperoxides proceeded partially by monomolecular cleavage, partially by formation of esters with palmitic acid.


[Spinning of rapeseed proteins].

Alkaline solutions of a mixture from rapeseed globulin and casein show plastic flow, which is influenced by protein concentration, relation of rapeseed globulin and casein, temperature and time of storage of the protein solution. The sodium hydroxide concentration with a great variability doesn't take effect on the rheological properties. With increasing content of casein in such alkaline solutions of rapeseed globuline and casein results an approach to NEWTONian flow. The spinnability of alkaline solutions of a mixture from rapeseed globulin and casein and the properties of the corresponding spun protein fibers are influenced by protein concentration, relation of rapeseed globulin and casein of the spinning solution and temperature of coagulating bath. The sodium hydroxide content of the spinning solution and the hydrochloric acid concentration of the coagulating bath with a great variability don't take effect. The spinnability of alkaline solutions of a mixture from rapeseed albumin starchsulphate and casein and the properties of the corresponding spun protein fibers compared to rapeseed globulin-casein mixtures are influenced additionally by sodium hydroxide concentration of the spinning solution and hydrochloric acid content of coagulating bath. The favourable influence on the properties of spun rapeseed albuminstarchsulphate-casein fibers isn't increased by a growth of the rapeseed albumin starchsulphate content more then 4% of the protein concentration of the spinning solution.


[Effect of starchsulfate on properties of protein fibers].

Admixture of starchsulphate to an alkaline spinning solution of proteins increases the thermostability of the corresponding spun protein fibers.


[Formation of dichlorvos residues on cereal products].

Dichlorvos should be used in mill rooms where milling products are stored. The contamination of foods stored in such rooms strongly depends on the mode of application, the concentration of the agent and the temperature. The authors deal with the extent of contamination under various conditions and with the degradation rate in contaminated flours.


[Field test for determination of mercury in cereals and cereal products].

By means of the method described, rapid semiquantitative mercury determinations may be performed without energy supply in cereals and cereal products. The mercury ions which are liberated by digestion with concentrated H2SO4 and KMnO4 are determined with the aid of a colorimetric method which is based on the formation of a coloured complex of mercury with di-beta-naphthyl-thiocarbazone. The method permits visual comparison of mercury concentrations ranging from 0.1 to 13 mug, revealing concentration differences up to 0,1 mug. The rate of recovery is 76%.


[Vitamin A determination in commercially produced feeds. 2. Vitamin A determination in mixed feeds].

On the basis of a study of methods for the determination of vitamin A in mixed feeds, it is shown that both the vitamin A determination according to CARR and PRICE and the determination of anhydro-vitamin A yield valid results. With regard to accuracy, easy performance and productivity, the determination of anhydro-vitamin A is the better suited method.


[In vitro study on effect of body weight on deiodination of L-diiodotyrosine and L-thyroxine in liver and kidney of rats on standard diets].

The effect of body weight on the deiodination of L-di-iodotyrosine and L-thyroxin in the liver and kidney was studied in vitro in male Wistar rats of same age, but differing in weight (light and heavy, respectively), which were fed a standard diet. In the livers of the heavy animals, the deiodination of L-di-iodotyrosine and L-thyroxin was significantly lower than in those of the light animals. As to the kidneys, no such difference was observed. From a comparison with literature data it is concluded that the reduction in deiodination in the livers of the heavy animals might be due to a reduction in thyroid hormone metabolism.


[In vitro study of deiodination of L-diiodotyrosine and L-thyroxine in liver of dietetically fat rats].

Beginning with the fifth week of life, male Wistar rats were fed a diet containing, respectively, 3 and 50 per cent fat (corresponding to, respectively, 7 and 75 per cent fat of total calories). The differences in body weight between the two groups were 64 per cent for 10-week-old rats, and 71 per cent for 6-month-old rats. For these animals, the extent of the enzymatic deiodination of L-diiodotyrosine and L-thyroxin was determined in liver homogenate supernatants. In the 10-week-old rats as well as in the 6-month-old rats on high-fat diet, the deiodination of L-di-iodotyrosine was significantly lower than in the animals on low-fat diet, whereas the diodination of L-thyroxin was significantly higher. It is concluded that the fat content of the diet exerts an inhibiting effect on the deiodination of L-di-iodotyrosine and an enhancing effect on the deiodination of L-thyroxin.


[Effect of diet on deiodination of L-diiodotyrosine and L-thyroxine in rat liver].

Male Wistar rats of same weight were used to study the effects of diets containing, respectively, 3 and 50 per cent (by weight) fat on the deiodination of L-di-iodotyrosine and L-thyroxin in the liver. For this purpose, liver homogenate supernatants were analysed. The deiodination of L-di-iodotyrosine was significantly lower in the animals on high-fat diet than in those on low-fat diet, whereas the deiodination of L-thyroxin was significantly higher. It is concluded that not the body weight, but the diet influences the extent of deiodination.