Metabolic effects of anabolic steroid on skeletal muscle.

The purposes of this investigation were to examine the effects of anabolic steroid treatment on protein synthesis in skeletal muscle and on steroid receptors. The experiments were conducted with 230 male albino rats maintained on a diet containing 20% protein. Anabolic steroids (methandrostenolone, methylandrostendiole, and Retabolil) were injected in doses of 0.5 mg/kg body weight. The animals were examined at rest and after swimming exercise of 15 min duration. Quadriceps and gastrocnemius muscle were used for analysis in all experiments. Protein synthesis was studied by means of 14C-leucine incorporation. It was found that anabolic steroid treatment resulted in an increased content of skeletal muscle protein: myosin, myofibrillar, and sarcoplasmic fractions. The activity of RNA-polymerase in skeletal muscle nuclei was increased. The results indicated that in skeletal muscle there were androgen receptors which were binding sites for 3H-testosterone and anabolic steroids. A model for the anabolic steroid action on the regulation of protein synthesis in skeletal muscle was proposed.


Physiological characteristics of sprint and endurance Masters runners.

Data were obtained from 13 sprint (age range 41-58) and 13 distance (age range 4-78) Masters track athletes. The mean VO2max value for the distance runners was 54.4 +/- 3 ml kg min compared with 47.2 +/- 2 ml kg min for the sprinters. The highest VO2max (71.0 ml kg min) was obtained on a 45-year-old distance runner while the lowest (27.3 ml kg min) was obtained on the oldest (78 years) distance runner. VO2max decreased by 34.5% from age 40 to 70 in the distance runner in spite of continued training that ranged from 40 to 120 miles/week. Maximum ventilation rates were 122.5 +/- 6.8 and 116.8 +/- 7.0 1 min for the sprint and distance runners, respectively. Percentage of body fat was 16.5 +/- 0.5 for the sprinters and 18.0 +/- 1.1 for the distance runners. Serum cholesterol values were 218.7 +/- 8.7 and 203.0 +/- 13.8 ml/dl, while triglyceride values were 101.5 +/- 8.2 and 84.1 +/- 9.3 mg/dl for the sprint and distance groups, respectively. These data indicate that, VO2max decreases significantly with aging despite the continuation of long distance training. Percent body fat and serum lipid levels were significantly lower in these athletes compared to those for sedentary adults, suggesting a protective effect against coronary heart disease. Only one subject had S-T segment depression during the exercise test.


Physiological characteristics of elite prepubertal cross-country runners.

Eight elite cross-country runners and eight normally active boys 8--11 years of age were studied. The runners were selected on the basis of success in regional and/or national championships. Two of them had the first to third fastest mile run times for their age groups in the U.S. for three years. Tests included submaximal and maximal treadmill runs, an anaerobic capacity bicycle test, a mile run, and various anthropometric measures. A best career mile run (BCM) was used for comparisons within the running group. At submaximal work levels of 5.6 and 7 mph (124, 161, and 187 meters/min) the values for heart rate (HR) and respiratory exchange ratio (R) were significantly lower for the runners than for the non-runners. The VO2max of the runners (56.6 ml kg min) was significantly higher than that of the non-runners (46.0 ml kg min). For all subjects combined, mile run time was highly correlated with percent VO2max and percent max HR at all submaximal running speeds (r greater than 0.8). The correlation coefficient between mile run time and VO2max was -0.88. Within the running group, however, BCM was unrelated to VO2max but was closely related to percent VO2max at 8 mph (213 meters/min) with 4 = 0.86, and to anaerobic capacity (r = -0.88). There were no significant differences between the groups in age, height, weight, max HR, and percent body fat. Thus the runners had higher aerobic and anaerobic capacities, and greater utilization of fat as an enrgy sustrate during submaximal work. Within the running group, anaerobic capacity and running economy were closely related to BCM time, whereas VO2max was not.


Thermal and circulatory responses to repeated bouts of prolonged running.

The purpose of this study was to determine the thermal and circulatory responses of seven runners (X VO2max = 66 ml kg min) to two bouts of high intensity prolonged treadmill running (PTR) [each 80-min at 70% VO2max] spaced by a 90-min rest. After the transition to exercise, oxygen uptake (VO2) and percent change in plasma volume remained constant throughout each PTR. Rectal temperature (Tr) and heart rate (HR) increased while stroke volume (SV) and cardiac output (Q) decreased during the course of each PTR. The pattern of response for each variable was similar for both PTRs. However, Tr and HR were higher and SV and Q were lower during the second PTR when compared to the first of each respective time period.


Low exercise ventilation in endurance athletes.

Previous studies have shown that endurance athletes are endowed with low ventilatory responses to chemical stimuli. The implications of this association have never been clear. Although recent evidence shows that exercise ventilation (VE) correlates with ventilatory chemoresponsiveness in a group of  athletes, the extent to which non-athletes may differ from athletes in this regard is unknown. We have examined the relationship between ventilatory chemoresponsiveness and exercise VE in a group of 7 non-athletes, and contrasted these findings with those obtained previously from 8 endurance and 8 non-endurance athletes. Correlation lines of exercise VE with chemical responses were similar in slope and intercept for both athletes and non-athletes. However, we found that non-athletes had greater exercise VE per unit metabolic rate (VO2 or VCO2), and greater ventilatory responses to O2 and CO2, when compared with endurance athletes at equal relative work loads (P less than 0.05). The lower exercise VE/VCO2 of endurance athletes as compared with non-athletes persisted in hyperoxia, indicating that factors other than differences in hypoxic sensitivity explain the lower exercise VE of endurance athletes. Low exercise VE may be the link between low ventilatory chemosensitivity and outstanding endurance athletic performance.


Cardiorespiratory health, reaction time and aging.

Visual simple and choice reaction time (RT) tests were administered to 64 male and female volunteers 23 to 59 years of age. One half of the subjects were runners involved in rigorous training programs averaging 42 miles per week. The other half of the subjects were sedentary adults. Eighty simple and 100 choice reaction time trials were given with a variable foreperiod ranging from 400 to 1100 msec. Five catch trials were given in both simple and choice reaction time conditions. The results indicated that there was a gradual decline in RT performance as age increased. However, this trend was not evident in the trained group. Reaction time remained constant with age within the trained group. It was concluded that a high state of cardiorespiratory training may prevent cognitive decrements in performance with age.


Neural and humoral signals for pulmonary ventilation arising in exercising muscle.

This review analyzes attempts to isolate and quantify the neurally and humorally mediated portions of the ventilatory response to moderate exercise. 1. Dejours' "neuro-humoral theory" postulates that, following a change from rest to moderate, constant-load exercise in man, the abrupt initial increase in VE is neurally mediated, and the subsequent gradual rise in VE is humorally mediated. However, no compelling evidence exists to support either of these hypotheses. Moreover, there is a plausible alternative method of partitioning VE into fast and slow components: the steady-state value of VE may be entirely due to the slow component. 2. The similarity between the kinetics of VE and VCO2 during exercise suggests that the ventilatory response may be primarily triggered by a signal that has its origin in the CO2 flux to the lung. Intravenous CO2 loading in resting animals produces such a flux, unaccompanied by possible neural signals arising from contracting muscles. However, experiments of this type have produced drastically conflicting results. 3. With cross-circulation techniques, the ventilatory response to neural signals from exercising limbs can be isolated, by sending the blood leaving these limbs directly into the venous system of another animal. Experiments of this type with anesthetized dogs led Kao and co-workers to conclude that the increase in VE during steady-state exercise is entirely due to neural signals originating in the exercising limbs. 4. In skeletal muscle, the kinetics of VO2 closely follow those of the concentrations of creatine phosphate and free creatine: a sensor of either of these concentrations could thus theoretically serve as a useful "metaboreceptor". The extracellular concentration of K+ in contracting muscles also changes rapidly enough to lead cardio-ventilatory adjustments, and thus might possibly trigger a neural signal involved in their control.


Overview of ventilatory control during exercise.

Practically every respiratory physiologist of the last 100 years has studied the ventilatory response to exercise. Yet we still do not know the cause of increased ventilation associated with exercise. This overview considers the problem from a broad observational point of view. Data from studies combining exercise with continuous inspired CO2 and "slug" CO2 breathing imply a feed-forward/feed-back structure for the ventilatory controller. The feed-forward stimulus is correlated to CO2 production. Feed-back senses arterial CO2 tension and acts to minimize the effects of correlation errors and correlation slope errors in the feed-forward path. This feed-forward/feed-back structure yields a regulated arterial CO2 and a tight coupling of ventilation to CO2 production. The feed-back mechanism acts via the carotid body, and indirectly via the central chemoreceptor. A variety of mechanisms are discussed that may be involved in providing the feed-forward stimulus. In particular, the intravenous loading experimental results are considered in terms of an appropriate feed-forward stimulus.


[New unit construction urologic endoscopes].

Drawbacks of serially-produced cystoscopes are considered along with their technical perfection. The calculation results for a new light-power optical ststem for cystoscope are reported and the structure of optical tube incorporated in those unified urological endoscopes with its main parameters are given. A conclusion is made regarding the technical perfection of currently produced Soviet cystoscopes.


[Optical properties of flexible fiberoptic endoscopes].

Optical properties of flexible fiber-optic endoscopes, requirements to them and methods of their testing are under consideration in this article. This results of the research performed became the basis for developing a State USSR Standards entitled "Medical endoscopic instruments with fiber optics. General technical requirements."


[Fiber endoscopes with structureless image].

Approaches to the removal of mosaic by special decomposition, composition and image scanning are discussed. This provided 6 times larger volume of the information transmitted. A principle of choosing parameters for endoscope oculars is offered and pictures showing ways to bend their distal end are presented.


[Comparative analysis of optical systems for illuminators in light guide apparatus].

The article deals with analysis of light-optic systems with halogen incandescent lamps incorporated into domestic light sources for fiber-optic apparatus, types OC-100, 0C-150 and OC-250, and for some foreign light sources of similar types. The recommendations given are aimed at the improvement of light-optic parameters of the systems where the lamp is built into the reflector.


[Effect of infiltrating water vapors on mercury-zinc elements in implanted electric cardiac stimulators].

A complex character of the water vapours effect on the energy source used in electrical pacemaker is investigated on the RMCC-1 type Hg-Zn element. The water vapours were shown to cause electrolyte effluence and hence the appearance of the leakage eddy currents amounted up to 22mA through the insulation of electrodes. The resulted charge loss reduce the clinical service term of the pacemaker electrodes. This can be avoided by the provision of equal water-vapours' partial pressure in the surrounding medium and in electrolyte, by means of special construction. At the doby temperature this requirement is achieved at the 27%-air relative humidity.


[Attachment to a fibergastroscope for cinematography].

The diagnostic horizon of endoscopy is being extended due to the record of endoscopic pictures on the cinema film. The accessories offered by the author allow successful application of the "Kiev-16" movie-camera jointly with the fibrogastroscopes produced by Olympus Co without camera, for cinema and photodocumentation.


[Genital tuberculosis in African female patients (author's transl)].

Genital tuberculosis in 76 Senegalese women and 82 Nigerian women, have been compiled from statistical tables covering a period of 10 years. The authors present the features of genital tuberculosis in african females. In most cases, diagnosis is made through peroperative findings or anatomo-pathological control of exeresis specimens; still, biopsy of endometrium, systematically performed on each patient consulting for sterility, gave opportunity to detect an important number of cases of genital tuberculosis in Nigeria. The frequency of this disease is low among other unspecific genital infections. Its medical treatment is effective on tuberculous infection but not on sterility which is an unavoidable sequella.


[Osteo-articular tuberculosis in African (author's transl)].

General, clinical and therapeutic features of osteo-articular tuberculosis in African, excluding vertebral localizations, are compiled from 81 records: The are: -- a frequency lower than in expatriated Africans and this indicates their special physical resistance when they live in their natural environment; -- frequently an easy diagnosis because of infected advanced foci with associated lesions; -- a surgical indication (curettage, resection, arthrodesis) as frequent as in vertebral localizations.


[Extrapulmonary tuberculosis in Africans (author's transl)].

Extra pulmonary tuberculosis are frequent in Africa and have a special severity due to delayed diagnosis and multifocal forms. Various punctures and biopsies may be necessary to demonstate the tuberculous infection. Even with modern treatment it too often implies important risks of severe sequelae.


[Pott's disease in African (author's transl)].

A study of anatomical clinical, and therapeutic features of Pott's disease in Africans from 131 cases treated by the same team and compiled from the principal series published during the last ten years in Black Africa. Anatomical features are related to the frequency of the disease (70 p. 100 of tuberculous osteo-arthritis), the elective lumbodorsal localization involving several vertebrae (gpenerally 3 or 4) and being sometimes multifocal. Clinical features are in part explained by the delay with which patients report to the hospital for the first time so that 80 to 90 p. 100 of the patients suffer from severe lesions (which are in their destructive phase in 30 p. 100 of the cases), with associated-complications (gibbosity, abcess, 50 p. 100; fistulae, 2 to 6 p. 100; paraplegie 23 to 25 p. 100; multiplefoci, 4 to 13 p. 100). Diagnostic difficulty mainly raised by "False Pott's diseases" (P. Bourrel), is considered. Therapeutics is studied; importance and place of the surgical treatment is emphasized; its various approaches are discussed. The authors report their surgical interventions on 89 patients out of 181 admitted: 64 direct approaches for simple Pott (with 70 p. 100 of good results and 20 p. 100 of satisfactory results), 25 operations for complicated cases of Pott (18 approaches for antero-lateral decompression and 5 laminectomies, with 22 satisfactory results).


[Surgical treatment of pulmonary tuberculosis in tropical environment (indications and technics) (author's transl)].

A study of 85 clinical records of patients with pulmonary tuberculosis who were operated in hospitals of South Vietnam and West Africa. Some common features may be noted: --an ongoing clinical evolution before the indication for a surgical intervention (more than 5 years in half of the cases); -- positive bacilloscopies in 70 p. 100 of the cases; -- bilateral lesions in one case out of three; -- unilateral lesions restricted to one lobe in one case out of two; -- surgery limited to a thoracoplasty for 48 p. 100 of the patients; for the remaining 52 p. 100, half underwent lobotomy, half pneumonectomy.


Diabetic nephropathy as the mode of presentation of diabetes mellitus.

Diabetic nephropathy have only rarely been described in patients who have minimal or no glucose intolerance. We herein report the case of a 59-yr-old man who presented with nephrotic syndrome and minimal glucose intolerance whose renal biopsy showed the nodular (Kimmelsteil-Wilson) and diffuse glomerulosclerosis lesions characteristic of diabetes. We critically review the literature on this subject, pointing out the pitfalls in diagnosis and establishing strict criteria for the diagnosis of diabetic nephropathy in patients wihout overt clinical diabetes.


Regulation of insulin biosynthesis in vivo by glucose in the newborn rat.

The effects of glucose on insulin biosynthesis in vivo were investigated in the 3-day-old rat. The extent of insulin synthesized was determined by following the incorporation of 3H-leucine into immunoreactive insulin (3H-IRI) and pancreatic proteins (3H-PROT). Blood glucose levels increased 2.3 +/- 0.2 g/liter and plasma insulin increased 208 +/- 10 muU/ml after an intraperitoneal injection of 3H-leucine plus glucose (2 g/kg, body wt) in neonates. Hyperglycemia resulted in a decrease of basal plasma specific radioactivity of leucine and 3H-PROT radioactivity by about 40%. Determination of the 3H-IRI/3H-PROT incorporation ratio shows that the glucose load induced a significant stimulation of insulin biosynthesis 120 min after the injections. The present data indicate that (1) short-term variations of blood glucose are efficient in the regulation of insulin biosynthesis, and (2) insulin biosynthesis in vivo is likely to operate at a basal level of blood glucose in the 3-day-old rat. The results suggested that the variations of blood glucose in a concentration range found under physiologic conditions may play a role in the regulation of insulin biosynthesis in vivo.


Amino-acid metabolism and liver ultrastructure in hyperornithinemia with gyrate atrophy of the choroid and retina.

Three patients with the rare hyperornithinemia with gyrate atrophy of the choroid and retina (HOGA) syndrome were studied to elucidate the metabolic derangement and its pathologic concomitants. Tenfold elevations of blood ornithine levels, decreases in lysine levels, and hitherto unreported decreases in blood glutamate and glutamine concentration were observed. The output of ornithine from muscle kidney and splanchnic beds was curtailed or reversed after intravenous glucose. Levels of ornithine in venous blood declined after oral glucose, and rose after intravenous arginine. Increased amounts of 3-amino-2-piperidone were found in the urine, but these did not increase after the arginine-induced increase in ornithine levels. Liver biopsies in two patients revealed a marked alteration in mitochondrial ultrastructure. These studies extend the knowledge of the metabolic and pathologic derangements in HOGA. These findings are consistent with a disorder of ornithine-ketoacid transaminase, but such a disorder might not account for all the observations.


Augmented lipolysis in rat adipose tissue upon repeated exposure to epinephrine.

A perfusion system was used to investigate the lipolytic response to epinephrine of minced epididymal fat pads from fed and 24-hr fasted rats. Epinephrine was infused at a final concentration of 1 X 10(-6) M for 60-min periods. Basal glycerol release from tissue and cells of fed animals was 3 mumoles/min/ml of sample. Epinephrine stimulated lipolysis 20-fold in tissue pieces. There was an additional two-fold increase during a repeated epinephrine infusion after 30 min with buffer alone. In contrast, tissue from fasted rats showed no difference upon successive infusions of epinephrine. Isolated cells of fed and fasted animals also produced peaks of equal magnitude on both exposures to epinephrine. Preincubation of fed tissue with anti-insulin serum did not abolish the augmented response to the hormone. Preincubation of the fed tissue for 90 min with omission of the first epinephrine exposure did not produce an augmented response. It is concluded that exposure of adipose tissue to 1 X 10(-6)M epinephrine will produce augmented stimulation of lipolysis on a second exposure. Fasting and isolation of cells abolishes the augmented response by a mechanism which does not involve removal of insulin from the fat cell.


A longitudinal study of bone-mineral content and intestinal calcium absorption in patients with chronic renal failure.

In 14 nondialyzed patients with chronic renal failure (CRF) and at the start of treatment a glomerular filtration rate (GFR) of 14--47 ml/min changes in bone mineral mass (BMM), expressed in percentage of the initial value, showed a significant correlation with the mean GFR during an observation period of 16 +/- 2 mo. During a predialysis period of 6 mo BMM decreased to 97.8 +/- 3.2% of the original value in 9 patients, while after 6, 12, and 16 mo of dialysis treatment, BMM in the same patients fell to 94.5 +/- 3.0%, 92.0 +/- 3.2% and 91.8 +/- 4.6% of the initial value. As after the onset of regular hemodialysis the fractional intestinal absorption of 47Ca does not decrease but even increases in most patients, the importance of the level of intestinal calcium absorption for the development of dialysis bone disease may be questioned.


Calorimetric results in man: energy output in normal and overweight subjects.

In order to test the practicability of 24-hr investigations with the gradient-free Vienna Whole-Body Calorimeter, energy output was measured over 24-hr periods in 18 human subjects. Heat loss was partitioned into dry and evaporative components. Sixteen female subjects were divided into normal-weight (less than 100% according to the Broca index), overweight (100%--120%), and obese (over 120%) groups. A male with severe hypothyroidism, and a female with no signs of impairment of thyroid function who had weight problems that were suspected to be due to low energy expenditure, were studied separately. Subjects reported that the calorimeter chamber was sufficiently comfortable for at least a 24-hour investigation. Overweight and obese subjects showed both greater total heat output and greater inter-individual variability than the normal weight group. Normal and overweight subjects were on steady levels of food intake that were representative of usual intake. For normal subjects there was a relatively close correspondence between energy intake and output, but not for overweight subjects. Thyroid hormone therapy produced a large increase in energy output in the hypothyroid patient. Energy expenditure was found to be unusually low in the patient with weight problems and was increased by about 50% after thyroid hormone administration.


Pathogenesis of acidosis in hereditary fructose intolerance.

An 18-yr-old man with a classical history of hereditary fructose intolerance (HFI) developed typical biochemical changes following an oral fructose load: fructosemia, hypoglycemia, hypophosphatemia, hyperuricemia, and metabolic acidosis. Hypokalemia (3.1 meq/liter) was also noted. Three aspects of this case expand the published literature on this syndrome: (1) Metabolic acidosis was found to be due to both lactic acidosis and proximal renal tubular acidosis (RTA). We could quantitate the relative contribution of each, and found that urinary bicarbonate loss due to proximal RTA accounted for less than 10% of the fall in serum bicarbonate. The major cause of the metabolic acidosis was lactic acidosis. (2) Hypokalemia was found to be due to movement of potassium out of the extracellular space rather than to urinary loss. Potassium may have entered cells with phosphate or may have been sequestered in the gastrointestinal tract. (3) The coexistence of proximal RTA and acidemia made it possible to study the effect of acidemia on the urine-blood partial pressure of carbon dioxide (PCO2) gradient in alkaline urine (U-B PCO2). The U-B PCO2 measured during acidemia was much higher at the same urine bicarbonate concentration than in normal controls during alkalemia, providing evidence in humans that acidemia stimulates distal nephron hydrogen-ion secretion.


Consumption of O2 and early detection of fa/fa genotype in rats.

Oxygen consumption was determined in 10--12-wk-old fa/fa and non-fa/fa rats at ambient temperatures of 10 degrees--40 degrees C. The fa/fa rats exhibited a lower oxygen consumption than non-fa/fa rats from 10 degrees--30 degrees C, but not at 35 degrees C and 40 degrees C. A lower oxygen consumption was also observed among fa/fa rats as early as 18 days of age, prior to the phenotypic expression of apparent obesity. Fourteen hundred microliter O2 consumed/hr/g body weight at STP was used as a value, below which future obese rats could be identified among 18-day-old pups from fa/+ X fa/+ crosses. Only a 10% error was found in the use of this value for the early identification of the fa/fa genotype.


Sterol balance in abetalipoproteinemia: studies in a patient with homozygous familial hypobetalipoproteinemia.

A new case of homozygous familial hypobetalipoproteinemia is reported in a 16-yr-old girl. Apoprotein B was absent from plasma and the patient had acanthocytes and steatorrhea, but minimal neurologic dysfunction. Total body cholesterol synthesis was assessed intermittently over a 30-mo period by sterol balance techniques. The rate of synthesis of cholesterol was higher (15.0 +/- 2.9 mg/kg/day) in the patient (8.3 +/- 0.4 mg/kg/day than in 3 control children, p less than 0.005). Bile acid synthesis was similar (4.6 +/- 1.8 versus 4.0 +/- 1.7 mg/kg/day) in the patient and controls, but total body sterol synthesis was significantly higher (19.6 +/- 3.0 versus 12.2 +/- 2.0, p less than 0.005). The absorption of orally administered [1,2,(3)H] cholesterol in the patient was low and less than 0.5% of the label appeared in the total plasma volume at all times up to 48 hr. Estimates of the extent that malabsorption of biliary cholesterol contributes to the enhanced excretion of neutral sterols in this case indicate that all of the increase can be explained on this basis. Thus, although the mechanisms for the increased sterol synthesis in this case may relate to the absence of chylomicrons and low density lipoproteins in plasma, the magnitude of the increase can be fully explained on the basis of a compensatory mechanism to maintain cholesterol homeostasis in the face of enhanced fecal losses.


A new electron microscope technique for the study of living materials.

In order to gain informations on the real structure of biological specimens the "wet technique" for electron microscopy has been developed. The construction and the working principle of a special microchamber are described. Applications of this technique for the investigation of blood cells, gametes and various bacteries are demonstrated by micrographs.


[A simple additional device for the Siemens electron microscope Elmiskop EM-101 to introduce specimen without air-contact (author's transl)].

A simple additional device is shown to introduce specimen without contact to air into the Siemens electron microscope EM-101. The construction, the function and handlinf of the modified specimen airlock is described. The device is used to study oxidable crystals by electron microscopy and diffraction, and might also be promising for ultracytochemical and molecular biological problems.


Medical applications of the radioisotope X-ray fluorescence analysis.

The X-ray fluorescence, induced by small, sealed-off radioactive sources, can be applied as very sensitive method of analysis of trace elements in biological specimens. The preparation and technique for the analysis of small (0.1 to 0.5 ml) or larger (more than several milliters) volumes of liquid samples will be described, and the principal patss of the devices for analyzing only one element or a series of them are presented. The measuring time for typical analysis ranges between 10(2) and 10(4) seconds. For a simple X-ray fluorescence analysis the sensitivity of the method is varying between 10 ppm and 100 ppm when measuring during 100 seconds. A large number of applications of this method in the medical field is listed, concerning the analysis of trace elements naturally present in biological samples, and the analysis of elements employed as "stable tracers" in order to follow a dynamic process, or in order to label blood components, such as erythrocytes, leukocytes and platelets.


Stereological analysis in scanning electron microscopy.

The traditional field of stereological analysis based on quantitative image analysis data is expanded to include scanning electron microscopy (SEM). Two major methodological advances enable useful results to be obtained: 1) Image recording of backscattered electrons using an annular semi-conductor detector; 2) Direct link between SEM and image analyser by means of an on-line coupling providing synchronisation of both sub-systems.


The evaluation of cell-densities and of nerve-cell-size distribution by stereological procedures in a layered tissue (cortex cerebri).

The procedure of a stereological investigation of the cytoarchitectonics in the cerebral cortex is described. The number of all cells and--in order to obtain a size-distribution--the area of nerve-cells are measured with the help of an optomanual system (MOP-AM). The values and the distance of the evaluation-field from the cortical surface are transferred to a magnetic-tape. The principle of the arrangement of the fields has been described in Microscopica Acta, Vol. 71. The actual results including their statistics are calculated with a table-computer by using stereological formulas and by considering the magnification and the shrinkage of embedding. The measurement of the latter is also mentioned. The results can be printed in the form of various tables for lines, superlines, layers and the whole cortex and in the form of a newly developed computer-graph. The latter demonstrates the size-distribution of the nerve-cells and their dependence on the distance of the cortical surface. The task of our present study--the aging of the human cortex cerebri--is briefly given.


Quantification of human sperm morphology and motility by means of semi-automatic image analysis systems.

Sperm morphology and motility are determined using a semi-automatic image analysis system under opto-manual control. The system consists of a microscope equipped with a drawing-tube, a digitizer-tablet, and a cursor interfaced to a small microcomputer. A light-emitting diode is mounted on the cursor, visible as a bright red pilot-light in the microscopic field. Sperm head and midpiece as well as the pathway of motile spermatozoa are traced with the cursor's red pilot light. The microcomputer calculates area, circumference, and length simultaneously. Motility and sperm density are determined altogether using microchamber technique. In a selected group of male subjects with normal, doubtful, and pathological semen analyses biometrical analyses of sperm morphology and motility were performed. Sperm morphology is best described by the variation of the head size and by the average midpiece width. Motility is best described by % motile spermatozoa and mean velocity determined 1 hour after semen collection. Biometrical semen analyses are superior to subjective evaluations regarding degree of information, objectivity, and reproducibility.


Lipid composition of Staphylococcus aureus and its derived L-forms.

Two strains of Staphylococcus aureus (Newman and Tazaki) and their derived L-forms were cultured in serum-containing broth and the differences in their lipid compositions were analyzed. Cardiolipin accounted for more than 50% of the total phospholipid phosphorus in L-forms, but for less than 25% in parent bacteria. The cardiolipin content of L-forms was very high through all growth phases, although it increased gradually as growth proceeded. Significant amounts of cholesterol and its esters were present in parent strains and L-forms, all of which incorporated serum cholesterol into the cell membrane. On the other hand, they could be detected in the L-forms but not in the parent strains when they were cultured in serum-free broth. To examine the ability of L-forms to synthesize cholesterol, the cholesterol content of L-forms cultured in serum-free broth was compared with that of the medium. The results indicated that staphylococcal L-forms could synthesize cholesterol and its esters. These differences in lipid composition suggested that modification of membrane lipids may occur as an adaptational change in response to the disappearance of the cell wall.


Accumulation of eosinophils and monocytes in lymphoid organs of chick-embryos. I. Effect of antigenic stimulation.

The effect of antigenic stimulation on the migration pattern of eosinophils and monocytes was studied during the embryonic stage in chickens. On the 13th embryonic day, chickens were injected with sheep red blood cells as antigen into the allantoic cavity and the relative frequency of oxidase positive cells (OPC) was determined as the total number of eosinophils and monocytes in the bursa of Fabricius, spleen, and thymus. Three and five days after the antigenic stimulation, the frequencies of OPC increased in both the spleen and thymus and then decreased to the normal level just before hatching. However, bursal frequencies of OPC were always low in both the cortex and medulla when compared with the controls. These events indicated that eosinophils and monocytes accumulated in the spleen and thymus after the antigenic stimulation. Furthermore, different frequencies of OPC among the embryonic lymphoid organs showed different responses in the migration of eosinophils and monocytes.


Accumulation of eosinophils and monocytes in lymphoid organs of chick-embryos. II. Effect of mitogenic stimulation.

The mitogen effect on migration of eosinophils and monocytes was studied in embryonic chickens. On the 13th embryonic day, chickens were injected with mitogens, such as concanavalin A (Con A), phytohemagglutinin-P (PHA-P), and lipopolysaccharide (LPS), into the allantoic cavity, and the mitogenic effect was estimated from the relative frequencies of eosinophils and monocytes by enumerating the number of oxidase positive cells (OPC) in the spleen, thymus, and bursa of Fabricius. Splenic frequencies of OPC increased in the embryos treated with mitogens. Similar influences were also detected in the thymic OPC. Higher responses were seen on the 18th embryonic day in the number of splenic OPC when embryos were treated with Con A or PHA-P than with LPS. These findings suggest that Con A and PHA-P are preferential OPC accumulation promoters. However, bursal frequencies of OPC in the cortex were low after mitogenic stimulations when compared with controls, although appreciable responses were detected in the bursal medulla after LPS stimulation. These results suggest that the migration pattern in the population of eosinophils and monocytes is affected not only by T cell mitogens but is also derived from LPS stimulation.


Increased sensitivity to lead -- animal model: feline porphyria.

Individuals with the genetically inherited condition of latent porphyria have been previously hypothesized (1) as being a potential high risk group to elevated lead exposure. More specifically, persons with either clinical symptoms of porphyria or the latent form who also are exposed to excessive lead may have their clinical symptoms exacerbated or possibly induced prematurely, respectively. This paper presents evidence that an animal model (i.e., domestic cats with congenital porphyria) may facilitate the testing of the previous hypothesis.


Can drinking water standards be reliably derived from industrial TLVs?

The accuracy of TLV derived drinking water standards is evaluated. When using the identical TLV conversion methodology which Stokinger and Woodward (1) used in deriving the standard for barium in drinking water, standards for arsenic, cadmium, chromium and lead offer 6, 200, 60, and 10 times less protection than the present drinking water standards, respectively. However, using the same methodology, the TLV derived drinking water standard for fluoride offers greater protection than the present standard by a factor of approximately 2. Thus, the use of the TLV conversion factor should be viewed in as one of many lines of potential evidence which should be reviewed in the standard derivation process - but it should not, if at all possible, be considered alone - as in the case of barium.


A little known cell in the gastrointestinal tract.

A little known cell in the gastrointestinal tract has been described. The confusion over terminology is discussed. The question of the undifferentiated cell type is also considered. Although well recognised by gastroenterologists they remain little known in general. Their function is unknown. The various possibilities are summarized.


Anoxemia as the cause of death in shock.

The case is presented that both hemorrhagic and septic shock are due to an inadequate oxygen supply to mitochondria of vascular muscle cells in peripheral circulatory beds. Mitochondria disintegrate in the presence of severe hypoxia; this is a normal response which does not, per se, indicate generalized cell damage. Irreversible shock follows when appreciable numbers of the muscle mitochondria become non-functional. The ATP available from glycolysis is inadequate to resynthesize the mitochondrial apparatus and oxygen cannot be used by the damaged mitochondria to produce the needed ATP through oxidative phosphorylation. In the absence of adequate ATP, the tone of these peripheral vessels must fall, leading to irreversible systemic hypotension and death. In hemorrhagic shock, mitochondrial hypoxia of smooth muscle cells is produced by decreased perfusion of the vasa vasorum in the constricted peripheral vessels; in septic shock there is direct competition for oxygen between bacterial cytochromes and muscle mitochondria.


Homo sapiens ascorbicus, a biochemically corrected robust human mutant.

Homo sapiens' gene pool contains a defective gene for the synthesis of the active enzyme protein, L-gulonolactone oxidase(GLO). The absence of GLO in the human liver blocks the normal mammalian conversion of blood sugar into ascorbate, leading to the potentially-fatal "inborn error of carbohydrate metabolism", the genetic disease, Hypoascorbemia (in the older nomenclature- scurvy). To survive, humans need exogenous sources of daily ascorbate. Most mammals have the intact gene for GLO synthesis and produce generous daily amounts of the liver metabolite, ascorbate; for instance, an unstressed 70 Kg goat is capable of producing over 13 grams of ascorbate daily and much more under stress. The recommended dietary allowance of 45 milligrams of ascorbate a day for human adults, now proposed and used by nutritionists, is grossly inadequate to restore Homo sapiens to a normal mammalian ascorbate physiology. To correct fully this human genetic defect and banish epidemic chronic subclinical scurvy requires daily intakes of ascorbate equivalent to, at least, the amounts synthesized by the other mammals. Humans kept on a long term regime of full correction of this birth defect show great salutary benefits in health maintenance, disease therapy and slowing of the aging process. This can be regarded as the creation of a new and more robust, longer-living, tough human sub-species, Homo sapiens ascorbicus, by the biochemical reversal of a primate mutation occurring some 60 million years ago. Some of the practical benefits and pathways of future clinical research are discussed.


Psychosocial dynamics in anorexia nervosa.

Anorexia nervosa represents a self-destructive struggle for separate identity, and cultural factors play a part in the present increasing incidence. This paper presents a broad view, which embraces family dynamics and the natural history of the disease, to clarify important issues in its management and prevention. Both family and individual psychotherapy may have a place in the patient's personal rehabilitation.


Colorectal cancer. A study of 230 patients.

Clinical presentation, risk factors, investigations, pathology and treatment were examined in a retrospective review of 230 patients with colorectal cancer. Many patients presented with symptoms not usually associated with colorectal cancer, such as pain in the upper part of the abdomen, and rectal bleeding separate from the stool. Iron deficiency anaemia was an uncommon presentation. Over all, one-third of patients had at least one risk factor for colorectal cancer. Risk factors such as adenomatous polyps and family history of colorectal cancer were more common than inflammatory bowel disease and polyposis coli. Although a delay in diagnosis was recorded in one-quarter of patients, the finding of a negative correlation between duration of symptoms and extent of spread suggests that the length of the symptomatic illness is not an important factor in prognosis. Contrary to surgical and medical teaching, only 43% of cancers were in the rectum and rectosigmoid area, and, hence, within reach of the standard sigmoidoscope. Surgical resection was performed in 76% of patients. Forty-three per cent of patients who underwent surgery developed at least one postoperative complication resulting in a longer stay in hospital.


Plasma carcinoembryonic antigen and erythrocyte sedimentation rate in patients with colorectal carcinoma.

Preoperative and postoperative plasma carcinoembryonic antigen (CEA) levels in patients with colorectal carcinoma have been reported to correlate with tumour mass and prognosis. The erythrocyte sedimentation rate (ESR) has previously been reported to be elevated in most patients with metastatic carcinoma. In this study of 17 patients with advanced colorectal carcinoma and of nine patients who were disease-free more than three years after resection of their tumour, the plasma CEA and ESR levels demonstrated a close correlation, both in frequency and in degree of elevation, with the disease status. Of nine patients who were disease-free more than three years after resection of their colorectal carcinoma, all except one had plasma CEA levels of less than 20 ng/ml and an ESR less than 20 mm in one hour respectively. The incidence of plasma CEA more than 20 ng/ml and ESR more than 20 mm in one hour in the locally advanced and distant metastases groups, as compared with those patients in the more than three years group, was increased at a level of statistical significance (P less than 0.05). This study showed that the ESR, an inexpensive and simple estimation, may be as effective as the estimation of plasma level of CEA in monitoring the disease status of patients with colorectal carcinoma.


Fibreoptic colonoscopy. Indications, results and complications.

Fibreoptic colonoscopy was commenced in the Edward Wilson Colon and Rectum Unit at Sydney Hospital in June, 1973. The experience of the first five years of its use is reported. Six hundred and twenty-six examinations have been performed in 568 patients. Fibreoptic colonoscopy has been of particular value in the diagnosis and treatment of colonic polyps. A total of 318 polyps were removed from 184 patients. Their distribution, size and histological features are recorded. Eight complications occurred in the 628 examinations (1.6%). There were six colonic perforations (1.2%) with one death, and two significant haemorrhages (0.4%). This incidence of complications is acceptably low, especially in view of the great benefits obtained by the patient from fibreoptic colonoscopy. The newer instruments, especially the medium length Olympus MB3 colonoscope, have greatly facilitated the examination and, combined with increasing experience, may significantly lower the incidence of complications in the future.


A long standing, much travelled rectal foreign body.

A case is reported of a plastic vibrator which was successfully removed from a 64-year-old male after having been resident in his rectum for a period of six months, during which time the patient endured a world trip, making it the longest standing, most travelled foreign body introduced into the rectum yet reported.


Pseudodelirium.

Two case histories are presented which illustrate the fact that acute functional psychoses may simulate delirium. It is suggested that the term "pseudodelirium" may alert clinicians to this possibility, and facilitate the earlier diagnosis and treatment of psychiatric illness.


Embolism in thyrotoxic atrial fibrillation.

Of 210 patients with thyrotoxicosis, 21 (10%) had atrial fibrillation. Five of these patients (24%) had systemic emboli (which were multiple in three patients, one of whom died) and two other patients had pulmonary embolism. Embolic disease is common in thyrotoxic atrial fibrillation, and anticoagulant therapy should be considered for all patients.


The red blood cell lithium/plasma lithium ratio. Significance in recurrent affective illness.

The red blood cell lithium/plasma lithium ratio in patients diagnosed as suffering from unipolar and bipolar affective illness has been investigated and a comparison made between responders and non-responders. No correlation could be demonstrated between the lithium ratio and the effectiveness of lithium treatment.


Cardiac valve replacement (1963-1979).

A 15-year experience (from 1963-1978) in cardiac valve replacements with mechanical prosthetic valves (caged ball or tilting disc types) and with bioprostheses (porcine xenografts) is reported. The actuarial survival rates for patients who received the caged ball type prostheses (Starr-Edwards) were 42% and 36% respectively for mitral valve-replacements at 12 and 14 years. The actuarial survival rate for patients who received the tilting disc type prostheses (Björk-Shiley type and later the Lillehei-Kaster type) was 74% at six to seven years. The actuarial survival rate for patients who had aortic valve replacement with a caged ball valve was 43% at 14 years, and for those who had a tilting disc valve it was 80% at six to seven years. Multiple valve replacements were carried out with combinations of prostheses. The actuarial survival rate for patients was 65% for triple valves, and 57% for double valves at 13 years. Bioprostheses are now our first choice as cardiac valve replacements. In 121 implants performed since 1977, there have been two operative deaths, but no late deaths. Bioprostheses, although less thrombogenic than mechanical valve prostheses, are less durable and some risk of thromboembolism remains.


Routine ultrasound screening in early pregnancy.

A normal range for ultrasonically determined fetal biparietal diameter (BPD) was established on 497 normal obstetric patients attending the Flinders Medical Centre, Adelaide. While composite ranges for mean BPD measurements derived from the literature appear to have wide application, the need is apparent to establish a normal range with standard deviations for local institutional conditions and patient populations. With the established normal range as a reference, a consecutive series of 756 patients had ultrasonic fetal BPD measurements performed before 24 weeks' gestation to confirm or establish gestational maturity. It was held that such a screening procedure was justified in view of the high incidence of initial uncertainty in gestational ageing in the population sampled, and the risks of iatrogenic prematurity in both abnormal and normal patients undergoing induction of labour or elective caesarean section.


Effect of mianserin on cardiac conduction.

A cardiovascular study of a new antidepressant, mianserin, given at 60 mg a day for a three-week period to 10 ambulant, moderately depressed patients is described. No effects on cardiac conduction were found by means of His bundle electrocardiography. Nine of 10 depressed patients improved while on the medication; mild sedation was the only side effect noted.


[Treatment of cimetidine-resistant gastric ulcer with carbenoxolone-sodium (author's transl)].

Case report on a successful treatment of a cimetidine-resistant gastric ulcer with carbenoxolone-Na. Administration of 1.0g cimetidine/d over a period of 8 weeks failed to reduce gastric ulcer size. Subsequent therapy with carbenoxolon-Na caused a complete healing of the gastric ulcer within 4 weeks. This case is discussed with respect to the possible advantages of a combined regimen with drugs of different mechanisms of action.


[The effect of pentoxifylline on liver perfusion: a comparative study in patients with liver diseases and in normal subjects, using 198Au-colloid-scintigraphy (author's transl)].

Using 198Au-colloid scintigraphy (Anger camera computer-system, 0.3-0.5 mCi radionuclide i.v.) the pattern of liver blood flow, i.e. liver perfusion volume per minute (LPVM), was monitored in 7 patients with liver metastasis (I), 8 patients each with chronic hepatitis (II) and liver cirrhosis (III) and in 10 healthy control subjects (IV). Reading were compared on a within patient basis for the following treatments: baseline control, after a single i.v. injection of 10 ml Trental (= 200 mg pentoxifylline) and after 10 ml physiological saline solution (= placebo). The alteration of LPVM ranged between +0.6 and -3.2% for the comparison baseline/placebo, between +9.7 and +40.8% for baseline/Trental and between +11.5 and +45.4% for placebo/Trental administration. The increase of the elimination constant was statistically significant for all groups and the augmentation of the LPVM for group II, III and IV.


[Effects of propranolol and metoprolol on beta-adrenergic metabolic responses (author's transl)].

In ten healthy volunteers infusion of 7 micrograms/kg orciprenaline produced typical changes in carbohydrate and fat metabolism due to beta-adrenergic stimulation. Pretreatment with intravenously administered propranolol or metoprolol significantly inhibited orciprenaline-induced changes in systolic blood pressure, heart rate and plasma FFA, potassium, glucose and glycerol levels. Propranolol (0.1 mg/kg) seemed to be more effective than metoprolol (0.2 mg/kg) even in inhibiting predominantly beta 1-adrenergic responses.


[Yellow nail syndrom--clinical signs and differential diagnosis (author's transl)].

This report describes 3 cases of yellow nail syndrom. The examination either did not reveal lymphedemas or only transitory edemas were found. But both typical changes of nails and chronic inflammation of the respiratory tract were found. Remarkably enough, two of our patients showed a decrease in serum immunoglobulin M (IgM). Both patients had a most serious disorder of the respiratory tract. In the form of a table this report contains a survey of the literature published hitherto about the combinations of symptoms of yellow nail syndrom occurring most frequently.


[Plasma aldosterone and electrolytes in primary and secondard aldosteronism (author's transl)].

Plasma aldosterone levels and the serum electrolytes potassium, sodium and magnesium of 38 patients with healthy adrenals were determined. Under physiological conditions there were no significant correlations between these parameters. In two patients with an aldosterone producing adenoma of the adrenals (syndrome of Conn) we found very low levels of potassium and low levels of magnesium. The levels of sodium lay in the upper normal range. Plasma aldosterone levels are raised strongly. After resection of the tumors the mentioned parameters normalized. In 16 patients with cirrhosis and ascites we generally found values of aldosterone, potassium, sodium and magnesium which lay in the lowest normal range. Under treatment with spironolactone the aldosterone levels raised and reached values which are characteristical of the syndrome of Conn. Potassium raised to the upper normal range, magnesium raised significantly, sodium diminished slightly.


[Echocardiography during ergometric exercise (author's transl)].

Radiological heart volume estimations and echocardiographic studies were performed on 30 male and 15 female middle distance athletes at rest, during supine ergometric exercise at 10 and 100 Watt and 1 minute after excerise. During exercise, there is an increase in cardiac output, in the small hearts of 6%, in the large hearts of 16%, due to a small enddiastolic increase and an associated decrease in the endsystolic left ventricular diameter. At rest and at 50 Watt, the cardiac output, corrected for body surface area, was practically the same for all volunteers, at 100 Watt the volunteers with the largest hearts had the highest cardiac output. This is interpreted as evidence for increased cardio-circulatory reserves. The contractility parameters at the various exercise grades varied dependant on heart size; when related to heart rate the variations were practically abolished. The results suggest that variations in the dynamics of small and large hearts are not primarily due to intrinsic factors but rather related to extrinsic factors such as sympathetic drive expressed by the changes in heart rate.


[Functional diagnosis by directional doppler-ultrasound in patients with Raynaud's disease (author's transl)].

7 patients with primary and 3 patients with secondary Raynaud's disease were studied by directional Doppler-ultrasound. Flow curves were registered of radial and ulnar artery in rest and during reactive hyperemia following ischemia and muscle work before and under medical treatment. Flow at rest and after provocation was much less than in normal persons. Effect of treatment could be demonstrated, so that this method seems to be very helpful in followup studies of patients with Raynaud's disease.


[Pharmacological treatment of chronic arterial occlusive disease (author's transl)].

Two thirds of the patients with peripheral arterial occlusive disease have to be treated conservatively, for only up to 30% can be revascularized by operative methods. Using the pharmacological differential treatment the grade of compensation and localization of the obliterative process has to be considered. Ignoring the usual basic therapy (elimination of heart failure and pathological bradycardia, systemic walking-exercise, anticoagulation etc.) intrafemoral long-term application of energetic phosphate (i.e. nucleotid-nucleosid-mixtures) leads to a positive result in nearly two thirds (n = 97 legs) with a degree of II to IV of Fontaine. Whereas the snakes' encyme Ancrod with the effect of defibrination was successful in almost 70% of the patients with arterial insufficiency (n = 45) including the degree II B (painless walking-distance under 100 meters). Energetic phosphates, applied to the arteria femoralis, are most successful in degree II with claudication intermittens. Ancrod should be used respectively for patients with pain during rest. These results are discussed with respect to compensation and localization of arterial occlusive disease, acute and chronic measurements of the hemodynamics by use of Doppler ultrasound and strain gauge plethysmography and with respect to variation of the concentration of the metabolic parameters lactate and pyruvate--the latter when defibrination was performed.


[Fibrinolytic treatment with urokinase in older phlebothrombosis (author's transl)].

28 patients with 1 to 6 week old occlusions of the femoral and/or iliac veins as well as the subclavian veins were treated with a standardised urokinase-heparin-scheme. The fibrinolytic therapy was generally performed over a period of 7 to 14 days. In 2 patients, the 1 and 6 weeks respectively old thromboses of the iliac, femoral and tibial veins, and in 4 patients the 5 to 16 days old thromboses of the subclavian veins could be dissolved completely, 16 patients showed clinically and phlebographically a substantial amelioration. In 6 patients no marked success was found.


[An evaluation of methods of diagnosing central nervous system metastases (author's transl)].

In 50 cases of histologically identified metastases of the central nervous system it was found that in cases of breast cancer and malignant melanomas the diagnosis of the primary tumor is the key to the diagnosis of the metastasis; bronchial carcinomas are usually found upon diagnosis of cerebral metastases; angiography, color scintigraphy and the computer tomography have a false negative rate of 10--15%, in cerebrospinal fluid protein levels are often increased (64%), and tumor cells are found in 18%.


[Transient ischemic attacks with intracranial tumors (author's transl)].

Transient ischemic attacks are not only the consequence of cerebral atherosclerosis. A woman of 48 years had transient ischemic attacks because of a meningeom narrowing the internal carotid artery. A steal syndrome in tumor vessels of a glioblastoma must be presumed in a man of 67 showing initial hemisyndrome with first transient, later on remaining palsy.


[Gastric carcinoid with brain metastases--a casuistical report (author's transl)].

A 63-year-old man developed a carcinoid tumor of the cardia with unusual metastases of the brain and a rapid lethal course. Clinical aspects of these tumors, their attachment to apudomas and their new morphologic respectively functional--morphologic aspects are discussed.


[High levels of CK and its isoenzymes produced by a thymus carcinoma (author's transl)].

A 63 years old female is described suffering from thymus carcinoma with increased levels of CK and CK-MB enzymes. The separation of the total CK enzymes into the isoenzymes CK-MM, CK-BB, and CK-MB showed a marked difference between the photometric and the immunological method. This discrepancy can be explained by postulating a molecule specific for thymus carcinoma, probably a new CK isoenzyme. The relevance of using the photometric method in cardiologic routine diagnostic is pointed out.


Anaerobic bacteria in late infections following orthopedic surgery.

Twelve patients with late anaerobic infection following hip or knee arthroplasty or tibia osteosynthesis are presented. Peptococci (Peptococcus asaccharolyticus, P. magnus, P. prevotii) and peptostreptococci (Peptostreptococcus micros, P. anaerobius, P. parvulus) were present in nine of the cases. Anaerobic gram-positive or -negative rods were found in three cases (Propionibacterium acnes, Actinomyces israelii, and Bacteroides fragilis). Antibodies against the isolated bacteria were detected in sera of nine patients. Anaerobic bacteria seem to be responsible for some of the late reactions that may follow arthroplasty or osteosynthesis.


[A serological study concerning the role of the golden hamster (Mesocricetus auratus) in transmitting lymphocytic choriomeningitis virus to humans (author's transl)].

A search for lymphocytic choriomeningitis (LCM) virus-specific antibody was conducted in 580 persons. One group consisted of 190 14-year-old to 17-year-old girls. In 149 of these hamster contact, either recently or in the more distant past, was certain; three had antibody. In 41 girls hamster contact was doubtful and one was positive. In a second group consisting of 390 persons of either sex and all ages the question as to association with hamsters was answered 123 times in the affirmative. Hamster contact was denied 251 times and uncertain 16 times. In sera from five individuals of this group antibody to LCM virus was detected; they all confirmed having had contact with hamsters.


Microwave scattering parameter imagery of an isolated canine kidney.

This paper describes a method for imaging biosystems using radiation in the microwave frequency range (3.9 GHz). The advantages of interrogation with microwave radiation are discussed in terms of its physiological significance. An electromechanical scanning system for imaging isolated organs and the subsequent image processing techniques are described. Imagery is presented for a phantom target and an isolated canine kidney. The kidney images are interpreted in terms of the known anatomical and functional organization of the organ. It does appear to be possible to distinguish cortex corticis corresponding to a high proportion of proximal and distal convoluted tubules, deeper cortical layers corresponding to a high population density of glomeri, a medullary outer zone corresponding to the loops of Henle as well as the collecting system, and the region of calyces/renal pelvis.


Assessment of errors in intensity measurements of pulse echo ultrasound using miniature hydrophones.

Total transmitted power and intensity distributions from diagnostic ultrasound systems have been measured with a radiation force balance and with a miniature hydrophone and instrumentation available in many medical centers. In assessing the accuracy of absolute intensity and power determinations from measurements of acoustic pressure with a hydrophone, ultrasonic power was computed from hydrophone measurements. This power value was compared with the power determined by a radiation force technique. On five pulse echo ultrasound systems, the ratio of the power measured with a radiation force balance to the power determined with the hydrophone varied from 0.25 to 5.5. These differences are attributed mainly to the known large variations in hydrophone response as a function of frequency, and possible time, since several other possible sources of error were evaluated and estimated to have a reasonably small net effect of 25%. The errors evaluated were those dealing primarily with measurement procedures.


Neutron spectra from 35 and 46 MeV protons, 16 and 28 MeV deuterons, and 44 MeV 3He ions on thick beryllium.

The energy spectra of neutrons produced by 35 and 46 MeV protons, 16 and 28 MeV deuterons, and 44 MeV 3He ions on thick beryllium were measured at angles of 0 degrees, 15 degrees, and 45 degrees with respect to the incident beams. The spectra were measured by the time-of-flight method for neutrons from the maximum energy down to 1 MeV. Neutron dose rates obtained from the zero-degree spectra by use of available tissue kerma factors agree with TE-TE ionization chamber measurements.


Detectability in computed tomographic images.

The detection limitations inherent in statistically limited computed tomographic (CT) images are described through the application of signal detection theory. The detectability of large-area, low-contrast objects is shown to be chiefly dependent upon the low-frequency content of the noise power spectral density. For projection data containg uncorrelated noise, the resulting ramplike, low-frequency behavior of the noise power spectrum of CT reconstructions may be conveniently characterized by the number of noise-equivalent x-ray quanta (NEQ) detected in the projection measurements. The NEQ for a given image may be determined either from a measurement of the noise power spectrum or from the noise granularity computed with an appropriate weighting function. A measure of the efficiency of scanner dose utilization is proposed which compares the average dose to that required by an ideal scanner to obtain the same NEQ.


Direct data link between a CT scanner and a radiation treatment planning system.

A direct data link between a CT scanner and a radiation treatment planning system has been developed. The link transmits the data serially over a coaxial cable using the pseudo-paper-tape punch and reader (serial PIO) interfaces. The data transmission rate with error-check is approximately 25,000 8-bit bytes/s. This translates to about 7 s for transferring a CT scan with a 320-pixel diameter.


Processing of incomplete measurement data in computed tomography.

Conventional approaches to computed tomography involve scanning the entire cross section and producing an image whose spatial and density resolution is uniform over its entire area. If the extent of each scan is restricted to the width of the lesion being investigated, then the x-ray dose is reduced, but a set of incomplete "truncated" projections is measured. Conversely, projections are "hollow" when their inner parts cannot be measured, e.g., when there is a metallic object within the body cross section. We present procedures for preprocessing incomplete projections so that images can be reconstructed from them using the convolution/back projection method.


Noise considerations in dual energy CT scanning.

Dual energy CT scanning (tomochemistry) has been proposed as a method for determining various parameters relating to the elemental composition of the tissues. In this paper, our aim is to study the relative noise inherent in two proposed techniques for dual energy scanning; a "two crystal" technique and a "two kV" technique. In the two crystal technique, a split crystal detector is used to simultaneously obtain the high and low energy data during one scan at high kV. The two kV technique requires two scans taken with widely different kV settings. We first review three commonly used approaches for utilizing the scan data to compute the relevant parameters. A theoretical formalism is constructed which aids in understanding these methods. Then this formalism is used to study the influence of CT image noise on measurement precision in the case where the unknown parameters are densities. It is shown that, (1) the unavoidable overlap in the spectral data obtained by the two crystal technique results in a much lower signal-to-noise ratio than can be obtained by using the two kV technique, (2) the necessity for hard filtration of the high energy beam in the two kV technique has not heretofore been appreciated, and (3) the dose for a given x-ray tube heat load is also lower with the two kV technique.


A fundamental accuracy limitation on measurements of brachytherapy sources.

The dose rate gradients in the first few centimeters away from brachytherapy sources are extremely high. Attempts at direct measurements of the dose rates in the near vicinity of such sources are made with the smallest detectors available. Nevertheless, it is not obvious that the agreement between reported measurements and theoretical calculations can be justified when the dose rate gradients across the detector volumes employed are so great. A figure of merit is derived here which indicates how well the dose averaged over the volume of the detector corresponds to the dose at the center of the detector. This figure of merit provides a means to assess the maximum accuracy one can expect to achieve in a measurement made at a given distance from a linear source based on the dimensions of the source and the dimensions and shape of the detector.


Measured neutron and gamma spectra from californium-252 in a tissue-equivalent medium.

A method of experimentally obtaining both neutron and gamma-ray spectra in a scattering medium is described. The method utilizes a liquid-organic scintillator (NE-213) coupled with a pulse-shape discrimination circuit. This allows the separation of the neutron-induced pulse-height data from the gamma-ray pulse-height data. Using mathematical unfolding techniques, the two sets of pulse-height data were transformed to obtain the neutron and gamma-ray energy spectra. A small spherical detector was designed and constructed to reduce the errors incurred by attempting spectral measurements in a scattering medium. Demonstration of the utility of the system to obtain the neutron and gamma-ray spectra in a scattering medium was performed by characterizing the neutron and gamma-ray spectra at various sites about a 3.7-microgram (1.5 cm active length) californium-252 source in a tissue-equivalent medium.


Testing cosolvent cryoenzymology on multi-enzyme systems.

Fluid mixed solvents appear to supply an effective tool for investigation of enzyme catalysis at subzero temperatures. Labile reaction intermediates may be stabilized, characterized and separated. Cycling of reaction processes and side reactions can be slowed or stopped to permit single turnover of individual molecular events, and kinetic response to temperature and other physical parameters can provide dynamic and thermodynamic analysis of single enzyme systems. Multienzyme systems can furnish reliable probes of potential, limitations and possible procedural artefacts of the method. Amply explored examples are supplied by the studies of two components of the soluble camphor hydroxylase and the hepatic R450LM2 in solution and in the subcellular microsomal organelles, to reveal labile single enzyme compounds and multienzyme processes.


Ultrastructure - function relationship in Chlamydomonas reinhartii thylakoids, by means of a comparison between the wild type and the F34 mutant which lacks the photosystem II reaction center.

The F34 mutant strain of Chlamydomonas reinhartii is deficient in photosystem II reaction centers. The E fracture faces of the thylakoid membranes of this mutant show a considerable reduction in the number of particles present ant in their size compared with the wild type. We conclude that the polypeptides associated with photosystem II reaction centers, which are missing in SDS polyacrylamide gel electrophoresis patterns of proteins from this mutant strain, are part of the EF particles and are required for assembly of these particles.


The terminal structures of feather keratin mRNA.

Terminal labeling of embryonic feather keratin mRNA with [3H]KBH4 followed by digestion with ribonuclease T1 and T2, alkaline phosphatase, snake venom phosphodiesterase, and nucleotide pyrophosphatase and analysis of the products by high voltage paper electrophoresis, indicated the presence of the sequence m7G(5')ppp(5')N at the 5'-end of the mRNA. Ribonuclease T1 and A digests of the terminally labeled, and also of unlabeled mRNA followed by fractionation on denaturing polyacrylamide gels indicated the presence of polyadenylate tracts ranging in size from 45 to 165 nucleotide at the 3'-end of the mRNA.


X-ray studies of the ovomucoid-DHPC system.

Complex of ovomucoid with 1,2 dihehadecyl-snglycero-3-phosphatidylcholine (DHPC) in water solution has been used as a model system for glycoprotein-lipid interactions. The structural parameters of this complex were determined with small angle-X-ray diffraction techniques. Knowing the repeat distance, the chemical composition of the association and the partial specific volumes of the components, the partial thickness of the glycoprotein, lipid and water layers can be determined and compared with the thickness of the lipid layers observed in pure lipid-water systems and lamellar associations in the absence of glycoprotein. The variation of the structural parameters at room temperature with the concentration of water was determined. Our results showed: the intersheet spacing increases from 112 to 157 A, the thickness of the hydrocarbon chain layers decreases from 49 to 40A and the thickness of glycoprotein layer increases from 62 to 100 A. In this case the glycoprotein-lipid interaction appears to be of weak electrostatic nature and to involve mainly the polar regions of the structure. Fluorescence experiments have also been carried out to confirm the X-ray data.


The use of pronase for electron microscopy of protein-complexed DNA.

A method is described which demonstrates the posibility of visualizing protein-complexed DNA by using pronase for both deproteinization and spreading of DNA for electron microscopy. The results show that proteolytic digestion is complete even under conditions of short formaldehyde fixation and pronase is an excellent substitute for cytochrome c for spreading of DNA. The pronase method is successfully applied to virions, native and partially denatured chromatin. The procedure is highly advantageous because it does not require preliminary isolation of DNA, can be applied to microamounts of material and permits the visualization of partial denaturation of DNA in chromatin.


Protein coding sequences in newly synthesized nuclear RNA from chicken immature red blood cells.

The contents of globin gene transcripts and other protein coding agene transcript (preferentially expressed in liver) within nuclear RNA from chicken immature red blood cells were analyzed by the method of cDNA hybridization. A comparison of the hybridization values obtained from steady state nuclear RNA and pulse labeled newly synthesized nuclear RNA demonstrated, that (a) there is a vast excess of globin gene transcripts over other individual protein coding transcripts and (b) the ratio of globin gene transcripts to the amount of other protein gene transcripts is nearly the same within both RNA species. We conclude, that in chicken immature red blood cells the globin genes are transcribed either at a much higher rate than other protein coding genes or that most of the transcription products of other genes transcribed at higher rates must be degraded during or very shortly after transcription. Moreover, an accumulation of both types of transcripts was observed, as the contents of these RNA molecules was higher within steady state nuclear RNA than within the newly synthesized RNA.


DNA degradation in isolated rat liver nuclei.

Purified rat liver nuclei were incubated at 4 degrees C. After different intervals of incubation aliquots of the nuclear suspension were taken and DNA was extracted by a common SDS-phenol-chloroform procedure. The fractionation of DNA by agar gel electrophoresis revealed large DNA fragments. It was shown that the well-known DNA degradation to monomers and its multiples is preceeded by an earlier breakdown of DNA into characteristic large fragments.


No stimulatory effect of added histones on DNA synthesis in isolated HeLa cell nuclei.

Contrary to some recent reports DNA synthesis in isolated HeLa cell nuclei was not stimulated by the addition of low amounts of histones neither in the presence nor in the absence of cytosol. The individual histone fractions H1, H2A, H2B and H3 also failed to stimulated DNA synthesis.


Elongation factor Tu-induced conformational changes of ribosomes detected by iodination.

The effect of elongation factor (EF) Tu, bound to the ribosome with the help of poly(uridylic) acid, Phe-tRNA and guanyl-5'-yl methylene diphosphonate, on the conformation and/or chemical environment of ribosomal proteins has been examined using, as a probe, protein iodination. Ribosomes complexed only with poly(uridylic acid) and Phe-tRNA have been used as a control. EF-Tu on the ribosome significantly increases the iodination of proteins S7, S10 and L3 and decreases that of S21 and L18.


Regulation of growth hormone messenger RNA.

In cultured rat pituitary cells, glucocorticoids regulate growth hormone production by modulating the number of growth hormone messenger RNA molecules. The effect is quite specific, since only a few other mRNAs are affected by the hormones. This response is demonstrated by assays involving cell-free mRNA translation and cDNA-RNA hybridization. Furthermore, the inducibility by the glucocorticoids is regulated by at least one other class of hormones, thyroid hormone. Thus, this system serves as a model for studying not only the glucocorticoid regulation of specific mRNA, but also the control of this regulation by other factors in the target tissue.


Effects of glucocorticoids on fibroblasts.

Mouse fibroblasts growing in vitro respond to glucocorticoids in a dose-dependent fashion by reduced rates of growth. The inhibition of growth observed in vitro is related to the topical anti-inflammatory action of glucocorticoids and to their capacity to inhibit wound repair. The cells growing in vitro possess a glucocorticoid receptor system that has been studied in some detail using [3H]triamcinolone acetonide as a radiolabeled ligand. The initial binding reaction occurs in the cytosol. The complex is then rapidly taken up in the nucleus of the cell by a temperature-sensitive process. In the nucleus, the complex exists in two forms, one of which is readily extracted by 0.3 M KCl solutions. A small amount of steroid-receptor complex is tightly bound to chromatin. Under normal incubation conditions, there is a constant cycling of steroid-receptor complex, and unbound receptor is generated back into the cytosol from the nucleus with a half-life of about 30 min. Regeneration of unbound receptor does not depend on protein synthesis and is a temperature-sensitive and energy-requiring process. Incubating the steroid-treated cells in the absence of glucose and in the presence of inhibitors such as cyanide or dinitrophenol leads to a loss of cytoplasmic steroid-receptor complexes, and an accumulation of the complex in the nuclear residual form, tightly bound to chromatin. With respect to nuclear effects of steroid treatment, we have found that incubating fibroblasts in vitro with glucocorticoids produces a prompt decrease in the amount of a satellite H1 histone found in these cells.


Glucocorticoid receptors and actions in rat thymocytes and immunologically stimulated human peripheral lymphocytes.

After reviewing briefly our earlier studies on glucocorticoid receptors and mechanisms in thymus cells, we have outlined results from the following two areas of current interest in our laboratories: the "life-cycle" of glucocorticoid receptors and complexes in thymus cells, and the levels of glucocorticoid receptors and sensitivity in immunologically stimulated human peripheral lymphocytes. Several of our results on energetics and kinetics of hormone binding to glucocorticoid receptors in rat thymus cells seem to require extension of the simplest model of hormone-receptor transformations in intact cells. ATP-depletion experiments suggest the existence of a nonbinding form of the receptor; "chase" experiments suggest reaction of hormone directly with nuclear-bound receptor; experiments on depletion and replenishment of cytoplasmic receptor using cortisol and dexamethasone suggest the existence of at least two subpopulations of nuclear-bound hormone-receptor complex. We have found that mitogen or immunologic stimulation of human peripheral lymphocytes in culture leads within 24 h or so to a striking increase in the number of glucocorticoid receptor sites per cell. We believe this increase may be due to partial synchronization of the cell population in a phase of the cell cycle in which receptor content is high. Contrary to the widely held view that mitogen-stimulated cells become insensitive to glucocorticoids, our experiments show that with respect to inhibition of thymidine and uridine incorporation and glucose uptake, the cells are highly sensitive to dexamethasone at 24, 48, and 72 h after stimulation with concanavalin A.


Mouse lymphoma cells: mechanisms of resistance to glucocorticoids.

S49, an established line of mouse lymphoma cells, has several characteristics useful for the genetic analysis of glucocorticoid action: (1) a stable pseudodiploid karyotype; (2) an efficient cytolytic effect of glucocorticoids, which appears to follow the same biochemical pathway as steroid hormone action in other systems; (3) appearance of rare steroid-insensitive clones that exhibit stable, heritable resistance to further glucocorticoid treatment; (4) rapid growth in suspension culture and high cloning efficiency in soft agar, allowing facile isolation of variant clones. Two hundred individual steroid-resistant clones of S49 cells have been isolated and analyzed to determine the origin of their resistance. Most of these variant clones (55 %) fail to bind [3H]dexamethasone at levels above background; 70--75 percent bind less than 30 % of the wild-type level. The remaining clones fall into three general groups with respect to the efficiency with which receptors are translocated to the nucleus following dexamethasone treatment: one class transfers less than 10 percent of labeled receptors to the nucleus, another transfers normal amounts, and a third localizes virtually all of the receptors in the nucleus. The four variant phenotypes have been respectively designated r-, receptor activity deficient; nt-, nuclear transfer deficient; d-, deathless (appears normal in binding and nuclear transfer); and nti, increased nuclear transfer. Physical characterization by sucrose gradient sedimentation and gel permeation chromatography reveals that wild-type receptors are approximately 90,000 daltons and nti receptors about 50,000 daltons. The affinities of variant and wild-type receptors for purified DNA in vitro are consistent with their respective nuclear binding characteristics in vivo. Genetic studies with these and other cell lines, combined with recently developed methods for purification and structural analysis of minute quantities of proteins, can provide the level of biochemical resolution required for a fundamental understanding of the molecular mechanism of steroid hormone action.


Structure-activity relationships in glucocorticoids.

Meaningful answers to the question of the relationship between glucocorticoid structure and activity have emerged. Structural change has predictable effects on susceptibility to the action of metabolizing enzymes, on receptor affinity, and on intrinsic activity. These effects are, in principle, amenable to mathematical modeling techniques. The fascinating possibility of being able to calculate receptor affinity directly from chemical structure has already been realized through the development of an equation [19] that allows the calculation of receptor binding of any glucocorticoid from structural parameters. Utilizing knowledge of the free energy contributions of the substituents and the hydrophobicity and A-ring conformation of the steroids, receptor affinity for a large number of compounds could be described in terms of four parameters. A general relationship was derived relating the equilibrium dissociation constant to a surface area term, a polar interaction term, and A-ring tilt term, and a size limitation function for the 9 alpha-substituent. The excellent correlation obtained suggests that these four factors are the major determinants of glucocorticoid receptor interactions. It is clear that the use of a mathematical relationship that defines the strength of steroid-receptor interaction is a valuable tool for investigating structure-activity relationships. This would be especially true in the design of steroid drugs. The use of a linear free-energy equation is superior to the assumption of substituent additivity in predicting binding affinities. This type of relationship will be useful in the preparation of steroids for use in affinity labeling studies and should be adaptable to other binding systems in which it is desirable to obtain synthetic analogs for more potent activity or specificity.


[Prostaglandin E1. Emergency therapy in infants with preductal coarctation of the aorta (author's transl)].

Three infants with preductal coartation, tubular hypoplasia of the aortic arch, and VSD were treated with Prostaglandin E1 (PGE1)-infusion to dilate the ductus arteriosus Botalli. Before PGE1-therapy the infants were treated with Furosemide and Digitalis, but they remained oliguric or anuric. During PGE1-infusion the pressure in the descending aorta rose and urine output increased significantly. Obviously the blood flow into the descending aorta via the ductus arteriosus was improved during PGE1-infusion. In all three cases surgery was successfull after PGE1-therapy. Before PGE1-therapy of preductal coarctation the diagnosis should be clear and also classical therapy with Furosemide and Digitalis should be tried.


[Neurodevelopmental examination of high risk infants (author's transl)].

While the high risk infants' prognosis for normal development has been greatly improved by modern neonatal intensive care, premature birth, low birthweight and perinatal complications involving compromised brain function still represent major risk factors. Different criteria for admission and assessment methods are the reason that recent publications cite neurological sequelae in high risk infants that range from 4.4 to 28%. The need for an effective screening instrument enableing the pediatrician to test and evaluate neurological function, maturation and integrity, is quite obvious. The author has selected a group of neurological items according to results of Touwen's (1976) longitudinal study on neurological maturation in infancy. In addition, Prechtl's (1968) optimality concept was applied in our study. This new standardized neurological examination was used to evaluate 163 high risk infants with a corrected age of 3 and 6 months. The results demonstrate statistically significant differences between the neurological status of full-term and premature infants, and similarly between those with minimal risk and perinatal brain distress. The rather steep increase of neurological optimality scores by age of 6 months implies a high rate of self-repair or catch-up in maturation of the nervous system. We speculate that early extrauterine stimulation of the premature does not accelerate the development of brain function in a similar way as it does other organ functions, but it may slow down maturation.


[Concentrations of hemoglobin, hematocrit and serum iron in healthy infants and children aged 1 month to 16 years (author's transl)].

10,126 determinations of hemoglobin concentration, 10,055 of hematocrit and 4,420 of serum iron were performed in 7,753 infants and children aged 1 month to 16 years to give normal values for this period in a large town. Both, concentrations of hemoglobin and hematocrit decreased during the 3rd and 8th month. The first decrease in serum iron level appeared later in month 4, the time of the second fall was identical with that of hemoglobin and hematocrit. In females, a third decrease of iron levels appeared with 13 years. Between the 2nd and 8th year of life, a period of instable iron nutriture became apparent. Concentrations of hemoglobin, hematocrit as well as serum iron depend on age. 0.4% of males and females showed a deficient concentration of hemoglobin. 2.9% of males and 1.1% of females had a low, nonacceptable hemoglobin value. Iron deficiency occurred in 8.5% of males and in 8.3% of females. It is probable that the number of children with a pre-latent or latent iron deficiency is much higher.


[Treatment of acute diarrheal disease in infants (author's transl)].

In the treatment of acute diarrheal disease in infants reinstituting the normal intestinal homeostasis is of primary importance. Prompt rehydration should be accomplished with a well balanced glucose electrolyte solution by parenteral or oral route. From a diet, given after rehydration, lactose and long chain fatty acids must be eliminated. Antibiotics, cholestyramine or elemental diets are to be reserved for special situations.


[Remarks concerning the treatment of hyperkinetic children with the so-called "diet poor in phosphate (author's transl)].

Compared with normal diets, the so-called "diet poor in phosphate" is really not poor in phosphate. Phosphate intake amounts only to 3% when ingested as food stuffs with phosphate additions permitted by law. The so-called "diet poor in phosphate" is poor in carbohydrates, dietary fiber and ascorbic acid. Animal proteins and fats, however, are high in this diet there by increasing the cholesterol intake. We cannot recommend this so-called "diet poor in phosphate" for children.


[Complications and survival rate in preterm infants and neonates treated with mechanical ventilation (author's transl)].

Between January 1972 and December 1976 201 preterm infants and neonates were treated with mechanical ventilation. These children were classified into 6 groups according to the indications for mechanical ventilation: P = respiratory failure caused by pulmonary disease; Z-P = respiratory failure caused by cerebral disturbance with simultaneous respiratory disease; Z = respiratory failure caused by cerebral disturbance; C = respiratory failure caused by cardiac disease; SCH = respiratory failure through shock; M = respiratory failure caused by mechanical disturbance; Bronchopulmonary complications developed in 70% of the survivors and in 60% of the fatalities. The most serious bronchopulmonary complications were infections which occured with similar frequency in all indication groups as late-onset complications, and air-leaks which occured as early complications. The latter complication was significantly higher (38%) in the first than in the other groups. The most serious extrapulmonary complications were seizures, intracerebral hemorrhages and septicemia. 71 of the 201 patients survived. There was a significant increase in the survival rate from 21.2% in 1972-1973 to 43% in 1974-1976. The survival rates differed significantly within the indication groups. The best result was found in the p-group followed by the Z-group. The highest mortality rate was found in the SCH and C-group.


[Oral immunization of newborn infants against pertussis].

A group of 148 newborn babies was subdivided into four groups. Subsequent to after oral application of killed pertussis bacteria (1-3 times; control) all developed agglutinating resp. precipitating antibodies. There was a clear relation between the given quantity of Oral Pertussis Vaccine and the antibody titer. The problem has been discussed, whether it will be possible to get a protection of newborn children against whooping cough within the first weeks of life and, simultaneously, to avoid side effects.


[Idiopathic hypercalcaemia. The effect of hypercalcaemia on renal function (author's transl)].

A case of idiopathic hypercalcaemia diagnosed in a six months old infant is reported. Nephrologic symptoms were conspicuous: decreased clearance, increased serum creatinin and urea nitrogen level, restricted ability of concentration, damage of the renal acidification; slight nephrocalcinosis was shown histologically. The serum calcium level and calcium excretion became normal under the treatment with hydrochlorothiazide and prednisolon. The function of the kidney and the general status of the infant significantly improved.


A cross-cultural study of cognitive development.

This Monograph summarizes a comparative study of recall memory among children from two Guatemalan towns and one American city. The age interval of greatest improvement in serial recall of pictures, words and orientations of dolls varied across settings by as much as 4-6 years, but performance improved with age in all communities. It was suggested that the activation of varied strategies to aid recall memory emerged in all children during the preadolescent years, but environmental factors, as yet unspecified, determined both the slope of the growth function and its asymptotic level.


The effects of beta-radiation on sister-chromatid exchanges in cultured human lymphocytes.

The incidence of Sister-Chromatid Exchanges (SCEs) due to beta-radiation was investigated in cultured human lymphocytes using the BrdU/Giemsa technique. Cultures treated continuously with 0.001 and 0.01 microCi of [3H]uridine showed no increase in either chromosome abnormalities or SCEs. Continuous treatment with 0.1 microCi resulted in a significant increase in chromosome aberrations but no increase in SCEs, while treatment with 0.2 microCi gave both an increase in chromosome aberrations and SCEs. Cultures given a 4-h pulse with 1.0 microCi showed a significant increase in both SCEs and chromosome aberrations. The results indicate that low levels of beta-radiation do not cause an increase in SCEs in human lymphocytes, and, that a number, if not all the exchanges observed at low levels of beta-radiation with autoradiography, may be spontaneous events.


Species variation in BrdUrd-induced sister-chromatid exchanges.

Peripheral blood lymphocytes from cattle, pigs, sheep and humans were cultured in the presence of 0.5, 1, 2, 5, 10 or 20 micrograms/ml of BrdUrd. Sister-chromatid exchanges were scored in 25 second-division metaphases from each donor at each level of the chemical. Dose--response curves for all 4 species increased steeply to 2 micrograms/ml; above this level, SCE numbers increased less rapidly but maintained a linear relationship to increasing BrdUrd concentration. Comparisons of the straight-line portions of the dose--response curves showed human cells to be significantly more sensitive to increasing BrdUrd level than cow or pig cells and different from sheep at the 10% level of confidence.


Defective recovery of semi-conservative DNA synthesis in xeroderma pigmentosum cells following split-dose ultraviolet irradiation.

In normal human fibroblasts we observe an enhancement of the recovery of the rate of semi-conservative DNA synthesis after split-dose UV-irradiation relative to a single total UV dose. The enhanced recovery is totally absent in both a xeroderma pigmentosum variant line and two xeroderma pigmentosum lines belonging to complementation groups A and C.


A seventh complementation group in excision-deficient xeroderma pigmentosum.

Cells from a xeroderma pigmentosum patient XP2BI who has reached 17 years of age with no keratoses or skin tumours constitute a new, 7th complementation group G. These cells exhibit a low residual level of excision repair, 2% of normal after a UV dose of 5 J/m2 and an impairment of post-replication repair characteristic of excision-defective XPs. They are also sensitive to the lethal effects of UV and defective in host-cell reactivation of UV-irradiated SV40 DNA.


The relation between reaction kinetics and mutagenic action of mono-functional alkylating agents in higher eukaryotic systems. I. Recessive lethal mutations and translocations in Drosophila.

The relationship in Drosophila males between chemical reaction pattern of mono-functional alkylating agents (AA), described in terms of primary alkylation pattern with DNA and proteins as well as the Swain--Scott s factor, and their biological effectiveness were investigated. The agents chosen for comparative analysis were the nitrosamides ENU and MNU, the methanesulfonic esters iPMS, EMS and MMS, the dialkylsulfate DMS, and the nitrosamines DEN and DMN. Parameters of their biological activity were mortality (LC50) of treated adult males, induction in post-meiotic stages of X-chromosomal recessive lethal mutations and 2--3 translocations after either adult feeding or injection. Induced frequencies of recessive lethals, determined for each AA with a range of concentrations, served as biological dosimeter for interaction with target DNA in the germ line. The results are interpreted as indicating for these AA a causal connection between the pattern of primary alkylation of DNA and the quality of genetic damage observed. 1. The agent with the lowest s value, ENU, and its pendant DEN, failed to produce translocations at mutation frequencies that reached 44% for ENU. The highest chromosome-breaking activity was attributed to AA with high s, MMS and DMS. For MMS, the proportions of translocations (T) to mutations (M) approximately reached a 1 : 1 ratio in stored spermatozoa, at a recessive-lethal frequency of 14%. Ability to break chromosomes, as indicated by the T : M ratios, decreased in the sequence MMS greater than or equal to DMS, MNU greater than DMN greater than EMS greater than iPMS greater than ENU = DEN. 2. Nearly the reversed sequence in relative mutagenci effectivenss was obtained when the (directly acting) AA were arranged on the basis of their CM4/LC50 ratios (CM4, the exposure condition producing 4% recessive lethals after injection): ENU greater than EMS greater than iPMS, MNU greater than MMS = DMS. 3. Among the AA, EMS had a somewhat unique position, in that it was slightly less effective in the translocation test, and also less cytotoxic but more mutagenic in the recessive-lethal test than one would expect from its s value. This is taken as an indication of the influence on biological effectiveness of factors other than the s value, e.g. methylation versus ethylation and the lipid/water partition ratio. An example of the latter was also provided by DMS which, although having the same s as MMS, with its 5-fold higher lipid/water partition ratio, was more toxic than MMS. 4. For those AA that were clearly active in the translocation tests--MMS, DMS, MNU, DMN and EMS--delayed formation of exchanges was observed. Only in 17 out of 555 translocation tests with positive response translocations were already found in progeny from unstored spermatozoa. Consequently, it was concluded that performance of storage experiments in Drosophila is an absolute necessity for the detection of this type of rearrangement by AA. 5...


Mutagenic activity of anticancer agent cis-dichlorodiammine platinum-II.

cis-Dichlorodiamminoplatinum-II (cis-DDP) has been widely used as an anticancer chemotherapeutic agent. The mutagenicity of cis-DDP was investigated in vitro and in vivo using sister-chromatid exchange analysis and the analysis of chromosomal aberrations. Parallel human lymphocyte cultures were incubated with and without the addition of BrdU at 4 concentrations of cis-DDP. Significant increases in SCE rate were observed at 0.25 micrograms/ml and higher, showing a clear dose-response relation between SCE rate and cis-DDP concentration. A significant increase in chromosome breakage and tetraradial figures was observed in BrdU free cultures treated with cis-DDP again showing a dose dependency. Analysis of the distribution of cells in the first, second and third division in cis-DDP treated cultures demonstrated the depressing effect of the drug on mitotic activity. In vivo analysis of SCE and chromosome aberrations in mouse showed that 13.85 mg/kg i.p. of cis-DDP produces significant increases in the rate of SCE and chromosome aberrations in bone-marrow cells.


Neural hyperexcitability in hyperkalemic periodic paralysis.

An electrophysiologic study of peripheral nerve excitability was performed in patients with hyperkalemic periodic paralysis (HPP) and in normal controls. It was found that a marked degree of neural hyperexcitability existed in all patients with HPP who showed cold sensitivity. The results suggest involvement of the nerve cell membrane in the proximal segments of peripheral nerve. This testing method may be of value in differentiating the cold-sensitive variant of HPP.