[Metabolic aspects of obesity].

[Metabolic aspects of obesity]. Classification of obesity in accordance with a new anatomical and functional criterion means that a hyperplastic and a hypertrophic form can be distinguished.  The distinction is of both academic and practical significance, since different metabolic changes are observed in the two forms.  Hyperplastic obesity appears early in life and is particularly intractable.  It is not usually accompanied by dysmetabolic signs, however.  Hypertrophic obesity, on the other hand, is accompanied by endocrine and metabolic alterations, marked by insulin resistance, sugar intolerance, hyperinsulinaemia, hypertriglyceridaemia, and hyperuricaemia.  Recent data are cited for the proposition that these changes constitute a closed pathogenetic concatenation creating a vicious circle.  Fatty acids play a particularly important part in this context, since they are synthetized, released, presented and oxidated to a pathological degree.


[Importance of enzymes in the synovial fluid.  Progress report]. The significance and importance of investigation of the synovial fluid enzymes in the main arthropathies are explanined.  Tables are given for the main enzymes studied, the cell compartments of origin, and data for their values in rheumatic diseases (as reported in the literature).  Stress is laid on the importance of enzymes belonging to the lysosomial compartment, both in the pathogenesis of the underlying inflammation and in the relation to anatomopathological lesions in the joints.  Attention is directed to the most widely accepted hypotheses.  These ten to see enzymes increases in breakdown of condrocytes, as inflammatory arthritis attributable to synoviocytes and leukocytes.  A personal opinion based on prior research is also presented.  Further work in this sector is urged a mean of learning more about the pathology of rheumatic diseases.


[Experimental analysis of some cardiovascular effects of Verapamil]. In vivo and in vitro experiments showed that Verapamil dilates the coronaries, prevents coronary spasm, produces Ca++-antagonism, offers protection against myocardial necrosis, prevents arrhythmia, reduces pressure, increases the purinergic reactivity and produces inhibition of platelet aggregation. It was devoid of competitive-adrenolytic activity in the heart and vessels. A methoxy derivative of the drug (D-600) had a negative inotropic and chronotropic action and was more hypotensive than Verapamil.


[The calcium-antagonistic fundamental effects of Verapamil on myocardial fibers and smooth muscle cells of the blood vessels]. Ca ions regulate the amount of ATP which is metabolized in the contractile system to produce mechanical energy. Since the consumption of ATP quantitatively determines the myocardial respiration rate, oxygen consumption is also Ca-dependent. Therefore, Ca-antagonistic compounds such as verapamil, D600 or nifedipine, by reducing the Ca supply to the beating heart, not only restrict ATP breakdown and mechanical activity but also myocardial oxygen demand. Moreover, Ca-antagonistic drugs lower the tone of vascular smooth muscle. This action leads to coronary vasodilation and a reduction in heart load because the peripheral vascular resistance is also diminished. All these factors contribute to an improvement of the cardiac energy balance in patients with coronary disease.


[Key-role of intracellular calcium overload in acute necrosis of the myocardium. Cardioprotection with verapamil]. Ca ions are highly cardiotoxic if their influx into the myocardial fibres becomes abundant. The intracellular Ca overload initiates a deleterious high-energy phosphate deficiency by excessive activation of Ca-dependent intracellular ATPases and by impairing the phosphorylating capacity of mitochondria. This Ca-induced high-energy phosphate exhaustion is a crucial point in the etiology of the myocardial fibre necroses produced in rats by large doses of beta-adrenergic catecholamines, particularly isoproterenol, or by a number of other cardiotoxic agents. Accordinly, the myocardium is sensitized to necrotization by factors which favour Ca overload (dihydrotachysterol, 9alpha-flourocortisol acetate, NaH2PO4). Conversely, the structural integrity of the hearts can be protected by any substance or procedure which prevents an excessive intracellular Ca accumulation, particularly by inhibitors of the transmembrane Ca influx, such as verapamil, D 600 or prenylamine.


[Venous infusion of nerapamil in the treatment of refractory angina pectoris and arrhythmia due to associated electric instability]. The therapeutic effect of Verapamil in 45 patients with angina that had failed to respond to other drugs is described. Angina was distinguished in terms of its clinical and ECG features. Verapamil was administered i.v., usually in infusions of 10-250 mg/day over periods of hours or days; alternatively, direct injections of 2,5-5 mg were employed. The effect on arterial pressure is particularly stressed. In the great majority of cases, there was a marked improvement in the symptomatology and in arrhythmic changes arising during angina. The importance of the therapeutic effects of the drug is examined and its possible mechanisms of action are discussed.


[The hemodynamic effect of verapamil by intravenous administration in middle-aged, subjectively healthy subjects at rest and during exercise]. After an intravenous injection of 0.1 mg Verapamil per kg body weight and during an infusion of 0.007 mg Verapamil per kg body weight and minute the heart rate increased, P,Q,-time increased, pulmonary vascular pressures increased. Aortic pressures decreased. No change in maximum dp/dt of the aortic pressure. The word maximum is still missing. Pre-ejection period decreased. During an exercise on a load of 650 kpm/min on average heart rate after Verapamil was increased, aortic pressures decreased, stroke work decreased and there were no signs of any negative inotropic effect.


[Anti-arrhythmic therapy with verapamil by intravenous infusion]. Rapid and slow venous infusion of various doses of Verapamil in a mixed series of 185 cases of arrhythmia since 1968 is reported. Results and electrophysiological and ECG changes observed for each type of arrhythmia examined are considered separately: atrial fibrillation-flutter, supraventricular paroxystic tachycardia (atrial and/or junctional), and hyperkinetic ventricular arrhythmia. An association of i.v. Verapamil and a quinidine salt per os is suggested as an alternative to cardioversion in cases of recent atrial fibrillation-flutter. Results obtained in the treatment of arrhythmia due to electrical instability following angina and of angina following arrhythmia are also described. A study of His potentials as the premiss for using Verapamil in subjects with stimulus conductivity changes, including W.P.W. syndrome, is also reported. I.v. Verapamil was used in association with atrial and/or ventricular electrostimulation, and/or with electrical counter-shock in cases of arrhythmia (mostly supraventricular) that were especially refractory. Attention is drawn to the use of Verapamil in the control of arrhythmia after electrical cardioversion.


[Clinical results with verapamil in intravenous administration in the emergency therapy of cardiac arrhythmias]. Verapamil was administered intravenously to 250 patients aged between 14 and 85, suffering from tachyarrhythmia of various type. The commonest heart conditions were hypertensive cardiopathy, acquired valvular defects, and ischaemic cardiopathy. The antiarrhythmia effectiveness of the treatment is shown by the excellent results obtained in sinus tachycardia, supraventricular paroxysmal tachycardia, high frequency atrial fibrillations and even in a patient with WPW syndrome and supraventricular paroxysmal tachycardia and in one of the 5 patients with ventricular tachycardia. Generally speaking, the treatment was continued orally in a dose of 240 mg per day, and it was possible to control the clinical situation with no side effects.


[Verapamil: an original anti-arrhythmic agent]. Verapamil was initially known for its anti-angina effect. When given in higher doses, it displays pharmacologically unusual anti-arrhythmic effects, since it opens up a new path in this still limited category of drugs. Experience gained in 310 cases has enabled useful doses to be established and had shown that Verapamil is very effective in the management of supraventricular rhythm disturbances. Its high dose administration modality in patients with primary insufficiency and in the aged was also determined.


Denervation supersensitivity in Horner's Syndrome. The mechanism of denervation supersensitivity was investigated, using the pupillary system as an experimental model. A pharmacological study was carried out in six patients with Horner's syndrome due to postganglionic lesions. Administration of cocaine 4 percent resulted in dilatation of the normal pupil, while subsequent instillation of phenylephrine (2.5-5 percent) produced equal dilatation in both eyes. The results of the study indicate that denervation supersensitivity of the pupil can be explained solely by impaired reabsorption of catecholamines.


Corneal anesthesia induced by soaps and surfactants, lack of correlation in rabbits and humans. Five commonly marketed bath and facial soaps and four commercially available hair shampoos were studied for their anesthetic effect on human and rabbit corneas. These compounds all produced anesthesia comparable to that induced by tetracaine hydrochloride 0.5 percent but lasting several hours longer in rabbits. None of the soaps or shampoos produced corneal anesthesia in humans. Studies of corneal anesthesia in rabbits may not be extrapolated to the human eye.


[Findings in the fundus oculi in gangrene]. A case of gas gangrene is described where gas was seen in retinal vessels. The suspicion of gas gangrene in this case arose through ophthalmoscopy.


Amyloid deposits of internal elastic lamina in temporal arteritis. Ten biopsy specimens from patients with temporal arteritis showed amyloid deposits replacing the arterial internal elastic lamina. In three cases the inflammatory reaction was very mild, but amyloidosis was advanced, thus suggesting a primary pathogenetic role for amyloid degeneration in temporal arteritis. The findings are compatible with those of systemic amyloidosis in patients with arteritis temporalispolymyalgia rheumatica syndrome in a few isolated instances.


Prevention of experimental obstructions in the retinal microcirculation. Arterial Fluorescein Studies. Platelet aggregates were formed in flowing blood by infusing ADP in the carotid artery of the dog. Under fluorographic examination, these aggregates were seen to lodge in retina vessels. Previous administration of gliclazide helped maintain normal retina circulation.


The fibrinolytic system in patients with diabetes mellitus with special reference to diabetic retinopathy. The fibrinolytic system has been studied in 168 patients with diabetes mellitus (DM) and compared to that of a group of 153 sex- and age-matched control subjects. The following determination were made: spontaneous fibrinolytic activity of the blood; fibrinolytic response to standardized venous stasis (stimulated fibrinolytic activity, "fibrinolytic capacity"); histochemical determination of fibrinolytic activators in the walls of superficial veins collected by biopsy. Diabetic patients were found as a group to have an impaired fibrinolytic system with the above fibrinolytic parameters decreased to various degrees in comparison with those of the controls. Less clear differences were observed between patients with and without ophthalmoscopically visible diabetic changes of the retina. However, patients with beginning angiopathy were found to have a significantly higher amount of fibrinolytic activators in their vessel walls than patients with more advanced retinopathy and without ophthalmoscopically detectable retinopathy. Furthermore, unlike patients without retinopathy, patients with retinopathy increased less or did not increase at all their spontaneous and stimulated fibrinolytic activity along the duration of the disease. The defective fibrinolytic system of diabetic patients may contribute to the occurrence of the vascular complications frequently seen in this disease. In the diabetic group, those patients who develop retinopathy show an impaired fibrinolytic defense with the duration of the disease.


[Hemorrhagic macular choroidopathy in young subjects]. The haemorrhagic macular choroidopathy is a characteristic and rather frequent disease, which is seen in young subjects. We observed it in 23 patients, aged between 12 and 51 years. The disease resembles the presumed histoplasmin choroiditis, described in the American literature. In our cases, histoplasmosis can nevertheless be excluded and in the American cases it is not proven. In fact, the etiology is still unknown, but in 13 of our cases the origin may have been a disseminated choroiditis.


[Clinical-neurological and electromyographical studies of inpatients isolated with selective pigmentary retinopathy]. 1. 37 patients with pigmentary retinopathy, seeming otherwise healthy, were thoroughly examined for fine symptoms in other parts of the body, in particular for neuropathies and for blood chemistry peculiarities. 2. In 19 cases some constitutional pathology was discovered, in 4 cases hearing was affected by inner ear changes. 3. Clinically patients behaviour was changed and with electroencephalgraphy an encephalopathy was found in 7 cases. 4. Electroencephalograms were in more than 50% of cases slightly abnormal. 5. A myastenic reaction, confirmed by electromyography, occurred in one case (but not in its sibling who had also a pigmentary retinopathy.) 6. In 14 cases electromyogram was showing a neurogenic damage. Motor nerve conduction speed was lowered in 2 cases, in 5 cases it was at the lower limit of normal. In 6 cases very long distal latence times were noted. In 2 cases action potential was shortened but this could not be considered as  a myopathy for certain. 7. In 6 cases a hyperlipoproteinaemia occurred.  In 2 cases a mild diabetes mellitus, in 7 cases uric acid level in serum was raised. The number of cases was too small to give a statistical importance to those findings. 8. Cerebrospinal fluid was found normal in all cases. 9. This study should lead to further investigations. In spite of the small number of cases one can presume that pigmentary retinopathy is not an independent defect but is a phenomenon of a polygenetic entity.


[Exudative diabetic retinopathy. A fluorescence angiography study]. For elucidation of the pathogenesis of the lipoidic depostis due to diabetic retinopathy, 40 patients (44 eyes) were submitted to fluorescence angiography in intervals of 4-6 months; the follow-up covered 1-3 years, the average time being 1.75 years. In 43 of 44 cases, disturbances of the permeability of retinal blood vessels were found, their extent correlating with the size of the exudate foci. An increased perfound, thier extent correlating with the size of the exudate foci. An increased permeation of the dye was closely connected with an increased exudation, and a decreased vascular permeability was connected with a regression of lipoidic deposits.


Total glenohumeral joint replacement.

Total glenohumeral joint replacement. Some of the anatomical considerations of the glenohumeral joint with respect to prosthetic replacement have been discussed. One approach to prosthetic design has been presented along with the early clinical experience with this design. It is hoped that this information will serve as a reference point for future work to be done in this area.


The rheumatoid shoulder.

The rheumatoid shoulder. The rheumatoid shoulder is a frequent manifestation in the rheumatoid patient. Most of the symptoms are of a mild to moderate degree and can usually be ameliorated by heat, massage, and gently exercise. Local injection therapy may be of value in selected cases. Strenuous exercise or manipulation is contraindicated. Tendon ruptures and rotator cuff tears are not amenable to surgical reconstruction and are adequately treated with a conservative regimen. Prophylactic synovectomy is not performed as a routine, because the majority of patients do not develop disabling symptoms. This procedure is usually restricted to the few patients who exhibit uncontrollable proliferative synovitis. Prosthetic replacement is employed for intractable pain with full anticipation of limitied mobility. Various designs of a "total shoulder" are undergoing clinical evaluation, but their application has not been defined.


The effect of moisture stress upon the hatching of Nematodirus battus larvae. An experiment was carried out to investigate the effect of soil moisture stress upon the hatching behaviour of Nematodirus battus. The method involved the use of polyethylene glycol solutions to maintain a steady osmotic pressure around a soil containing N. battus eggs, which were ready to hatch. Different concentrations of polyethylene glycol (creating different moisture stresses) were found to affect the numbers and the rate of egg hatching markedly.


Variations in the water content of the larvae of Nematodirus battus during the hatching process. During a series of experiments on the ecology of Nematodirus battus observations were made on the uptake of water by eggs containing third-stage larvae.  It was found that, as they approached hatching, the water content of the larvae increased markedly, then fell immediately after they escaped from the shell.  The method of measuring the water content, using interferometry, is also described.


Intestinal pathology associated with Trichostrongylus colubriformis infection in sheep: histology. Observations were made on the histology of tissues from the first 6-10 m of the small intestine from both sheep infected with Trichostrongylus colubriformis and from uninfected controls.  In uninfected animals, and in distal samples from infected lambs, villi were tall and covered by tall columnar epithelium, the intestinal crypts were convoluted and the lamina propria was only moderately cellular.  In tissues with sub-total villus atrophy and a convoluted surface, the superficial epithelium was usually low columnar, often with an indistinct brush border.  More severely affected mucosa was flat, with low surface epithelium and protruding crypt openings.  The flat surfaces frequently had leaks of eosinophilic material and polymorphonuclear cells between enterocytes, or through erosions in the epithelium.  Such defects were smaller and less frequent in mucosa with a convoluted surface.  There were increased mitoses in intestinal crypts and a heavy inflammatory cell infiltrate in the lamina propria.  Mast cell, globule leucocyte and theliolymphocyte numbers were not increased in infected sheep.


Intestinal pathology associated with Trichostrongylus colubriformis infection in sheep: vascular permeability and ultrastructure of the mucosa. Increased permeability of capillaries and venules, labelled with colloidal carbon, was observed in the superficial mucosa of the small intestine of sheep infected with Trichostrongylus colubriformis.  The labelled vessels were restricted to infected portions of the gut, and the intensity of labelling appeared to be related to density of the worm population.  Open junctions were seen between endothelial cells in permeable vessels.  In moderately atrophic infected intestine, enterocytes were domed, had sparse, short, distorted microvilli and many polyribosomes.  Tight junctions between enterocytes seemed to be intact and distended intercellular spaces were seen.  In more severely atrophic mucosa, enterocytes had distended mitochondria and endoplasmic reticulum, bizarre shapes, and the continuity of the epithelial sheet was occasionally disrupted.  There was oedema in the lamina propria and neutrophils were seen in migration to the lumen of the gut.  The possible mechanisms inducing these changes and their significance in terms of plasma protein loss and intestinal function are discussed.


Studies on immunity with three species of avian trypanosomes. The ability of three species of avian trypanosome, Trypanosoma corvi, T. bouffardi and T. everetti, to protect against heterologous and homologous challenge has been studied in susceptible birds.  None protects against challenge with either or both of the other two species and mixed infections can be obtained experimentally.  With T. bouffardi, both apparently sterile and premune states exist after initial infection and the host is immune to challenge with homologous strains; heterologous strains sometimes break this immunity and produce shorter, lower parasitaemias.  T. everetti remains in the circulating blood for long periods at low levels and challenge doses with the homologous strain result in a slightly elevated parasitaemia for a few days.  T. corvi produces a degree of immunity after the initial infection which usually results in a reduced second parasitaemic peak of shorter duration when birds are challenged with a homologous strain.


Observations on the bionomics of Pseudolynchia canariensis (Diptera: Hippoboscidae). Host suitability, reproduction, effects of temperature on reproduction and pupal development, effects of humidity on pupal development and the effects of photoperoid on puparial deposition, pupal development and adult emergence were studied in a laboratory colony of Pseudolynchia canariensis.  Flies were observed to lack strong host specificity.  Puparia were produced at regular 24 h intervals by flies maintained at 30 degrees C, averaging 8-8 puparia per female.  Optimum temperature for colony maintenance was observed to range between 26-6 and 30-0 degrees C.  Temperatures of 13 and 37 degrees C were lethal to pupae.  Humidity and photoperiod did not markedly affect pupal development.  Puparial deposition and adult emergence occurred only during the photoperiod.


Laboratory studies with some recent anticoccidials. The activities of monensin, lasalocid and halofuginone against Eimeria tenella, E. brunetti and E. necatrix have been studied under laboratory conditions.  Complete control of experimental infections in the chick, separable from toxicity, was not obtained with monensin, but was achieved with the other two compounds at levels of 150 and 6 ppm in the food respectively.  All three compounds appear to inhibit coccidial development very early in the life-cycle, and to have a fairly rapid lethal effect, monensin and lasalocid more so than the febrifugine derivative.  In vivo observations have been supplemented with in vitro studies.  Some discussion of the difficulties of relating laboratory experiments to field performance is given.


Fine structure and development of schizonts, merozoites and macrogamonts of Eimeria acervulina in the goblet cells of the duodenal epithelium of experimentally infected birds. The fine structure of trophozoites, schizonts, merozoites and macrogamonts of Eimeria acervulina found in goblet cells of the duodenal epithelium of chicks is described and compared with the corresponding stages formed in other epithelial cells.  Complete schizogony, with the formation of mature merozoites, occurred freely in goblet cells.  Developing macrogamonts (but no microgamonts) were rarely found in goblet cells.  The stages observed were confined to the cytoplasm of the host cell above the Golgi apparatus and were usually seen between the mucous granules.  The stages seen appeared normal, and contained similar structures to corresponding stages developing in other cells.  The finding of developing stages of E. acervulina in goblet cells provides further evidence that site specificity of Eimeria at the cellular level is not as strict as previously thought.


Genetic factors in susceptibility of Biomphalaria glabrata for different strains of Schistosoma mansoni. Biomphalaria glabrata selected for genetic differences in susceptibility to infection with a Puerto Rican strain of Schistosoma mansoni were exposed to miracidia of a strain of S. mansoni from St Lucia.  The St Lucian strain was less infective than the Puerto Rican.  Results suggested that in snails susceptible to the Puerto Rican S. mansoni differences in susceptibility to the St Lucian straing were determined by a single gene, with insusceptibility dominant.


Feeding of Boophilus microplus larvae on a partially defined medium through thin slices of cattle skin. Larvae of the cattle tick Boophilus microplus will attach to thin (0-3--0-5 mm) slices of cattle skin and engorge on a partially defined medium at 35 degrees C.  Forty-seven to 83 per cent of the larvae had engorged by 8 days, and 51--71 per cent of these moulted to nymphs.  Tissue culture medium alone allowed little growth unless supplemented with dialysed, freeze dried bovine serum (7 per cent, w/v).  This medium could be further difined by substituting purified bovine serum albumin (Cohn fraction V) for the dialysed bovine serum.  In one experiment, nymphs of Haemaphysalis longicornis engorged and later moulted to adults.  Skin slices were used fresh or after freeze-drying and storing at --25 degrees C.  The possible uses of the culture method are discussed.


The number and morphology of trypanosomes in the blood and lymph of rats infected with Trypanosoma brucei and T. congolense. The thoracic lymph duct of rats infected with Trypanosoma brucei and with T. congolense was cannulated at different stages of infection.  Trypanosomes were always present in the lymph of rats infected with T. brucei, wheras they were absent or very scarce in the lymph of rats infected with T. congolense.  There were greater fluctuations in the numbers of trypanosomes in the blood than in the lymph.  The intra- and extravascular populations of T. brucei differed: stumpy forms were present only in blood; dividing forms were usually more numerous in lymph.


Nematode parasites of Puerto Rican tree frogs, Eleutherodactylus spp: two new species and a proposal of Poekilostrongylus gen. nov. (Trichostrongylidae). Poekilostrongylus puertoricensis gen.nov., sp.nov. is proposed for nematodes recovered from Eleutherodactylus coqui, in Puerto Rico.  The new genus is similar to Oswaldocruzia Travassos, 1917, but lacks longitudinal ridges on the cuticle.  Oswaldocruzia lenteixierai Viqueras, 1938, is partially redescribed, and a key to the genera of the Oswaldocruziinae is given.  Thelandros (Parathelandros) garciai sp.nov. is described from E. antillensis and E. portoricensis.  Strongyloides sp. was found in E. antillensis and Aplectana spp. (females) were recovered from E. locustus, E. richmondi and E. coqui.


The lethal effect of mebendazole on secondary Echinococcus granulosus, cysticerci of Taenia pisiformis and tetrathyridia of Mesocestoides corti. Oral administration of mebendazole at a rate of 1 g/kg feed (approximately 50 mg/kg body weight/day) for 14 days killed mature and immature cysticerci of Taenia pisiformis in rabbits, and multiplying tetrathyridia of Mesocestoides corti in mice.  Progressive degrees of parasite damage caused by mebendazole treatment could be assessed by histological examination of calcereous corpuscles.  A single subcutaneous injection of 10 percent mebendazole in carrier, at a rate of 100 mg/kg body weight, resulted in the death of all M. corti tetrathyridia in mice within 4 weeks, but the drug in saline was slowly mobilized and was relatively ineffective.  Neither subcutaneous injections of mebendazole in saline or in carrier could kill cysticerci of T. pisiformis within 5 weeks, but the drug in carrier was effective after several months.  Mebendazole in saline was effective when injected intraperitoneally, but adhesions often resulted from this route of administration.  Echinococcus granulosus protoscoleces administered to mice by intraperitoneal injection were rapidly encapsulated by host lymphoid cells.  The vesiculating protoscoleces were all contained within a fibrous capsule for more than 2 months after infection, but by 4 months almost all had grown free of the host reaction.  Treatment of the encapsulated protoscoleces with mebendazole in feed for 14-21 days caused collapse of the outer cysts and death of the germinal membrane of all but the innermost protoscoleces.  Six weeks later, however, cysts had regrown from surviving germinal tissue and a further treatment with mebendazole in feed for 14-21 days again did not destroy all germinal cells.  Treatment of the 4-month-old scoleces with mebendazole in feed for 14 days caused all cysts to collapse and destroyed practically all E. granulosus germinal tissue.  Three subcutaneous injections of mebendazole at fortnightly intervals, of drug in saline at 500 mg/kg body weight, or in carrier at 100 mg/dg body weight, were required in order apparently to kill all secondary cysts of E. granulosus.  Host lymphoid cells were not able to traverse the laminated membrane of either untreated or collapsed cysts, and it has been shown that only a small amount of living germinative tissue is required to produce a new E. granulosus cyst.  These factors could contribute to the relative ability of E. granulosus cysts to recover from mebendazole treatment, compared with cysticerci or tetrathyridia.  The effectiveness of mebendazole thus seemed to depend on the formulation of the drug and its route of administration.  Mebendazole is probably the first anthelmintic to have a lethal effect on larval cestodes.  When applied orally there do not appear to be any adverse effects due to treatment.


Latrogenesis imperfecta--a new pediatric problem. In this medical age which relies heavily on electronic and technologic advances, the physician is often willing to place unwarranted confidence in laboratory data regarding his patients. In those unusual situations in which the patient is not directly examined, e.g., prospective screening or prenatal diagnosis, treatment errors can be made. These acts of commissions are initiated by interpretation of laboratory data and can result in detrimental effects to the patient. The term iatrogenesis imperfecta has been designated to describe this situation.


The pathology of neonatal osteomyelitis. The examination of multiple bones from a child who died of complications of septicemia and osteomyelitis elucidated the pathologic processes of infantile osteomyelitis. From a metaphyseal focus, there is spread in several directions. Most important, the infection can spread across the growth plate, along transphyseal vessels, to penetrate the epiphysis. Areas of direct destruction of growth plate were frequent findings, and allowed another route into the epiphysis.


Maternal thyroid status and the incidence of respiratory distress syndrome: evaluation of a proposed relationship. In order to establish whether maternal thyroid hormones cross the placenta and produce surfactant in the fetus, possibly reducing the incidence of respiratory distress syndrome (RDD), a retrospective analysis of low-birthweight infants was undertaken. Results indicate that maternal thyroid hormones play a negligible role and that any thyroid mediation would result from fetal thyroid activity.


Plasma corticoids in the respiratory distress syndrome and in normal infants. Serial plasma samples for corticoid determination were obtained during the neonatal period in 16 infants with RDS (eight of whom died) and 44 healthy babies. The median corticoid level in the eight infants with RDS who was considerably higher than that of patients with RDS who survived, or the normal babies. The median corticoid level in the surviving RDS infants was statistically greater than that of the normal controls, but the actual difference was only 1.9 mug/100 ml. Simultaneous pH, PCO2, PO2, HCO3- and corticoid measurements were obtained serially in five patients with fatal RDS. However, the correlation between plasma corticoids and the acid-base determination was poor in all but one infant. It is concluded that infants are able to respond to severe physical stress in the neonatal period with an appropriate rise in plasma corticoid concentration, but lesser degrees of illness may cause only minimal changes in corticoid levels.


Neonatal bromide intoxication: prenatal ingestion of a large quantity of bromides with transplacental accumulation in the fetus. A 27-year-old woman who was 34 weeks pregnant was admitted in a semicomatose state. Five days later she gave birth to an infant who demonstrated significant CNS depression. Elevated blood levels confirmed bromide intoxication in both the mother and infant secondary to chronic maternal bromide ingestion (Nervine). Simultaneous determinations revealed a higher initial serum bromide level in the infant compared to that of the mother in spite of a subsequent more rapid rate of disappearance in the neonate. It is suggested that the drug history obtained from the pregnant woman include nonprescription medications containing bromides. This possibility should also be included in the differential diagnosis in infants exhibiting evidence of CNS depression, particularly those born to mothers classified as neurotic or psychotic.


Hemophilus influenzae meningitis at the Children's Hospital Medical Center in Boston, 1958 to 1973. Three hundred ninety-seven children were admitted to the Children's Hospital Medical Center, Boston between 1958 and 1973 with H. influenzae meningitis. The annual rate of admission and the percent of all cases of bacterial meningitis were not changed from that of the preceding decade. The age incidence was strikingly similar to that reported from this hospital for 1920 to 1932.


Treatment of severe apnea in prematures with orally administered theophylline. Twelve premature infants with primary apnea were treated with theophylline as an alternative to mechanical ventilation.  There was a significant (P smaller than .005) reduction in the mean daily number and the severity of apneic episodes after treatment.  The only significant side effect noted was a rise in heart rate.


The pediatric pneumogram: a new method for detecting and quantitating apnea in infants. A clinically useful diagnostic method has been developed for detecting and quantitating periods of apnea in pediatric patients.  This procedure, called the pediatric pneumogram, permits the continuous recording on magnetic tape, for periods of up to 13 hours, of the respiratory pattern of infants utilizing an impedance technique.  This test has been employed successfully in a variety of infants to evaluate respiratory activity and has permitted the objective documentation of apneic and cyanotic episodes, as well as an assessment of the eff ectiveness of therapy.


Chemoreceptor reflexes in preterm infants: I. The effect of gestational and postnatal age on the ventilatory response to inhalation of 100% and 15% oxygen. We studied 16 "healthy" preterm infants (birthweight, 1,000 to 2,000 gm) 94 times during postnatal life to define the effect of gestational and postnatal age on the ventilatory response to 100% and 15% oxygen. They were given air, then 100% oxygen for two and five minutes respectively (No.=63) or 21%, 15% and then 21% oxygen for five minutes each (No.=31). We measured respiratory minute and tidal volumes, frequency, heart rate, and alveolar PCO2 and PO2. We used the magnitude of the immediate change in ventilation during during 100% and 15% oxygen breathing to test peripheral chemoreceptor function. The immediate decrease in ventilation with 100% oxygen and the immediate increase in ventilation with 15% oxygen were statistically similar at different gestational and postnatal ages. The late increase in ventilation (five minutes) with 100% oxygen was also similar at different ages. However, the late decrease in ventilation with 15% oxygen was not present at 18 days of age. These findings suggest that: (1) the peripheral chemo-receptors are active at least from 28 weeks of gestation and are probably not important in triggering periodic breathing or apnea in preterm infants, and (2) the preterm infant matures his response to hypoxia and is able to sustain hyperventilation with low oxygen by 18 days of age.


Chemoreceptor reflexes in preterm infants: II. The effect of gestational and postnatal age on the ventilatory response to inhaled carbon dioxide. We studied nine "healthy" preterm infants (birthweight, 1,000 to 2,000 gm) 58 times during postnatal life to define the effects of gestational and postnatal age on the ventilatory response to carbon dioxide. The infants were given air and 2% and 4% carbon dioxide in air to breathe for five minutes each. We determined respiratory minute and tidal volumes, frequency,heart rate, and alveolar PCO2 and PO2. We measured ventilation with a nosepiece and a screen flowmeter, using a constant flow-through to eliminate valves and reduce diad space. Analysis were made during the fifth minute while the baby breathed the various gas mistures. The slope of the carbon dioxide response increased 42% from 32 to 37 weeks gestation (P smaller than .05) and 62% from 2 to 27 days of age (P smaller than. 025). However, the intercept at .3 liter/min/kg was the same at different gestational ages, but significantly greater at 2 compared with 27 days of age (P smaller than.05). We sugest that the unresposiveness primarily dependent on the mechanical abnormalities of the lung.


Rapid diagnosis of sickle cell disease at birth by microcolumn chromatography. Accurate specific diagnosis of sickle cell disease can now be made at birth on routinely obtained cord blood samples by microcolumn chromatography.  The method uses a small column of a cation ion exchange resin, CM-Sephadex, and a single developer that allows definitive rapid distinction of hemoglobin SS, AS, AC, SC, and CC, within two hours.  Seventy-five samples or more per day have been analyzed by one technician in a laboratory without special precautions or equipment.  In a program which has been initiated on a large, totally unpredictable obstetrical service in Los Angeles, 10,401 consecutively born infants have been studied for hemoglobin type without regard to racial origin.  Three SS infants, 1 SC, 143 AS infants, and 37 AC infants as well as several with other abnormal hemoglobins have been identified without interfering with the routine operation of the delivery rooms of the obstetrical service.  The diagnosis of sickle cell disease has been confirmed on subsequent examinations of the infants.  The feasibility of using microcolumn chromatography as a rapid, accurate, inexpensive, and easy method for the rapid diagnosis of sickle cell disease in newborns has now been established.


Percutaneous carciac catheterization of the neonate. A modified Seldinger percutaneous approach for catheterization was used for cardiac evaluation and monitoring of infants weighing less than 4,520 gm. From January 1968, through April 1971, 160 left- and 230 right-sided cardiac procedures were done. After July 1969 81% of all left-and 42% of all right-sided procedures were done percutaneously. After October 1969 catheters were also inserted percutaneously in 20 infants for intensive care monitoring. During this period three children were noted to have dimished pulse on discharge, two were noted to have vascular thrombosis, and two had episodes of bleeding from the catheter site requiring transfusion of fresh blood. Both instances of vascular thrombosis occurred in infants with monitoring catheters. The percutaneous method of catheter insertion into the femoral vessels offers a safe method for cardiac catheterization of the neonate and of insertion of monitoring catheters where the umbilical route is not feasible. Vessel continuity is also preserved, providing a route for repeated studies if necessary.


The application of acoustic impedance measurements to pediatric clinical practice. This article provides background information on acoustic impedance testing and illustrates utilization of test results in pediatric clinical practice.  Acoustic impedance measurement devices are presently being used successfully by hearing screening programs and by otorhinolaryngologists in clinical and hospital settings.  As a diagnostic tool, the acoustic impedance bridge can have particular applicability in dealing withe young children and other  difficult-to-test populations.  Impedance measurements can provide physicians with objective information about the condition of the middle ear, oftentimes more accurately than either otoscopic examination or standard audiometry.  The technique described can assist physicians in diagnosing middle-ear diseases and in monitoring the effects of otological treatment.


Relationship of maternal and infant iron stores as assessed by determination of plasma ferritin. Using plasma ferritin derminations, iron stores have been evaluated at the end of pregnancy in 26 women and followed sequentially in their healthy, full-term infants.  It has been shown that the iron storage status of the mother does not affect the iron status of the infant.  Determinations of plasma ferritin in the infants have demonstrated that by 6 months of age the iron status of the infant reflects the adequacy of the dietary intake of iron.  In the absence of effective iron supplementation during the first six months, plasma ferritin levels fall to low levels, indicating the depletion of iron stores in the infant.


The modification of pediatrician activity following the addition of the pediatric nurse practitioner to the ambulatory care setting: a time-and motion study. Time and motion studies were performed before and after PNPs began working in the offices of three pediatricians and the emergency room of a municipal general hospital.  Pediatricians' activities changed in different ways, but all benefited by the generation of available time.  The three pediatricians in office settings gained the equivalents of 21.6%, 21.7%, and 36% of the working day by the addition of the PNP.  Physicians working in the emergency room gained 14.7% during that time of day the PNP was present.  PNP visits with patients were longer than those of the pediatricians, the average length of time being related directly to that of the associate physician.  Patients interviewed perceived no difference in personal characteristics between pediatricians and PNPs in three of the four settings.  In the fourth setting, both were at high levels, but the pediatrician ranked higher than the PNP.


DiGeorge's or the III-IV pharyngeal pouch syndrome: pathology and a theory of pathogenesis. Six new cases of the III-IV pharyngeal pouch syndrome were encountered at autopsy among 897 consecutive pediatric autoposies. All occurred in patients with conotruncal cardiac anomalies. The anatomic characteristics of the heart defect suggest a possible mechanism for the pathogenesis of this developmental anomaly. It is postulated that premature involution of the thyroidea ima artery, which is the principal embryonic blood source to the 3rd and 4th pharyngeal pouches and the ultimobranchial body, may be the critical event in the embryogenesis of the syndrome. Hemodynamic alterations in the course of anomalous morphogenesis of conotruncal anomalies may favor premature involution of certain vessels including the left 4th aortic arch and the thyroidea ima. Deficiencies of thymus, parathyroid glands and ultimobranchial tissue ("C" cells) may be the consequence of vascular deprivation during embryogenesis. These cases are discussed with regard to the proposed mechanism of pathogenesis and the influence of varying quantities of thymus upon peripheral lymphoid tissue. Both embryologic and clinical data support the possibility of a deficiency of ultimobranchial tissue. The range of minor and inconstant anomalies seen in patients with this syndrome is presented.


[Chemotherapeutic combinations of mutually potentializing drugs. 1-Application to the treatment of breast cancers]. 27 patients suffering from disseminated carcinoma of the breast with at least two visceral metastases, and two had become resistant to conventional chemotherpy and hormones, received a combination of, in the present trial, vincristine followed by cyclophosphamide with 5-fluoro-uracil. Chemotherapy was administered intermittently: each cycle of treatment lasted 6 days and was followed by a period without treatment of 25 days. Haematological tolerance was satisfactory. No serious incidents occurred during two years use of the combination. 20 out of 27 patients showed objective tumour regression of more than 50 p.cent lasting for more than 6 months, whilst 9 showed apparent complete regression of the malignant lesions. There was one complete failure. Chemotherapy was continued in all cases after regression of the neoplastic process was obtained.


[Chemotherapeutic combinations of mutually potentiating drugs. 2-Application to the treatment of bronchial cancers]. 16 patients suffering from primary bronchial tumours which had recurred after surgery and/or radiotherapy and with spread involving at least one visceral or lymphatic metastasis received chemotherapy consisting of the administration of vincristine followed by a combination of CCNU and 5-fluorouracil. Each cycle of treatment lasted 6 days and was restarted only after an interval of 30 days on average, this being necessary for haematological recovery. With the doses of CCNU used, thrombocytopaenia occurred only during the fifth cycle of treatment and made it necessary to increase the interval between subsequent courses to five weeks. All of the patients included in the study have now been followed up for between six and eighteen months. Two patients are presently in complete remission without apparent radiological, clinical or bronchoscopic signs. In seven other patients there was tumour regression greater than 50 p.cent persisting for four to six months. In seven, the therapeutic effect was transient or nil.


[Cancer of the transverse colon: a cancer diagnosed too late]. Study of 48 cases carcinoma of the transverse colon, undergoing surgery over a period of 6 years from 1968 to 1973 led to the following conclusions: diagnosis is often later because of the calibre of this part of the colon and hence little occlusive tendency. The best operation appears to be right and transverse hemicolectomy with ileo-colic anastamosis and resection of the gastrocolic ligament, where recurrences occur, along the edge of the greater curve of the stomach.


[Postoperative intraabdominal suppurations due to Ristella. Clinical, bacteriological and therapeutic characteristics]. From 1972 to 1974, 8 intraabdominal postoperative suppurations due to Bacteroides have been observed at Hospital Beaujon. Three characteristic features of such infections have been analysed: the high frequency of associated jaundice; the difficulty of isolation of the Bacteroides; their specific sensitivity to some antibiotics. In 5 patients, jaundice related to the bacterial infection has been observed; jaundice was of the cholestatic type; it was mainly due to conjugated hyperbilirubinemia; in approximately 50 p.cent of the cases, serum alkalin phosphatases activity and serum glutamic-pyruvic transaminase activity were moderately elevated; the presence of jaundice did not seem to have any influence on the prognosis. The frequent association to Bacteroids of enterobacteria makes isolation of the Bacteroides difficult. The necessity of some precautions in the handling (storage at 4 degrees C or immediate inoculation in anaerobic conditions) is emphasized. Bacteroides are always resistant to penicillin and to the other broad spectrum antibiotics usually effective enterobacteria. They are sensitive to tetracyclins (5/8), lincomycin (2/4), clindamycin (2/3), rifampicin (8/8), pristinamycin (7/7), carbenicillin (3/3), erythromycin (8/8) and chloramphenicol (8/8).


[Gentic study of paroxystic familial polyseritis. 72 cases]. Study of the mode of hereditary transmission of familial paroxystic polyserositis in Lebanon led us to conclude that the disease was transmitted in a dominant fashion. In almost one third of our families, dominant transmission was certain or probable. In the other families, dominant heredity was not excluded if the hypothesis, supported by many facts, of incomplete penetrance is accepted. The possibility that certain forms of the disease are dominant and others recessive cannot be rejected, but in the absence of biological proff of this genetic heterogeneity it cannot be confirmed. The majority of the patients, as is usual in the disease, were male. The highest risk groups in the Lebanese population are Armenians and Shiite Moslems


["Pearl-string artery" with mesenteric localization]. Angiorgrams sometimes show regular and symetrical corrugations of the arterial outline. The shadows have been given various names: pearl string arter, bamboo pattern and so on. Involved arteries are mostly those of the extremities, especially the lower limbs. The authors have found a case involving the mesenteric artery. Usually, there is no pathological state of the arterial wall. Thus, surgical action is unnecessary.


[Arterialization technic of the venous net work in the foot]. The amputation of the lower extermity can be avoided in many patients, particularly in diabetics by means of the arterialization of thevenous net of the foot, whenever the classic techniques of revascularization cannot been used for the magnitud of the arterial lesions below the knee. This arterialization uses two venous autografts: one in the leg functionning as a channel and the second functionning as a regulator or a temporary discharge. This technique, used in three diabetic patients with gangrenous lesions of the foot, has allowed to avoid amputation in two of them.


[Hypovolemic shocks simulating severe pulmonary embolism. 20 cases]. Twenty cases of hypovolemic shock of various etiologies in which initial diagnosis was massive pulmonary embolism are analyzed. The error was due to intensity of respiratory failure symptoms and electrocardiographic changes suggesting acute cor pulmonale. However, although constant, hypoxemia was mild and easily corrected by oxygen administration. Hypovolemia was confirmed by low central venous pressure (CPV EQUALS 1, 3 cm H20); in 7 patients, right heart catheterism showed lowered cardiac output associated to low ventricular filling pressures (VFP). Rapid blood volume expansion simultaneously corrected in all cases both shock and clinical signs of "respiratory failure", while CVP increased only slightly. These findings suggest that CVP must be carefully checked when faced with a clinical picture of massive pulmonary embolism and if low, rapid blood volume expansion must be performed under CVP monitoring, in order to rule out hypovolemic shock.


[Right renal arteriovenous fistula after nephrectomy with streptococcal endarteritis]. The authors add a new case, to the 41 already published, of arterio-venous fistula of the renal pedicle after nephrectomy, with the peculiarity of its presentation as a prolonged fever resulting from streptococcal bacterial endarteritis at the site of the fistula (3rd case in the literature). Surgical treatment in association with massive and prolonged antibiotic therapy resulted in recovery.


[Pericardial effusions and mediastinal radiotherapy. 4 cases]. The authors report 4 cases of chronic pericardial effus-ons appearing several months after high dose mediastinal irradiation for Hodgkin's disease. They describe their clinical characteristics and course. The difficulties of differential diagnosis are mentioned, in particular recurrence of malignancy and tuberculosis. They stress the reserved long term prognosis and the absence of any specific therapeutic approach. The increasing use of madiastinal radiotherapy suggests that the incidence of such manifestations will increase.


[Quantitative functional exploration of the salivary glands. Measurement of salivary elimination of technetium 99]. The authors propose a method for the quantitative functional exploration of the salivary glands using two objective criteria, on the one hand the level of fixation in the parotid of technetium 99m injected in the form of its pertechnate and on the other hand by the fraction of radioactivity found in different specimens of saliva collected in the course of a test carried out using a pharmacological agent free of toxic effects--lemon juice. The quantitative results obtained and its simplicity render the method particularly useful in evaluating the course of salivary function in all forms of disorder, pathological or iatrogenic.


[Catheterization in orificial aortic stenosis]. By virtue of its relative simplicity and its rapidity, the investigation of aortic stenosis recently perfected (and used with a satisfactory percentage of success and without important incident) deserves wide usage in haemodynamic and angiograpnic laboratories. Even if it does not always provide the solution to a particularly delicate problem, which is often of vital importance, it provides data which, modifiable and better used, should provide an adequate notion of the anatomical and physiopathological state in aortic stenosis.


[Reversible encephalopathies caused by bismuth salts. 5 further cases]. The authors report five new cases of myoclonic encephalopathy caused by bismuth salts with a characteristic and constant clinical picture. The signs regressed when treatment was stopped.


[Septicemias of superinfection in resucitation. Their prevention by restriction of antibiotics]. Nosocomial septicemias supervened during the 15 trimesters following the opening of a new built critical care unit were reviewed. During the five first trimesters the incidence of nosocomial septicemias was 5.9 p.cent. It increases to 10.7 p.cent (p smaller than 0.001) during the five following trimesters. Then a drastic restriction in antibiotic administration was performed, including withdrawal of any prophylactic antibiotherapy, preferential use of penicilline G to prevent infection by Clostridium and cocci Gram positive species surinfection, and, in case of bacterial proved infection, use of a narrow spectrum adapted antibiotic for a time as short as possible. During the 5 trimesters following the application of this antibiotic restriction, the incidence of nosocomial septicemias dropped to 5.7 p.cent (p smaller than 0.001). This phenomenon was related to the lowered incidence of the Gram negative bacilli septicemias from 11.1 p.cent to 4.8 p.cent (p smaller than 0.001) while the incidence of Gram positive cocci septicemias remained unchanged. These results strongly suggest the responsibility of the overuse of antibiotics in the determination of nosocomial septicemias and the efficiency of a drastic antibiotic restriction upon the surinfection of patients hospitalized in a critical care unit.


[Chronic pancreatitis, pancreatic cancer: differenciation by ultrasonics]. Analysis of the ultrasound patterns obtained in 63 pancreatic tumours and 147 cases of chronic pancreatis shows a considerable difference in the two conditions. The echostructure is mainly dense and reflexogenic in chronic pancreatitis and trans-sonic in carcinomata.


[Diagnosis of hyperparathyroidism: value of jugular catheterization for radioimmunologic determination of parathormone. 1st results]. Value of venous blood sampling by jugular catheterisation with radioimmunological estimation of parathormone in the diagnosis of hyperparathyroidism. Initial results.


[Approach to the dorso-lumbar joint by sub-pleuro-peritoneal route]. The authors expose an access to the dorsal-lumbar spine through sub pleuro-peritoneal way. There are two interesting points to it: - A very wide open access allowing every surgical gesture from D9 to L3 according to the necessities. - The relative mildness of post-operative sequels, regarding the extra serous form of this way. The use of this access should allow to widden the surgical informations relative to the dorso-lumbar articulation.


A model for chromatin sub-structure incorporating symmetry considerations of histone oligomers. Symmetry considerations of the kind of structures which can be generated when dimers of histones f2al-f3 and f2a2-f2b interact lead to the following conclusions: chromatin subunits based on closed-shell structures give rise to discrete, non-interacting nucleoprotein subunits with the histones arranged at random along the DNA chain; open structures based on infinite helices give rise to highly ordered, regular arrangements of dimers. A model is proposed in which helical polymers of f2al-f3 and f2b-f2a2 form a central core with the DNA helically arranged around it. The helical repeat contains 9.6 turns of B-form DNA and one molecule each of f2al, f2a2, f2b, f3 and f1. The pitch of the helix is 53Angstrom and the other diameter 130Angstrom. The protein molecular repeat is 106Angstrom.


Preparation and separation of d(pT)-10-n oligonucleotides. A series of oligomers having the general formula d(pT)-10-n, n varying from 2 to 20, has been prepared by enzymatic joining of d(pT)-10, annealed on poly dA, employing T-4 polynucleotide ligase. The oligomers could be separated on 8 or 12% polyacrylamide gels. Such oligomers may prove useful as molecular weight markers and initiators for various polymerases.


The use of s-2-cyanoethyl phosphorothioate in the preparation of oligo 5'-deoxy-5'-thiothymidylates. An improvement of our strategy for the stepwise synthesis of oligo 5'-deoxy-5'-thiodeoxyribonucleotides [Chladek and Nagyvary (1972) J. Amer. Chem. Soc. 94, 2079] involves the use of 5'-O-tosylthymidine 3'-S-2-cyanoethyl phosphorothioate. The displacement of the tosylate by thymidine 3'-phosphorothioate and subsequent alkaline deblocking afforded the dinucleotide (Tps)2. The process of displacement and deblocking was repeated three more times at an average yield of 30 percent per step. The corresponding bifunctional derivative of deoxyadenosine was found much less reactive and practically unsuitable for repeated chain elongation. The ORD and CD spectra of the analogs are similar to those of the natural oligonucleotides.


Studies on the structure of replicative intermediates in bacteriophage M13 single stranded DNA synthesis. Pulse-labeled replicative intermediates in M 13 single stranded DNA synthesis can be separated by dye-buoyant density centrifugation into two major fractions: Supercoiled molecules (RI I) containing viral strands of more than one genome length, and "relaxed" molecules (RI II) with labeled DNA chains shorter than unit length. It is postulated that RI II molecules might be formed in vivo by site-specific nicking of RF I molecules.


A possible role of the 5' terminal sequence of 16S ribosomal RNA in the recognition of initiation sequences for protein synthesis. Extensive complementarity is found between the 5' end of 16S ribosomal RNA and protein synthesis initiation sites of bacteriophage RNA. Hybrids can be constructed from base sequences of 16S-RNA and two initiation regions on phage RNA. A model is proposed for the involvement of 16S-RNA in the unfolding of hairpin loops containing the initiation codon AUG.


Polynucleotide fragments from the 28S ribosomal RNA of insects. If RNA is extracted from the ribosomes which had been isolated from frozen-thawed tissue of Galleria mellonella, the 28 S RNA, when heated or treated with urea, dissociates into seven different species of polynucleotide fragments. They were designated as R1, R2, R3, R4, R5, R6, and R7, whose molecular weights were estimated to be 1.15x10-6, 0.75x10-6, 0.55x10-6, 0.40x10-6, 0.30x10-6, 0.25x10-6, 0.20x10-6 daltons, respectively. It is likely that R1 and R5 arise from a single nick in original 38 S rRNA. Experiments with isolated R1 suggest that it is made up of a hydrogen-bonded complex of R2 and R4. R5 is a complex of R6 and an unidentified species, X. It is suggested that these fragments result from nicks which are introduced, secondarily, in the phosphodiester bonds by an endogenous endonuclease(s). Since the secondary nicks are limited in number and located in specific points of the molecule, it appears that the reaction is quite specific. It was also shown that the 28 S aphid RNA, which apparently lacks the primary nick, is susceptible to nicking.


[Quantitative analysis of polypeptides by disc electrophoresis in pore gradients]. The quantitation of components in a complex mixture of proteins of Pseudomonas denitrificans separated by disc-electrophoresis in the linear pore gradient of polyacrylamide gel was studied. The problem of a poor staining of proteins in the presence of a detergent was solved by a high resolving power photography. A linear correlation between the amount of protein in the fraction and the intensity of amide black staining was extablished. In comparison to the wild type of P. denitrificans the aldehyde negative mutant showed significant changes in protein fractions amounting to 30% of total protein, according to the densitometrical data. It is suggested that the changes are related to the protein migration in fractions rather than to an additional synthesis in different protein fractions.


[Determination of the total quantity of carbohydrates in dried yeast]. Different colourimetric methods for measuring carbohydrates in yeast have been compared.  A method using 5% phenol aqueous solution in the presence of concentrated sulphuric acid has been developed to quantitate carbohydrates.  The method has been described as applied to an analysis of dry yeast.


[Selection of fungi--alkaloid producers--by the method of thin layer chromatography]. Microscopical fungi of the Penicillium genus were studied by thin-layer chromatography to select potential producers of alkaloids.  A procedure for selection was developed to include microbial cultivation, extraction and conduct of qualitative and quantitative reactions on thin-layer chromatograms with routine alkaloid reagents.  The cultures furnishing these reactions were selected for futher isolation and identification of products.


[Use of the SF-4 spectrophotometer as a universal densitometer during column chromatography and gel filtration]. The paper describes an installation consisting of an SF-4 (SF-4a) spectrophotometer equipped with a flow cuvette and of an ink recorder.  The installation allows registration of biological substances during their fractionation on columns.


[Use of a freeze-drief culture of Leuconostoc mesenteroides for the synthesis of dextran]. The influence of a prolonged storage of the freeze-dried culture Leuconostoc mesenteroides strain SF-4 on its capacity for the dextrane synthesis has been studied. The culture has maintained its normal viability for 12 years (the observation time) without changes in the cell morphology and capacity for the dextrane synthesis. The structure of dextrane synthesized by the revived culture L. mesenteroides has been similar to that of dextrane synthesized by the culture L. mesenteroides preserved via passages.


[Phosphorus metabolism in yeasts, oxidizing hydrocarbons during active aeration of the medium]. Variations in the phosphorus and nitrogen assimilation by hydrocarbon oxidizing yeast C. guilliermondii K-5 were followed upon an active aeration of the medium  Changes in the phosphate forms of the acid-soluble and acid-insoluble fractions were found.  By the end of the lag-phase the content of all phosphate forms, except stable polyphosphates, increased.  At the onset of the active budding the content of labile phosphates, belonging to acid-soluble phosphates, increased.  As the culture developed, the content of these forms decreased and increased slightly in the growth phase with a negative acceleration.  Acid-insoluble polyphosphates were accumulated in the culture as long as it grew.  In the growth phase with a negative acceleration these polyphosphates were hydrolyzed.  This was responsible for an increment of all phosphates in the acid-soluble fraction.  The same pattern occurred in the dying phase of the culture.


[Methods of increasing the activity of extracellular esterase, beta-fructofuranosidase and proteases of wine yeast]. Upon regular fermentation changes in the activity of the enzymes esterase, beta-fructofuranosidase and protease of the yeast Saccharomyces mini of the Parkent I race were examined.  The maximum activity of the enzymes occurred in the stationary phase of the yeast growth.  An increase in the activity of the above enzymes was shown possible during a prolonged stabilization of the stationary conditions in the process of a continuous chemostat cultivation of wine yeast.


[Effect of temperature on the activity of enzymes hydrolyzing non-starch polysaccharides]. The temperature optimum and thermal stability of endo-beta-glucanase, beta-glucanase, pentosanase and cellobiase from the enzymic preparations used in the brewing industry to treat high amounts of unmalted barley--citorosemin Px, citorosemin P10x, amylosubtilin G10x and brew-n-zyme--were measured.  In order to determine the termerature optimum the enzyme activity was assayed under standard conditions.  It was found that the temperature optimum for endo-beta-glucanase of all preparations was 50 degrees, for beta-glucanase and pentosanase--40 degrees, for cellobiase--70 degrees C.  The thermal stability of endo-beta-glucanase from amylosubtilin G10x and brew-n-zyme in the aqueous solution was higher than that from ditorosemin Px and P10x.  The thermal stability of the latter preparations noticeably increased in the presence of substrates.


[Synthesis of mucolytic enzymes by thermophilic strains of microorganisms]. The paper presents data on the accumulation of biomass and the rate of enzyme synthesis on nutrient media of different composition by two thermophilic microorganisms isolated from soil--Bacterium sp. 1641 and Actinomyces sp. 10.


[Effect of cyclic compounds on pigment formation in Aspergillus niger cultures]. The mycelial pigment os Asp. niger VP has been fractionated into four fractions ehose solubility is similar to melanin pigments obtained from other sources.  The addition of pyrocatechol, L-aspartic, benzoic, kojic and salicylic acids to the liquid Capek medium stimulates the fungal growth but diminishes the yield of fractions of the melanin pigment from the mycelium.  Cinnamic acid does not influence the growth but also decreases the yield of the pigment.  DL-tyrosine stimulates the fungal growth and produces no influence on the total yield of fractions 2, 3 and 4 from the mycelial pigment.  All the cyclic compounds enhance the pigmentation of the culture liquid and give rise to the formation of fractions 2 and 3 of the melanin pigment.  This latter constitutes a substantial portion of the dry matter of the fungal cell.  The pigment content in the mycelium is much higher than that in the culture liquid of the corresponding culture.


[Effect of yeast disintegration conditions on protein properties]. The influence of the cellular treatment with the aid of a vibrocolloidal mill on the model proteins--albumin and yeast glutelin was studied.  The treatment of the model proteins in methylene chloride using the vibrocolloidal mill did not change the protein solubility.  By analytical centrifugation, electrophoresis in polyacrylamide gel and gel filtration it was shown that these proteins underwent no destruction.


[Study of the fractional composition of protein substances in gluten by the gel-chromatographic method]. The fractional composition of protein substances of the gluten was studied by gel chromatography.  The gluten proteins from the mormal wheat flour and eurygaster damaged wheat flour were compared.  The content of the high molicular weight fraction was measured for the gluten of weak and normal flour.  The fractional composition of gliadin from the normal and weak flour was investigated.  The molecular weight of gliadin from eurygaster damaged grain was shown to change during autolysis.


[Detection of retinaldehyde in mouse liver]. Vitamin A metabolites were studied in the liver of white mice, hamsters, guinea-pigs and rabbits after a single administration of retinyl acetate per os.  In addition to retinol and retinyl palmitate, the mouse showed retinaldehyde which accumulated in the liver in the maximum concentration 3 hours later after the vitamin administration.  Retinaldehyde isolated on aluminium oxide by means of TCA was examined with respect to absorption spectra in the UV-light, NaBH4 reduction with subsequent isolation of anhydrovitamin A from the reduced product as well as to absorption peaks in reactions with SbCl3 and thiobarbituric acid.


[Fatty acid composition of polar lipid fractions of ripening wheat]. By thin-layer chromatography on silica gel L (Czechoslovakia) monoglycerides, diglycerides, free fatty acids and triglycerides were isolated from free lipids of ripeining wheat.  The composition of free fatty acids of these fractions was studied by gas-liquid chromatography.  The following fatty acids were identified and quantified: C10:0; C12:0; 14:0; C14:1; X15:0; C16:0; C17:0; C18:1; C18:2; C18:3; C20:09  Linoleic, palmitnic, oleic, stearic and linolenic acids accured in large quantities.  The wheat ripeinig was followed by a decrease in the sum total of saturated and an increase of the sum total of unsaturated fatty acids.  During ripening the content of biologically important linoleic acid increased: in monoglycerides from 42.6 to 19.5%, diglycerides from 51.0 to 62.4%, in free fatty acids from 48.8 to 51.0% and in triglycerides from 54.5 to 61.1%, whereas the content of palmitinic and linolenic acids diminished.


[Isolation and properties of saponins from rhizomes of Dioscorea deltoidea Wall]. From the rhizome D. deltoidea a new trisaccharide of diosgenine has been isolated.  This compound is diosgenine-3 (alpha-L-rhamnopyranosyl (1-->2gl)-beta-D-glucopyranosyl-(1-->4 gl)-beta-D-glucopyranoside.  This trisaccharide has been termed deltonine.  The rhizome D. deltoidea has also displayed furostanolic tetrasaccharide which is a mixture of delta5-furostene-3beta, 22, 26-triol-3beta-deltotrioside-26beta-D-glucopyranoside and its alkoxyderivative.  This tetrasaccharide has been termed deltoside.  The rhizome has also small quantities of diosgenine-3-beta-D-glucopyranosyl (1-->4)-beta-D-glucopyranoside.


[Correlated interrelationships between the concentrations of chorionic gonadotropin, progesterone and estriol in normal pregnancy]. A study was made of 151 healthy pregnant women at periods of from 4 to 41 weeks of pregnancy. There was revealed no correlation between the level of excretion of the CG and estriol, and also of the CG and pregnandiol from the 7th to the 41st weeks of pregnancy; consequently CG played no role in the regulation of steroidogenesis in the placenta. Between the levels of CH and progesterone in the blood there existed a significant positive association from the 4th to the 7th week of pregnancy; this correlation disappeared from the 8th week. Consequently, the CG retained its steroidogenic action on the corpus luteum of pregnancy. The activity of the corpus luteum in respect to progesterone production decreased considerably as soon as the 7th week of pregnancy.


[The functional state of the sympathetic-adrenal and pituitary-adrenocortical systems during chronic neuro-emotional stress]. A study was made of the function of the sympatho-adrenal and hypophysio-adrenocortical systems by the indices of catecholamine and corticosteroid urinary excretion in the dispatchers of railway lines during the day and night, at rest and shift work associated with the nervous-emotional strain.  The working activity both during the day and night produced a 1.5--3-fold increase in catecholamine and corticosteroid excretion.  Night work was accompanied by disturbance of the normal circadian variations in the activity of the systems under study  After work the function of the hypophyseo-adrenocortical system was restored on the second day of rest; as the the sympathico-adrenal system function--it failed to become completely normalized during the mentioned time.


[Clinico-roentgenologic studies in toxoplasmosis patients with various endocrine diseases]. The authors present clinical and roentgenological characteristics of toxoplasmosis revealed in 46 of 128 patients with neuro-endocrine form of diencephalic syndrome, cerebro-hypophyseal nanism and hypogenitalism, examined for toxoplasmosis.  Congenital toxoplasmosis was found in 29 and chronic acquired--in 17 cases.  It was noted that the clinical picture of both the congenital and of the chronic acquired toxoplasmosis in patients with endocrine diseases was varied due to affection of different organs and systems of the organism.  Of great significance in the complex clinico-laboratory diagnosis of congenital and chronic acquired toxoplasmosis was the roentgenological method of study.  Roentgenological changes in the skull of the patients with endocrine diseases and toxoplasmosis were expressed in the presence of calcifications of various shape and size (from 2 mm to 2 cm), calcification of the dura mater in the frontal portion and the area of the sella turcica, and hyperostosis.  Diagnosis of congenital and chronic acquired toxoplasmosis in patients with endocrine disturbances should be based on the results of complex clinico-roentgenological and laboratory studies.


Insulin effect on creatine transport in skelatal muscle (38464). Isulin is shown to directly enhance both the rate of transport and the uptake of cretine in vitro in isolated rat skeletal muscle. This action of the hormone on creatine transport is similar to that reported for the transport of some amino acids and sugars.


The inhibition of macrophage migration inhibtory factor (38485). Analogs of EACA were capable of inhibiting the in vitro activity of macrophage migration  inhibitory factor (MIF). The most active analog of EACA  in terms of MIF inhibition had four methyl groups separating an acetylated amino group from a free carboxyl group. This compound, acetylated 5-amino valeric acid, was capable of inhibiting completely MIF activity in vitro at a concentration of less than 10-6 M without demonstrating any appreciable antitryptic activity, even at 10-3 M. Antitryptically active EACA did not inhibit MIF except at very high concentrations (10-2M). Further, the most purified preparations of MIF obtained from aqueous extracts of thymus that we have studied contained no significant proteolytic activity upon denatured hemoglobin at pH 3-8. Therefore, we do not correlate anti-tryptic with anti-MIF activity in vitro.


[The dynamics of changes in the concentration of luteinizing hormone in the pituitary and the blood during postnatal development of male rats]. The authors describe a specific and sensitive biological method of determination of luteinizing hormone (LH).  There was shown a linear relationship between the LH dose gradient and the amount of testosterone determined in the blood flowing from the testes.  Sensitivity of the method--5 nanogram/ml.  Linear dependence--5--45 nanogram/ml.  Dynamics of the changes in the LH concentration in the hypophysis and the blood of male rats in the course of postnatal development--from the 1st to the 43rd day was studied.  There were distinguished 6 peaks of increase in the LH content in the hypophysis: on the 4th, 7th, 19th, 27th, 37th and the 43rd day after birth; blood LH concentration persisted at a relatively constant level--within the range of 1.33--4.39 gamma per cent.  No LH was revealed in the blood on the 4th, 19th, and 24th days after birth.


A simple method for long-term drug infusion in mice: evaluation of guanazole as a model (38488). A simplified technique for iv infusion in unrestricted DBA/2-J inbred mice has been described. The method, which involves direct cannulation of the tail vein with polyethylene tubing, is suitable for routine use. Guanazole, an antileukemic agent with a short plasma half-life, was evaluated as a model compound. After administration for 47 hr at the rate  of 0.3  ml/hr, guanazole (30 mg/ml) caused a marked inhibition of incorporation of 14 C-uridine, administered 15 min before sacrifice, primarily into DNA of spleen, thymus and bone marrow in decreasing order. Inhibition of incorporation into RNA was less marked but followed a similar pattern. The effects on the incorporation of uridine in nucleic acids of kidney, heart and brain were minimal. Increased incorporations into RNA and DNA occurred in liver. The data for the hemopoietic and lymphoid organs, namely spleen, thymus and marrow, are consistent with the reported immunosuppressive and mylelosuppressive effects of the drug and also with the inhibition of ribonucleoside diphosphate reducaste by guanazole.


Plasma abnormal prothrombin and microsomal prothrombin precursor in various species (38492). Abnormal, biologically inactive forms of prothrombin have previously been shown to appear in the plasma of cows or humans given coumarin anticoagulants. We have previously shown that a protein with similar properties increases in the liver of rats given these vitamin K antagonists, and have postulated that this protein represents the liver precursor to plasma prothrombin. Eight species, rats, mice, guinea pigs, hamsters, rabbits, calves, dogs, and chickens, have now been surveyed for both plasma abnormal prothrombin and liver precursor activity. Large amounts of plasma abnormal prothrombin were found in the bovine, substantial amounts were seen in the chick, and small amounts in rat and mouse plasma. With the exception of the bovine, all anticoagulant treated animals showed elevated levels of liver precursor activity in microsomal preparations. The relationship of these observations to the mechanism of action of vitamin K is discussed.


[Pyruvate kinase isoenzymes in the kidneys of rabbits with insular insufficiency]. Two isoenzymes of pyruvate kinase--PK-1 and PK-2 were obtained from the cortical layer of rabbit kidney by the method of chromatography on DEAE-cellulose.  Starvation of rabbits for 10--16 days and alloxan diabetes produced no significant changes in the specific activity of PK in the soluble fraction obtained from the cortical layer of rabbit kidney.  However, there were significant shifts in the isoenzymatic spectrum of the PK of the kidneys in rabbits with alloxan diabetes: the activity of the PK-1 increased considerably and significantly, and the isoenzyme PK-2 disappeared almost completely.


Postnantal cerebellar hypoplasia and dysfunction following methylazoxymethanol acetate treatment (38495). Swiss albino mice were injected postnatally with 0.05 ul of MAM-ac/g body weight. The mice were sacrificed at 0, 5,10, 15,20, and 25 days. Cerebellar, whole brain and body weights were determined. The treated mice generally showed smaller body weights reflecting the general toxicity of MAM-ac. There was no statistical difference between the whole brain weights of the two groups, when the loss of cerebellar weight was taken into account. Significant differences between the cerebellar weights of control and treated animals were shown at each sacrifice time. It is the conclusion of this study that those differences in weight reflect the destruction induced by MAM-ac during the first 5 days of postnatal life and are not due to a continued degeneration. As for general developmental and behavioral dysfunctions,the treated mice showed delayed eye opening and fur appearance, and by day 25, exhibited a tremorous altered gait.


[Changes in the subcommissural organ of white rats with age]. Histological and histochemical methods were applied to the study of 82 male rats of different age (newborn, 1-, 2-, 5-, and 17-month-old).  Microstructure of the subcomissural organ (SCO) was investigated; the height of its ependyma was measured.  In rats at all the age groups studied ependymocytes secreted substances of glucoproteid nature; a moderate content of RNA persisted in the cells, and also a high activity of non-specific esterases.  Secretory activity of ependymocytes increased with the growth of the animals, remaining high in adult rats; it  fell in the old animals.  Age changes of the SCO consisted in the reduction of the height of the ependyma, of the number of cell layers in it and atrophy of the villi.


[The reaction of the supraoptic nucleus of the hypothalamus and diuresis during thyroid gland restitution following discontinuation of 6-methylthiouracil]. There is a marked reduction of diuresis (revealed by water load) during the action of 6-methylthiouracil (MTU). In the course of the thyroid gland restitution (after the discontinuance of the 6-MTU action) the diuresis at first becomes intensified and then it repeatedly either becomes diminished or enhanced. Secretory activity of the cells of the supraoptic nucleus of the anterior hypothalamus also becomes alternately enhanced and diminished. Dynamics of the shifts in this activity failed to correlate with the "ricochet" enhancement of the thyrotropic function of the hypophysis, which occurred on the 11th restitution day and corresponded to the "ricochet" enhancement of iodine consumption by the thyroid gland. Thus, there was no association between the state of the cells of the supraoptic nucleus and the changes in the thyrotropic function of the hypophysis.


[The function of thyroid glands subjected to deep freezing (--196 degrees)]. The function of the thyroid gland transplanted after being frozen to --196 degrees C was studied in experiments on rats.  The gland was transplanted to thyroidectomized animals.  Glands frozen without the use of cryoprotective agents and also in the presence of a cryoprotector--polyethyleneoxide with a mol. wt. of 400 (PEO-400) were used.  Besides, a study was made of the effect of different rates of chilling on the thyroid gland.  In assessment of the gland function a determination was made of tissue respiration, of I-131 consumption, and blood thyroid hormone content.  To assess the cryoprotective effect of PEO-400 and for the choice of its optimal concentration the NMR method and roentgenostructural analysis werea applied.  The thyroid gland proved to take and to retain its capacity to hormone formation after its freezing to the temperature of --196 degrees C according to a special program in the presence of PEO-400.


Cell surface: transfer of cellular adhesive properties from cell to cell by induced membrand altrations (38496). Lymphocytes formed aggregates around Sepharose beads to which Concanavalin A had been coupled. Many of these aggregates consisted of multilayers of cells. The cell-cell interactions distal to the beads appeared to be a result of an induced membrane change at the cell-Sepharose bead interface.


Colon cancer induction in mice by intrarectal instillation of N-methylnitosorurea (38498). The same total dose of 9 mg of N-methylintrosourea (MNU) was given intracetally to two groups of ICR/Ha mice by  by varing the dose rate and frequency. Thirty individual doses of 0.3 mg each three times per week induced large bowel neoplasms with high incidence after the 17th week, compared with six doses of  1.5 mg each three times per week which also led to leukemia in all mice until the  18th week. Small adenomatous nodules of the lung appeared in almost all mice of both groups. In the large intestine, adenocarcinomas and adenomas were found in the distal colon and rectum, and squamous cell carcinomas at the anal canal. Intrarectal instillation of carcinogenic chemicals such as MNU to mice is a good method to develop animal models for colon carcinogenesis,and also other target organs.


The inhibitory effect of theophylline on the incorporation of 3H-deoxycytidine and 3H-thymidine into thymocyte DNA. In short term cultures of rat thymic lymphocytes, theophylline caused an early inhibition of incorporation of 3-H deoxycytidine into DNA without influencing the incorporation of 3-H-thymidine. Over a 4-hr incubation period, the inhibitory effect of theophylline on 3-H-deoxycytidine uptake into DNA remained at approximately 40%, while the suppression of 3-H-thymidine uptake increased to 20%. The results indicate that since there is a difference in the effect of the ophylline on the incorporation of 3-H-deoxycytidine and 3-H-thymidine into the DNA of thymus lymphocytes, inhibition of uptake of these deoxynucleosides by theophylline does not necessarily reflect inhibition of DNA synthesis or cell turnover.


Radioimmunoassay of serum pancreatic amylase in normal and pancreatectomized pigs (38504). A double antibody radioimmunoassay has been developed that is capable of assaying and discriminating small amounts of pancreatic amylase even in the presence of amylase isoenzymes. Assays on adult pigs indicate a mean serum concentration of pancreatic amylase of 2.4mug/ml. To date, no other technique can offer such a discrimination of the pancreatic amylase in the circulation. Following pancreatectomy, the amount of radioimmunoassayable amylase in the circulation disappeared within 48 hr. This was reflected by a simultaneous decline in the serum amylase enzyme activity. Within 48 hr after pancreatectomy, the serum amylase enzyme activity had declined 60%. Thus, in pigs, the pancreas contributes significantly to the circulating amylase levels.


Myocardial extraction of labeled long-chain fatty acid analogs (38509). The single circulation myocardial extraction of terminally iodinated hexadecenoic acid (77 plus or minus 11.0%) is approximately two times the extraction of 18 carbon fatty acids (33 plus or minus 5.2%) prepared by iodination of double bonds. The results compare favorably with natural 28 carbon steraic (70 plus or minus 7.5%) and oleic (61 plus or minus 7.8%) acids labeled with carbon-11 in the carboxyl group. It is concluded that terminally radioiodinated long chain fatty acids can be used as substitues for in vivo investigations of fatty acid distribution and in particular may be useful as a regional mycardial blood flow indicator.


Infantile auditory exposure and unusual response to antipsychiotic drugs (38510). Reserpine and prochlorperazine were administered in separate experiments to adult CAW:CF1 mice and to adult LVG:LAK hamsters that had recovered from audiosensitization induced by 30 sec of doorbell sound during a critical period of infantile development. In contrast to controls that showed tranquilization in response to these drugs, the previously audiosensitized animals o both species responded with a high incidence of convulsive seizures. The proconvulsant effect of reserpine and prochlorperazine in previously audiosensitized mice was present one hour after drug administration, but had subsided 20 hr post-administration. The proconvulsant effect of reserpine in previously audiosensitized mice was shown to be dose-dependent. The proconvulsant effect of reserpine in previously sensitized hamsters was present 100 days after reserpine and prochlorperazine are poorly understood, possible mechanisms are discussed. Environmental noise during early inantile development appears to have significant residual effects persisting into adult life. This study has shown that idiosyncratic responses to antipsychotic drugs in adult laboratory animals can result from infantile auditory exposure, and it is speculated that human idiosyncrasies to psychoactive drugs may be similarly based.


Prostaglandin administration to pregnant rats: effects on pituitary-target gland systems of mother, fetus and neonate (38512). Acute administration of PGE-1 in graded doses (0.25-1.0 mg) to pregnant rats in late gestation (21st day) induced significant release of TSH, prolactin and LH from the maternal, pituitary. Plasma levels of PRL and TSH were elevated (three- to fivefold) in cesarean sectioned mothers given 4-5 sc injections of PGE-1; higher doses also stimulated LH release. Comparable increases in blood TSH and PRL levels were also found in their newborn but no indication of enhanced hormone release from the fetal hypophysis was noted. Histologic alterations were observed in the ovary (luteal cell hypertrophy, cytopasmic clearing, nuclear condensation, sinusoidal distension) of mothers receiving PGE-1 treatment. Thyroidal radioiodine accumulation in mother, fetus and neonate were usually decreased whereas thyroid: blood radioactivity ratios were consistently incrased. It is concluded that PGE-1 treatment of th pregnant rat near term stimulates release of hormones from the pituitary in mothers (TSH, LH, PRL) and in their newborn (TSH, PRL). The results also strongly suggest that PGE-1 administration may induce morphologic and functional changes in target endocrines (ovary, thyroid) by direct and separate actions.


Functional anatomy of the testicular vascular pedicle in the rhesus monkey: evidence  for a local testosterone concentrating mechanism (38513). The detailed anatomy of arteries and veins in the testicular pedicle of the rhesus monkey, with special emphasis on an area of extensive surface contact between these vessels in the spermatic cord, is described. The mean plasma testosterone concentration in blood from the testicular artery was significantly greater than the mean for samples collected simultaneously from the contralateral femoral artery in 11 monkeys. These observations are interpreted as supportive of the hypothesis that a hormone concentrating mechanism involving the local transfer of testoterone between the vessels of the pampiniform plexus and the spermatic artery exists in the male-rhesus monkey.


Arachidonic acid and bocine corpus luteum function (38514). Injections of arachidonic acid directly into the corpora lutea of normal cattle at the 12th or 13th day of the estrous cycle resulted in (a) a decline in jugular vein plasma progesterone levels from an average of 6 ng/ml to 2.5 ng/ml (p smaller than0.05), (b) an immediate rise in PGF levels in ovarian venous plasma, and (c) a sharp rise in jugular vein plasma estrogen levels. Jugular plasma estrogen peaks were associated with each ovarian vein PGF Peak in each animal; jugular plasma LH levels did not change. These results show that the bovine ovary can convert arachidonic acid to PGF and that arachidonic acid administered directly into the corpus luteum results in partial regression of the corpus luteum.PGF appears to stimulate estrogen production by the ovary in the absence of measurable changes of plasma LH.


Dextran potentiation of the canine lymphocyte response to plant mitogens (38515). Peripheral blood lymphocytes from Beagle dogs were separated using a dextran sedimentation technique. Lymphocyte cultures were stimulated by the plant mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM), both in the presence of dextran and after dextran had been removed from the medium. It was found that dextran acted synergistically with both PHA and PWN and greatly potentiated the mitogenic response of the lymphocytes. The routine use of dextran in separating blood lymphocytes for culture purposes should be reevaluated in light of these findings.


Vasoactive intestinal polypoptide: inactivation in liver and potentiation in lung of anesthetized dogs (384699). The role of the liver and the lung in the inactivation or potentiation of the biological activity of the vasoactive intestinal polypeptide (VIP) was examined in five anesthetized dogs. Infusions of the peptide were made into the right ventricle, the left ventricle, and the portal vein. Each animal received 4 doses, ranging from 0.29 to 2.23 mug/kg. Systemic arterial blood pressure, tidal volume, breathing frequency, and minute ventilation were continually monitored. The biological effects of the peptide were measured in terms of (a) the fall in arterial blood pressure; and (b) respiratory stimulation. Infusions of the peptide into the portal vein produced either no effect or significantly weaker effects (p smaller than 0.01) than infusions into the right  ventricle. The latter infusions were moderately more potent (p smaller than 0.05) than infusions into the left ventricle VIP thus appears to be effectively inactivated during passage through the liver. The apparent increase in biological potency of the peptide during its passage through the lung may be attributable to the release of additional vasodilator substances, or to further activation of the peptide.


The disposition of dapsone and monoacetyldapsone in the dog (38516). Four female dogs receiving 1.0 mg dapsone (DDS)/kg iv exhibited logarithmic decline of plasma levels of DDS with a mean half-time of disappearance (T-1/2 of 11.7 hr. No evidence of acetylation of DDS to monoacetyl DDS (MADDS) was found. An equimolar dose of MADDS was deacetylated slowly to DDS by the same dogs. The mean T 1/2 of MADDS was 6.5 hr, significantly less than that of DDS. In 2-hr plasma samples after these doses of drugs, protein-binding of DDS and MADDS averaged 71 and 84%, respectively. Tests of protein-binding of the two drugs in vitro confirmed the observations in vivo.


Neutral amino acid transport in cultivated human skin fibrovlasts (38521). The accumulation of neutral amino acids was studied in cultivated human skin fibroblasts. Transport was blocked by sulfhydryl binding agents, but proceeded without inhibition in the presence of metabolic blocking agents. Both sodium dependent and sodium independent compononets of neutral amino acid accumulation were found. The sodium dependent component preferentially transports short chain amino acids, while the sodium independent system transports long chain amino acids. These components operate simultaneously and with overlap of substrate specificity. Both may function as parts of a single neutral amino acid transport system.


Serum hexosaminidase activity in man under simulated diving conditions (38523). The activities of serum hexosaminidases from human divers before, during and after simulated dives was measured. Decreases in hexosaminidase A activities were observed in the 1000 FSW saturation dive, whereas an increase in hexosaminidase A activity was observed during decompression in the subsaturation dives at 400 FSW and 650 FSW.


Induction of extra nephrons in unilaterally nephrectomized immature rats (38525). The normal number of glomeruli per kidney in the rat rises from about 10-4 at birth to approximately 35 times 10-3 at 50 days of age. When one kidney is removed at birth the remaining one produces an average of 63% more nephrons than normal by 70 days. Unilateral nephrectomy of successively older rats results in progressively less augmentation of the nephron complement in the remaining kidney up to 50 days, beyond which age the kidney loses its ability to  produce new nephrons.


Human adipose tissue lipoprotein lipase: comparison of assay methods and expressions of activity. There was a positive correlation in normal man between heparin releasable lipoprotein lipase and lipoprotein lipase of ammonium hydroxide homongenate of acetoneether powder in adipose tissue. Heparin releasable as lipoprotein lipase activity was about twice as high as the enzymatic activity in acetone powder, even though 40-70% of the original activity remained in the tissue after incubation with heparin. This might indicate that activation of the enzyme is associated with its release by heparin from tissue. The lipoprotein lipase activity per unit weight and per fat cell were affected differently by obesity: In obese subjects lipoprotein lipase per unit weight was propotionally lower than the activity per fat  cell. The expression of activity per fat cell appears to avoid the effect of obesity, and hence increased fat cell size, on values obtained.


Increased hypothalamic norepinephrine in genetically hypertensive rats following administration of diphenylhydantoin (38407). DPH administration to GH rats caused changes in NE concentration in the hypothalamus, cerebellum and medial lower brainstem which resulted in circadian differences in the effect of this drug on the catecholamine. These effects have not been reported previously. Further investigations on the effect of DPH on neurotransmitters are fully warranted.


Chemotactic deactivation of human eosinophils by the eosinophil chemotactic factor of anaphylaxis (38527). Purified human eosinophils demonstrate diminished chemotactic responsiveness (deactivation) after incubation with the eosinophil chemotactic factor of anaphylaxis (ECF-A). The deactivation is rapid and selective in that ECF-A deactivated human eosinophils more markedly than neutrophilic or mononuclear leukocytes. The eosinophil can also be deactivated by C5a which is eosinophilotactic, and there is cross deactivation between C5a and ECF-A. Deactivation may be an important physiologic control mechanism enabling the eosinophil to remain at sites of ECF-A release in order to manifest its regulatory functions in immediate hypersensitivity reactions.


Development of thyroidal responsiveness to  estrogen in the maturing rat (38471). The incidence of thyroid disorders around the time of puberty is frequent in human females. The  influence of estrogen on thyroid function during this period has been controversial. Female rats hypophysectomized at 21, 30 or 50 days of age were treated with either 17beta-estradiol (E-2) or TSH or a mixture of E-2 and TSH. Determinations were then made of thyrodial 131I-uptake, organic 131I, and 131I excretory patterns. In 21-day old animals, E-2 alone had no effect on thyroidal 131 I uptake, whereas in 30-day or older animals E-2 significantly increased 131I uptake. TSH or TSH-E-2 combinations markedly increased 131I uptake in both groups. Thyroidal 131I was shown to be almost exclusively protein-bound in each instance. No difference was observed between 21 and 30-day old rats with respect to 131I excretory patterns,except for decreased urinary output in the TSH-E-2 groups; this decrease, however, appeared to be partially attributable to an increased thyroidal uptake of iodine in these animals. The results suggest that the thyroid gland becomes responsive to estrogen only at or around the time of puberty.


Hormone and glucose responses to serial cardiac puncture in rats (38465). Serial, apparently basal radio-immunoassayable plasma insulin and growth-hormone values were obtained when fast-knock down ether anesthesia was used. Radioimmunoassayable prolactin was elevated at the second, third, and fourth bleedings but cause no apparent increase in circulating insulin levels. The elevation in plasma glucose may also have been a transient effect of sympathetic stimulation which simultaneous inhibited insulin release.