The Hurler syndrome: treatment of cultured Hurler fibroblasts with normal human serum. Prolonged replacement of fetal calf serum by normal human serum for the enrichment of medium during tissue culture of Hurler fibroblasts resulted in increased acid mucopolysaccharides in the cells and in the medium. The predominant intracellular mucopolysaccharide had the characteristics of dermatan sulfate when Hurler cells were treated with either serum. Normal human serum contains a nonspecific coreective factor capable of augmenting the loss of 35SO4-AMPS from Hurler cells, but not from normal cells. Fetal calf serum and Hurler serum have similar corrective factor activity for labeled Hurler cells. The corrective factor activity of all three sera was recovered from reconstituted dialyzed ammonium sulfate precipitates. The corrective factor of normal human serum did not increase degradation of mucopolysaccharide, but increased secretion of macromolecular and large oligosaccharide components. Failure of the corrective factor of normal human serum to effectively decrease the dermatan sulfate content of Hurler cells during prolonged exposure may be a quantitative phenomenon due partly to the brief duration of corrective factor activity and partly to increased synthesis of mucopolysaccharide.


A comparative study of the effect of some steroid hormones on the response of rats to other drugs. The effect of a series of steroid hormones on the pentetrazol convulsing action, hexobarbital narcotic action and hepatic drug metabolizing enzyme activities was determined in rats. All steroid compounds used antagonized the pentetrazol effect: the most potent was cortisone and the least potent testosterone. Glucocorticoids and androgens shortened the hexobarbital sleeping time and increased the hepatic drug metabolizing enzyme activity. Estradiol exhibited the opposite effect, whereas progesterone and desoxycorticosterone did not affect these two parameters.


Radiochromatography of 5-3H-uridine derivatives found in trichloracetic and soluble fractions of mouse brain, liver, muscle and blood. Trichloracetic acid soluble fractions from the mouse brain, liver, muscle and blood were chromatographed in three solvent systems after a subcutaneous injection of 5-3H-uridine (boric acid -- ethanol -- water -- ammonium hydroxide; n-butanol -- acetic acid -- water; IM ammonium acetate -- 95% ethanol). The amount of uridine converted to uracil in the brain and blood highly prevailed over that phosphorylated to UMP. On the contrary, the amount of 3H-;uracil was small in the LIVER AND MUSCLe, the majority of 3H-uridine being converted to UMP.


The infraslow potential oscillations in developing chick embryo brain. Correlations with neuronal activity. The correlations between infraslow potential oscillations [ISPO] and EEG activity were studied in the brain hemispheres and optic lobes of chick embryos from the 15th to 21st day of incubation. 1. The ISPO of the optic lobes remained unchanged during and after peripheral optic stimulation -- not only in 17-day-old embryos (the prefunctional stage), but also in 19- and 21-day-old embryos, in which optic evoked activity in the optic tectum is already well developed. 2. The intracerebral administration of strychnine, GABA and sodium glutamate had no effect on the ISPO of the brain hemispheres in 15-day-old embryos. 3. The effect of these neurotropic drugs in 20-day-old embryos varied. Strychnine evoked concomitant activation of ISPO and the EEG, sodium glutamate simultaneously depressed both activities, while GABA inhibited EEG activity without affecting ISPO patterns. 4. These results supported our conclusion that neuronal activity plays a secondary role in the ISPO generation process in developing brain tissue.


Rat liver homogenate hydrolases splitting N-acetyl-L-tyrosine ethyl ester. Using gel filtration on Sephadex G 200, three fractions splitting N-acetyl-L-tyrosine ethyl ester (ATEE), termed I, S and II, were found in rat liver homogenate. In molecular size, electrophoretic mobility and thermolability, fractions I and II correspond to the ATEE-splitting enzymes contained in rat serum. The liver fraction S had a different surface electric charge and was relatively stable at high temperatures. Apart from ATEE, it splits certain ester and amide bonds of synthetic substrates. Purified fraction S increased vascular permeability in guinea pigs. Differential centrifugation of liver homogenate showed that fraction S and fractions I and II were localized differently in the subcellular particles.


Blood volume in inbred strain BALB/c, CBA/J and C57BL/10 mice determined by means of 59Fe-labelled red cells and 59Fe bound to transferrin. Circulating red blood cell (RBC) and plasma volume was determined in male inbred strain BALB/c, CBA/J and C57BL/10 mice by parallel use of the 59Fe-labelled RBC dilution and the dilution of 59Fe bound to transferrin. The whole blood volumes values derived from the venous haematocrit and plasma volume were about double the values calculated from the venous haematocrit and circulating RBC volume. Comparison of the two methods thus explains the marked differences in different studies of blood volume in mice and shows that correct values can be obtained only by parallel measurements of RBC and plasma volume by separate methods, or by correcting the venous haematocrit to whole body haematocrit. Combination of the labelled RBC method and the 59Fe-transferrin method showed the blood volume values in the above strains of mice to be 10.35 +/- 0.16, 7.32 +/- 0.10 and 7.94 +/- 0.15 ml/g b.w. respectively. The ratio of whole body to venous haematocrit in these strains was was 57.3 +/- 1.6%, 68.0 +/- 1.8% and 69.5 +/- 2.2%. Significant interstrain differences were demonstrated in RBC, plasma and blood volume and in the venous and whole body haematocrit and their ratio.


Specific dynamic action of a high-protein diet and its significance for thermoregulation in the golden hamster. As a result of the specific dynamic action of a high-protein diet the resting metabolism of golden hamsters within the zone of thermoneutrality is increased on a average by 40%. The specific dynamic action diminishes markedly, with declining environmental temperature. It is concluded from this results that part of the heat produced by the specific dynamic action of a high-protein diet leads to a rise in the lower critical temperature in the zone of thermoneutrality by 2 degrees C.


Involvement of biogenic amines in drug-induced aggressive pecking in chicks. Pairs of neonate chicks were administered psychoactive agents and pecks against each other were recorded during 4-hr test sessions. The first experiment assessed where drug-induced aggressive pecking could serve as a useful anti-depressant screening model. Although pecking was induced by tricyclics, d-amphetamine, and L-Dopa, ineffective agents included a MAO inhibitor (pargline) and a tricyclic indole antidepressant (iprindole). These data cast doubt on the validity of the chick pecking model as a specific antidepressant tests. A second experiment attempted to determine where different amines were involved in pecking induced by an antidepressant and a CNS stimulant. Pairs of chicks were pretreated with various doses of amine antagonists, and a standard dose of imipramine (IMI) or d-amphetamine (AMP) was administered. Haloperidol completely antagonized AMP but not IMI pecking, while phentolamine and propranolol did not modify AMP pecking, suggesting involvement of dopamine. Pecking induced by IMI was partially antagonized by a dose of methysergide ineffective in modifying AMP pecking. Neither phentolamine nor propranolol blocked IMI pecking. Serotonin was further implicated in IMI pecking in a third experiment, whether chronic PCPA pretreatment significantly decreased IMI, but not AMP pecking. These data suggest that aggressive pecking induced by AMP and IMI may be mediated by different amine systems.


[Segmental angiography of the liver with laparoscopy and electro-coagulation. Selective hepatography (author's transl)]. Segmental angiography of the liver with laparoscopy and electro-coagulation has high diagnostic value. The circulatory systems of the liver may be studied selectively or in various combinations. Morphologic lesions as well as functional disturbances of liver arteries and veins, the portal vein and to a certain degree lymph vessels can be visualized precisely. An improved indication for shunt operations and a more reliable prognosis may be achieved by direct transhepatic pressure measurements, especially within the hepatic artery and portal vein. An early diagnosis of the Budd-Chiari-Syndrome is enabled by the combined segmental veno- and portography which could not be achieved by the known techniques so far. Complications are rarely seen. In 1070 examinations there was one suspicion for bilihemia, one case of hemobilia, and one case of a subcapsular hematoma. Twice a liver lobe was perforated. There was never a permanent damage to the patient. Biochemical and nuclear medicine studies are suggested.


[37 tumors of the jejuno-ileum].

[37 tumors of the jejuno-ileum]. The present paper reports on 37 primary tumours of the jejunoileum, of which 19 malignant and 18 benign. The authors emphasize the difficulty of establishing a diagnosis before the onset of one of the dramatic complications in the evolution of tumours of the small intestine. The patients were admitted for the following complications: occlusive syndrome -- 28 cases (72.9%), peritoneal syndrome -- 6 cases (16.2%) and hemorrhagic syndrome -- 3 cases (8.1%). All the patients with a peritoneal and hemorrhagic syndrome had malignant tumours.


[Use of the excluded jejunal loop for resolution of some accidents in surgery of ulcers and the biliary tract]. The specific risks of certain procedures applied in surgery of the bile ducts and duodenal ulcers are discussed (Lehey catheterism, retrograde cholecystectomy with primary severing of the cystic duct for cholangiography). Three accidental lesions of the common bile duct were successfully solved by anastomosis of the left hepatic, right hepatic and respectively commen hepatic duct with the excluded jejunal loop by the Roux-Y method. The importance of intraoperative cholangiohepatography for established immediately the biliary areas that have to be shunted into the excluded loop, is emphasized.


[Surgical treatment of atresia of the small intestine]. Three cases of atresia of the intestine, one of which with multiple atresia of the small intestine, are reported. All three cases recovered. The surgical procedures applied for correcting atresia are discussed. In all the cases end-to-back anastomosis in an extramucous layer was performed, extramucous suture being considered as sufficiently resistant and having the advantage of not stenozing the intestinal luman. This type of suture proved efficient not only in the case of multiple atresia but also in the presence of peritonitis lesions.


[The role of continuous extension in the appearance and prevention of joint stiffness]. Based upon a six years' experience the author uphold that continuos extension with an articular suprajacent point of fixation creates a static, reciprocal pressure between the articular surfaces and exposes to articular rigidity. Continuous extension with an articular subjacent point of fixation and gradual flexion of the knee is a preventive method of great clinical value, ensuring consolidation of the fracture focus within a short interval and maintenance of the articular function.


[Our experience in the treatment of pseudarthrosis of the carpal schaphoid bone]. The present paper reports on 20 cases of old fractures and pseudoarthrosis of the carpal scaphoid operated in the Clinic of Ortopaedics and Traumatology of the "Brîncovenesc" Hospital and followed up over an 8 year period (1965--1972). The treatment, exclusively surgical, consisted in: osteosynthesis with corticospongious graft, combined with styloidectomy (9 cases); excision of the necrosed fragment and styloidectomy (7 cases); and one case each of osteosynthesis with aid of a screw, simple styloidectomy, explorative arthrotomy and arthrodesis of the wrist. The best result were obtained after osteosynthesis with styloidectomy, performed for various forms of pseudoarthrosis with moderate ischemia, and after partial scaphoidectomy for necrosis with a small proximal fragment.


[Role and value of the footprint in evaluation of the development of congenital talipes equinovarus]. The author points out the importance of the plantogram in appraising the evolution of the principal component deformities in congenital equinovarus tailipes, under treatment or not. There are two kinds of pantograms, "contact" plantogram orientative in the redressment of supination, and "necessarily contact" plantogram for the redressment of adduction.


[Limits of hemodilution in the treatment of hemorrhagic shock]. Clinical analysis of 168 cases of hemorrhagic shock of the 230 cases of hemorrhage and injuries admitted to the 2nd Surgical Clinic of Timisora between 1970 and 1973, showed that the administration of blood substitutes (crystalloid and colloid solutions) may be extended with good results in the management of hemorrhagic shock up to a hematocrit of 20%, respectively 7 g Hb. This treatment implies a careful selection of the cases, based upon objective criteria (listed in the text), so that the none administration of blood should not involve any risks. Even in the cases in which blood tranfusion is indispensable, hemodilution reduces to a great extent the amount of blood required.


[41 hepatic resections].

[41 hepatic resections]. Clinical and therapeutical aspects are discussed with reference to 41 cases of malignant and benign tumours of the liver for which various types of hepatic resections were performed. The high mortality rate (22%) and short postoperative survival (less than a year) in malignant tumours of the liver plead for limited hepatic exeresis in cancer. Hepatic exeresis in benign tumoural pathology gave better, but nevertheless restricted, immediate and late results. Hepatic scintigraphy with colloidal 198Au and 131I rose bengal proved to be useful both preoperatively for determining the quality and quantity of the intact hepatic parenchyma and for late, postoperative follow up of the hepatic regeneration process. Moderate intraoperative hypothermia was used as an adjuvant method, allowing for the approach of broader hepatic exeresis by scissural access and longer clamping of the hepatic pedicles and inferior vena cava.


[Post-caustic gastric stenosis].

[Post-caustic gastric stenosis]. Two cases of postcaustic antropyloric stenosis are reported. The lesions developed 3 and respectively 5 weeks after ingestion of the caustic substance and surgery for complete stenosis was performed 35 and 56 days after the initial accident. In both cases antropylorectomy with gastroduodenoanastomosis of the Péan-Billroth type I, in two layers, was performed. Integrity of the esophagus and good function of the anastomotic mouth, appraised by the clinical symptomatology and evolution of the radiologic aspect, showed that at least in some cases it is possible to apply the curative intervention 5-6 weeks after the accident, without a previous shunt being necessary.


[Radioclinical and morphological comparisons in non-lithiasic gallbladder diseases]. Confrontation of the clinical, radiologic and morphologic data in a lot of 274 patients operated for non-lithiasic cholecystopathies during the 1966-1972 period, led to the following conclusions: - the painful choleic syndrome whose duration and frequency increase progressively, refractory to the conservative treatment, is a basic criterion in establishing the surgical treatment; - any change in the radiologic image of the gallbladder, especially those evoking a partial or totally inefficient contractile effort are of diagnostic value, suggesting the necessity of the operation, when confirmed by a similar clinical context; - the morphologic substrate consists in inflammatory lesions (infiltrations, atrophy of the mucosa, sclerosis), or degenerative lesions (cholecystoses) due to the reaction of the gallbladder walls to the irritative-chemical action of the bile hyperconcentrated by intermittent stasis caused by an incomplete cystic obstacle; - both types of lesions may determine with time obstruction of the cystic duct (acute cholecystitis), changes in the choledochoduodenal confluence (odditis), co-affection of the pancreas and liver (cholecystopancreatitis, chronic reactive hepatitis); - the late results lend support to the surgical treatment in such circumstances.


[Apparatus for hourly determination of diuresis]. The description is given of an apparatus with a clock-like mechanism imparting to a disk a 45 degrees rotation every 60 minutes in order to transfer the end of a vesical catheter from one graduate cylinder to another. This apparatus offers the possiblity of an hourly collection of urine for a continuous follow up of the clinical and therapeutical evolution, facilitating survey of the patient especially in acute renal insufficiency of varied etiology and in diabetic coma. The hourly diuresis diagram, including the qualitative data of the samples collected, furnishes basic information for research in intensive therapy. The apparatus built with local resources, is cheap and runs silently by means of intermittent electric impulses (220 V), is easily maintained in good conditions and guaranteed against corosion and clogging of the mechanisms.


[Angiographic study of the colonic vessels with a view to esophagoplasty]. Variants of the colic vessels were studied angiographically in 34 cadavers, drawing up an original classification of the colic arteries arising from the lower mesenteric artery. Sixteen variants of the left colic artery were found, which were grouped into five main types, the classical type being encountered in only 22.6% of the cases. In one case the lower mesenteric artery was absent. In coloesophagoplasty better results were obtained with the isoperistaltic transverse colon than with the upper ileocolon in 64% of the cases and similar results in 20%; in 16% of the cases the latter operation was preferable.


[Postbulbar duodenal ulcer].

[Postbulbar duodenal ulcer]. In a total of 1430 patients with gastro-duodenal ulcerative disease that have been operated the authors recorded 102 cases of duodenal ulcer in the posterior area of the bulb (7%), of which 63 also had various types of complications such as: penetration (36), stenosis (14), perforation (7), hemorrhage (4), hemorrhage and perforation (2). Six differentiated surgical techniques were employed: Reichel-Polya resection and extirpation of the lesion (30), Reichel-Polya resection with extirpation of the lesion, ligature of the duodenal stump without plugging and with epiploonoplasty (34), Reichel-Polya resection with exclusion of the ulcer (35), excision-suture with gastro-entero-anastomosis (1), excesion-suture with canula draining (1), transfixiant ligatures for hemastosis (1). A total of 23 postoperative complications were recorded with 6 deaths. By making an early diagnosis and by carrying out surgery in post-bulbar ulcers with intricated attacks, resisting medical treatment, in the pre-complication stage, these conditions being possible to achieve by a narrow cooperation with internists and by an individualization of the technique, the risks and the difficulties will be reduced with regard to closure and the morbidity, as well as the lethality following surgery will be reduced.


[Bilateral pulmonary resections for bilateral bronchiectasis]. The present paper reports on 6 cases of bilateral bronchiectasis in patients aged 11 to 63 years, treated by simultaneous bilateral pulmonary resection and 1 case of bilateral bronchiectasis in which 14 segments were resected successively. Surgery by simultaneous bilateral approach and associated resection of the affected areas is a procedure that should be indicated, in the authors' opinion, only in carefully selected cases in which not more than 13 segments have to be resected. The indications and contraindications of surgery in bilateral bronchiectasis are discussed, preference being given to the simultaneous approach. In the cases reported at most 11 1/2 segments of the four pulmonary lobes affected were resected in a single stage; in 1 case 14 segments were resected successively, the resection exceeding in amplitude all similar one published until now. The immediate and late postoperative evolution (lesional and functional) were favourable, which pleads for a reconsideration of the approach to bilateral bronchiectasis and the application of the surgical treatment recommended, within the limits described.


[Patch with ileum in continuity for duodenal parietal defect after extended nephrectomy and right hemicolectomy (invasive renal cancer)]. An observation is presented of a patient with right renal cancer that invaded the caecum and the ascendant colon, as well as the descending duodenum. Enlarged nephrectomy was performed and right hemi-colectomy and resection of the antero-lateral wall of the duodenum. Termino-terminal ileo-transversostomy was performed and the duodenal defect was "patched" with the last ileal loop and its serosa.


[Surgical or isotopic synovectomy?].

[Surgical or isotopic synovectomy?]. A total of 40 patients were treated, suffering with chronic rheumatic arthropathies of the knee, by synoviorthesis with 198Au. The patients were followed for more than 3 years. Good results were obtained in 90% of the cases. The advantages are considered of the isotopic synovectomy (synoviorthesis with 198Au), as compared with surgical synovectomy. Isotopic synoviorthesis is a non-surgical procedure of destruction-reconstruction of the pathological synovial. The method has a local and a general immuno-depressing effect (reduction of the abnormal protein generation, of the chondrolytic activity of the synovial and of the permeability disturbances from various chronic exsudates in the knee articulation). The knee articulation is particularly well suited for the use of these therapeutical method. The secondary effects and the organism irradiation are minimal.


[A method of osteosynthesis in supracondylar transverse fracture of the humerus in children]. A new surgical technique is described for the osteosynthesis of the supra-condylar transversal fracture of the humerus in children with an unique central transolecranian and transcondylar brooch. Intra-operative radiography is indispensable. The position for immobilization is very important. Temporary perforation of the diarthrodial cartilage and of the conjugation cartilage does not lead to functional or osteogenesis disturbances.


[Test for evaluation of the effectiveness of hormone treatment in carcinoma of the prostate]. Cytological examination of superficial epithelial cells systematically sampled at the level of the navicular fossa of the urethra in 61 patients with prosthatic carcinoma that had underwent surgery or that had not been operated, in whom longterm treatment with oestrogens was applied led to the conclusion that the caryopyknotic index shows variable increases, in some cases attaining more than 30-40%, in direct connection with the amount and the duration of administration of the oestrogen substances. The results obtained are encouraging and suggest the possibility to apply an objective test in the application and the evaluation of the efficiency of a hormonal treatment.


[Atypical postoperative peritonitis].

[Atypical postoperative peritonitis]. In the present conditions of development of the medical sciences the wide and varied use of pre- and postoperative antibiotherapy, to which is added the complex therapy carried out in the intensive-care unit, have changed the course of the dramatic postoperative peritonitis that at present do not develop any more according to the classical symptomatology. The key to success in these cases is the discovery as rapidly as possible of the moment when peritoneal infection has started to develop in view of applying the only correct treatment--reintervention. The present study makes an analysis of 32 cases and stresses the atypical evolution of postoperative peritonitis: contracture, pain, high fever and hyperleukocytosis cannot be considered any more as constant and certain signs. Meteorism and gastric stasis that is prolonged or that developes after 4-8 days following surgery are the most frequently encountered of the signs and are considered to be the most important. Exploratory laparotomy is the most correct attitude in dubious cases.


[Uremigenic cholangitis].

[Uremigenic cholangitis]. The treatment is presented, applied in a case of severe angiocholitis complicated by acute renal failure, known in the literature under the name of uremigenic angiocholitis. After three emergency hospitalizations, two interventions consisting in surgical drainage, de-shocking procedures, treatment of the hepato-renal failure and applications of wide-range antibiotics for the treatment of infection the angiocholitic phenomena disappeared and the hepato-renal failure is on the way to recovery. At this moment of the evolution the patient developed atrial fibrillation that was improved by Narcotan anesthesia. The efficiency is remarked of the treatment with large amounts of Furosemid in the anuric period, as a means to avoid extra-renal depuration.


[Complications of splenectomy].

[Complications of splenectomy]. The present study is an analysis of complications developing after a total of 200 splenectomies carried out for various indications: primary hypersplenism (83), secondary hypersplenism following portal hypertension (72), diseases of the hemopoietic system (24), parasitic and infectious splenomegalies (13), rupture of the spleen or of splenic artery aneurisma (8). A number of 68 patients (34%) had a total of 73 complications following surgery. Of these 60 have recovered (30%) while 8 (representing 4% of the total), died. A total of 22 local or general septic complications were noted, as well as 20 complications generated by disturbances of the balance of fluids and/or of the coagulation system, 19 pleuro-pulmonary complications, 6 complications that were not specific for splenectomy, 5 pancreatic complications and 5 cases of hepatic failure.


[Muscular clearance after administration of phenoxybenzamine in shock]. The authors made an experimental investigation in the dog concerning the evolution of the muscular clearance of phenoxybenzamine in the course of de-shocking procedures. The animals were shocked by hemorrhage and were treated by perfusion of volemic mass and administration of phenoxybenzamine. This substance was flowed in paralell with the hemodynamic parameters and the rhythm of the diuresis. It was noted that the direction and the amplitude of changes concerning the half-life of Na131I do not depend on the blood pressure.


[Difficulties in diagnosis and surgical treatment of subacute and chronic thyroiditis]. Out of a total number of 875 cases of thyroid affections of various origins, hospitalized in the two surgical clinics of Tîrgu-Mureş, the authors selected 16 cases of subacute and chronic thyroiditis. They indicate the difficulties encountered in establishing the diagnosis before surgery, a fact that determined wide excisions in extremely difficult local conditions. They suggest, as a first therapeutic attitude, a conservative treatment with steroid drugs, antibiotics and roentgentherapy (when necessary), and, if such treatments fail, or when malignancies are suspected, as well as compression phenomena have developed, surgical treatment preceded by an extemporaneous anatomo-pathological examination. When thyroiditis is diagnosed surgery should be limited to decompressing incisions.


[Involvement of the thyroid gland in clinical shock (anti-shock action of propylthiouracil)]. Propylthyouracil, a synthetic anti-thyroid drug, was given intravenously in ten patients in a severe shock condition and its action was followed on the blood cathecholamines. This was assessed in venous blood according to a modified colorimetric method by Manuhin, before and 30 minutes after the substance was perfused. Although statistically non-significantly the two amines show a tendency to fall after the administration of the drug. In line with a series of previous studies carried out in various institutes of chemical and pharmaceutical research the drug was given for the first time in humans in shock conditions. Discussing the results obtained the administration of propylthyouracil is recommended, as an adjuvant therapy in severe shock.


[Pleuropulmonary diffusion in some subdiaphragmatic suppurations]. Two cases are presented of subphrenic suppurations (right perinephretic phlegmon and suppurated hepatic hydatic cyst), that developed fistulae in the lung and the pleura. The evolutive modalities are discussed the diagnostic difficulties and the corresponding therapeutic attitudes.


[Upper digestive hemorrhages of ulcerous nature (management and experience)]. A number of 135 cases were examined, presenting with superior digestive hemorrhage of ulcerative origin. The analysis of the cases was made by two comparable groups. In the first one of the groups the volemic re-equillibration was based on the administration of blood and surgery was carried out, in principle, on a "cold" condition. In the second group volemic re-equillibration was achieved exclusively with isotonic non-colloidal volemic solutions that were administered before, during and after surgery (0.9% NaCl solution and 5 g% glucose solution in equal amounts). Surgery was performed as an emergency and vagotomy was made, as well as surgical hemostasis. The results obtained have allowed for the conclusion that, by providing efficient surgical hemostasis and volemic re-equillibration with isotonic non-colloidal solutions blood transfusion and its untoward side-effects can be avoided.


[Serum cholinesterase in anesthesia and surgical shock]. The evaluation of the serum cholinesterase activity in various experimental conditions (anesthesized dogs, operated on or not, in shock intoxicated with carbon tetrachloride) indicated various degrees of inhibition of this enzyme, peaking in imbalances that developed during shock or in the carbon tetrachloride intoxication of the animals.


[Major scoliosis, over 100 degrees, in adults. 183 surgically treated cases]. Most severe scoliosis and kyphoscoliosis are not unfrequent in European countries. The purpose of their treatment is not only cosmetic but, often, vital. Patients are hypotrophic and their vital capacities usually very poor. Since 1952, the authors have treated (partial, reduction and fusion) 183 patients: with curves above 100 degrees (101 degrees-203 degrees). Reduction was obtained by distraction cast or halo-traction. Surgical treatment (one or two stages) used Harrington rods and fusion with a large amount of iliac bone. These procedures are dangerous for the medullary function. Controls must be performed during the operative distraction. Follow up studies demonstrated the stability of the obtained reductions.


[Orthopedic reduction of scoliosis by Maguelone's technic. Indications and first results]. The authors describe an original technique for rapid closed reduction of scoliosis (Maguelone technique). It is based on mild distraction in suspension associated with derotation without pressure points. It is painless and efficient. In 50 cases it was followed by a conservative treatment using plaster casts. In 15 other cases it was the first stage of a surgical treatment of the deformity.


[Treatment of severe recurvation of the knee in poliomyelitis. Role of olecranization of the patella]. The authors have treated two cases of severe genu-recurvatum after poliomyelitis by a locking operation. They fused the patella to the tibia by grafting, realising an anterior shelf-operation. Full flexion was preserved, hyper-extension was decreased. The indications of this operation are discussed and compared with these of tibial osteotomies and capsulorraphies.


[Treatment of post-traumatic cubitus varus in children. A propos of 32 cases]. The authors have reviewed 32 cases of severe varus deformity following supra-condylar fractures in childhood. The sequellae were mainly cosmetic, the function being preserved. All cases were treated by supra-condylar osteotomy fixed by screwing. The technique is described. The results were satisfactory in 20 cases.


[Inguinal tumor due to synovial cysts of the hip]. The authors operated on a tumorlike synovial cyst of the hip, associated with an idiopathic osteonecrosis of femoral head. So far, about fifty cases have been reported in the medical litterature with various names, and association with hip joint disease. The problems of diagnosis are discussed.


[Lumbrical plus syndrome].

[Lumbrical plus syndrome]. A rare case of paradoxical extension of the medius finger - the so-called lumbrical plus finger syndrome-is described. At operation was found a fibrous adherence of the third lumbrical at the sheath of the flexor digitorum profundus. Some of pathological mechanisms are discussed. A satisfactory result was obtained after the resection of the tendon of the second lumbrical.


[Surgical repair of chronic instabilities of the cruciate ligaments of the knee]. The authors have developped a technique aiming at replacing the anterior cruciate ligament by the tendon of gracilis muscle derouted through the intercondylar region and acting as an active transplant in 32 cases. In 20 other cases replacement of the posterior cruciate ligament was obtained by the use of the tendon of semi tendinosus muscle acting as a passive neo-ligament. The follow-up study demonstrated 87 p. 100 of good results after isolated tears of the anterior ligament and 83 p. 100 after isolated tears of the posterior ligament. 21 times an additional plasty of the medial ligament had to be performed. In these combined lesions results were less favourable.


Phospholamban: a regulatory protein of the cardiac sarcoplasmic reticulum. Accelerated calcium transport into the sarcoplasmic reticulum (SR) of the heart may mediate the inotropic actions of agents that act to increase adenosine 3',5'-monophosphate (cyclic AMP) within the cell. Studies in our laboratory have shown that ATP-dependent Ca uptake by cardiac microsomes rich in SR is enhanced by pretreatment with bovine cardiac cyclic AMP-dependent protein kinase (cyclic AMP-PK). Ca2+-activated ATPase is increased concomitantly with Ca uptake, stoichiometric coupling of 2 moles of Ca2+ taken up per mole of ATP hydrolyzed remaining constant. The steady state level of Ca binding is not increased by cyclic AMP-PK pretreatment, suggesting that the turnover rate of the transport system rather than the number of transport sites is increased. Phosphorylation of the SR by protein kinase is half-maximal at approximately 10(-7) M cyclic AMP, a value similar to that which gives half-maximal stimulation of both Ca uptake and Ca2+-activated ATPase. Over 80 percent of the 32P associated with membrane protein is identifiable as phosphoserine and phosphothreonine. The 32P is incorporated into a 22,000-dalton protein as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This protein, which we have tentatively named phospholamban (lambda alpha mu beta alpha psi usilon epsilon omega = to receive) appears to particiapte in the regulation of calcium transport by the heart's SR and may play a role in the inotropic actions of drugs, such as epinephrine, which act upon the cyclic AMP-PK system.


A possible explanation for the peculiar contractile behavior displayed by rat heart muscle. Because it is generally agreed that the sarcoplasmic reticulum plays an important role in regulating the intracellular availability of Ca2+, the ability of rat microsomal fractions to accumulate Ca2+ was compared with that of microsomal fractions similarly prepared from guinea pig heart muscle. Despite a relatively high level of basic ATPase enzyme activity (19.2 +/- 2.6 muM Pi/mg of microsomal protein/10 min) rat microsomal fractions consistently accumulated significantly (p less than 0.001) less Ca2+ than did the guinea pig preparations, irrespective of whether the incubation medium contained oxalate. The microsomal yield obtained from the rat hearts was not significantly different (p less than 0.8) from that obtained for guinea pig heart muscle. Rat mitochondria similarly accumulated significantly less Ca2+ than did the guinea pig mitochondria. These observations substantiate a general hypothesis that rat heart cells may possess a relatively high intracellular concentration of free Ca.


Calcium uptake and ATPase activity of microsomes from heterotopically transplanted rabbit heart. Heterotopic cardiac transplantation was performed in rabbits. The calcium uptake and ATPase activities of microsomal fraction were studied in three groups (group I, normal controls; group II, early transplants; group III, late transplants) during severe rejection as characterized histologically and electrocardiographically. Group III showed a significant decrease in calcium uptake but no difference in ATPase activity compared with groups I or II. The results demonstrate that in the rejecting transplanted hearts there is an uncoupling of microsomal calcium uptake from this ATP splitting function.


Role of mitochondrial calcium metabolism in the altered contractility of pressure-hypertrophied right ventricular myocardium. Pressure-hypertrophied right ventricular myocardium (RVH) demonstrates paradoxically increased oxygen consumption (MVO2) related to increase- in vitro energy-linked mitochondrial calcium flux. The present experiments were designed to measure mitochondrial Ca retention in intact RVH and relate changes in mitochondrial Ca metabolism to altered RVH contractility and relaxation. Sixteen cats were pulmonary artery banded and their hearts plus paired controls were perfused with 45Ca-labeled Krebs-Henseleit (30 degrees C) at 120 beats/min for 10 min. Papillary muscles from both right ventricles were studied in a muscle bath. Mitochondria were isolated from the right ventricles and retained 45Ca measured. At the length at which active tension is developed (Lmax) papillary muscle abnormalities were, for reduced active tension, 6.9 gm/mm2 +/- 0.6 SE for control, 4.0 +/- 0.6 for RVH, p less than 0.001; for slower contraction rate, 40.8 gm/mm2/sec +/- 6.3 control, 16.9 +/- 2.8 RVH, p less than 0.001; for slower relaxation rate, 22.0 gm/mm2/sec "/0 1.5 control, 11.1+/- 1.6 RVH, p less than 0.001; for greater time to peak tension, 317 msec +/- 7 control, 408 +/- 13 RVH, p less than 0.001; for greater relaxation time, 590 msec +/- 29 control, 800 +/- 39 RVH, p less than 0.001. Retained 45Ca of mitochondria was increased from 16.75 +/- 0.96 nM/mg of protein for control, to 20.82 +/- 0.98 for RVH, p less than 0.005. This increase in mitochondrial 45Ca retention correlated (r = 0.93, p less than 0.001) with the decreased rate of papillary muscle relaxation. These data show an increased 45Ca retention of mitochondria in pressure-induced RVH and relate this biochemical abnormality to a decreased myocardial relaxation in this state.


Effects of hemodynamic overload on canine myocardial myosin. After mild banding of pulmonary artery in dogs there was a rapid elevation in protein and RNA synthesis, followed by an elevation in myosin content and myosin ATPase activity. There was an increase in myosin ATPase activity when K+ or Ca++ was used as activator effector but not with the cations, Mn++ or NH4+. Concomitant with an increase in myosin ATPase activity there was a decrease in one of the C1 light chain components, previously named C1d.


Cardiac myosin: preparation, ATPase in chronic heart hypertrophy. A low myofibrillar ATPase seems to be established definitely in several experimental models of chronic heart hypertrophy as well as in humans, but the biochemical pathogenesis of this defect is still unclear. Three different preparations of myosin were studied. Their purity was estimated by measuring MgATPase or by polyacrylamide gel electrophoresis. The first preparation was highly contaminated by actin and tropomyosin; the second was rather pure, and the third (chromatography on DEAE-Sephadex) was pure but slightly denaturated. Heart myosin CaATPase (ionic strength 0.6 or 0.06) was decreased in chronic aortic insufficiency in the rabbits (CAI) when all three preparations were tested. Two (molecular weight 18,000 and 26,000), sometimes three light subunits were found in heart myosin. Their charge and molecular weight are normal in CAI. The third subunit (molecular weight 15,500) was found in control as well as in CAI. Search for an inhibitor was unsuccessful since the two myosin ATPases are additive. The nucleoprotein peak separated from myosin during chromatography was identical in control and CAI. Therefore, myosin seems to be abnormal in CAI.


Cardiac glycoside receptor in potassium depletion. Ouabain binding capacity of cell membranes is directly related to (Na+ + K+)-ATPase activity. The extent of ouabain inhibition of (Na+ + K+)-ATPase is a measure of ouabain receptor sites occupied. Dissociation constants of the ouabain-receptor complexes are identical in all organs in a single species but vary among different species. K+ decreases the association rate constant of the ouabain receptor interaction without altering the dissociation rate constants. Titration of digoxin-inhibited (Na+ + K+)-ATPase from guinea pig heart with digoxin antibodies shows a reversal of the inhibition at lower antibody concentrations in the presence of K+ than in the absence of K+. It is concluded that digitalis intolerance in acute hypokalemia reflects the increased affinity of the cardiac glycoside receptor under these conditions.


Cardiac effects of ethacrynic acid, a Na+, K+-ATPase inhibitor. To test hypotheses relating positive inotropic effects of cardiac glycosides (CG) to inhibitory effects on Na,K-ATPase, cardiac actions of other inhibitors were examined. Ethacrynic acid was studied using microelectrode recordings of dog Purkinje fibers (DP) and cat papillary muscle (CP), and isometric recordings of CP at Lmax stimulated at 1/sec (36.5 degrees C). Results with all doses (20-200 gamma/ml) were similar, differing only in latency. Actions of ethacrynic acid on electrical activity of DP and CP were, chronologically: increase in duration of the action potential (AP), and decrease in dV/dt, overshoot, and resting potential. In CP an initial increase (2-5 min) in contractility (10-15 percent) was followed by decreased in active tension and dP/dt with parallel increases in resting tension and duration of contraction. ATP levels were unchanged, eliminating the possibility of ethacrynic acid acting as a metabolic poison. Simultaneous recording of contractions and AP in CP showed that the positive inotropic effect was always associated with a lengthening of the AP. In a series of CP, ouabain (2 gamma/ml) always increased contractility when ethacrynic acid had already reduced it by 75 percent. These results suggest that Na,K-ATPase inhibition is not responsible for the inotropic effects of CG.


Kinetic studies on inhibition of dog heart Na+,K+-dependent ATPase by K+,Mg2+-aspartate: comparison with ouabain. Both K+,Mg+-dependent D,L-aspartate and D,L-aspartic acid are noncompetitive inhibitors of dog heart Na+,K+-ATPase acting at the overlapping site as does ouabain. For the Na+,K+-ATPase, the salient effects of K+,Mg+-D,L-aspartate and/or D,L-asartic acid were: 1) decrease in maximal velocity (V) for ATP as substrate with unchanged Km; 2) for sodium as an allosteric modifier of Na+,K+-ATPase activity, a decrease in V without any alteration in n as measure of cooperativity between activating sites; 3) for potassium, a decrease in V and n as well as an increase in K0.5 values. Thus, for enzyme activity in the presence of sodium and ATP, a high affinity to potassium was reduced by D,L-aspartic acid.


Halothane decreases actomyosin ATPase activity: a possible mechanism of the negative inotropic effect. Like all inhalation anesthetics, halothane (CF3CHBrCl) has a dose-dependent negative inotropic effect on cardiac muscle. The mechanism of the action has not been determined, although effects on glycolysis, mitochondrial respiration and calcium kinetics, and sarcoplasmic reticulum ATPase activity have been suggested. Previous studies of the effect of halothane on the ATPase of contractile protein suffered from design and dosing defects. We have measured ATP splitting by canine cardiac natural actomyosin using extraction and equilibration procedures described previously (Honig, C. R. and Reddy, Y. C. 1973, J. Pharmacol. 184: 330-338). Drug dosing calculations were facilitated by measurement of the partition coefficient of halothane in protein. Halothane shifted the Ca++ concentration effect curve for actomyosin ATPase activity to the right. The maximum depression occurred at pCa 7.0 or 6.5. The effect was dose dependent with less than 10 percent depression at threshold and 50-60 percent depression at peak. Enzyme inhibition was antagonized by high Ca++ concentration, and was reversed by removing halothane from the reaction mixture. We suggest that inhibition of ATP utilization by the contractile system may be a mechanism of the in vivo myocardial depression produced by halothane.


Myocardial mechanics at various stages of the cardiac hypertrophy induced by a transitory work load in the rat. Cardiac hypertrophy was induced in rats by abdominal aortic constriction lasting 5-28 days. In other rats, release of aortic constriction after 5 or 15 days led to hypertrophy regression, which was completed within 15 days. Left ventricular papillary muscle study during cardiac hypertrophy demonstrated an early but transitory decrease of tension development and shortening velocity, a prolonged contraction duration, a slowed relaxation, and a reduced response to changes in the stimulation rate. After hypertrophy regression, the prolongation of contraction persisted; mechanical performance was similar to control, except for increased peak isometric tension in early released animals. These findings indicated that anomalous excitation-contraction coupling may be related to the hypertrophy process itself and that prolonged contraction could act as a compensatory mechanism.


Cardiac hypertrophy due to physical exercise--an example of hypertrophy without decrease of contractility: unreliability of conventional estimation of contractility by simple parameters. In 100 young, male Sprague-Dawley rats, a long term swimming training (2 hr/day for 8-12 weeks) produced an increase in heart weight of 10 percent, and an increase of about 15 percent in the relation of heart weight to body weight compared with control rats of the same age and initial weight. In examinations of the mechanical properties of the whole ventricle as well as of trabecular preparations, there was no evidence of impaired myocardial contractile ability because of the swimming training. Some parameters for the estimation of "contractility" increased, whereas others decreased. At a muscle length near lmax, the developed force and the maximal rate of force development were slightly augmented. The results reveal the limited value of some indices of contractility. Alterations in the shape of the contraction curve must to be considered adequately in order to avoid misinterpretations.


The composition of connective tissue macromolecules from bovine respiratory system. Connective tissue macromolecules, glycosaminoglycans, glycoproteins, collagen, and elastin were isolated from different parts of the respiratory system and characterized. The materials included bronchiolar tissue, gas-exchange tissue, lung pleura, and tracheal mucosa. The similarity of the macromolecular composition of lung pleura and tracheal mucosa suggests a common cellular component in these structures. The high concentration of GAG and collagen in bronchiolar tissue is consistent with the cartilagenous nature of this tissue. Particularly interesting is the high content of heparin in all pulmonary structures, a relatively greater content of hyaluronic acid in gas-exchange tissue, and a high content of heparan sulfate and dermatan sulfate in vascular tissues. Elastin also occurs as a major fibrous structure. Although the biologic role of these connective tissue macromolecules has not been established, certain functional relationships are inferred.


Lymphocyte ATP-ase activity in treated cases of Hodgkin's disease. The ATP-ase activity was determined in lymphocytes isolated from peripheral blood in 41 patients with Hodgkin's disease and 50 healthy controls. All patients were previously treated with irradiation or cytostatic drugs and 17 patients were under maintenance therapy at the time of investigation. A significantly increased ATP-ase activity was found in lymphocytes from patients with Hodgkin's disease. The individual activities were unrelated to the clinical stage of the disease, but correlated to the histological classification of the lymphatic tissue. Significantly lower lymphocyte ATP-ase activity was found in patients under maintenance treatment with immunosuppressive drugs, especially if the patients had previously been irradiated. It is suggested that the ATP-ase activity of circulating lymphocytes is related to the immunological activity against the presence of the malignant cells in Hodgkin's disease.


Induced transfer of higher plant chloroplasts into fungal protoplasts. Chloroplasts isolated from spinach leaves have been transferred in large numbers into protoplasts of Neurospora crassa with the help of polyethylene glycol. The chloroplasts show high photosynthetic activity--at least until the time of uptake--and the protoplasts continue to show active cytoplasmic streaming after chloroplast uptake.


Another look at Pereyra's stint urethropexy. Twenty-five women with stress incontinence had stint urethropexy as described by Pereyra. Unqualified success was achieved in only 53%. These cases are analyzed and criteria suggested for selecting patients suitable for stint urethropexy.


An endoscopic technique for removal of suture bound surgical drains. The simplicity and low invasive nature of the endoscopic method make it worthy of trial for the removal of surgical drains inadvertently sutured to structures of the abdominal wall.


Anti-inflammatory activity of thiabendazole and its relation to parasitic disease. In 6 differnet animal assays in the laboratory, thiabendazole had clear anti-inflammatory effect, though it was less potent than aspirin in all assays. These findings add support to clinical suggestions that the drug may have anti-inflammatory properties in man. Such properties may contribute to the clinical response observed following the use of thiabendazole in cases of trichinosis, cutaneous larva migrans, visceral larva migrans, dracunculosis and scabies. In parasitic infections in which corticosteroids are commonly used in clinical management, notably trichinosis, the fact that thiabendazole does not appear to have immunosuppressive activity may confer an added clinical advantage.


A standard for human plasmin.

A standard for human plasmin. An international collaborative study involving ten laboratories was undertaken to assess the suitability of a preparation of human plasmin in 50% glycerol to serve as a single standard for the bioassay of plasmin activity. The study included examination of the stability of the proposed standard and comparisons between assay methods. The results suggest that the human plasmin preparation coded 72/379 is suitable to serve as a standard. It is sufficiently stable to define the unit of plasmin activity for several years at or below 4 degrees C and for short periods at about 20 degrees C. The preparation has been assigned a potency of 8 units per ml. The International Committee on Thrombosis and Haemostasis (Basle, 1974) has recommended the use of this material as a standard.


Influence of norepinephrine and exercise on lipolysis in adipose tissue of diabetic rats. The lipolytic effect of norepinephrine (NE) in adipose tissue in vitro was studied before and after exercise in non-fasted rats with severe, untreated streptozotocin diabetes. It was observed that: 1. NE in increasing concentrations stimulated glycerol release in vitro to an equal extent from the adipose tissue of nondiabetic and diabetic rats. However, the re-esterification of free fatty acids (FFA) in adipose tissue in vitro was decreased by NE in diabetic rats as compared to normal rats. 2. During exercise NE further decreased the re-esterification of FFA in vitro in adipose tissue of diabetic rats. 3. Exercise did not change NE-induced glycerol release in vitro in the adipose tissue of diabetic rats. 4. In diabetic animals the increase in plasma glycerol and FFA during exercise was correlated inversely with the NE-induced release of glycerol and FFA from the adipose tissue of the same animals after exercise. The lipolytic effect of NE is not significantly different in adipose tissue of diabetic and nondiabetic rats. By decreasing the re-esterification of FFA in vitro, NE is probably responsible for the observed increase in the release of FFA in vivo, a likely energy source in severely diabetic animals.


[Studies on the effect of radiation on electrolyte changes and metabolism of the myocardium. V. Changes in enzyme activities and glycolysis metabloites due to radiation]. The behavior of enzyme activities, substrates and metabolites of glycosis as well as of the pentose phosphate shunt following local irradiation (250 to 6000 R surface dose) is biochemically investigated in the guinea-pig's myocardium. During irradiation, an activation of phosphorylase-a is going on while the total phosphorylase content remains unchanged. Enzyme activities of hexokinase and phosphofructokinase are increased in dependence on dosage as well as time. The glycogen content is being reduced; tissular concentration of the metabolites glucose-1-phosphate, glucose-6-phosphate, glyceraldehyde-3-phosphate, glycerol-3-phosphate, and pyruvate increases following irradiation; the content of fructose-1,6-diphosphate, dihydroxyacetonephosphate, and lactate is decreased. The activity of glucose-6-phosphate dehydrogenas is slightly inhibited, whereas 6-phosphogluconate-dehydrogenase remains unaffected.


Initial events in radiation-induced atheromatosis I. Activation of lysosomal enzymes. Local irradiation of the carotid artery of the hypercholesterolemic rabbit with 2000 rd of X-rays gives rise to infiltration of lipid droplets in the intima and media, becoming visible 3 days after the irradiation. At the same time, acid phosphatase and beta-glucuronidase become activated. These enhanced activities are localized in different cells of the arterial wall. Acid phosphatase activity is localized in the intima, while the beta-glucuronidase activation is found preferentially in the media. A functional heterogeneity of the lysosomal content of the different cells is suggested. A model for the development of the radiation-induced atheromatosis is presented.


The synthesis of testosterone and estradiol-17beta by the gonads of neonatal rats in vitro. The rate of synthesis of estradiol-17beta by the ovary, and of testosterone by the testis of the newborn rat have been studied in vitro using tissue homogenates. Quantitative estimation of these steroids has shown a peak of activity in the ovary between 8 and 12 days post partum of 63 pg/mg tissue/hr, compared with 6 pg/mg/hr at day 6, and 19 pg/mg/hr at day 14. Testosterone synthesis in the testis is most active on day 1 (3.1 ng/mg/hr), declining steadily to 1.1 ng/mg/hr on day 11. Adult testicular tissue under the same conditions synthesised 0.5 - 1.0 ng testosterone/mg/hr. These results are consistent with other observations which have suggested a transient period of active steroidogenesis immediately after birth in the rat, but the time during which steroid synthesis is elevated has been more clearly defined. The methods described here provide a model system for the study of synthetic steroids and other drugs which may affect the sexual differentiation of the hypothalamus by altering gonadal steroidogenesis.


[Pseudomonas aeruginosa--the causative agent of infection in birds]. Pseudomonas aeruginosa was isolated from the viscera of diseased and dead birds (young and adult chickens) as well as from 9 poultry houses on seven farms. Its typing was performed on the basis of the blue-green coloration of the cultures, their hemolytic activity, the pleasant odour of lime-tree, the growth in culturing at 42 degrees C, the presence of the pyocianin pigment, and the positive results of the cytochromoxidase test after Gaby and Hadley and the biochemical test after Kovacs. The pathogenicity of the agent was demonstrated through the experimental parenteral infection of chicks, albino mice, and guinea pigs. Pseudomonas aeruginosa cultures showed weak sensitivity and good resistance to the various drugs tested. Most active proved streptomycin, kanamycin, and spectam.


The malformations of the urinary system in autosomal disorders. Data from the world literature about the pathology of the urinary system in autosomal chromosomal disorders are analyzed and compared with our own morphological investigations of this system in 63 cases of chromosomal disorders (Patau's, Edwards', Down's, Orbeli's, Wolf-Hirschhorn's syndromes, partial trisomy B and inversion of chromosome 2). The urinary system is most frequently involved in "cat-eye", triploidy, Orbeli's, Patau's and Edwards' syndromes. All known malformations of the urinary system are observed in children with chromosomal diseases, except infantile polycystic kidney and medullary "sponge" kidney. The authors recognize specific and nonspecific abnormalities of the urinary system. Nonspecific abnormalities, as simple renal dysgenesis, may be observed in all chromosomal disorders. Specific abnormalities are found only in certain chromosomal diseases. These malformations are an excess of embryonal lobulation of the kidney with the increase of its weight and cystic changes (Patau's syndrome), crossed renal ectopy with fusion and horseshoe kidney (Edwards' syndrome), unilateral renal agenesis (Orbeli's syndrome), hypospadia (Wolf-Hirschhorn's syndrome). A possible pathogenesis of malformations of the urinary system in chromosomal disorders is discussed.


Early glomerular changes in streptozotocin diabetes of the guinea pig. This work was to study--using morphometric methods--whether glomerular alterations are demonstrable in the guinea pig kidney even in streptozotocin diabetes of only short duration. In 25, 50, 100 and 150-days diabetes was investigated the blood sugar, the glucose tolerance test, histological and morphometric studies. Storage of glycogen in the kidney was to be found in numerous treated animals whereby it was evident that the cells of the macula densa showed no storage. The morphometric studies performed under blind conditions have shown that with a duration of diabetes of 50 and 100  days the number of cells in the mesangium is increased and that an increase of the mesangial matrix is demonstrable. Hence the mesangium is in the foreground of the initial alterations in diabetes mellitus.


Employment of synchronized cells and flow microfluorometry in investigations on the JB-1 ascites tumour chalones. In most experimental ascites tumours the growth rate decreases with increasing age and cell number. This decrease is caused by a prolongation of the cell cycle and an increasing accumulation of non-cycling cells in resting (or quiescent) G1 and G2 compartments. In cell-free ascitic fluid from the JB-1 ascites tumour in the plateau phase of growth lowmolecular-weight substances have been found which reversibly and specifically arrest JB-1 cells in G1 and G2. The present paper describes an in-vitro model for testing the effect of the humoral growth inhibitors contained in the ascitic fluid. The test system is based on synchronized JB-1 cells analysed by flow-through cytofluorometry. Addition to the synchronous cells of a ultrafiltrate (less than 50000 Daltons) of the JB-1 ascitic fluid was found to induce a complete, but temporary arrest of the cells at the G1-S border.


[Clinical assessment of 2 methods of radiotherapy of breast cancer]. The results of treatment in 324 patients with breast cancer are analysed. 159 females prior to surgery were subjected to irradiation of the mammary gland and axillary lymph nodes. Supra-subclavicular and parasternal zones were treated after radical mastectomy. The mammary gland and all regional zones of lymph outflow were irradiated prior to surgery in 165 patients. In stage 1, 3 and 5-year results of treatment were found to be identical in both series (88%). In stage II 62% of females in the first group and 77% in the second group survived for 3 years and 60% and 75% -- for 5 years, accordingly. In stage III a 3-year survival made 51% and 65% and a 5-year survival -- 25% and 49%, correspondingly. The rationality of preoperative irradiation of the mammary gland and all zones of lymph outflow is emphasized.


[Colposcopic and cytological studies in pretumorous and malignant changes in the cervix uteri]. 814 patients with various pathological changes in the uterine neck were subjected to the complex investigation, taking into consideration the fact that all specialists should be equally competent in their fields. Diagnostic errors were analysed in each method of investigation in relation to a histological conclusion in every series of patients. The diagnosis of preinvasive cancer proved to be most difficult. The number of errors was less in microcarcinoma. The organization of large colpocytological centres in big cities is advocated.


[Diagnosis of malignant neoplasms in ambulatory practice (based on data from a random examination)]. The ambulatory-polyclinic network is the first step of the patient's address and investigation for basic forms of malignant tumors. As a result of the analysis of 2361 ambulatory case reports, it was found that in 70.7% of cases the correct diagnosis was established not by medical specialists of the outpatient clinics but in oncological institution where these patients were directed for a consultation.


[Some epidemiological factors in the incidence of female genital cancer in the Azerbaijan SSR]. In the structure of cancer morbidity of the female genitalia in Azerbaijan SSR within a ten-year period (1957-1966) cervical cancer occupies the first place--86.6%, it is observed more frequently among Russian female population (46.4 per 100 000 wives) and more rarely among aboriginal female population (7.1 per 100 000 wives). Of 2488 patients with cervical cancer 24.5% showed previous lesions against which background cancer would arise. Patients with cervical ruptures, advanced erosions, polyps should be identified as high-risk groups of cervical cancer.


[Clinical picture and therapy of gastroschisis (author's transl)]. The results of operative treatment of gastroschisis have been improving in recent years. The survival rate is now between 50 and 60 p.c. It is very important to perform primary repair as soon as possible after birth. According to our own experiences resection of the bowel should be avoided as it gives a poor prognosis. Combined malformations of gastroschisis are very rare and their treatment should be tired since there is no other alternative. An own successfully treated case of combined malformations of gastroschisis with atresia of the small bowel is presented. Stenosis of the duodenum and tubular duplication are described


Microbial oxidation of dehydroepiandrosterone and related compounds. The oxidation of dehydroepiandrosterone (DHEA), 4-androstene-3, 17-dione, and estrone with Streptomyces roseochromogenes NRRL B-1233 was studied. The oxidation products were isolated and identified as as 16alpha-hydroxy-DHEA, 16alpha-hydroxy-4-androstene-3,17-dione and 16alpha-hydroxyestrone. The yields of these three products were 85%, 41% and 18%, respectively. This indicates the substrate stereospecificity of 16alpha-hydroxylase of the organism. An interrelationship between cell growth and the formation of 16alpha-hydroxylated steroid was observed in any case. For formation of 16alpha-hydroxy-DHEA, 16alpha-hydroxylase showed good activity at DHEA concentration of 3.47 x 10(-4)M. In the case of DHEA, 16alpha-hydroxy-4-androstene-3,17-dione and 5-androstene-3beta, 16alpha, 17beta-triol were obtained after the yield of 16alpha-hydroxy-DHEA reached the maximum yield for about 30 hr. The oxidation pathway of DHEA is discussed.


Biosynthesis of [7-3H]16 alpha-hydroxy-dehydroepiandrosterone having high specific activity. Biosynthesis of [7-3H]16alpha-hydroxy-dehydroepiandrosterone in high specific activity has been studied. [7-3H] dehydroepiandrosterone (13.9 C/mM) in trace quantity was oxidized by Streptomyces roseochromogenes (NRRLB-1233) for 5 min at 27 degrees C. The radioactive products were chromatographically separated, identified and their radiochemical purity established by isotopic dilution analysis. [7-3H]16alpha-hydroxy-dehydroepiandrosterone (2.5 x 10(7) dpm) was obtained by microbial hydroxylation of substrate (1.9 X 10(9) dpm). In some cases [7-3H])5-androstene-3beta, 16alpha, 17beta-triol in a small amount of radioactivity could be found at the prolonged reaction for 30 hr.


[Repression of urease biosynthesis in Neurospora crassa by ammonium ions]. The regulation of the synthesis of the enzyme urease (urea amido hydrolase E.C. 3.5.1.5.) in Neurospora crassa was investigated. The biosynthesis of urease is repressed by ammonium ions. Under ammonium excess conditions the specific activity of urease decreases from 0.980 to 0.180 mumoles NH3/min/mg protein. By addition of cycloheximide it was shown that ammonia influences the synthesis of this enzyme. Enzyme induction by the substrate could be excluded. Even under the conditions of highest repression a specific activity of urease of 0.180 mumoles NH3/min/mg protein was measured. Possible causes of this constitutive enzyme level are discussed.


[Influence of overweight on the load-capacity of the supporting and locomotion system in women]. 119 50-year-old women were examined with regard to connections between apparatus of locomotion and overweight. Middle-aged women with overweight compared with women with normal weight more frequently complain of podalgias and of by Schober's signs objectifyable sacrodynias. Compared with women with normal weight in them a more frequent hyperlordosis can be established. The percentage of the degenerative spondylopathies of 61% and of the densitometrically established osteoporosis of 25.4% in the total material corresponds with literary data. There are no differences between women with normal weight and overweight. In contrast to persons with normal weight persons with overweight have only somewhat more frequently the combination of hyperlordosis with degenerative processes of the lumbar vertebral column. The biconcavity index established at the lumbar vertebral bodies is in the lower region in persons with overweight as well as in persons with normal weight. Osteoporotic lumbar vertebral bodies show a decreased frequently of spondylosis. There is no correlation between the radiological parameters established at the lumbar vertebral column and the objectified by Schober's signs decrease of the function of the lumbar vertebral column. A decreased height of the plantar arch and a correlating with this bredth of the step plane of the foot in adipose persons compared with normal persons we regarded as an expression of the increased load of the foot, also in such cases where a connection with the more frequent foot-complaints could not be ascertained. Perhaps it corresponds with that fact that only the developing flat-foot causes complaints. In general a positive correlation is to be found between the frequency of sacrodynias and podalgias.


[Catabolic processes in the rectal mucosa. Light and electron microscopic studies]. The phagocytosing activity of macrophages and fibrocytes of the lamina propria was examined by means of light and electron microscopy; the material had been obtained through 121 biopsies performed on patients ranging in age from 3 weeks to 43 years (113 taken from the rectum, 8 from the small intestine). The phagocytosing activity of the stroma has been known since the studies of v. Möllendorf, Clara, Patzelt, Maximov, Malatzkaya carried out on guinea pigs, rats, birds and a few human embryos. In recent years this problem has been raised again by some American authors. Our studies close the gap existing for the age group ranging from birth to the 16th year. It was demonstrated that the rate of this activity is much higher than hitherto assumed by Askar, Ekuan and Hill, Azzopardi and Evans. The authors discuss the reasons for these discrepancies in the finding, and the origin and composition of the substances ingested.


Extramedullary manifestation of the blastic phase of chronic myelocytic leukemia: A chromosome study. Two patients with extramedullary manifestation of the blastic phase of chronic myelocytic leukemia (CML) are reported. 100% of the metaphases derived from extranedullary sites were aneuploid. Despite the absence of blastic changes in the bone marrow and the peripheral blood, a significant proportion of the metaphases derived from these tissues also showed aneuploidy. It is suggested that maturation and differentiation of aneuploid myeloblasts are influenced by their environment.


[Examinations of the possibilities to nitrosate nicotine and nornicotine and of the formation of N-nitrosonornicotine in the stomach of smokers (author's transl)]. It was examined how easily the tobacco-smoke constituents, nornicotine, and nicotine, are nitrosated in an acidic aqueous medium, and if a formation of nitrosamines in the stomach of smokers is possible after swallowing amine-containing saliva. More than 10% of the nornicotine present in tobacco-smoke is dissolved in saliva during smoking. While from the tertiary amine, nicotine, only a small yield of N-nitrosonornicotine was obtained, from nornicotine an about 50 times higher yield of nitrosocompound was formed than from N-methylbenzylamine, a secondary amine of moderate basicity and hence of moderate reactivity toward the nitrosating agents. The amounts of nitrite in the neutral stomach contents varied between 15 and 250 ppm; in the acidic stomach contents no nitrite was detected. No increase was observed during cigarette smoking. In 61 gastric juice of volunteers who smoked a total number of 280 cigarettes no nitrosonornicotine and no nitrosopyrrolidine (pyrrolidine is present in tobacco-smoke in similar amounts as nornicotine) was detected (detection limit: 5 ppb).


[Light and electron microscopic studies for classification of pituitary adenomas (author's transl)]. 85 surgically removed pituitary adenomas were studied by light and electron microscopical and in part immunohistochemical methods. The tumors were histogically classified and reexamined by the ultrastructure. Histochemically the adenomas could be differentiated in acidophil adenomas (1. group, 41%), mucoid cell adenomas (2. group, 6%), and chromophobe adenomas (3. group, 37%) whereas oncocytic adenomas (4. group, 16%) could be identified only in plastic-embedded sections. About half of the acidophil adenomas were highly differentiated and showed structures which correspond to those of normal STH cells (subgroup 1.1). 1 adenoma consisted of cells of prolactin type (subgroup 1.2). The other acidophil adenomas were differentiated to a lower degree and showed no resemblance to the structures of normal acidophil cells. The 5 mucoid cell adenomas were proved to be with all methods highly differentiated adenomas of ACTH-cell type (subgroup 2.1). TSH-cell adenomas (subgroup 2.2) and lower differentiated mucoid cell adenomas (subgroup 2.0) were lacking in our collection. More than one third of the chromophobe adenomas showed well developed endoplasmic reticulum and Golgi complexes. The other had little and small organellas that resemblances to immature stem cells were evident. The oncocytic adenomas were identified in plastic-embedded sections by their fine-granular structures which were based ultrastructurally not on small secretory granules but on closely arranged mitochondrias.


Variation of stemline karyotype in a HeLa cell line. 100 karyotypes of a HeLa cell line (modal number 69) were studied in details. It was observed that the stemline cells of this "triploid" somatic cell population showed high degree of chromosomal polymorphism. It has been discussed that the stemline cells have number of extra chromosomes (or parts of chromosomes) which are not essential for the genetic integrity of this cell population. A loss of some of these chromosomes (or their parts) does not induce any appreciable change in the genetic make-up of these cells. The broken chromosomes lose their identity and are grouped together with the non-homologues, when the Denver system of classification is followed. However, it has been argued that in absence of any other acceptable system for classification, the Denver system can still be employed for analyzing human chromosomes both at diploid and abnormal heteroploid level. It has been held in contrast to the pseudo-stemline concept that these cells in general, have the essential genes in common and are responsible for the genetic make-up of this cell line and constitute together the stemline of this somatic cell population.


Long term effects of a single dose of dimethylnitrosamine on the rat liver. A single injection of DMNA induces in hepatocytes different lesions which are revealed by the mitoses following a partial hepatectomy. The inhibition of mitotic activity, the appearance of micronuclei and the development of hyperplastic nodules were investigated. The results show that the delay between the DMNA treatment and the induction of mitotic activity influences differently the evolution of these changes. The lesions reponsible for the inhibition of mitotic activity and the production of micronuclei are produced when DMNA is given before hepatectomy. They remain unchanged for a long period and are still present five weeks after the injection of the carcinogen. They have disappeared after 10 weeks. On the contrary, the lesions leading to the formation of hyperplastic nodules are at their greatest when DMNA is given at the time of the DNA synthesis following hepatectomy. The data of the present work are compared with previous results obtained by combining X irradiation and hepatectomy.


Focal loss of alkaline phosphatase and increase of proliferation in preneoplastic areas of the rat urothelium after administration of n-butyl-n-(4-hydroxybutyl)-nitrosamine and n-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide. Development of tumours of the urinarY bladder was studied in 59 Male and female Sprague-Dawley and Wistar rats with combined enzyme-histochemical and autoradiographic methods after oral application of n-butyl-n-(4-hydroxybutyl)-nitrosamine (BBN) and n-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT). as the first carcinogenic lesion detectable by light-microscopy a focal, sharply defined irreversible loss of alkaline phosphatase activity was consistently demonstrated in the urothelium, which appeared normal histologically and cytologically. In about 2/3 of the cases, NADH-diaphorase activity was markedly reduced in identical regions. The enzyme-deficient areas are to be considered as preneoplastic, because papillomas and carcinomas developed from them through different stages of hyperplasia. As a rule, these also were characterized by total loss of alkaline phosphatase activity and attenuation of the NADH-diaphorase in all parts or circumscribed areas. Autoradiographically 3H-thymidine-labelling index revealed a 43.2-fold (BBN) and 22.6-fold (FANFT) increase, respectively, in the enzyme-deficient areas, as compared with the surrounding emzyme-containing urothelium. After 54 hrs of continous labelling, there was a mean 3H-thymidine-labelling index of 54.9% in the enzyme-negative regions. The physiological mode of regeneration was no longer maintained in the areas of enzyme deficiency as there was an increased proliferation of suprabasal cells. Areas of papillomas that showed a marked attention of NADH-diaphorase had a 3H-thymidine-labelling index 4.5 (BBN) and 3.1 (FANFT) greater than the surrounding areas with preserved enzyme activity. Since loss of alkaline phosphatase activity occurs regulary and consistently after application of carcinogens with chemically different structures it appears to indicate the initial phase of tumor development in the urinary bladder of the rat.


[Experiments and theoretical cell kinetic calculations on the problem of in vivo synchronization with vincristine in L 1210 ascites tumor cells and crypt cells of the mouse (author's transl)]. Experiments are described on synchronizing L 1210 ascites tumor cells and jejunal crypt cells of the mouse with vincristine. In both cases the percentage of mitoses increases to a peak value 4 hrs after application of vincristine and decreases during the following 8 hrs ("releasing time") to the level of the normal mitotic index. Following this first mitotic peak no futher peak of neither the mitotic nor the labeling index was observed during 48 hrs in L 1210 ascites tumor cells and during 38 hrs in crypt epithelia. Thus, in both cell types it was not possible to obtain a synchronizing effect by applying vincristine. Based on cell kinetic considerations it was examined whether peaks of the mitotic as well as the labeling index can be expected at all under the given circumstances. The results show that the theoretical course of the mitotic index coincides with the measured values. This means that no peak of the mitotic index can be expected from the theoretical point of view. In calculating the time course of the labeling index the theoretical curve proved to depend to a high degree on the variations of the cycle time which are not known in detail, especially not after application of vincristine. However, the theoretical conditions show that also in the case of the labeling index no peak can be expected. This agrees with the experimental results. The general significance of a long "releasing time" of 8 hrs or more for the lack of a synchronizing effect is discussed.


Transplacental induction of neurogenic tumors in BD IX rats by intragastric administration of ethylnitrosourea precursors. The concurrent daily intragastric administration of ethylurea at two dose levels (50 mg/kg and 100 mg/kg bodyweight) together with one dose level of sodium nitrite (50 mg/kg bodyweight) by a stomach tube to pregnant BD IX rats from day 15 to day 22 of gestation resulted in the induction of neurogenic tumors in all offspring. Since both ENU-precursors alone do not produce neurogenic tumors, these results are evidence of ENU formation from its precursors under the influence of gastric juice. Differences in the survival time and the incidence of tumors at both dose levels were not significant. The amount of ethylnitrosourea synthesized in the animals was very close at both dose levels, and was dependent on the amount of sodium nitrite applied. The experimental results are consistent with the conclusion, that the rat fetuses had been exposed to a total amount of about 60 mg/kg ethylnitrosourea. Neurogenic tumors dominated with 98% incidence over the non-neurogenic. The incidence of neurogenic tumors per rat was high (6.0 for Group I and 6.7 for Group II). Neurogenic tumors were equally distributed among the central and peripheral nervous systems. The neurogenic tumors induced with the precursors of ethylnitrosourea were morphologically similar in all aspects to those induced with the carcinogen itself and could be classified as oligodendroglioma, astrocytoma, mixed glioma, anaplastic glioma, glioependymoma, ependymoma, and neurinoma. Three unusual tumors were found: one early anaplastic "septum ependymoma" in the dorsal column of the spinal cord, and two special mixed tumors of the cranial nerves, i.e. a neurinoma with portions of an oligodendroglioma and a neurinoma with parts of an invasive ependymoma.


Ultrastructure of primary lymphosarcoma of testis. A case of primary lymphosarcoma of testis was studied by light and electron microscopy. The fine structure of the lymphosarcoma cells was simple and monotonous. The cytoplasm was scanty and contained normal-looking organelles. Free ribosomes were abundant and the Golgi apparatus was well developed. The nuclei were large and irregular in shape with prominent nucleoli. "Nuclear pockets" enclosing material similar to the cytoplasmic ground substance were found infrequently. Remnants of disintegrating cells were also encountered.


In vitro growth of neoplastic rat glial cells. An ependymoma was induced in the brain of a BD-IX rat by repeated doses of MNU. In vitro grown cells of the tumor were fibroblasts and stellate cells considered to be glial. Reimplantation of these cells into the brain of another BD-IX rat resulted a tumor growing in the meninges. This tumor was then repeatedly transplanted over several passages. Its gross morphology resembled that of a sarcoma; however, glial in cells could be demonstrated with silver methods. A cell line derived from the first transplanted tumor group proved to contain S-100 protein in traces in the first passages in vitro. Explanted cells of the primary ependymoma were cloned. Two clones were established, RGL 1 and RGL 2. The cells of both clones resembled morphologically the stellate elements of the primary explant. RGL 1 contained S-100 protein. It was cloned again in the 16th subpassage. Four clones were established. Only 1 contained S-100 protein in traces. The clone RGL 1 had a subdiploid karyotype with a modal number of 39 and a large submetacentric marker. It was subcloned in the 25th passage with two clones, both having a karyotype of 41 chromosomes.


[Skin transplantation in the study of chemical carcinogenesis. III. Reduced papilloma-formation after initiation during epidermal hyperplasia induced by skin grafting or by a single application of the cocarcinogen TPA]. Skin autografting or a single painting with the cocarcinogen TPA was used to induce epidermal hyperplasia in the back skin of C3H mice. Initiation by intragastric application of the carcinogen DMBA during this state of hyperplasia and subsequent promotion by repeated application of the cocarcinogen TPA led to decreased papilloma-formation, as compared to mice of a control group which had not been pretreated before initiation. Reports by others referring to increased susceptibility of replicating epidermal cells to the effect of initiation thus cannot be confirmed. The reduction of papilloma-formation can most probably be ascribed to effects of local inflammation, either preferentially but unspecifically damaging initiated cells, or facilitating a specific immune response against tumor-associated transplantation antigens of prospective tumor cells.


Cellular- and permeability-changes in the peritoneal cavity of mice after injection of endotoxon. Injection of endotoxin into the peritoneal cavity of mice causes an early emigration of PMN-leucocytes and therafter a decrease in macrophage count. The number of lymphocytes shows only a transient increase. One and 2 injections of endotoxin rise the fibrinogen and protein level of the peritoneal fluid. A simple test for measuring the change in permeability (and lymph circulation) was described ("congo red elimination's test"). Changes in permeability occur after a latent period of 2 hours following endotoxin administration, culminate during the 1st day and last about 3-4 days. The possible mechanisms of the above phenomena are discussed.


Adjuvancy of streptococcal nucleic acids. A study was performed to find out whether or not RNA and DNA isolated from Group A streptococcal cytoplasm does possess adjuvant activity. The findings obtained indicate that the adjuvancy of streptococcal RNA is very similar to that of poly I:C. The adjuvant activity of poly I:C is characterized by its capacity to increase the number of pre-existing hemolysin-producing spleen cells and by its ability to increase the development of 19S and 7S producers early in the 12-day-period of primary immune response. The adjuvancy of streptococcal DNA was considerably less pronounced than that of RNA. Neither poly I:C nor streptococcal RNA and DNA were found to be capable of increasing the process of priming for the secondary immune response.


[Studies on the in vitro formation of antibodies. III. Induction of primary and secondary immune response in vitro]. Peritoneal cells from normal, unimmunized mice (female NMRI, 28-32 gr) produced in vitro primary and secondary immune response after induction with the bacteriophage T2 6 hours or 7 day resp. after establishing the cultures. We confirmed the induction of a primary and secondary immunological response in vitro in the very same culture by the following data: 1. In vivo the donor animals were not in contact with the antigen used. We found neither the phage nor its host E. coli B in the gut of 97 mice investigated and no humoral antibodies against T2. The kinetics of humoral antibody production in vivo by different doses of T2 also showed that there are no related or identical antigen structures incorporated in our animals. 2. The T2 neutralizing activity in the culture medium after the first induction had the sedimentation constant of 19.7 +/- 2.3 S (n = 9) but the activity found after the second induction sedimented with 8.1 +/- 0.7 S (n = 10). 3. The primary activity was more sensitive to mercaptoethanol than the secondary. 4. Complement was bound by the complex T2 + neutralizing activity.


Cytochemical studies of rosette-forming cells. Two types of rosette-forming cells were identified: rosette-forming cells with membrane-bound receptors for sheep erythrocytes (E-RFC) and rosette-forming cells with Fc receptors (EA-RFC). In both types of lymphocytes the activity of acid phosphatase, beta-glucuronidase, non-specific esterase and the content of glycogen were studied. A significant difference was established between E-RFC and EA-RFC lymphocytes as concerns acid phosphatase activity; corresponding mean values being 72.4 +/- 7.5 respectively 44.4 +/- 4.5 (p less than 0.01). As oppose to the acid phosphatase activity the glycogen was significantly higher in EA-RFC lymphocytes (mean 67.2 +/- 6.9), as compared with E-RFC (mean 41.6 +/- 9.2). It seems to us that estimations of acid phosphatase activity may be of value in differentiating 2 populations of lymphocytes.


[Study of anti-T-agglutinins in active and inactivated human sera (author's transl)]. Anti-T-agglutinins were found in 252 of 283 human sera investigated applying the two-step neuraminidase test and using an RDE-preparation of czechoslovakian origin. Storage and heating of the sera was followed by a reduction or loss of T-agglutination dependent on the time of incubation at 4 degrees C and 56 degrees C. This was proved to be caused by the inactivation of the anti-T-agglutinins and not by the loss of complement. T-transformed erythrocytes absorb anti-T-agglutinins completely. However, they are rarely found in eluates of anti-T-sensitized erythrocytes. The two-step neuraminidase test is a simple and reliable method for the detection of anti-T-agglutinins in human sera.


Immunosuppressive activity of heterologous antimacrophage sera. Antisera against rat macrophages were raised in rabbits and tested individually, serologically and in vivo, by injecting 1.5 ml/100 g into LEW rats 1 and 4 days following a graft of CDF rat skin. 1. Erythrocyte absorption reduced the mean lymphocytotoxic titer of antimacrophage sera from 1:16 to 1:1, but yielded strongly immunosuppressive sera. They extended the graft survival time from the normal rate of 11-14 days up to 217 days. 2. Additional absorption with lymphocytes reduced this activity significantly, but still yielded very active sera (graft survival up to 83 days). 3. After the procedure for serologically exhaustive absorption was repeated, an in vivo control for exhaustive absorption of anti-lymphocyte antibodies was performed. The results showed that the double-absorbed sera did not exhibit reduced immunosuppressive activity. 4. The above activity was found in 9/16 antisera. Seven antisera were inactive in vivo, though they showed similar in vitro activity with respect to their toxic titers against macrophages. These results confirm and extend our earlier functional and morphological studies on AMS. They are discussed in relationship to the controversial data from literature.


Antiglobulin test for titration of antilymphocyte globulin. An antiglobulin assay, derived from the indirect Coombs' reaction has been adapted to the titration of antilymphocyte globulin (ALG). Ten different ALG preparations have been investigated by this test and titres obtained are satisfactorily correlated with skin allograft survival in monkeys, rosette inhibition and mixed lymphocyte reaction inhibition. The antiglobulin test has also proved to be valuable for the monitoring of ALG-therapy in patients as well as for studying the mode of action of this potent immunosuppressive agent.


The effect of ethyl alcohol and beta-propiolactone inactivated vaccinia virus on the development of skin immunity and the production of hemagglutination inhibiting antibodies in guinea pigs, rabbits and monkeys. The efficacy of hemagglutinin containing preparations of vaccinia virus in eliciting skin immunity and hemagglutination inhibiting antibodies has been studied in guinea pigs, rabbits and monkeys. The preparations, grown on chorioallantoic membranes from chick embryos, have been tested both in the form of live vaccine and after inactivation with ethyl alcohol and beta-propiolactone. Statistical analysis of the results, comprising data from 200 guinea pigs, 80 rabbits and 100 monkeys, shows that there is a strong correlation between hemagglutination inhibiting antibodies and skin resistance, both when the anti-hemagglutinin is produced in response to live as well as inactivated vaccinia virus.


Heteroagglutinins and spontaneous rosette-forming cells in obese strain (OS) chickens. Sera of OS chickens with spontaneous autoimmune thyroiditis (SAT) and of normal white Leghorn (NWL) controls, aged 4-20 weeks, were studied for the presence of heteroagglutinins to sheep (SRBC) and rabbit red blood cells (RRBC). Significantly higher frequency and titers of SRBC- and RRBC-agglutinins were found in OS as compared to NWL birds, the difference being more accentuated with RRBC. The number of spontaneously rosette-forming peripheral blood lymphocytes (RFC) with SRBC and RRBC was determined in 20-week-old OS and NWL chickens. The number of RRBC-RFC was found to be significantly elevated in the OS. The value of RFC did not correlate with the individual heteroagglutinin titers. RFC and heteroagglutinin secreting cells are considered to be nonidentical. These results are discussed in the light of the previously established hyperreactivity of the B-dependent portion of the immune system in OS chickens.


Interactions of the third component of complement (C3) with cross-linked dextran. II. Demonstration of an alternate pathway activation as binding mechanism of C3 to cross-linked dextran. In previous investigations we could show that incubation of cross-linked dextran (Sephadex) with normal human serum results in the binding of the third component of complement to the Sephadex beads. In this paper, data are presented which demonstrate that not only human but also guinea pig C3 reacts with Sephadex and that this binding is due to an alternate pathway of C3 activation. This conclusion was drawn, since a) C3 is bound also from guinea pig serum with total deficiency of C4, b) the reaction can be completely blocked by EDTA but only diminished by EGTA and c) the reaction turned out to be temperature dependent with an optimum at 37 degrees C and could be abolished by diluting the serum more than 1:16. The ability of cross-linked dextran to activate C3 via the alternate pathway seems to be due to conformational changes, since in our experiments soluble dextran of the same source was found to be ineffective in this respect. Implications from these findings and possible applications are discussed.


The effect of antibody and complement on perfused hearts: a model for the study of xenograft rejection phenomenon. An in vitro heart perfusion system was developed to study the effect of antibody and complement on hearts in vitro, as a model to quantitatively evaluate factors involved in xenograft rejection. Both guinea pig and rabbit hearts were tested with various reagents. Perfusion of hearts with normal autologous or "homologous" sera did not induce rejection, while "heterologous" sera, normal or immune, arrested cardiac function. Either the inactivation of certain complement components or the absence of antibodies against heart tissue prevented rejection as determined by lack of change in electrocardiogram and alterations in ultrastructure. Antibody alone had no effect. A lethal effect of C6-deficient rabbit serum on guinea pig hearts was prevented by 2 antihistamines, Chlortripolon and Benadryl.


Determination of the antigen binding capacity of antisera to collagen by gel filtration. Significant differences in the antigen binding capacity of different antisera to collagen of identical haemagglutination titres were demonstrated by using gel filtration for the isolation of collagen-anticollagen immune-complexes. A partially degraded collagen was used as the antigen. The influence of antigen concentration on antigen binding capacity was investigated with 2 antisera of different avidity. The distribution of antibody-bound antigen among IgM- and IgG- peaks indicates the participation of both immunoglobulin classes in the formation of collagen-anticollagen immune-complexes.


Cytological changes and antigen capture in chicken spleen during the secondary immune response to homologous and cross-reacting antigens. It was demonstrated by autoradiography using 125I-labeled antigens that in the secondary response to bovine serum albumin (BSA), a considerable amount of antigen is localizing in the germinal centers (GC) of chicken spleen prior to the onset of antibody production. A similar early antigen capture, although of a lesser degree, was also noted when birds originally immunized with BSA were injected with human serum albumin (HSA) on a second occasion. Early antigen localization in GCs was scarcely demonstrable in the primary response. Since antigen capture requires specific antibodies, it was concluded that the antigen binding cells correspond with B lymphocytes of GCs formed during the primary immune response or with their descendants. On antigenic stimulus, these cells transform to antibody producing cells after one or more mitoses. GCs can therefore be regarded as memory units composed of cells committed to one and the same antigen. Cells of the thymus-system probably play a cooperative role in the antigen-induced formation of GCs.


Correlation between the results of the migration inhibitory factor production test with DNA and the severity of the disease in the systemic lupus erythematosus patients. A correlation was made between the severity of clinical symptoms of SLE and the results of the migration inhibitory factor (MIF) production test. For this purpose 10 patients with various manifestations of SLE were examined by MIF production test before and after the immunosuppressive therapy. A good correlation between the actual clinical stage and the results of the MIF production test was found. The successful immunosuppressive therapy turned the positive MIF production into the negative one in most of the observed patients. The MIF production test is therefore recommended as a good complementary test for the estimation of the actual state of the SLE.


Lymphokines in sensitized rats (II). Skin reacting factors and lymphnode activating substances originating from thymocytes. In vivo activity upon draining popliteal lymphnodes of lymphokine-containing thymic cell culture supernatants from rats sensitized to PPD was studied after subcutaneous injection into footpads of normal recipients. Also inflammatory skin responses after intradermal injection of the same supernatants into the same untreated animals were studied. It appeared that only concentrated culture supernatants from antigen-stimulated thymic cell cultures were able to cause paracortical changes in draining lymphnodes after subcutaneous injection, and inflammatory skin reactions after intradermal injection in untreated animals in contrast to control supernatants. The results confirm the hypothesis that a population of cells must be present in the thymus of the sensitized rat which is able to produce lymphokines after contact with specific antigen.