Critical pulmonary valve stenosis with intact ventricular septum. This study presents our experience in the surgical management of the newborn with critical pulmonary stenosis and intact ventricular septum. During the last decade we have seen 11 such patients, with a mean age of 2.3 days (maximum 6 days) and a mean weight of 3.6 kilograms (maximum 4.5 kilograms). The primary operation was a valvotomy in 7 patients (one of whom also had a systemic-pulmonary shunt), a commissurotomy with cardiopulmonary bypass in 3 patients, and a shunt alone in 1 patient. One infant died on the second postoperative day and another died following reoperation at 4 months. The other 9 patients were all alive and progressing satisfactorily when last seen. Five of these patients were beyond their third postoperative year and the longest survivor was at 7.9 years. Four of the long-term survivors had undergone reoperation. Our choice of operation remains transventricular valvotomy, although an open procedure utilizing cardiopulmonary bypass presents an attractive alternative. A systemic-pulmonary shunt as an addition to either of these operations is unnecessary. The perioperative use of prostaglandin E brings about substantial improvement in the early results.


Long-term observation of pacemaker electrodes. A follow-up study of 328 consecutive patients treated between 1959 and 1967. Epicardial electrodes implanted in 20 patients between 1959 and 1962 had a short-term effectiveness. A change to endocardial stimulation was later necessary in 15 of these patients. Endocardial electrodes inserted between 1962 and 1967 in 306 patients were included in this study; 121 (40%) of these patients survived for 10 years or more. Seventy-five (62%) of the long-term survivors had no problems with their electrodes. In 39 of these patients the stimulation thresholds were measured after both 5 and 10 years and found to be 2.3 +/- 0.6 volts and 2.2 +/- 0.8 volts, respectively. Hence, long-term complication-free endocardial pacing can be accomplished.


The effects of deep hypothermia and circulatory arrest on systemic metabolic state of infants undergoing corrective open heart surgery: a comparison of two methods. Fortyone of 187 infants undergoing corrective surgery for their congenital cardiac lesions using profound hypothermic circulatory arrest were randomly selected for metabolic studies. Deep hypothermia of 21 to 22 degrees C core temperature was reached by two different techniques: 1. Perfusion cooling by extracorporeal circulation (ECC-C) 2. Surface cooling with ice bags combined with perfusion cooling (SC + ECC-C) After circulatory arrest (34.2 min. ECC-C v.s. 46.7 min. SC + ECC-C) bypass rewarming was used in both groups. The metabolic reaction to these interventions are described. No significant differences in acid base status in oxygen consumption, lactate concentration, serum electrolytes (K+, Na+, Ca++,Cl-) and serum enzyme activity (CPK, alpha-HBDH, LDH, SGOT, SGPT) could be demonstrated between the two groups of patients during the entire course of cooling, circulatory arrest and rewarming. The glucose concentration was significantly lower in the ECC-C group during the entire period of operation. Total cooling time was significantly shorter in the group without surface cooling. (ECC-C: 12 min, v.s. SC + ECC-C: 64 min). Since no favourable effects of the SC + ECC-C method on systemic metabolism could be demonstrated and operative results were similar we now prefer the time-saving ECC-C technique.


Heart valve replacement with the St. Jude medical prosthesis -- first clinical results --. Starting in February 1978 52 St. Jude Medical Prostheses have been implanted in 47 patients (age 13--73 years) in aortic, mitral and tricuspid positions. Perioperative death occurred in 3 cases. Post mortem examination of these patients showed unimpaired valvular function. There were no other complications in an accumulated total valve time of approximately 300 months. Prior to surgery and post-operatively, several hemolytic parameters were analyzed. There was only a mild elevation in Serum LDH (285 +/- 10 iV/L). Fifteen patients underwent recatheterization 3 months postoperatively. The mitral valves did not reveal an enddiastolic gradient at rest, while the aortic valves had a peak to peak gradient of 8 +/- 2.1 mmHg. A standardized stress consisting of an infusion of isoproterenol was used. The results were compared to results obtained in patients with Björk-Shiley prostheses under identical conditions and did not show a significant difference. The preliminary hemodynamic findings correlate with preceding in vitro results and preclinical data, and the first clinical experience is promising.


Management of extensive lesions of the lower trachea using emergency cardiopulmonary bypass. Rapid cardiopulmonary deterioration in patients with extensive lesions of the lower trachea presents a serious challenge in the emergency care. Conventional methods may prove inadequate to achieve airway control and to stablilize the critical condition. Severe airway obstruction and/or massive air leakage are the main causes of failure. An aggressive operative approach is mandatory. Institution of emergency cardiopulmonary bypass for resuscitative purposes and definitive surgical repair of those life-threatening uncommon tracheal lesions seems essential to us. Two cases, managed according to this concept, are presented.


HLA compatibility in couples with children suffering from acute leukemia or aplastic anemia. The frequency of common HLA-A and -B antigens were determined in 30 couples having a child with acute leukemia (AL), 34 couples having a child with aplastic anemia (AA) and 58 random couples with healthy children. An increased frequency of couples sharing at least two common antigens was observed in parents of both AL and AA children.


Responsiveness to insulin of glucose metabolism in cultured rat and human arterial smooth muscle cells. Smooth muscle cells growing in the primary culture derived from outgrowths of the intimal-medial explants of both rat and human arteries were used. The 72-hr sequential glucose uptake by the cells of both species in culture dishes was enhanced only slightly with time by the addition of insulin to culture medium, and this enhancement was statistically not significant. The glucose conversions to CO2  and lipids by the rat and human cells dissociated for tracer study were not affected significantly during the 2-hr incubation by the insulin addition in vitro. The smooth muscle cells of both species cultured for a week in medium enriched with insulin and then dissociated revealed the significantly increased glucose conversion to lipids, while the increase in the glucose coversion to CO2 was not significant in these cells. Thus, the smooth muscle cells of both rat and human seem to show significant metabolic response to chronic, but not acute, exposure to insulin. Therefore, it is likely that the persistent change in the insulin level may lead to abnormal metabolic state in the artery.


Bronchogenic carcinoma producing ectopic steroid hormones. A patient with steroid hormones or androgen producing bronchogenic adenocarcinoma was presented. Clinically he had a mediastinal mass and bilateral multiple pulmonary nodules which showed a rapid growth despite cancer chemotherapy. At postmortem examination, radioimmunoassay of the tumor tissue revealed androgen and their precursors. The mitochondria of the tumor cells resembled those of cells in the zona reticularis of the adrenal cortex.


The use of the anti-Acholeplasma activities of Streptomyces culture filtrates for the screening of new antibiotics. A screening method for new antimicrobial agents from streptomyces culture filtrates was developed. Three different types of test organisms were used for determining the antimicrobial activities of the culture filtrates: they were (a) an antibacterial activity test against Staphylococcus aureus, (b) an antimycoplasmal activity test against Acholeplasma laidlawii, and (c) a cytotoxicity test against HeLa-S3 cells. The active filtrates showing antimicrobial spectra (anticellogram) which did not match those of known antimicrobial agents were used for further purification to obtain new antimicrobial agents. Of these screening methods, antimycoplasmal activity against Acholeplasma laidawii was the most sensitive for discriminating new compounds contained in the filtrates of known antibiotics.


Long-term observation of arachnoid villi after subarachnoid hemorrhage: an electron microscopic study in dogs. The sequential electron microscopic examinations were carried out on arachnoid villi of the dog after subarachnoid hemorrhage (SAH). A few days after SAH, red blood cells were accumulated and degenerated in the villi. 10 days after SAH, remarkable phagocytosis and micropinocytosis were observed in the arachnoid villi, which may suggest increased metabolic activity of the arachnoid cells. 30 days after SAH, increased cellularity in the arachnoid villi developed and intercellular spaces became very narrow. 90 days after SAH, the arachnoid villi demonstrated many cytoplasmic filaments and hemidesmosome-like structures in the arachnoid cells, as well as narrowed intercellular space and increased cellularity. Microfibrils increased and structures resembling basal laminae were observed in the stromas. These morphological alterations may have a relation to the disturbance of absorption of cerebrospinal fluid.


Disintegration of urinary calculi by laser beam: drilling experiment in extracted urinary stones. Disintegration of urinary calculi was attempted by the use of laser beam. As a first step, drilling of extracted urinary stones was attempted using a continuous wave CO2 laser and a pulse ruby laser. Stones were drilled easily by either laser beam. The power around 10 W of continuous CO2 laser beam was sufficient to drill through the stone.


Direct evidence for recurrent inhibition in sliced brain preparation of the cat's visual cortex. To reveal the recurrent inhibitory circuit in the visual cortex, a depolarizing current was applied through a glass microelectrode to an impaled cell in an in vitro slice of the visual cortex obtained from a cat anesthetized with pentobarbital. The cell reported here produced inhibitory postsynaptic potentials (IPSPs) following single spikes or bursts of spikes which were elicited by intracellularly applied current. This observation indicates that IPSPs have been mediated by the recurrent inhibitory circuit via axon collaterals of the impaled cell.


Effects of verapamil on the contractile force in the glycerinated dog heart muscles. The effect of Ca-antagonist on the contractile apparatus was investigated in glycerinated cardiac papillary muscle preparations obtained from canine hearts. The results showed that maximal developed tension (P0) was enhanced significantly by 5 mg/liter of verapamil, and the augmentation of contractility was dependent on the concentrations of verapamil. As a conclusion, Ca-antagonist appeared to be a potentiating agent of the contractile force on the contractile apparatus.


[Comparison between conventional X-ray diagnostics and computed tomography as techniques for irradiation planning in renal carcinoma and carcinoma of the bladder (author's transl)]. In order to obtain quantitative results by means of a comparison between irradiation planning with X-ray diagnostics and planning with cross-sectional computed tomography in abdominal tumors, therapeutic programs have been established twice for the same patients, each time using one of the two techniques. Fifteen patients with renal carcinoma and 24 patients with cancer of the urinary bladder have been examined.


[Late results after preirradiation of mastocarcinomas (author's transl)]. The results of 80 cases treated with preirradiations are described. The follow-up observation time was longer than ten years. The results are statistically evaluated. It must be emphasized that lenticular skin metastases could be prevented in most of the cases. Eleven cases of double mastocarcinoma were submitted to follow-up examinations. Only two of the patients whose first and second tumors were preirradiated showed a survival time of twelve to fourteen years.


Radiation-induced changes in cell proliferation kinetics in uterine cervix cancer. In vitro double labeling autoradiography for measuring the labeling index, duration of S phase and potential doubling time has been used to assess the effect of a single and fractionated test dose of irradiation in uterine cervix cancer applied in 21 patients. Tumor-labeling index fell significantly in those tumors which had a high labeling index before irradiation, and these cases were found later to exhibit a good radiation response. Duration of S phase which ranged between 9 and 27 hours prior to irradiation was increased. Differences between the potential doubling time and the actual doubling time suggest a massive cell loss in tumors which were, for the most part, of exophytic type. Fractionated irradiation provides more reliable informations than a single dose and is useful for investigation of dynamic changes in the kinetics of an asynchronous cell population.


Anatomo-radiological study of a case of post-radiotherapeutic osteolysis of the hip. Anatomo-radiological study of a case of osteolysis of the femoral head and neck in a 56-year old male who had recieved, 22 years earlier, an intense radiotherapeutic treatment for a soft tissue tumour of the corresponding hip region. The treatment is considered as being the main etiological factor responsible for the bone lesions. The latter seems to have been favored by an indolent joint due to a thoracic cordotomy for post-irradiation pains; it may have been prepared by a secondary osteodystrophy which preceded the radiotherapy and seems due to two previous surgical excisions.


[Three dimensional optimization method for the interstitional afterloading therapy (author's transl)]. The authors present a new method for the interstitial therapy working with an Ir-192 source which is displaced step by step. After having been fed with the tumor parameters, the computer calculates for every stopping point the duration of stay of the source which provides a threedimensional optimization. The practical application of the method is discussed and the optimization procedure is compared with other similar methods.


[The small Esssen high-pressure oxygen chamber for experimental animals (author's transl)]. A small translucent high-pressure chamber is introduced which has been exploited for local irradiation of tumour-bearing mice. The chamber has particularly proven to be valuable for high-pressure oxygen therapy together with simultaneous irradiation but can be used also for normal pressure and for gas other than oxygen. The chamber is shown during operation and a diagram illustrates design and technical data.


[An improved method to stimulate water and biological tissues in relation to linear interactions with photons and fast electrons (author's transl)]. Radiation physical problems in clinical dosimetry often need for their experimental solution the linear coefficients of interaction between radiation and irradited matter. Using modified material parameters (the products of mass density and the earlier defined effective material parameters) it was possible to derive an improved method to calculate the composition of an equivalent for a material to be substituted. The method is described and its usefulness demonstrated by some examples. A geometric analogue facilitates the solution if a computer is not available. Some comparisons are made between this method and the basic data method of White.


Influence of whole body irradiation on intraperitoneal immunity in a syngeneic mouse lymphoma system. DBA/2 mice were immunized against the syngeneic SL2 lymphoma by two injections with irradiated lymphoma cells or by two injections with irradiated cells followed by one injection with unirradiated cells. Whole body irradiation (500 rad) of the immunized mice caused a significant decrease in the number of peritoneal macrophages and lymphocytes. The spleen weight showed a transient decrease. However, whole body irradiation did not cause a significant decrease of the survival time of immunized mice challenged intraperitoneally with SL2 lymphoma cells.


Heterocyclic steroids-part VIII: Studies on the total synthesis of racemic 2-phenyl-7-methyl-3-oxa-A-nor-14 beta-estra-1,5(10),6,8-tetraen-17 alpha-ol. 2-Phenyl-6-methyl-4-oxo-4,5,6,7-tetrahydrobenzofuran (II) is converted into racemic 2-phenyl-7-methyl-3-oxa-A-nor-14 beta-estra-1,5(10),6,8-tetraen-17 alpha-ol (VIII).


Bile acid sulfates. III. Synthesis of 7- and 12-monosulfates of bile acids and their conjugates using a sulfur trioxide-triethylamine complex. The 7- and 12-monosulfates of chenodeoxycholic acid, deoxycholic acid, and cholic acid were prepared by sulfation of the protected bile acids with sulfur trioxide-triethylamine in pyridine overnight and were isolated by precipitation as the p-toluidinium salt after removing the protecting group(s). The taurine conjugates were obtained by conjugating the bile acid sulfates with taurine in hot dimethylformamide (DMF) in the presence of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). A new procedure of preparing glycine conjugated bile acid sulfates by direct conjugation of the bile acid sulfate triethylammonium salt with ethyl glycinate in boiling chloroform in the presence of EEDQ is also described. The advantage of these procedures over other procedures are their simplicity and their higher yields (tyically above 90%) The thin layer chromatographic mobilities of these sulfates are presented. The influence of side chain and hydroxyl group configurations on the properties of bile acid sulfates is briefly discussed.


Serum levels of corticosterone and 18-hydroxy-11-deoxycorticosterone in the female rat at the high and low points of the circadian rhythm. Serum corticosterone (B) and 18-hydroxy-11-deoxycorticosterone (18-hydroxy-DOC) levels were determined in female rats at the high (1800 h) and low (0600 h) points of the circadian rhythm. In order to carry out these studies, a rapid and accurate non-chromatographic radioimmunoassay method was developed for the measurement of 18-hydroxy-DOC in peripheral blood and similar methodology was used for the B assay. In quiescent rats both steroids were dramatically elevated at 1800 h as compared to 0600 h. The serum levels of B and 18-hydroxy-DOC determined at 1800 h fifteen minutes following stress did not differ significantly from the levels determined following a similar stress at 0600 h. There was a good correlation (r = 0.91) between the levels of B and 18-hydroxy-DOC and it appears that both steroids are regulated by ACTH.


In vitro metabolism of 4-androstene-3,17-dione and testosterone by rat submaxillary gland. Tritiated 4-androstene-3,17-dione and testosterone were incubated with submaxillary gland homogenates of male and female rats. The metabolism was predominately reductive. In 15 and 180 min incubations submaxillary tissue converted 4-androstene-3,17-dione chiefly to androsterone. Less testosterone, 17 beta-hydroxy-5 alpha-androstan-3-one, 5 alpha-androstane-3,17-dione, 5 alpha-androstane-3 alpha, 17 beta-diol, and 4-androstene-3 alpha, 17 beta-diol were also identified. Testosterone was converted to the same products plus 4-androstene-3,17-dione. 5 alpha-Androstane-3 alpha, 17 beta-diol was the major testosterone metabolite. Qualitatively the metabolism by male and female submaxillary gland was similar.


Photohydration of testosterone and 4-androstene-3,17-dione in aqueous solution. Irradiation of testosterone, 4-androstene-3,17-dione, or their "half-molecule" 4,4a,5,6,7,8-hexahydro-4a-methyl-2(3H)-naphthalenone in dilute aqueous solutions with ultraviolet light of 254 nm wavelength caused rapid addition of water across the olefinic bond with formation of 5,17 beta-dihydroxy-5 alpha-androstan-3-one, 5-hydroxy-5 alpha-androstane-3-17-dione, and 9-hydroxy-10-methyl-2-decalone, respectively. Time-lapse spectrometry in the ultraviolet region showed that the photohydration of the androgenic steroids was extremely efficient and virtually free of the side reactions. Preparative photolytic reactions carried out in water-methanol solutions allowed isolation and characterization of photoproducts.


Simultaneous radioimmunoassay of serum testosterone and 5 alpha-dihydrotestosterone without chromatography. When characterization of the specificity of an antiserum for radioimmunoassay (RIA) is performed by the conventional method, the conditions under which interference occurs are not respected because of the lack of specific antigen. We have studied the behavior of antisera reproducing the real environment existing in unknown samples, in which antigen, interferent and tracer complete simultaneously. A testosterone (T) antiserum and a 5 alpha-dihydrotestosterone (D) anti serum were characterized by setting up two distinct hapten recovery tests in the presence of both the hapten and the crossreactant added to steroid-free serum in various concentrations in order to reproduce multiple concentration ratios. These samples, together with the standard curves samples (prepared by 'spiking' steroid-free serum with known concentrations of T or D) were extracted and subjected to T-RIA and D-RIA without purification. The results have shown that the interferent-induced incremental ratio is a linear function of the ratio of the levels of cross-reactant and hapten via a proportionality factor inversely correlated to the antiserum specificity. By means of this function, the overestimated T and D levels found in samples after 'extraction only' have been corrected and the resulting values have shown acceptable correlation with the corresponding levels determined after column chromatography.


A novel fluorinated derivative of diethylstilbestrol. The synthesis of the diethylstilbestrol (DES) derivative with fluorine atoms present in the positions ortho to the hydroxyl in each ring is described. In vitro studies in a system containing horse radish peroxidase/H2O2 demonstrate extensive oxidation of tetrafluorodiethylstilbestrol to the corresponding dienestrol derivative. Tetrafluorodiethylstilbestrol and DES had comparable in vivo uterotropic activities at a dose of 100 microgram/kg. Competitive binding experiments demonstrated 20-25 fold reduced interaction with the mouse uterine estrogen receptor. This compound may be useful as an experimental estrogen in distinguishing between the biological and toxic effects of DES.


Radioimmunoassay of 2-hydroxyesterone and 2-methoxyestrone in human urine. An assay for the quantitative determination of 2-hydroxyestrone and 2-methoxyestrone in human urine is described. The analytical procedure involves several purification steps: XAD-2 column chromatography of urine (1 ml), hot acid hydrolysis under reducing conditions, extraction with benzene/ethyl acetate, separation of monophenolic steroids from catecholestrogens by the formation of borate complexes, and partition between different solvents. Quantitation is achieved by radioimmunoassay using highly specific antibodies. For correction of procedural losses [6, 7-3H2] 2-hydroxyestrone and [6, 7-3H2] 2-methoxyestrone are used as internal standards. The method is highly specific as checked by comparison to a double-isotope-derivative method and a newly developed gas chromatography-mass spectrometry procedure. Using this method the urinary excretion of 2-hydroxyestrone and 2-methoxyestrone was studied in children, men, cycling, pregnant and postmenopausal women. Special interest was focussed on the molar ratios of 2-hydroxyestrone to 2-methoxyestrone and the so called "total estrogens" which vary markedly within the different groups investigated. The excretion of 2-hydroxyestrone is especially favoured in women during the menstrual cycle and pregnancy.


Metabolism of progesterone in the pregnant sheep near term: identification of 3 beta-hydroxy-5 alpha-pregnan-20-one 3-sulfate as a major metabolite. Two pregnant ewes near term were given a single injection of progesterone-4-14C via the left jugular vein, and serial blood samples were taken from the right jugular vein at 5 min intervals over a period of 40 min. Radioactive steroids in the plasma were separated into unconjugated and conjugated fractions which were further isolated and analysed by established methods. The injected hormone was rapidly metabolized with a half-life of approximately 10 min and metabolic clearance rate about 3.5 liters min. The bulk of the metabolites was found in the sulfate fraction from which a major metabolite was identified as 3 beta-hydroxy-5 alpha-pregnan-20-one. From the unconjugated fraction, 20 alpha-hydroxy-pregn-4-en-3-one, a known minor metabolite was also isolated. No radioactive estrogens were found. It is concluded that a major portion of circulating progesterone in the pregnant ewe near term is cleared by 5 alpha-reduction of ring A, followed by sulfo-conjugation.


Improved synthesis of 5 beta-cholestan-26-oic acids. An improved method for the synthesis of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestan-26-oic acid and 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestan-26-oic acid is described. The method involves an Arndt-Eistert rearrangement of the corresponding diazoketone obtained by the action of diazoethane on 3 alpha, 7 alpha-diformyloxy-5 beta-cholane-24-carboxylic or 3 alpha, 7 alpha, 12 alpha-triformyloxy-5 beta-cholane-24-carboxylic acid chloride. The products are obtained in good yield and no isomeric 27-nor- 24-methyl acid contaminants are formed as encountered in the commonly employed Kolbe synthesis.


Determination of the configuration of epimeric diols of vitamin D3 series by mass spectrometry. The mass spectral elimination of water in epimeric 1,3-diols of vitamin D3 (colecalciferol) series has been investigated. It was found that the mass spectra of these steroisomers differ sharply in the relative intensities of the ions M-H2O (m/e 382) and a-H2O (m/e +/- 34), where ion a (formed via formal cleavage of the 7, 8-double bond) is characteristic of vitamin D3 and its derivatives. So while epimeric 1, 3-diols of vitamin D3 series have very close UV and NMR characteristics, the comparison of the ratios of the peaks M-H2O and M.+, a-H2O and a, respectively, makes it possible to distinguish between stereoisomeric 1 alpha, 3 beta-, 1 beta, 3 beta-, 1 alpha, 3 alpha- and 1 beta, 3 alpha-diols using their mass spectra.


Synthesis of C-19 deuterium labelled steroids. Preparation of the synthetically useful steroid intermediate 19-d3-androst-4-ene-3,17-dione (Ia) together with its 19-d2-(Ib) and 19-d1-(Ic) analogues is described. The conditions and work-up of the synthesis have been designed to eliminate tedious chromatographic separation and purification steps thus enabling decigrams of material to be conveniently prepared using standard laboratory apparatus. The deuterium label in the C-19 angular methyl group is inert to normal chemical exchange processes, thus offering the opportunity for synthesis of more complex, biologically active, stable labelled steroids, whose metabolism can be studied mass spectrometrically.


The source of progesterone in preimplantation rabbit blastocysts. In vitro and in vivo synthesis of progesterone, sequestration of progesterone from the surrounding medium, and its subsequent conversion to metabolites was investigated in 146 hr post coitus preimplantation rabbit blastocysts. No significant conversion of 3H-pregnenolone to 3H-progesterone was observed throughout the 8 hr incubation. Progesterone content in blastocysts and culture medium did not change during the course of an 8 hr incubation. This suggests that the failure to detect incorporation of label into progesterone was not due to the presence of a large endogenous pool of pregnenolone. Significant uptake (p less than 0.05) of 3H-progesterone from the incubation medium was observed as was significant conversion of the 3H-progesterone to unidentified metabolites. Therefore it would appear that the preimplantation rabbit blastocyst is not capable of de novo synthesis of progesterone from pregnenolone prior to implantation but sequesters progesterone from the surrounding medium and converts it to progesterone metabolites.


The identification and characterization of a new C19O3 steroid metabolite in the rat ventral prostate: 5 alpha-androstane-3 beta, 6 alpha, 17 beta-triol. This study represents the first report of the formation of 5 alpha-androstane-3 beta, 6 alpha, 17 beta-triol (6 alpha-triol) by prostatic tissue. The 6 alpha-triol has been identified by rigorous methods and a chemical synthesis of this triol has been accomplished. This 6 alpha-triol is the major metabolite of 5 alpha-androstane-3 beta, 17 beta-diol (3 beta-diol) in the rat ventral prostate. A minor metabolite of 3 beta-diol has been identified as 5 alpha-androstane-3 beta, 7 alpha, 17 beta-triol (7 alpha-triol). Using a variety of C19 androstane substrates, the 6 alpha- and 7 alpha-triols were always found as the major components of the total 3 beta-hydroxy-5 alpha-androstane metabolites produced by the ventral prostate. Following intraperitoneal injection of 3H-3 beta-diol, both 6 alpha- and 7 alpha-triol were formed in vivo by the ventral prostate and found in the blood. The 6 alpha- and 7 alpha-triols were found to possess no androgenic activity when tested by the ventral prostatic growth bioassay in the castrate rat.


Reversible interaction between androgen binding protein and testicular macromolecules causing inhibition of androgen binding activity. Sertoli cells in culture isolated from immature rat testes secrete androgen binding protein (ABP) in the culture medium. Binding activity of ABP in concentrated medium was estimated with equilibrium dialysis against 1 nM dihydrotestosterone at 4 degrees C. The ABP protein activity was inhibited approximately 50% through addition of cytosol preparations from testis or liver, but not from brain tissue, to the concentrated culture medium; this inhibition remained constant for at least two days. The inhibitor is probably a macromolecule, because the activity could not be removed by charcoal treatment and dialysis. The percent inhibition of ABP binding activity was increased when increasing amounts of cytosol were added, it decreased in the presence of increased concentrations of androgens, but it was not influenced by variations of the concentration of ABP. Inhibition of androgen binding to ABP by cytosols in the presence of 1 nM testosterone could be reversed after dialysis in the presence of 10 nM testosterone. These results suggest a reversible competition between testosterone and the testicular macromolecule for ABP. The occurrence of this interaction between ABP and a testicular macromolecule can explain the variable results of estimated ABP binding activity in testis cytosol preparations.


The carotid bifurcation plaque: pathologic findings associated with cerebral ischemia. Embolization from or decreased flow through cervical carotid and vertebral arteries causes ischemic stroke syndromes. Specific pathologic findings were studied in 50 symptomatic patients who underwent 69 carotid endarterectomies. Detailed analyses of their carotid plaques included correlations between photographs of gross specimens, microscopic findings, angiograms, preoperative symptoms and long-term postoperative follow up. Carotid plaques were primarily fibrous with significant (greater than 70%) stenoses encountered in 70% of the arteries. Stenoses were due to simple fibrous thickening in only 20%; the remainder due to intraplaque hemorrhage, atheromatous debris and, least often, luminal thrombus with or without ulceration. Intramural hemorrhage was frequent in plaques associated with focal neurologic symptoms and may have preceded localized collections of atheromatous debris. Ulceration occurred in 1/3 of all plaques, symptomatic or not. It is concluded that the carotid plaques start as fibrointimal thickening evolving to symptomatic stages by the occurrence of one or more of a number of pathologic changes, intraplaque hemorrhage being prominent. A single rational therapeutic regimen seems impossible until patients can be classified according to their pathologic changes diagnosed non-invasively.


Scanning electron microscopic study of endothelial cells of cerebral arteries from spontaneously hypertensive rats. Endothelial cells of the cerebral arterial system in spontaneously hypertensive rats were investigated by scanning electronmicroscopy and found to show progressive changes such as increased microvilli, numerous plasmalemmal pits, enlargement of the cells and well-developed marginal folds. Regressive changes, such as balloon-like protrusions and crater-like cave-ins, were also observed. Platelet adhesion to the injured endothelial surface of cerebral arteries was frequent. The significance of these changes in the development of hypertensive cerebrovascular lesions is discussed.


The electrocardiogram in stroke: relationship to pathophysiological type and comparison with prior tracings. The author reviewed electrocardiographic records of 150 patients with acute stroke and 150 age- and sex-matched controls, to assess the relative frequencies of ECG abnormalities among the pathophysiologic categories of stroke, and to distinguish new abnormalities at the time of the stroke from those noted on prior tracings. Of the 150 patients with stroke, 138 (92%) showed ECG abnormalities. The most common abnormalities were also changes from prior tracings: QT prolongation (68 patients, 45%), ischemic changes (59, 35%), U waves (42, 28%), tachycardia (42, 28%), and arrhythmias (41, 27%). Patients with cerebral embolus had a significantly increased frequency of atrial fibrillation (9 patients, 47%); and with subarachnoid hemorrhage an increased frequency of QT prolongation (20, 71%) and sinus arrhythmia (5, 18%). The frequencies of QT prolongation and ischemic changes related strongly to admission systolic pressure but not to mortality. Stroke patients had an increased frequency of pathologic Q waves (30 patients, 20%) and left ventricular hypertrophy (39, 26%), but these were not new findings at the time of the stroke. The results are consistent with an interaction of underlying hypertensive or atherosclerotic cardiovascular disease, sympathetic hyperactivity, and possibly myocardial necrosis, in producing ECG changes.


Transient ischemic attacks. Retrospective study of 150 cases of ischemic infarct in the territory of the middle cerebral artery. Transient ischemic attacks (TIA) are episodes of abrupt beginning, consisting of subjective or objective neurological dysfunction of short duration, with complete recovery of neurological function in the course of 24 hours. With this definition, the authors carried out a retrospective study of 150 patients suffering from ischemic infarct in the brain in the territory of the middle cerebral artery. Thirty-eight percent of the patients had had TIAs before their cerebral infarct. The symptoms, in order of frequency, were motor, sensory deficits, alterations of speech and vision. Most of the patients had a definite cerebral infarct, occurring one month after the last TIA; the symptoms of both processes were remarkably similar. The authors studied the angiographic characteristics, pharmacological and toxic antecedents, and associated diseases in these patients. The study indicates that TIA may be the first manifestation of cerebral vascular disease.


Hypertension and acute focal cerebral ischemia. Infarction and edema after occlusion of a middle cerebral artery in cats. Hypertension was produced in 8 cats by nephrectomy and wrapping the opposite kidney. Subsequent occlusion of one middle cerebral artery caused ischemic infarcts that were larger than those of 8 normotensive cats. The larger infarcts may have been caused by increases of ischemic cerebral edema resulting from changes in the cerebral endothelial barrier induced by hypertension. In addition to increasing the likelihood of strokes, hypertension in humans may predispose toward larger cerebral infarcts.


Occlusion of the vertebral or basilar artery. Follow up analysis of some patients with benign outcome. Ten patients with angiographically verified occlusion of the basilar or vertebral artery have been followed for an average of 2.75 years. None has developed further ischemia after the initial stroke, and 4 patients survived without any clinical deficit. In occlusive disease of the posterior circulation, the critical period for deficit acquisition is at the time of occlusion. Extent of the deficit depends on the rapidity of development of adequate collateral circulation, and the presence of distal embolization at the time of occlusion. Some patients survive basilar occlusion without permanent deficit.


Brain hemorrhage from intracranial tumor. Brain hemorrhage from an intracranial tumor was encountered in 7 males and 6 females during a 4-year period. In 5 patients, hemorrhage was responsible for the first signs of a previously unsuspected neoplasm. The intracranial lesion was demonstrated by computed tomography (CT scanning) in each patient. Characteristic CT scan findings included: a neoplastic core (high or low density); small, multifocal clots usually at the margin of the tumor; and, surrounding, often extensive, edema. Enhancement of the tumor tissue with intravenous injection of 60% Hypaque was observed in the 8 patients so studied. The regions which were enhanced had a peripheral distribution corresponding to the site of hemorrhage. Microscopic examination demonstrated 7 glioblastoma multiforme, 1 oligodendroglioma, 4 metastatic carcinomas (including 1 each of bronchogenic carcinoma, melanoma, hypernephroma, and adrenal carcinoma), and 1 hemangiopericytoma. High-grade malignancy and extensive, abnormal vascularity appeared to be predisposing factors.


EEG monitoring for induced hypotension for surgery of intracranial aneurysms. EEG was monitored at bilateral scalp sites outside the operative field during hypotensive aneurysm surgery in 21 patients. Mean arterial blood pressure at axillary level was 50-60 mm Hg (average 55 mm) for 1.9-5.3 hours (average 3.6). Four new deficits were noted immediately post-operatively, all related to the operated site: these were attributable to intra-operative rupture with forced vascular clipping, vasospasm, or edema. In no instance was hypotension solely responsible for a new deficit. EEG showed persistent slowing in relation to surgery in only 1 patient, where aneurysmal rupture led to severe hypotension, forced clipping of 1 posterior cerebral artery, and subsequent brain stem infarction. In the 3 other patients with fresh focal postoperative deficits, no persistent intraoperative EEG changes were observed. EEG monitoring did not detect ischemia in these 3 patients because 1) hypotension was moderate and did not per se cause new deficit, and 2) EEG electrodes did not survey the area at maximal risk, namely the operative field. EEG scalp electrodes near but outside the operative site do not seem useful for monitoring cerebral function in the region of aneurysm surgery. Epidural or cortical electrodes in the operative field may prove to be more useful.


Dissecting aneurysms of the basilar artery in 2 patients. An uncommon consequence of intracranial vascular disease is the intramural dissection of blood or "dissecting aneurysm". A 69-year-old man with chronic subarachnoid hemorrhage from a posterior fossa mass lesion and a 30-year-old man with migraine and a brain stem stroke illustrate the diverse etiologic, clinical, radiographic, and pathologic characteristics of this unusual lesion.


Isoproterenol treatment of visual symptoms in migraine. Six patients with transient or permanent visual loss associated with migraine are presented. In 3 patients with monocular and one patient with binocular episodes of transient visual loss subsequent visual episodes were relieved by prompt inhalation of isoproterenol. The authors review the possible mechanisms of action of isoproterenol in migraine and present evidence to support the prophylactic use of isoproterenol to prevent transient and possible persistent visual loss in patients with migraine.


Quantitation of carotid stenosis with continuous-wave (C-W) Doppler ultrasound. Two methods for determining the degree of stenoses developing on the origin of the internal carotid were tested using non-invasive Doppler ultrasonic imaging (DOPSCAN) of the carotid bifurcations. Spectral analysis of Doppler audio recordings was utilized in determining the maximum frequencies found within the stenosis, as well as the ratio of the frequency downstream to the stenosis, to the frequency within the stenosis. The theoretical relationships between blood flow, velocity, and pressure drop are defined for all grades of stenosis and they predict that carotid flow will not be reduced unless the lumen diameter is less than 1.5 mm. At critical diameter reductions, below 1 mm, the frequencies in human carotids do not exceed 16 KHz because turbulence limits peak velocities. If the maximum systolic frequency exceeds 5 KHZ, when 5 MHZ probes are directed at a 30 degree angle from the body axis, there is always present stenosis up to diameters of less than 3.5 mm by x-ray angiographic measurements. Frequency ratio studies confirm that plaque growth is not symmetrical but they did not improve x-ray angiography correlations because of the limitations of x-ray in measuring cross sectional areas from projection films and limitations of the spot size of x-ray tubes.


Preservation of ischaemically injured canine kidneys with hypertonic citrate solution: the importance of mannitol. The ability of hypertonic citrate solution to preserve ischaemically injured canine kidneys was investigated. It was found that if mannitol was given i.v. before ischaemia and again after graft revascularization, kidneys subjected to 30 min of warm ischaemia could be preserved for 24 hr, maintaining immediate life-sustaining function.


Changes in internal carotid artery flow velocities with cerebral vasodilation and constriction. Non-invasive Doppler-shift ultrasound, together with spectral analysis, have been used to study the changes in internal carotid artery flow velocity patterns that occur with cerebral vasoconstriction and vasodilation provoked by over-breathing and breath-holding. Significantly different waveform shapes, characteristic for each vessel, were demonstrated from the internal and external carotid arteries, making identification of the internal carotid certain. In 5 healthy subjects over-breathing for 3 minutes significantly lowered the mean height of the internal carotid waveform by an average of 32% (p less than 0.001). Breath-holding for 40-60 seconds raised the mean height by an average of 31% (p less than 0.001). The pulsatility index of the waveforms varied inversely to mean height. These results show that the effects of cerebral dilation or constriction are easily detected by flow-velocity changes in the internal carotid artery.


Extracellular fluid of the kidney preserved by the Collins technique. Hilar drainage fluid of dog kidneys was analyzed as an approximation to renal extracellular fluid after preservation by flushing with chilled high K-low Na solution (Collins C4) followed by ice-cold storage for 24 and 48 hr in a bath of flushing medium. Compared with the medium, Na and Cl were increased to 30 mM/liter and K decreased slightly to 93 mM/liter. Glucose decreased, whereas lactate, lactic dehydrogenase, and creatine phosphokinase increased by significant amounts in both the drainage fluid and bath. The inulin space of the undrained kidney average 37% of wet weight. Calculated intracellular Na and Cl concentrations averaged 50 and 37 mM/kg cell water while K remained within normal limits. A significant fraction of red blood cells retained during initial flushing entered the effluent during storage. Bath and effluent composition of a human cadaver kidney approximated those of a dog.


Flow disturbances at the apex and lateral angles of a variety of bifurcation models and their role in development and manifestations of arterial disease. Dye flow patterns were studied in 12 glass model bifurcations with angles of 45, 90, 135, and 180 degrees, and area ratios of 0.78, 1.03 and 1.27. At the apex, the dye formed a saddle zone, and streamlines from the core which entered this region were swept over the upper and lower surfaces to enter the lateral angles. Qualitatively, the shape and size of the apex played a key role in this effect. Boundary layer separation occurred in the lateral angles, and increased as flow into the branch was reduced. If the branch was occluded, a complex vortex developed in the first few diameters of the branch, and no flow occurred beyond this, even though the occlusion was about 20 diameters downstream. The results were comparable with steady and pulsatile flow. The implications of these results for the localization of atherosclerosis are discussed.


Improved performance of the isolated rat liver when perfused with purified bovine serum albumin. Three groups of isolated rat livers were perfused at 35 C with Krebs-Ringer bicarbonate buffer containing commercial bovine serum albumin (BSA) which had been purified by gel filtration on a column of Sephacryl S-200 and used within 12 hr of purification, or BSA which had been purified by gel filtration and stored at -70 C until used. The ability of livers to produce bile, retain potassium, and to maintain a constant level of glucose in the perfusate was greatly improved in the presence of purified albumin which had not been frozen. Such livers also showed the highest rates of urea synthesis, but the rate of release of aspartate aminotransferase (GOT) from cells and the bile salt content of the bile produced were similar to those found with unpurified BSA. Livers perfused with purified albumin which had been stored in the frozen state were slightly inferior to those perfused with nonfrozen albumin in their ability to produce bile and urea, to retain potassium and GOT within cells, and to maintain a constant concentration of glucose in perfusates. The concentration of bile salts in the bile produced by this group was also lower than that found with the other two groups. Overall, isolated rat livers benefited from perfusion with purified albumin, although freeze storage of this material rendered it slightly inferior to the nonfrozen material in its ability to support the liver.


Fluctuation of lipid peroxides and related enzyme activities at time of stroke in stroke-prone spontaneously hypertensive rats. The levels of lipid peroxides, determined as thiobarbituric acid reactive substances (TBARS), and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), were examined in the blood from stroke-prone spontaneously hypertensive rats (SHRSP), with and without cerebral lesions, and normotensive Wistar Kyoto (WK) rats. The levels of TBARS in the blood from healthy SHRSP were not significantly different from those of WK rats, while the values of SHRSP (male) with stroke were more than twice as high as those of healthy SHRSP. The activities of SOD and GSH-Px in stroke SHRSP were also statistically different from those of healthy SHRSP.


[Ultrastructure of the DNP fibrils and of the interchromatin granules in isolated nuclei of the rat liver]. The structural organization of DNP fibrils and interchromatin granules of isolated rat hepatocyte nuclei has been studied in various conditions of chromatin solubilization. When observed either in nuclei fixed in situ or in a solution containing 20 mM TEA and 1 mM MgCl2, a DNP fibril consists of globular structures 20--25 nm in diameter. In the nuclei fixed in a magnesium-free solution (20 mM TA), nucleosome structures are revealed in DNP. Condensation of chromatin results from interaction between 20 nm globular fibrils, whereas the complete dispersion of chromatin is a consequence of its conversion into the nucleosomal form. In the conditions of both DNP structuralization and dispersion, the nuclei are revealed to contain zones of interchromatin granules connected by thin fibrils. It is assumed that the different compactness of these granular-fibrillar complexes and of the regions of condensed chromatin may be used for their separation and fractionation.


[Cytochemical characteristics of the neurons of the external geniculate body in the rabbit brain in a period of visual function recovery after deprivation]. To study the properties of the external geniculate body, both neuron protein concentration and content were measured cytophotometrically in the cytoplasm of the above neurons taken from nomal animals and animals transported to normal conditions of illumination only after 2.5 months of visual deprivation, where they were put just after birth. The normalization of protein concentration and content has been observed in the neuron cytoplasm and in the surrounding structures. The magnitude of changes observed was related to the size of the neurons. It is supposed that some portion of neurons may exist in the external geniculate body having different degrees of dependence upon the visual impulsation. Mechanisms of possible rearrangement of the neuron metabolism in the geniculate body during the restoring period are discussed.


On schizophrenia prognosis based on data of a clinicogenetical study. Peculiarities of the clinical picture of schizophrenia were studied in a group of patients in which less than a half (785) patients had the aggravating fact and in two hereditary-aggravated groups: siblings (109 patients) and parents--children (118 pairs). Prognostic significance of the genetic factor, sex and age was studied as related to peculiarities of the clinical picture of schizophrenia. Hereditary aggravation is shown to be of a decisive importance for schizophrenia prognosis.


[Effect of visual deprivation on the cytochemical differentiation of neurons in the separate laminae of the rabbit superior colliculus]. The neurons of lamina II, III, VII of the superior colliculus are interferometrically shown to develop features of cytochemical underdevelopment in response to the exclusion of specific visual impulsation. Of the neurons of the lamina studied, lower protein contents in their cytoplasm and nuclei are characteristic, in addition to smaller sizes in comparison with normal ones. A definite specificity of these changes is revealed, which is explained by morphofunctional peculiarities of the neurons of the lamina of the superior colliculus studied.


[Effect of the alkylating agent dipin on the induced proliferation of hepatocytes. I. The kinetics of the cell population]. The alkylating drug dipin was injected to mice 2 hours before a partial hepatectomy. Liver regeneration was characterized by a decrease of the intensity of 3H-thymidine label, an increase of the labeled cell index, absence of mitoses, constant number of binuclear cells. The analysis of these data has shown that dipin causes a sharp (more than by 2 times) increase of the S-period and prolonged (up to 6--20 days) blocking of cells in the G2-period. No phenomenon of unbalanced growth was recorded. No changes in duration of prereplicative period, or in the volume of proliferative pool were recorded. The increase of mitotic cycle periods resulted in the cell population synchronization: by the end of the second ay more than a half of hepatocytes were in S-period, by the end of the third day about 80% of cells passed to G2-period.


[Effect of calcium ions on neutral red binding by skeletal muscle plasma membranes and the mechanism of Ca2+ sorption]. Evidence on the influence of Ca2+ on the binding of neutral red by plasma membranes of skeletal muscle is dealt with. It is suggested that the binding of Ca2+ occurs according to the principle of bimolecular binding. It is suggested that the Ca2+-binding sites with high affinity may control the process of calcium transport by plasma membranes.


[Destructive changes in the outer perimembrane layers (glycocalyx) of Zajdela ascites hepatoma cells under the action of UV radiation]. Immediately after far (254) nm and near (300--380 nm) UV light in small and moderate doses alcian blue sorption by glycocalix of Zaidela ascitic hepatoma cells decrease, which is indicative of destruction and solubilization. The effect of UV light on the cell surface is compared with the action of trypsin. Contribution of the damage of outer perimembrane layers to the lethal effect of UV light is discussed.


[Effect of thyroxine on the duration of the phases of the hepatocyte mitotic cycle at different times of day]. The lengths of the synthetic phase (S) and postsynthetic gap plus a half of the mitotic time (G2+1/2 M) has been investigated in hepatocytes of control and thyroxine-treated male white rats using percent labeled mitosis curves after injection of isotope at 10, 16, 22 and 4 o'clock. In the control, the minimum lengths of G2 lasted 3.0 hours without being changed during 24 hours. On the contrary, G2+1/2 M and S varied from 3.2 to 4.4 and from 8.0 to 9.5 hours, accordingly. A prolonged administration or hormone induced changes in duration of all the above phases whose alterations in thyroxine-treated group of animals showed 2.0--3.0, 2.9--3.4 and 6.4--11.3 hours, respectively. During 24 hours, there was observed a characteristic pattern of changes in the labeling index (LI) of both groups of animals. It has been established for both the groups that the increased in LI coincides with the shortening of S-phase. The data allow to conclude that some intracycle mechanisms may exist controlling the cell division and exerting their effects on the cells at the end of G1-phase and during G2-phase. Thyroxine is a regulator of cell proliferation, and its effect was found to occur due to the intracycle mechanisms of cell cycle kinetics.


[Variability of the C-segment sizes of chromosomes 1, 9, 16 and Y in the human chromosome set]. The investigation of chromosome polymorphism by quantitative methods is a rather hard task. The manual method for measuring C-segments of chromosomes 1, 9, 16 and Y in man is suggested, which is not difficult, being reasonably precise for the population research. Metaphases of the average level of chromosome condensation were taken for analysis. Only the C-segments were measured without measuring chromosomes. The negative chromosome image was 4000-fold magnified, compared to the chromosome natural size, and the boundaries of C-segments of each chromosome were five-fold dotted on a sheet of paper specially printed for this purpose. C-segments were measured by magnifying glass with 0.025 mcm scale unit. For every individuum, C-segments were measured in 5-7 cells only. The data are presented on the estimation of measurement errors and on individual (intercellular) and population (interindividual) variations of C-segments of chromosomes.


[Effect of the alkylating agent, dipin, on induced hepatocyte proliferation. II. An increase in the DNA synthesis period]. The alkylating drug dipin was injected to mice 2 hours before a partial hepatectomy. The duration of DNA synthesis of proliferating hepatocytes was determined by means of cytophotometry of DNA mass in the nuclei, labeled with 3H-thymidine 30 hours after the operation. The DNA mass was doubled simultaneously in diploid and tetraploid nuclei within 18-26 hours. The DNA in labeled nuclei of the control mice was doubled in 8 hours. The kinetics of 3H-thymidine incorporation at different stages of S-period was similar in alkylated and normal cells.


[Change in the selectivity of the sodium channels of a nerve fiber membrane under the action of veratrine]. The ionic currents of the nodal membrane were measured under voltage clamp conditions. The membrane being +40 mv. The replacing of the external Na+-ions to K+- and NH4+-ions have showed that the relative pearmeabilities of the veratrine-modified channels calculated from the constant field theory are arranged in the following row: PNa:PK:PNH4 = 1:0.29:0.61, which differs from the same row for the normal channels. The decreasing of the slope of current-voltage relations of the modified channels with the replacing of Na+-ions to K+- and NH4+-ions is the evidence of a more strong binding of these ions to external mouth of the modified channel compared to the binding of Na+-ions.


[Histochemical and ultrastructural characteristics of embryonal hepatocytes exposed to chloridin (pyrimethamine)]. Single injection of chloridine to rats on the 13th day of pregnancy causes the disturbance of morphofunctional processes in embryo hepatocytes, stimulates granular endoplasmatic reticulum development and glycogen accumulation, increases the number and size of lysosomes, breaks their integrity, produces destructive changes in mitochondria. Activity of lysosomal enzymes with depolymerazing action increases already 30 min after the drug injection, their histopography changes, DNA content decreases.


[Comparative study of the action of procaine and benzocaine on normal and aconitine-modified sodium channels]. Ionic currents of normal and aconitine modified sodium channels of the Ranvier node membrane were measured under voltage clamp conditions. The experiments with local anesthetics in the external Ringer solution have showed that dissociation constant (Kdis) of normal channel-anesthetic complex for procaine is 0.27 + 0.03 mM, and for benzocaine is 0.68 +/- 0.04 mM. With aconitine modified channels, Kdis increases and becomes 1.32 +/- 0.5 mM and 1.52 +/- 0.3 mM for procaine and benzocaine, respectively. It is ascertained that the development of aconitine effect is inhibited by neutral benzocaine to a lesser extent than by procaine. It is shown that the aconitine effect cannot be reversed by a high concentration of anesthetic. Hence, it appears that aconitine and anesthetic receptors do not coincide.


[Clonal analysis of a transplantable rat seminoma]. The study of rat testis seminoma by the method of clonal analysis and ectopic transplantations has shown that typical and anaplastic types are different stages of tumor progression in the course of which atypical and anaplastic features of the seminoma cell elements increase. It does not seem inconceivable that the spermacytic form, never encountered during our investigation of 400 tumors, may be an independent seminoma form incapable of transforming into a typical one. A spindle-cell form of seminoma has been described most frequently occurring during transplantation of a typical seminoma into testis and during cloning. The obtained evidence permits to consider the small dark cells of the seminoma as being cambial cells of the tumor which occur abundantly in growing tumors, and are absent in tumors with ceased proloferating. At later stages of the seminoma development, the small dark cells may be absent, their function being performed practically by all tumor cells. Acinar structures found in part of clones from lungs and in the majority of transplants from eye anterior chamber suggest a histogenetic relationship between the typical seminoma and embryocarcinoma, and thus enable us to regard the latter as the most differentiated variants of the seminoma.


[Photoreactivation of cells and phages injuried by ultraviolet radiation in the ecological long-wave band]. Photoreactivation (PR) was measured after inactivation by far (254 nm), middle (300-315 nm) and near (315-400 nm) UV radiation of Paramecium caudatum and 8 strains of Escherichia coli differing in PR and dark repair capability. PR volume was high and practically the same after irradiation by far and middle UV, but PR was not observed in near UV-inactivated cells of all the strains. It is proposed that pyrimidine dimers are not significant in near UV lethal lesions in cells, as near UV-irradiated phages (T7 and lambdacI 857) are not photoreactivated in undamaged host bacterial cells.


[Ultrastructure of tumors arising from Schwann cells]. Ultrastructural changes have been studied using 67 tumors originated from the Schwann cells. Tumors were induced by means of methylnitrosourea injection with a week intervals. Both benign (fascicular and reticular) and malignant neurinomes were obtained. Main morphological changes were found in the Schwann cells. The tumor cell ultrastructure appeared to be definetely related to the degree of the tumor maturity. The results obtained may suggest that the fine structure of neurogenic tumors is also characteristic of their normal prototype--the Schwann cells.


[Autoradiography of lysed L cells with labelled 3H-lysine]. Using the method of fibr-DNA autoradiography, 3H-lysine labeled L cells were examined. Fibr-labeled structures as long as 400 mkm were revealed. The pattern of labeling along fibres was same as when cells were labeled with 3H-thymidine. In cross experiments when 3H-lysine and 3H-thymidine were used simultaneously, the pattern of labeling remained the same. The data obtained may evidence that the complexation of new synthesized histones with DNA takes place synchronously with the replication, and in the points of chromosome replication.


[Effect of low-molecular nonelectrolytes on caffeine skeletal muscle contracture in the rat]. Contractures induced in rat fast (EDL) and slow (SOL) skeletal muscles by 0.03--3 mM of caffeine in conjunction with rapid cooling of muscle from 30 to 0 degrees C (rapid cooling contructures, RCC) were studied. Uprising speed and tension of RCC were dependent on caffeine concentration and cooling gradient. The minimal necessary temperature, below which contractures still developed, was +6 degrees. The initial temperature did not play any important role. Optimal conditions for RCC (when its tension reached 80--200% of twitch) were: cooling from 30 to 0 degrees, and concentrations of caffeine being 5 mM for SOL, and 6--7 mM for EDL. Disruption of T tubules caused by the removal of glycerol and urea (400--600 mM) from muscle fibers did not influence the RCC tension. During the first hour of the removal, relaxation rate of RCC was lowered. In the presence of 400 mM of urea and 600 mM of 1.3-dimethylurea (the latter did not disrupt the T-system), RCC was depressed by 90%, and the rate of tension development was greatly lowered, while twitches remained unchanged. This effects could be reversed during non-electrolyte removal. This may suggest that Ca2+ release is inhibited selectively by urea and by dimethylurea.


[Effect of proteolysis inhibitors on the phagocytic activity and the cytoplasmic enzymatic activity in the leukocytes of white mice]. The injection of proteolytic inhibitors changes phagocytosis and metabolism of leucocytes in different ways. The polyvalent inhibitor, inhitril, increased phagocytosis but does not change digestive activity of leucocytes. Activities of acid phosphatase, peroxidases and succinatedehydrogenase as well as glycogen contents are seen decreased, whereas activity of glycerophosphate dehydrogenase increases, and that of lactate dehydrogenase does not change. Anti-tryptic serum decreases phagocytosis, both digestive and enzymatic activities of leucocytes, glycogen accumulation being observed. Anti-kallikrein serum decreases phagocytosis and activity of lactate dehydrogenase, and does not change glycogen accumulation and activities of digestion and of acid phosphatase. In addition, activities of succinate-, glycerophosphate dehydrogenase and peroxidase increase.


A survey on spontaneous atherosclerosis of camels (Camelus dromedarius) in Iran. In a survey carried out on 200 camels (Camelus dromedarius) from different parts of Iran, three cases were diagnosed positive for atherosclerosis on gross and microscopic examination. A sex and age predilection is suspected. The complications of atherosclerosis were not present. To the best of the authors' knowledge this is the first report of atherosclerosis in camels.


Crossbreeding of exotic and indigenous cattle in Nigeria--haematological correlates. The blood values of the German Brown, N'Dama and their three-quarter, half and quarter hybrids were studied to ascertain if and how some haematological parameters changed with crossbreeding. It was found that the red blood cell (RBC) and white blood cell (WBC) count and packed cell volume percentage (PCV) were significantly higher (P less than 0.01) in the N'Dama than in the German Brown; the crosses had values which were intermediate as compared to the two parent breeds. Generally, the changes in the mean blood values paralleled changes in the expected genotypes resulting from crossbreeding of the two parent breeds. The tendency of the blood values to change in direct proportion to the degree of N'Dama contribution was strongest for the WBC, followed by the PCV and RBC, respectively. A small random sample for leucocyte differential count did not reveal any differences amongst the genotypic groups.


Experimental infection of domestic pigs with the virus of peste des petits ruminants. Pigs could be subclinically infected with PPRV by inoculation or contact with infected goats. There was no evidence that the virus could spread to uninfected pigs or goats and pigs are not considered important in the epidemiology of PPRV.


Oxfendazole--anthelmintic activity in Egyptian goats artificially infected with gastrointestinal nematodes. The recently developed benzimidazole anthelmintic, oxfendazole, was tested against artificial nematode infestations in Egyptian goats using oral dosing at 4.5 and 2.8 mg/kg. A 100% clearance of mature and immature Haemonchus contortus, Trichostrongylus axei, Ostertagia circumcincta, Coopera curticei, Bunostomum trigonocephalum and Chabertia ovina was obtained at the 4.5 mg/kg level. Very high levels of clearance against the mature worms were obtained at 2.8 mg/kg but the drug was less effective against immature worms at the lower dose rate. PCV, hemoglobin concentration and total erythrocyte counts declined after infection but became significantly (P less than 0.001) raised in treated animal.


A preliminary investigation into the control of trichostrongylosis in calves in Kenya. A series of 3 grazing experiments was carried out to collect data relevant for designing techniques to prevent trichostrongylosis in dairy calves in Kenya. In the first experiment 1 week in/5 weeks out rotation was compared with set stocking. The results indicated that rotation is not an effective control measure. In the second experiment the effects of daily removal of faeces from the field were investigated. This practice also had a limited effect in controlling nematode infection in calves. The third experiment concentrated on the influence of nutrition level. It was shown that feeding level does affect the growth rate but its effect on the course of the egg output was not clear-cut. The results also indicated that the dry season greatly reduces herbage infestation.


Acute diesel fuel poisoning in goats.

Acute diesel fuel poisoning in goats. The clinical, haematological and pathological features of an outbreak of diesel fuel poisoning in a group of goats are described. The major clinical signs were dullness, pneumonia and nervous signs.


Study of women who did not respond to screening for cervical cancer. Demographic and social factors influencing the population response to cervical screening programs have been studied. Age, marital status and, to a lesser extent, place of birth and socio-economic status were the most relevant factors. On the other hand, the reasons for nonparticipation were mainly the lack of information and motivation. Personal invitations, the recall of women who did not present on the first call, and the setting up of decentralized smear collection clinics proved to be useful tools to increase attendance.


Histopathological evidence in support of the association of elevated proton spin-lattice relaxation times with the malignant state. The pulsed nuclear magnetic resonance technique was explored for its potential diagnostic value in human cancer. Measurements of proton spin-lattice relaxation times (T1) of cellular water protons of normal and malignant esophageal tissues showed elevated T1 values in the latter. In some cases, tissues which appeared normal on gross examination assumed as uninvolved tissues had T1 values higher than the other grossly uninvolved tissues and often closer to the T1 of the corresponding tumor tissue. A histopathological study of the assumed uninvolved areas also studied for the T1 values was therefore undertaken. A preliminary study demonstrated the presence of malignant cell groups or clusters in some of the uninvolved samples with higher T1 compared to the true uninvolved tissues, which had a normal histological picture and low T1 values. This observation has brought out the importance of histopathological studies in addition to relaxation studies to comprehend contributory factors to relaxation. Secondly, it lends support to the thesis of elevated T1 values being characteristics of the malignant state.


Preliminary study on the carcinogenic activity of the fungicide manganese ethylenebisdithiocarbamate in the adult newt. Triturus cristatus carnifex. Percutaneous exposure of adult newts to the fungicide manganese ethylenebisdithiocarbamate (maneb) at 3 concentration levels (0.5, 2.5 and 5.0 ppm) for a total of 19.23 weeks did not result in the induction of any neoplasms.


Cyclophosphamide and iphosphamide against Lewis lung carcinoma: evaluation of toxic and therapeutic effects. In the present report, investigations have been carried out to evaluate toxic and therapeutic effects of cyclophosphamide vs its isomer iphosphamide. Cytostatic action of the 2 drugs was assayed on the murine Lewis lung carcinoma (3LL). It has been observed that iphosphamide is less toxic as compared to cyclophosphamide (LD50 IP LD50 CP = 1.5); on the other hand, to reach the same therapeutic effectiveness on 3LL, an iphosphamide dose 1.6 - 2 times higher than that of its parent compound is necessary.


Endocrine differentiation in basal cell carcinoma. Argyrophilic cells have been found in 2 different basal cell carcinomas (BCC), and membrane-bound endocrine-like granules, in the carcinoid range, have been observed in 4 consecutive cases of such tumors. It is postulated that BCC can occasionally display cells showing an endocrine differentiation.


Clear cell carcinoma of endometrium.

Clear cell carcinoma of endometrium. Three cases of clear cell carcinoma of the endometrium are here reported. Clear cell carcinoma is a rare and aggressive type of endometrial adenocarcinoma. Patients are older and are in the menopause much longer than are patients with typical endometrial carcinoma. This fact may reflect the presence of counterbalanced sex hormones in the process of carcinogenesis.


Prognostic value of the Kiel classification of malignant non-Hodgkin's lymphomas. The aim of the present research was to evaluate the prognostic value of the Kiel classification of malignant non-Hodgkin's lymphomas. For this purpose a series of 100 consecutive, previously untreated adults with advanced malignant non-Hodgkin's lymphomas was analyzed. The median age of the patients was 54 years; 61 patients were males. Although the number of the various groups considered was limited, a statistically significant difference (p less than 0.001) was found in the median survival of patients with lymphomas of low-grade malignancy (lymphocytic, lymphoplasmacytoid, centrocytic, centroblastic-centrocytic lymphoma) and lymphomas of high-grade malignancy (centroblastic, lymphoblastic, immunoblastic lymphoma). A difference in survival (p less than 0.001) was also observed among the patients with lymphocytic lymphoma and those with centroblastic-centrocytic lymphoma, whereas no significant difference in survival was found between the histological subtypes of high-grade malignant lymphomas. Our observations support the opinion that the Kiel classification is useful in clinical practice to distinguish the histological types with a better prognosis from those with a worse one; in addition this classification appears to be of conceptual value.


Hepatic enzymes in Hodgkin's and non Hodgkin's lymphoma. Serum alkaline phosphatase levels in patients with Hodgkin's and non-Hodgkin's lymphoma were studied. The findings were correlated with clinical stage, particularly hepatic involvement, and histologic findings. Serum levels of other hepatic enzymes (SGOT, 5,N and gamma GT) were also measured. The usefulness of these studies for clinical staging was described, as well as speculation on the observed differences in Hodgkin's and non-Hodgkin's patients.


Clinical data and estradiol receptor evaluation in breast cancer biopsies. To determine the correlation between the response to the estradiol receptor test and some fundamental properties of the tumor and the host, a study was conducted on 337 patients. Primary carcinomas, including lobular carcinomas, and recurrences or metastases are characterized by similar frequencies of response to the estradiol receptor test (68% positive, 26% negative and 6% borderline), while normal breast tissue is characterized by a higher frequency of negative results (3% positive, 71% negative and 26% borderline). Postmenopausal patients show a shift of estradiol receptor levels towards higher values with respect to premenopausal patients. Contemporaneously, an increase in estradiol receptor concentrations with patient age is observed. The clinical stage appears in influence estradiol receptor content only in postmenopausal patients, for whom an increase in the tumor size is accompanied by a decrease in the estradiol receptor levels. The apparent association constant of the receptors assumes values ranging from 1.5 to about 300 X 10(9) M-1 and does not appear to be related to either the type of tumor tissue or to the clinical stage of the tumor, age, or menopausal status of the patients.


A preliminary report of a pilot trial in adjuvant chemotherapy of primary melanoma. It is well known that level of skin invasion and tumor thickness are significant prognostic factors in the evolution of primary melanoma. The prognosis of primary melanoma Clark III to V skin invasion level and more than 1.5 mm thick confirms this statement. Even the prophylactic dissection of regional lymph nodes has not improved results. In an attempt to obtain better results in the treatment of primary melanomas, a pilot trial was carried out combining surgery and adjuvant chemotherapy. A group of 21 patients with Clark III, IV and V level primary melanoma who underwent adjuvant polychemotherapy (velba + dactinomycin + procarbazine) for 1 year after surgery showed a very low incidence of recurrences (5%) after 24 months of observation. The historical control group, with the same level of tumor skin invasion, treated only surgically had in the same follow-up period a recurrence rate of 65%. This difference was statistically significant (p less than 0.01). All patients who received adjuvant chemotherapy survived 2 years whereas survival was 77% (p less than 0.05) in the surgical historical control group. Favorable results with the same protocol of adjuvant chemotherapy were not obtained in the group of 16 patients with stage II melanoma when compared with primary tumors. However, 4 recurrences were observed after 12 months of observation; toxic side effects of adjuvant chemotherapy were mild and tolerable. Considering the insufficient number of clinical trials with adjuvant chemotherapy, as well as sometimes controversial results, further randomized clinical studies are needed to establish the actual value of this conbined method in the treatment of primary melanoma with a high risk of dissemination.


17 beta-estradiol, 5 alpha-dihydrotestosterone, progesterone and cortisol receptors in normal and neoplastic human endometrium. Using the value of 0.24 fmoles/microgram DNA as breaking point between high and low binding capacities, we quantified receptors for 17 beta-estradiol (ER), 5 alpha-dihydrotestosterone (DHTR), progesterone (PR) and cortisol (CR) in normal and neoplastic human uterine tissues. Concerning receptors occurrence, significant relationships were observed between ER and PR, ER and DHTR, and DHTR and PR. A direct correlation between the presence of ER and tumor grading was found: PR was less frequent in grade II and absent in grade III endometrial carcinoma, however this was not a significant correlation. In endometrial carcinoma at least 1 of the receptors was detected in 67-91% of the cases, 3 receptors (ER, DHTR, PR) in 56%, and all 4 receptors in 45%. The simultaneous detection of multiple receptors could play an important role in determining hormone response.


Xeroradiography of bone and soft tissue tumors. Xeroradiography was used for the study of 233 cases of bone and soft tissue tumors, both benign and malignant, 177 of which were histologically proven. In 150 cases, comparative x-ray films were also available. In bone tumors, xeroradiography was more effective than film radiography in 33 cases (44%), less effective in 16 cases (22%) and the 2 techniques were substantially equivalent in 25 cases (34%). In soft tissue tumors, xeroradiography was more effective than film radiography in 59 cases (78%), less effective in 2 cases (3%) and equivalent in 15 cases (19%). Xeroradiography is held to be a useful second-line technique in selected bone tumors, in particular for the study of trabecular structure, periosteal calcifications and cortical bone. In the field of soft tissue tumors, xeroradiography can be a promising first-choice examination in the presence of a mass or when a recurrence is suspected. The advantages and drawbacks of this technique in both types of tumors are reviewed and discussed.


Histopathological study of an imperfect type ganglioneuroblastoma. Based on their observations, the authors stress the occurrence of 2 histological varieties of ganglioneuroblastoma; the former characterized by a combination of undifferentiated with mature typical ganglion cells, the latter revealing a combination of undifferentiated with pleomorphic atypical cells. After demonstrating the ganglion origin of pleomorphic cells, attention is focused on the difficulties involved in the diagnosis of the second type of ganglioneuroblastoma, which in the author's view should be included in the present classifications of ANS tumors.


[Findings on the knowledge of self-examination of the breast]. A research on the degree of knowledge about the problem of breast self-examination was carried out in a group of 500 women in the Out-patients Department of the Cancer Institute in Milan. The women were given a questionnaire to fill up at home and to return at the moment of the medical examination. The analysis of data showed that, though the level of education of the subjects was fairly good, the knowledge and the practise of the periodical self-examination as a method for an early diagnosis was very low. 70% of the women declared to have some knowledge about the method, but only 9% declared to practise it regularly.


Effects of some pyrrolic and dihydropyrrolizine esters on mouse skin: a preliminary study. Groups of male BALB/c mice were given 33 to 35 treatments during 52 to 54 weeks with 5 ester alkylating agents. Two of these (I and II) were potential metabolites of carcinogenic pyrrolizidine alkaloids; the others (III-V) were chemically similar synthetic compounds. Each dose of 0.5 or 1.0 mumol, in acetone, was applied to the shaved dorsal skin. A control group received acetone. Three skin tumours and 2 preneoplastic lesions were found among 9 mice receiving the compound IV, the agent giving the slowest chemical alkylation reactions. No skin tumours were seen in the other groups. The results suggest that the relationship between carcinogenic potential and alkylating reactivity in this series of compounds should be further investigated.


Macrophages in skin cancer: quantitative and functional studies. The number of tumor-infiltrating macrophages was estimated in 43 patients with skin cancer, including 18 cases of squamous cell and 25 cases of basal cell carcinoma. Macrophages were identified in cell cultures by 2 assays, namely phagocytosis and resistance to detachment by trypsin. The average percentage of adherent cells for the 2 groups of skin tumors was 4.5 +/- 2.6 and 10.2 +/- 5.2, respectively, and the difference was statistically significant. Follow-up studies after surgical excision of the primary neoplasm showed a relatively low macrophage content in 2 of the 4 cases in which local recurrences occurred. Preliminary functional studies suggested that soluble factors may be released by neoplastic cells, accounting for the inhibitory effect of tumor cell supernatants on macrophage chemotaxis in vitro.


Correlation between clinical response to bilateral oophorectomy, estrogen receptors and urinary androgen excretion in 49 patients with advanced breast cancer. The aim of this study was to find out if it is possible to predict the clinical response to bilateral oophorectomy in premenopausal patients with advanced breast cancer. Two methods of determination were used before oophorectomy: 1) the presence of estrogen receptors in the tumor tissue; 2) the urinary concentration of androgens. The clinical response to oophorectomy was evaluated after a six-month follow-up. Determinations carried out on 49 patients showed that a significant correlation exists between clinical response to oophorectomy and androgenic activity alone or in combination with estrogen receptors when both tests give concordant results.


Variations in serum copper and ceruloplasmin levels in advanced gastrointestinal cancer treated with polychemotherapy. Serum copper and ceruloplasmin levels (SCL, SCeL) in 57 patients with advanced cancer of the stomach (35 cases) or large intestine (22 cases) treated with polychemotherapy were studies. In gastroenteric cancer, SCL, which are already high in untreated patients, have a tendency to increase further in cases of progression of the disease, while they seem to significantly decrease in cases of remission. SCeL during the trial appeared to be correlated to the clinical evolution of the disease only in the case of stomach cancer. In large intestine cancer, SCeL did not show any significant variation in relation to the normal range. These observations, in particular on the behavior of SCL in the neoplasms of the digestive tract, are in accordance with the results of other studies. The authors are inclined to attach a diagnostic and prognostic value to the variation in SCL and SCeL in gastrointestinal cancer.


Combination chemotherapy with 5-fluorouracil and methyl-CCNU for the treatment of advanced gastrointestinal cancer. Sixteen patients with advanced gastrointestinal cancer (colorectal 12/16, gastric 4/16) were treated with a combination of 5-fluorouracil (5-FU) plus 1-(2-chlorethyl)-3(4-methyl-cycloexyl)-1-nitrosourea (Me-CCNU). The therapeutic program consisted of orally administered Me-CCNU (140 mg/m2) and intravenous 5-FU (9.5 mg/kg by bolus injection for 5 days). The cycles were repeated at 6-week intervals. At the beginning of the therapy, 11/16 patients were in performance status (PS) 0-1 and 5 patients in PS 2-3. Eight patients developed early progressive disease between the 1st and 2nd course of therapy. Only a minor tumor response was observed in the remaining 50% of the patients. However, the patients with stabilized disease lived longer (11.8 months) than non-responders (3.5 months).


Endometrial adenocarcinoma with psammoma bodies. Psammoma bodies were found in less than 9% of 235 cases of endometrial carcinoma, considering both biopsies and surgical specimens. They may originate in papillary adenocarcinoma and do not indicate a slightly infiltrating or a well-differentiated tumor. The clinical profile of patients closely resembles that of women with endometrial carcinoma, but survival appears worse.


Angioimmunoblastic lymphadenopathy with dysproteinemia complicated by Kaposi's sarcoma. A case of clinically and morphologically typical angioimmunoblastic lymphadenopathy (AILD) in a 68-year-old man during a prolonged antibiotic treatment for urinary infection is presented. Lymph node biopsy at first showed findings suggestive of an exhaustion of the germinal center immunological activity (like those characterizing angiofollicular lymph any clear transition into malignant lymphoma. The course of the disease was characterized by the occurrence of opportunistic infections (toxoplasmosis, herpes zoster), and finally by the onset of a cutaneous Kaposi's sarcoma. The possible relation of AILD to Kaposi's sarcoma is discussed, and the main clinical and morphological data of the case of AILD (about 200) reported in the literature are reviewed.


A computerized cancer patient information system. The purpose of this study was to realize a computer system for cancer data automatic processing. A clinical research in oncological practice is usually time consuming and often not reliable or deceiving because of a number of various errors. Until now, only a few information systems have been specifically designed for cancer data processing, and these have a limited capacity of autonomous data elaboration. Our system, based on an original computer program, can compile, store and process essential data on cancer diseases, with a high degree of reliability and high speed of elaboration. Input and output of this system are simplified and user oriented, without limitations for the subject at study on clinical research, and no particular training of the physicians involved is necessary.


Ewing's sarcoma: an approach to radiological diagnosis. All the pertinent radiographs of 83 patients with histologically proven Ewing's sarcoma were reviewed. Forty-nine patients were in the pediatric age group, and 34 were adults. The mean age, the symptoms and time from symptoms to diagnosis were evaluated in the 2 groups. The site of primary involvement was in 54% the long bones, 35% the flat bones, 8% the small bones and 3% extraosseous. For the primary site we considered the diagnostic results of the standard radiographic investigations and in some cases the usefulness of angiography, xeroradiography and telethermography. At presentation we also evaluated the possible diffusion of the disease with standard radiographic surveys (chest and skeletal, including limbs) and with foot lymphography in selected cases. In this way, 57 patients (69%) were considered to have localized disease. In this group, we also considered the value of the periodic radiographic follow-up, which enabled us to disclose the appearance of metastases (chest 64%, bone 54%, lymph nodes 11%) in 28 cases (49%). Finally, we made a comparison of the different radiologic and epidemiologic findings between children and adults.


[Effect of vitamin A in significant doses on incorporation of (14C) retinol, acceptor capacity of tRNA and activity of certain enzymes in tissues and plasma membranes of cells in the presence of Guerin's carcinoma]. In rats with Guerin's carcinoma the weight and size of the tumour is twice as low when significant doses of vitamin A are administered. Under these conditions the acceptor capacity of tRNA of the small intestine mucosa as well as the intensity of [14C] retinol incorporation into plasma membranes of its cells decrease essentially, whereas in the mucosa itself the radioactivity remains high. When studying the activity of alkaline phosphatase, amylase in the mucosa and arginase in the liver, a disproportion is found in changes in the enzymes activity on the surface of the small intestine mucosa and in the mucosa homogenate, that may be due to a change in the state of the cell membrane apparatus when the tumour is formed. Under the effect of significant doses of vitamin A there might occur thelysis of the tumour cell membranes, which results in the metabolism normalization.


[Metabolism of rat brain nonhistone proteins following alteration of nervous system function and training]. Metabolism of total nonhistone nuclear proteins (NNP) of the rat brain was studied in three groups of animals: trained, pseudotrained and control. Protein synthesis and degradation were estimated by determining NNP specific radioactivity 1, 3, 6 and 9 weeks after the precursor, 14C-lysine, injection. The experimental results indicate that there are two fractions of NNP which differ in their metabolic rates. The half-life of the first "short-living" group of proteins is 5-10 days and that of the second "long-living" one is 18-21 days. It is shown that there is a significant difference in specific radioactivity and metabolic rate between the "short-living" fractions of NNP isolated from the brains of trained or pseudotrained rats, on the one hand, and control rats, on the other hand. Possible participation of the brain total nonhistone nuclear proteins in the mechanisms of alterations of the central nervous system function and learning is discussed.


[Effect of hydrocortisone and insulin on changes of oxidative phosphorylation after neutron irradiation]. Total double irradiation of rats with a fast neutron flow does not affect oxidative phosphorylation in the liver mitochondria but causes an essential decrease in the intensity of phosphorylation in mitochondria and chemoluminescence in blood serum of animals. Postradiation multiple administration of hydrocortisone intensifies the radiation inhibition of oxidation and phosphorylation of mitochondria and insulin administration stimulates phosphorylation in the liver mitochondria and the intensity of chemoluminescence in blood serum of rats. Hydrocortisone in combination with insulin has a less pronounced stimulating effect on phosphorylation than insulin, but the intensity of chemoluminescence in this case is higher than under the effect of each preparation separately.


[Identification of multiple molecular forms of lactate dehydrogenase during isoelectric focusing with ampholines in polyacrylamide gel thin layer]. Multiple molecular forms of lactate dehydrogenase fractionated by isoelectric focusing with ampholines in the polyacrylamide gel thin layer were identified in the supernatant fluid of the myocardium and liver homogenate of the intact rats and rabbits. Differential detection of the enzyme fractions was based on differences in their substrate dependences and sensitivity to specific inhibitors. Simultaneously the analysis was made for the partially purified preparations of lactate dehydrogenase five isoenzymes from the same sources obtained by means of the preparative electrophoresis in polyacrylamide gel and ion-exchange adsorption on DEAE-Sephadex A-50. The isoelectric points of the identified fractions are determined. It is shown that redistribution of the enzyme multiple molecular forms within the pH gradient is subordinated to a certain strictly regularity: fractions from LDH1 to LDH5 occupy successively the sites in a weak-acid, neutral and weak-alkaline regions of the pH gradient.


[Effect of thymosine on oxidative phosphorylation in mitochondria of mouse liver in the dynamics of chemical carcinogenesis]. Oxidative phosphorylation in the mice liver mitochondria with chemical carcinogenesis was studied as affected by thymosine. It is found that under chemical carcinogenesis the energy metabolism (fraction III) lowered and administration of thymosine in the early periods of carcinogenesis favoured an increase in the indices up to the control level. In the late period of carcinogenesis the mentioned effect was not observed. The favourable effect of thymosine on the oxidative phosphorylation was associated with an increase in the immunological indices in the animals under experiment. It is supposed that the activity of thymosine as a hormonal factor includes participation in the energy metabolism regulation.


[Formation of 7-dehydrocholesterol ketoderivative - cholesta-4,7-dien-3-one in stomach and intestinal rat tissues]. Incorporation of [2-14C] sodium acetate into 7-dehydrocholesterol ketoderivative, cholesta-4,7-dien-3-on, was studied in the tissues of the rat stomach secretory and esophageal parts and in the mucous and serous membranes of the small intestine. Cholesta-4,7-dien-3-on is shown to form not from [14C]cholesterol but from [14C] dehydrocholesterol. Incorporation of the label into the compound under study is established to be maximum 6h after isotope administration. The formation of cholesta-4,7-dien-3-on is the most active in the mucous membrane of small intestine and secretory part of the stomach. An assumption is advanced on the relation between the oxidative transformation of 7-dehydrocholesterol and secretion of hydrochloric acid by the animal mucous tissue.


[Application of sucrose density gradient in disk electrophoresis of proteins]. The methods are suggested when either fluid with the sucrose density gradient or the combination of sucrose with polyacrylamide gel are used as a zonal carrier in disk electrophoresis. Possibility is shown and conditions are selected for concentration and subsequent separation of proteins in the fluid with the sucrose density gradient in disk electrophoresis as narrow zones with clear boundaries. By the methods proposed the sarcoplasmic proteins of the rat myocardium and incorporated creatine kinase isoenzymes were separated.


[Effect of prolonged loading with lysine on distribution of free amino acids in the brain]. Prolonged loading with small amounts of lysine and a mixture of lysine and metabolism cofactors evokes considerable shifts in the distribution of the amino acid pool in the rat cerebral cortex. Under the influence of lysine the functional activity of the central nervous system improves.


[Effect of detergents on pancreatic ribonuclease]. It is established that the activity of pancreatic ribonuclease does not change under the effect of nonionic and some ionic detergents within a concentration range of 0.5-5.0 mg/ml and decreases in the presence of DS-Na and cetavlon (1.0 and 2.5 mg/ml, respectively). Studies on kinetics of ribonuclease thermoinactivation in the presence of different detergents showed a stabilizing effect of cetavlon and DS-Na in a concentration of 1 mg/ml.


[Changes in threonine and Na+ counterflow absorption in rat small intestine under the effect of insulin and F-]. The in vivo experiments showed that insulin intensifies the threonine absorption and Na+ counterflow in the rat small intestine. Fluorine inhibits considerably the threonine absorption. The possible mechanism of the insulin and fluorine opposite effects on the threonine absorption in the small intestine is under discussion.


An investigation of a spread energy method for medical ultrasound systems. Part one: theory and investigation. A medical ultrasound device using a Golay code is proposed and investigated theoretically. The code enables the spread energy method to be used to help overcome the restraints of the parameters of resolution, peak power and penetration.


Species differences in decompression.

Species differences in decompression. In an effort to bring together the diverse laboratory-animal decompression studies, a literature review and statistical evaluation were undertaken. Although 22 different species that had been used in decompression studies were identified, systematic data were available for only 7 of these species: man, goat, dog, guinea-pig, rat, hamster, and mouse. Mathematical functions using physiological data on these seven species were developed to estimate 1) saturation time (the time for the body to equilibrate after an increase in hydrostatic pressure), and 2) no-decompression saturation-exposure limits (the maximum saturation-exposure pressure from which an abrupt return to 1 ATA can be tolerated). Data from man, rat, and mouse were used to develop physiological relationships for two additional decompression variables: change in pressure-reduction limits associated with increased exposure pressure and time to onset of decompression symptoms. Finally, data on rats for two other decompression variables, gas elimination time and optimum decompression stop time, are discussed in the hope that this will stimulate additional animal laboratory research in other mammalians. The general functional relationships developed in this paper provide a preliminary and rough means for extrapolating among species the decompression results obtained during animal laboratory experiments.


Combined effects of ethanol and hyperbaric air on body sway and heart rate in man. Eight amateur divers took part in crossover experiments to study the combined effects of ethanol (0.72 g/kg b.wt.) and hyperbaric air (4 and 6 ATA) on heart rate and body-sway movements. Body sway with open and closed eyes was measured in lateral and sagittal directions by a statometer device. In the alcohol condition, there was an initial increase in body sway corresponding to the acute phase of ethanol intoxication. At a mean blood alcohol concentration of 0.77 mg/ml, this increase in body sway was statistically significant (P less than 0.01) compared with the alcohol-free condition. At 90 min from start of drinking, body sway scores at 1 ATA were not significantly different from alcohol-free measurements. On raising the pressure to 4 and 6 ATA, increased body sway occurred in both alcohol and alcohol-free conditions and, moreover, the rate of increase was more extreme in the alcohol condition. Significant pressure-alcohol interactions were established, suggesting a potentiating action of alcohol on the increase in body sway induced by acute exposure to high pressures of air. Heart-rate measurements with and without alcohol were not significantly different, although increases in ambient pressure caused a drop in heart rate in both conditions.