Beta2-microglobulin excretion and autoimmune phenomena in endemic Balkan nephropathy. Quantitative determinations of beta2-microglobulins were carried out in 335 urinary samples collected from 335 subjects living in villages with a high rate of morbidity and mortality from endemic Balkan nephropathy. Three months after the first determination of beta2-microglobulin excretion, blood and urine samples were obtained from 19 patients with high values and from 19 with normal values of beta2-microglobulins. The results of the biochemical and immunological investigations performed on these samples suggest that the tubular alteration is the first lesion. The autoimmune phenomena elicited by the tubular alteration may contribute, by an antigen-antibody complex disease mechanism, to the appearance of glomerular secondary lesions.


Hyaline pleural plaques and asbestos bodies in 198 randomized autopsies. In 198 randomized autopsies of adults, hyaline pleural plagues were found in 49 men and 17 women; bilateral in 47 cases, unilateral in 19. No correlation between previous pr present pulmonary disease and hyaline plaques was found. Asbestos bodies were found in nine men and five women; nine out of these 14 cases with asbestos bodies also had hyaline pleural plaques.


Diagnostic significance of alpha1-fetoprotein, bile antigen VIII and Australia (HB) antigen in primary cancer of the liver. The diagnostic significance of the presence of alpha1-fetoprotein in the serum of patients with primary hepatic tumors was investigated. The presence in the serum of bile antigen VIII correlated with the clinical state might suggests a cholangioma. Antigen HB(Australia) being seldom encountered in the hepatomas from our geographical area cannot be implicated in the process of viral oncogenesis.


Longitudinal studies of immunological parameters in Farmer's lung. A group of patients with serum precipitins against M. faeni culture filtrate antigens and with clinically proven farmer's lung disease was examined. A group of precipitin-negative farmers with comparable antigen exposure and with unrelated forms of pulmonary disease served as control. Immunoglobulins G and A were elevated at first consultation in the majority of the acute cases of farmer's lung. Immunological parameters normalized during corticosteroid medication and antigen avoidance. Autologous complement (C) consumption by M. Faeni antigens proved valuable for diagnostic purposes. Despite normalizing immunological factors and subsiding symptomatology, C-consuming antibody levels remained constant.


Isolated mitral valve replacement with the Björk-Shiley tilting disc valve prosthesis. A six-year review and a comparison between the Delrin and the pyrolytic carbon disc models. Replacement of the mitral valve with the Björk-Shiley tilting disc valve prosthesis was performed in 203 consecutive patients with isolated mitral valvular disease at Karolinska Sjukhuset, Stockholm, Sweden, during the 6-year period ending December 1975. Results with the Delrin and pyrolytic carbon disc prostheses were analysed with actuarial techniques and compared in terms of mortality rate, incidence of thrombo-embolism and frequency of re-operation. Early (4%) and late mortality rates (7.5 deaths per 100 patient years) were similar with both types of prostheses. No case of primary mechanical prosthetic failure was encountered. The pyrolytic carbon disc prostheses have obviously decreased the incidence of systemic emboli from 9.6 to 5.3 per 100 patient years and so far eliminated mortality due to embolization. This benefit is probably related to the increased opening angle from 50 degrees to 60 degrees in the pyrolytic carbon disc model, which causes less resistance to blood flow. Thrombotic obstruction of the prosthetic valve, however, has been a persistent problem in the order of 3.3 incidences per 100 patient years. Only one patient in twelve involved was referred to our clinic and could be saved by an emergency re-operation. The development of the ring-shaped radiopaque marker in the tilting disc occluder provides a valuable tool for instant diagnosis of partly or completely obstructed disc motion caused by thrombosis. Disc motion can be easily visualized by cineradiography or fluoroscopy. Early diagnosis of and emergency operation for thrombotic obstruction of the prosthesis will reduce the mortality due to this dangerous complication.


Visualization of a guinea pig T lymphocyte surface component cross-reactive with immunoglobulin. Thymus-derived lymphocytes (T cells) show exquisite specificity in recognition of antigens, but the nature of the cell surface receptor is controversial. Although antigen recognition mediated by immunoglobulin variable (V) regions remains the minimal hypothesis, it has been extremely difficult to definitely establish the presence of immunoglobulins on these cells. Chicken antibodies, produced against the (Fab')2fragment of mouse immunoglobulin G (IgG) and purified by binding to and elution from IgG-Sepharose 4B, bind to an endogenously synthesized surface component of guinea pig T cells. The binding occurred via a cross-reaction with murine k chain and a heavy chain determinant localized in the Fd region, and was visualized by immunofluorescence and immunoelectronmicroscopy using both transmission and scanning techniques. These data provide direct evidence for the presence of a surface component related to immunoglobulin on T lymphocytes.


Severe adverse reactions to contrast media: a simplified means of recognition and treatment. Severe adverse reactions to contrast media appear to fail into two major categories: (1) histamine response and (2) vagus response. Treatment of these major reacions is simiplied once the cause is recognized. Pulse rate is a simple means of determining which effect is being observed, and appropriate treatment can be instituted without undue delay.


Colostomy and colostomy closure.

Colostomy and colostomy closure. A series of 181 adult patients subjected to colostomy was studied, almost all of whom had disease rather than injury. The complication rate was 28 per cent. One hundred of these patients had a subsequent colostomy closure with a complication rate of 17 per cent. Of the patients who had both procedures, 35 (35 per cent) had one or more significant complications. The causes and prevention of these complications are described.


alpha-Fetoprotein values in monkey (Macaca mulatta) pregnancy. The pregnant rhesus monkey's (Macaca mulatta) potential as a model for understanding the dynamics of alpha-fetoprotein (AFP) metabolism in human pregnancy was evaluated. AFP levels in maternal and fetal serum and amniotic fluid were determined by radioimmunoassay. Significant correlations were found between decreasing maternal serum, fetal serum and amniotic fluid AFP concentrations and increasing gestational age. However, these data are not consistent with the AFP changes reported in human pregnancy. It appears that this animal has limited applicability as a model in this aspect of human pregnancy.


Studies on the neutralization of rabbit antibodies to human factor VIII. The capacity of normal and haemophilic cryoprecipitates to neutralize the anticoagulant effect of rabbit antibodies to human factor VIII (anti-VIII) was assessed using a quantitative estimation of antibody. About 4 times as much anti-VIII could be neutralized by normal factor VIII as was required to neutralize clotting activity. This suggests that there are probably several antigenic sites intimately associated with factor VIII clotting activity, quite apart from any antigenic sites which may be detected using antibodies directed against other components of the factor VIII complex. The neutralizing capacity of factor VIII was only slightly greater for the rabbit antibodies employed in this study than has been previously reported for antibodies of human origin, thus indicating only minor differences in specificities. Additional evidence in support of this concept was the finding that cryoprecipitates prepared from haemophilic plasmas previously recognized as either lacking or possessing the capacity to neutralize antibodies of human origin neutralized least or most quantities of rabbit antibodies, respectively.


Primary liver cell carcinoma (PLCC) in the Northern Guinea Savanna of Nigeria. There is a high prevalence of primary liver cell carcinoma in the Guinea Savanna country of Nigeria, one of the highest frequencies in the world. The highest frequency of the tumour was among males aged 20 to 49 years. The clinical and laboratory findings are similar to those found in other series in Africa. Alpha1-foeto-protein occurred in 85% of cases while HBsAg was noted in 49% of cases.


Epilepsy epidemic due to benzahexachlorine. A report of eight cases with grand mal seizures secondary to accidental ingestion/exposure to benzahexachlorine has been presented. Persistant neurological signs and biochemical tests have been described. Seizures affected even the domestic animals like cows and buffaloes. Discussion of various clinical syndromes, treatment of organochlorine pesticide and their persistence in human body for years after removal from source of exposure is emphasized. Preventive measures are recommended. the authors are not aware of any similar reports from this part of the country.


Effect of hydroxyethyl starch on platelet function following granulocyte collection using the continuous flow cell separator. Hydroxyethyl starch (HES) was used as sedimenting agent in the course of granulocyte collection on seventeen normal donors, using the continuous flow cell separator (CFCS). No clinical bleeding was noted in any of the donors. In spite of a 21 per cent mean reduction in postcollection platelet count, all donors had platelet counts within normal limits precollection and postcollection. Postcollection platelet adhesiveness increased in five donors, remained the same in one donor and declined in ten donors. Except in one donor there was no change in previously normal platelet aggregation to adenosine diphosphate or collagen. In the dose used, 500 ml, the infusion of 6% hydroxyethyl starch as an adjunct to granulocyte separation using the continuous flow cell separator does not appear to adversely affect platelet number and function.


Fetal cell counting as an evaluation of Rh prophylaxis with antenatally administered anti-Rh O (D) gama globulin. Fetal cell counts were performed on pregnant women at 34 weeks' gestation following an injection of Anti-Rh O (D) gamma globulin at 28 weeks' gestation. In cases where the fetus subsequently proved to be Rh O (D) positive and ABO compatible, the fetal cell detection rate and the mean number detected detected were considerably less than those where the fetus was Rh negative. Postpartum fetal cell counts after one and two antenatal anti-Rh O (D) gamma globulin injections were also less when the baby was Rh positive than when the baby was Rh negative. These findings provide evidence that antigen clearance is definitely part of the mechanism involved in Rh prophylaxis by the use of anti-Rh O (D) gamma globulin.


Scanning and transmission electron microscopy of human prostatic acinar cells. Benign hyperplastic and neoplastic human prostate tissue samples were obtained by needle biopsy, transurethral resection or open prostatectomy. Acinar cells of both types of tissues were examined in the scanning electron microscope. It had been reported previously that adenocarcinoma acinar cells were more heterogeneous in size and shape than BPH acinar cells; the purpose of this study was to determine if there were surface morphology differences between the two types of tissues. Acinar cells were found to be extremely heterogeneous in their surface morphologies; three major types of surface morphologies were present - microvillous, ruffled, and bare. Within each class of surface morphology there was heterogeneity, both in size and density, of surface structures present. Microvillous, ruffled, and bare cells appeared to be present in normal, BPH, and neoplastic acini with no significant qualitative or quantitative differences in surface morphologies. Infrequently, it was possible to distinguish between well-differentiated and poorly-differentiated carcinomas because cells of the latter tissues were present in sheets rather than acini and appeared flat and totally devoid of surface detail. The SEM studies also sought to determine a marker to establish the origin of prostate tissue culture cells as normal, BPH or cancerous. Surface morphologies from tissues could be traced into the tissue cultures; again, three types of cells are present - bare, microvillous, and ruffled. However, since surface morphology does not appear to be a distinguishin feature of the pathology of the tissue it cannot provide a distinguishing marker for the origin of tissue culture cells. Scanning electron microscopy also provided an opportunity to observe possible secretory mechanisms and products in the prostate acinar cells.


In vitro culture of human prostatic tissue. A procedure is described which yields a significant percentage of long-term mixed cell cultures of human prostatic tissue. Attempts were made to suppress the proliferation of stromal fibroblasts and to characterize the cultured cells as those of prostatic origin. The problems associated with establishing epithelial cell lines are discussed.


[Blood proteins of calves and their 1st-calver mothers during the early post-natal period]. The calves of the Red Spotted breed and their first-calver mothers were subject to the study of total proteinemia and of the changes in protein fractions before parturition and in a ten-day period of post-partal development. The relations between these parameters were also studied. Calves up to the 10th day of life show a rise in total proteinemia whereas cows show insignificant changes. The level of albumins in calves exhibits a slight fluctuation, whereas in mothers it increased before parturition, followed by a drop which lasted until the end of the test period. alpha-globulins show a decreasing tendency in calves from the fourth day of age and have higher values than in cows. beta-globulins in cow blood serum before parturition increase. The level of gamma-globulins in calves rises until the end of the first week of life. A linear correlation dependence was found between the values of beta-globulins in cows and calves in the first two post-partal days and between the value of beta-globulin level of mothers prior to parturition and of calves at birth. In gamma-globulins the correlation dependence is always significant, starting the first day after birth.


[Gentamycin binding with blood proteins]. An 'in vitro' microbiologic method was employed to follow up the activity of gentamycin diluted in bovine and swine sera and bound to proteins isolated from them, in the course of continuous storing. It was found that the protein solutions of gentamycin retain their activity for one year under refrigerator conditions (4 degrees C), whereas with the freeze-drying of these solutions storage could be effected at room temperature. It was established through the method of balanced dialysis that gentamycin binds with the proteins of swine sera, and to a largest extent with native serum (30 per cent) and to a lower one--with globulins (15--16.2 per cent). The protein complexes of gentamycin proved entirely reversible and the process of binding was shown to have no influence on the minimal bacteriostatic concentration of the antibiotic with regard to Bacillus mycoides HB2.


[Serum proteins of cows suffering from nymphomania]. Investigated were a total of 25 cows of the Bulgarian Brown breed manifesting the classical symptoms of nymphomania, along with other 25 normal cows as control animals. It was found that the total protein in the blood serum increased, coupled with a drop in the albumin fraction and a statistically significant rise of the gamma-globulin fraction. Suggested was the use of the coefficient albumin: gamma-globulin instead of the coefficient albumin:gloubulin. The new coefficient was shown to be more suitable and indicative of nymphomania. In cows with nymphomania the value of this coefficient was below 0.95.


[Possibilities for the clinical use of 5-azacytidine]. The authors report the structure and mechanism of 5-azacytidine action. This drug was first synthesized in the Institute of Organic Chemistry and Biochemistry of Czechoslovak Academy of Sciences (Prague) and used experimentally for leukemia L1210 and leukemic AKR mice and clinically for treatment of acute leukemia in children, in particular.


[Cross-reacting epithelial antigen of ectodermal origin in mouse tumors]. Cross-reacting antigen (CR-antigen) previously found by indirect immunofluorescence in cell elements of murine multilayer epithelial cells (except corneal epithelium) to play the role of antigenic label of cover epithelia of ectodermal origin was found in mice tumor cells, related histogenetically with multilayer epithelium (transplantable proventricular cancer, two strains of squamous-cell cervical cancer in mice). CR-antigen was observed in transplantable breast adenocarcinoma and in transplantable mice teratocarcinoma.


[Further study of spontaneous virus production using transplantable HEp-2 cells as a model]. Two maxima of optic density were observed at zones of gravity 1.27 g/ml and 1.15-1.16 g/ml by sedimentation equilibrium in sucrose gradient of cultural fluid, obtained from the transplantable cells of the HEP-2 strain and concentrated by ultracentrifugation. These fractions thus isolated were tested for presence of RNA- and DNA-dependent DNA-polymerase. The structures with the density of 1.15-1.16 g/ml were identified with the oncornaviruses on the basis of characteristics flotating density, presence of RNA-dependent DNA-polymerase. Analyses of products of RNA- and DNA-dependent polymerases reaction, flotating density of oncornaviral nucleotides in sucrose and CsCl gradients are presented. The optimal conditions for reverse-transcriptase reaction of virions of D type viruses are characterized.


[Immune defect diseases in childhood].

[Immune defect diseases in childhood]. The immune reactions of man may be subdivided into two main types, the antibody-bound and the cell-bound immunity. The effect of these two systems is realised by two different lymphocyte populations: T- and B-cells, which may show isolated or combined congenital defects and are known as primary immune defects. Antibody deficiency diseases are the by far most frequent congenital diseases. Concerning the frequency the combined and cellular immune defects follow. At present the diagnostic possibilities are already largely developed. Immune defect diseases have much contributed to the understanding of the normal immune reactions. Though these diseases also nowadays still have an extremely bad prognosis, there exists already for some forms a therapy in form of the transplantation of bone marrow, which is able to restore the defect immune system.


[Immune complexes and their pathogenetic significance]. The specific binding of antigens by antibodies leads to the development of antigen-antibody-complexes. Apart from the connected with this and desirable immunological protection immune complexes, however, may also have an pathogenic effect on certain conditions (e. g. transmission of the capacity of phagocytosis), depositing themselves in the vascular regions concerned, activating complement and after binding to cell membranes causing the release of unspecific mediators. Finally these lead through increased vascular permeability, local ischaemia and hyperaemia, respectively, and the release of proteolytic enzymes to a lesion of the tissues. In a series of in most cases chronic inflammatory diseases depositions of immune complexes may be proved in the tissues concerned. However, it is difficult to establish exactly in the individual case, whether they considerably participated in the development of the clinical picture. By analogies to experimentally produced immune complex diseases at least some entities of diseases (e. g. lupus erythematodes disseminatus) or defined local alterations of the tissues (e. g. glomerulonephritis of immune complex type) may be defined pathogenetically.


The possible role of the carcinoembryonic antigen (CEA) and other carcinofetal antigens in maligant and benign diseases of the gastrointestinal tract. In the present review we have discussed antigens, principally the CEA, which have their well defined place in the clinical management of the (malignant) diseases of the gastrointestinal tract. Though the immunological diagnosis of neoplasia is one of the research areas where the most effort and hopes are invested, it is also there, that the carcinofoetal antigens have the least usefullness at the moment. However, studies like those undertaken by Edgington and Plow are probably pointing out if not proving, that even relatively simple procedures like further purification of the antigen can improve its tumor specificity and consequently its diagnostical value (1975). Following their results the final verdict is not spoken yet as to whether CEA (or any other CFA) will even be more than an adjunctive tool in the diagnosis of malignant tumors specially those of the G.I. tract. The 0.6% of "false" positives these authors have obtained in their series with their highly purified CEA-S (against the 30% usually seen with classical CEA preparations) are provocative: one will have to discuss the question, on which grounds the decision "false positive" has been reached and whether these cases are not simply "clinically silent", hence true positive observations. The problem then would be shifted away from the CEA test (or any other CFA test) toward the improvement of all the other conventionally employed diagnostical measurements, which should allow the early confirmation--and localization--of a beginning neoplasia, which has been screened out by an immunological test. Until this is not warranted, the CEA test has its definite place and vocation at the present time in the follow-up of the treated cancer patient, whatever therapy he has received.


Intravenous chemotherapy with syndronization in advanced cancer of oral cavity and oropharynx. Sixty-one patients with locally advanced squamous cell carcinomas of oral cavity and oropharynx were treated with chemotherapy, intravenously applied, in addition to radiation and/or surgery. An attempt was made to synchronize the tumor cell population by application of low doses of Vinblastine and the subsequent chemotherapy was based on the uptake of 99m-Tc --labelled Bleomycin in the tumor as an indication of synchronization. Increased number of mitoses in aspiration biopsy specimens and shift in the DNA distribution pattern on DNA histograms were taken as indicative of synchronization. A 50--100% regression of the tumor was achieved in 19 out of 38 patients with residual or recurrent tumors. The results were better in those patients, who received chemotherapy based on individual Tc-Bleomycin uptake curves. In 23 patients with previously untreated T3 tumors of oral cavity and oropharynx the results were somewhat better, but there was not statistically significant improvement on attempts with synchronization in this small series. There were no serious complications connected with chemotherapy.


Analysis of an antistaphylococcal serum alpha globulin. Previous studies in this laboratory have shown that normal human serum contains an alpha globulin possessing lethal and antirespiratory action for staphylococci. In this study further description of the antistaphylococcal macromolecule is presented. The antistaphylococcal protein was shown to be homogeneous by both isoelectric focusing in sucrose density gradients and sodium dodecyl sulfate electrophoresis. An analysis of the chemical composition of the antistaphylococcal serum protein indicated the alpha globulin to be a glycoprotein composed of 22.5% carbohydrate and 77.2% protein as determined by amino acid analysis. The total carbohydrates included 11.08% protein-bound hexoses. 0.86% hexosamines, 4.3% sialic acid and 6.3% fucose. The mean isoelectric point, determined by isoelectric focusing in the range pH 3-6, was 4.73. Molecular weight studies on Sephadex G-200 dextran gel columns calibrated with proteins and glycoproteins indicated the molecular weight of the antistaphylococcal macromolecule to be 55,000-74,000 daltons respectively. SDS-gel electrophoresis indicated the molecular weight of antistaphylococcal serum protein was 62,000. Thus the antistaphylococcal alpha globulin does not appear to be related to other known serum bactericidins.


[Carcinogenic polycyclic aromatics and metabolities as possible components of emissions (author's transl)]. In the last five years investigations of environmental samples by high resolution-low voltage mass spectrometry succeeded in better separations of aromatic compounds than with any other method before. In light fuel oil, in dusts from a highway and from towns and in the emissions of an oiloven for households namely at least 200 and up to 500 cyclic and polycyclic aromatic types of compounds of different molecular formulas were detected. From these many types of compounds contained oxygen and some sulfur. In the present study the question is discussed which known carcinogens can be among this abundance of types of compounds. For this purpose at first the carcinogenic polycyclic aromatics with formulas CnH2n+Z, CnH2n+ZO, CnH2n+ZO2 and CnH2n+ZS and the metabolites containing oxygen are listed according to the characteristic of the mass spectrometric method. Pure hydrocarbons there are 62 and sulfur containing 2 carcinogenic compounds with all together 29 different molecular formulas. In the following some comments are made on the methods of analyzing polycyclics. Judged by molecular formulas all samples mentioned can include the CnH2+Z- and the Cn H2n+ZS-carcinogens almost completely. Beyond that in the emissions of the oiloven the occurrence of all carcinogens containing oxygen is possible. Besides these emissions contain aromatics which have the same molecular formulas and perhaps the same structures as for metabolites of carcinogenic polycyclics have been determined up to now. Among these probably are also epoxides considered as proximate metabolites.


[Regional chemotherapy of malignant brain tumors with endolumbar methotrexate injection]. Chemotherapy with endolumbar methotrexate injection was carried out on 52 patients suffering from malignant cerebral tumors. Of the patients, 44 had previously undergone an operation with subtotal removal of the neoplasm. The dosage and method for administering the methotrexate injection, and the duration of treatment have been determined. Chemotherapy with methotrexate results in a decrease in the size of the neoplasm which can be recorded by means of instrumental methods of examination. The pathomorphological analysis indicates a distinctly destructive effect of the preparation on malignant cerebral tumors.


[Membrane antigens of the agents of glanders and melioidosis]. Double immunodiffusion in gel test was used to determine the antigenic composition of the preparations of membranes isolated from the lysozyme spheroplasts of glanders (strain No. 10230) and melioidosis (strain No. C-141) causative agents. The membranes of these microbes proved to contain antigens of cell walls, lipopolysaccharides and the thermolabile membrane antigen proper. A study of antimembrane sera in the agglutination and immunofluorescence tests demonstrated a heterogeneity of the glanders and melioidosis strains under study by the membrane thermolabile antigen.


[Study of the effect of the sera of patients with rheumatism on the blast transformation in the mixed lymphocyte culture]. The authors studied the influence of the blood sera of 23 patients suffering from rheumatism on blast-transformation of lymphocytes obtained from healthy persons, in mixed cultures: 4 sera stimulated it, 5--depressed, and 14 produced no effect. Among patients whose sera depressed the blast-transformation persons with a more severe cardiovascular insufficiency prevailed. The content of IgG, IgM and alpha2-globulins in these sera was greater.


[Antigenic determinants of blood serum proteins detected in the structure of hepatitis B surface antigen by the method of affinity chromatography]. Tropism of the antigen of hepatitis B to the antibodies against normal serum proteins was revealed by the method of affine chromatography; this pointed to the possibility of the presence in the HBs-antigen structure of some antigenic determinants of the serum proteins or to the association of serum proteins with the HBs-antigen. A change of the isoelectric spectrum of the HBs-antigen and its tropism in affine chromatography to the antibodies against serum proteins possibly depended both on the nonhomogeneity of the antigenic determinants included into the composition of the antigen, and on the presence of the HBs-antigen--HBs-antibody or HBs-antigen--serum proteins complexes.


[Cellular and humoral indicators of antibody formation in rats with liver lesions caused by the antihepatocytotoxic serum]. As revealed, antihepatocitotoxic serum caused a sharp suppression of antibody genesis in rats at the early period (the 3rd day) after its 5 administrations; this was indicated by a marked reduction of the antibody-forming cell count in the spleen and reduction of the circulating antibody titres (hemolysins and hemagglutinins). Along with this, antibody formation was stimulated in the liver in the course of the whole month of study. By the end of the month suppression of antibody formation was replaced by its stimulation.


The efficacy of intravenous mexiletine on ventricular ectopic activity. Twelve patients with severe ventricular dysrhythmias were treated by one single dose of 250 mg of mexiletine injected intravenously over a 15 min. period. All patients showed some antiarrhythmic response. In 9 cases, the ventricular premature beats were totally or almost totally abolished up to 20 to 100 min. after the end of the infection. In most patients (5/7), there existed a correlation between the plasma concentration of the drug and the antiarrhymic action. However, the drug levels were not different in the good responders as compared to the poor responders or in those who manifested a prolonged antiarrhythmic activity as compared to the others. Side-effect appeared in three cases and consisted of vomiting, tremor, and episodes of sinus arrest.


Electron microscopic cytochemistry for demonstration of sodium fluoride sensitive adenyl cyclase in normal human epidermis. Adenyl cyclase activity in normal human epidermis was detected by an electron microscopic cytochemical technique. The sodium fluoride sensitive receptors were demonstrated on the outer sheath of the cell membranes. Adenyl cyclase activity was demonstrated in the basal cells and in the 4-5 lower layers of the Malpighian cells, while the superficial layers, stratum granulosum and stratum corneum showed no activity. The findings confirm and extend previous biochemical studies and provide a clue to the conception of the adenyl cyclase enzyme as a transmembrane arranged system.


Investigations on the binding sites of the basement membrane zone for pemphigoid antibodies in vitro. II. Immunohistochemical reactions of the reactive groups. In continuing our studies on the characteristics of the antigenic structures of the basement membrane, procedures used in histochemistry for the identification and blocking of reactive groups have been adapted in this present work to the pretreatment of cryostat sections of guinea-pig tongue. These sections have then been studied by the indirect immunofluorescence method. By means or reagents, which produce a reversible extinction of the basement membrane fluorescence produced with pemphigoid sera, it proved possible to determine the existence of certain chemical groupings which bind the anti-basement membrane antibodies, namely: free carboxyl groups deriving from amino acids, hydrogen bridges in which the hydroxyl groups from the carbohydrates in the antigen are probably involved, bonds involving the free aldehydes of the antigen (either cross-links from aldehydes, or formation of Schiff's bases with amino groups of the antibodies), and lastly, to a lesser extent, disulphide bonds. The antigen/antibody reaction probably occurs in the neighbourhood of the alpha-glucosido-beta-galactosido-hydroxylysine. A reaction model has been developed from these findings. There were also some indications that the antigenic structures of the intercellular substance are chemically related to those of the basement membrane. The cell nucleus antigens, on the other hand, appear to possess different chemical properties.


Studies on carrier protein in contact dermatitis: macrophage migration inhibition by soluble epidermal substances as carrier proteins. The migration of peritoneal exudate cells from picrylchloride-sensitive guinea pigs can be inhibited by the water-soluble proteins present in the picrylchloride-treated guinea pig epidermis. Further examination of these proteins revealed that antigens were present in fractions with the molecular weights ranging between 10 000 and 200 000.


Assessment of chromium allergy: features of patch test reactions at electron microscopic resolution. The possible correlation of clinically recorded test reactions and morphological changes at electron microscopic resolution in human subjects allergic to chromate (CrVI) was investigated. The effect of simple occlusion and of vehicles, e.g. distilled water, an alkaline buffer, and petrolatum was also studied 72 hours after application. The results indicate that even simple occlusion causes reactive changes in living epidermal cells. These changes become conspicuous in occlusion with distilled water, more pronounced with petrolatum, and were destructive in the case of the alkaline buffer. Chromate solutions produced varying degress of morphological change but were less pronounced in a vehicle of distilled water, compared with the changes seen when the chromate was combined with the alkaline buffer. Destructive cellular changes were observed in the electron microscope even in sections from test ares where no macroscopical reactions were recorded. When the clinical evaluation of hypersensitivity was done 72 hours after the application of the patch test the morphological changes were too advanced to provide specific pathognomonic information.


Pruritogenic activity of prostaglandin E2. The itch and erythematous responses induced by intradermal injection of histamine and PGE2 were studied in human skin. Both compounds produced a sensation of itch. The histamine-elicited flare reached a maximum in 3 min and had disappeared after 1 hours. PGE2 induced a similar flare reaction initially, but it was gradually replaced by a smaller, dusky and well delimited erythema. The itch and the flare-like erythema induced by either histamine or PGE2 were alleviated when the subjects were pretreated with the antihistaminic drug chlorcyclizine, thus indicating that at least part of the PGE2 response may be mediated via histamine release. However, when given combined in a mixture, histamine and PGE2 elicited itch of longer duration and flare of larger area than could be accounted for by simple additive histamine effects. Thus, PGE2 seems to potentiate the itch and flare responses induced by histamine in human skin.


Microvascular effects of a topically applied cationic triphenylmethane dye (crystal violet). The effects of local application of crystal violet on the microcirculatory system are reported. The testing system consisted of vital microscopy of the cheek pouch of the hamster and microangiography of rabbit's ear. It appeared that the early microcirculatory disturbances caused by a dilute aqueous solution of crystal violet were transient, whereas considerable tissue toxicity was shown in the long-term experimental model. A direct cytotoxic effect is suggested.


Delayed hypersensitivity and febrile acne conglobata. Delayed hypersensitivity reactions were investigated in 5 patients with febrile acne conglobata. Each of them had febrile periods, large abscesses and leukocytosis. They reacted negatively to tuberculin 10 TU/ml, to Schick toxin, to oidiomycin, to trichophytin as well as to 25 common contact allergens. DNCB did not induce sensitization in those 4 patients in whom it was carried out. However, the transforamtion of lymphocytes by phytohaemagglutinin (PHA) was normal. Five of 7 control patients with cystic or ordinary acne had positive tuberculin test reactions and 3 of them were sensitized to DNCB.


Lichen planus: an ultrastructural study. Ultrastructural features of skin lesions are described in 11 patients with lichen planus. Keratinocytes and melanocytes in the basal layer show loss of nuclear membrane, disappearance of nucleoli, homogenization of nuclear material, and aggregation of tonofilaments around the nucleus to resemble cells in the late prophase of the mitotic cycle except that there is no clumping of chromosomes. These cells undergo fibrillar transformation to form densely packed fibrillar bodies (colloid bodies) which are the size and shape of normal cells and frequently have cytoplasmic organelles. Ten per cent of the mainly lympho-histiocytic cells in the dermal infiltrate show changes such as multiple cell membrane discontinuities, disintegration of cytoplasm, and breaks in the nuclear membrane with spilling of nuclear substance either into the cytoplasm or the extracellular space. The shape, size and occasional fibrillar changes in the nuclei and cytoplasm of these cells resemble colloid bodies. Contact sites frequently occurred between cells in the dermal infiltrate, especially between lymphocytes and macrophages. It appears that primary injury to the basal layer cells occurs during the early phase of the mitotic cycle and antigen from this primary site may evoke a cell-mediated type of hypersensitivity reaction. Colloid bodies evolve from cells which have injured nuclei and undergo fibrillar transformation. Dermal as well as epidermal cells may contribute to colloid body formation.


Pachyonychia congenita Jadassohn-Lewandowsky: a disorder of keratinization. A 15-month-old boy with pachyonychia congenita is described. The patient also had follicular keratosis, leukokeratosis of the tongue, and blisters on the soles. Histopathological examination of the follicular keratosis showed hyperkeratosis and acanthosis. Horny plugs were located in sweat pores. By electron microscopy abnormal keratinization was demonstrated.


Penicillamine-induced pemphigus foliaceus. A 61-year-old man suffering from active generalized scleroderma developed pemphigus foliaceus after 9 months of D-penicillamine therapy, 900-1200 mg daily. At the same time, he developed proteinuria. Upon discontinuation of the drug, the proteinuria quickly resolved, but the bullous disease was still active one year later, with development of fresh blisters and intercellular deposits of immunoglobulin G and complement C3. The theory is proposed that D-penicillamine alters the epidermal cement substance, rendering it antigenic and thus initiating a vicious circle.


Isolation and characterization of soluble epidermal antigens reactive with pemphigus antibodies. The antigenic substance reactive with pemphigus antibodies was isolated from the soluble component of guinea pig epidermis by affinity chromatography. The substance was a protein of molecular weight 18 000 and consisted of RNA and hexose.


Treatment of resistant psoriasis with oral 8-methoxypsoralen and longwave ultraviolet light (PUVA). A treatment schedule and a follow-up study. Thirty-one patients with resistant psoriasis were treated with 8-methoxypsoralen orally, followed by irradiation with long-wave ultraviolet light (PUVA). The initial irradiance was 1.4 Joule/cm2, increased by 0.5 Joule/cm2 at the following exposures, to a maximum of 4.2 Joule/cm2. The 8-methoxypsoralen dosage was approximately 0.5 mg/kg body weight. In 17 patients psoriasis cleared completely after 10.8 +/- 3.4 exposures (mean +/- S.D.). In 12 patients the healing was almost complete after 14.5 +/- 5.8 exposures. Adverse effects were negligible. After clearing, the patients were followed without further therapy. Psoriasis recurred in approximately half of those patients followed for more than 2 months, on average 5 weeks after cessation of treatment. PUVA is an effective and agreeable therapy for recalcitrant psoriasis. Further studies must be carried out to evaluate the risks of a long-term treatment.


Treatment of pityriasis capitis (dandruff) with econazole nitrate. 63 patients of both sexes with pityriasis sicca or steatoides were examined for presence of Pityrosporum ovale on the scalp. Only those cases in which very numerous yeasts were seen in all squamae present in the preparation were considered positive. According to the severity or duration of  pityriasis, 60% of the patients in this population represented severe cases and 38% refractory cases. A solution of econazole nitrate was applied as a spray, morning and evening, for a period of 10 to 20 days (mean). The overall assessment of the clinical effects of econazole nitrate indicated 56 favourable results, with complete disappearance of objective clinical signs in 47 cases; the course of pruritus proceeded roughly parallel with that of the objective signs. The mycological checking of the clinical results, performed at least 7 days after the conclusion of therapy, disclosed 6 failures and 57 successes. In 17 patients, the microscopic examination of squamae was complemented by culture before and after treatment: in all cases, the culture, positive before econazole nitrate therapy, became negative after treatment, thus confirming the results of direct examination. These data suggest that Pityrosporum ovale plays a pathogenetic part in pityriasis simplex capitis.


A haemorrhagic bullous eruption of the hands caused by phenylbutazone: a report of 3 cases. Three patients developed a haemorrhagic eruption on the hands after taking phenylbutazone. The reaction appeared within two weeks of taking the drug and is probably an allergic capillaritis. All patients showed generalised capillary fragility with a positive Hess test which became negative within a week of stopping the drug. A mechanism is suggested for the development and distribution of the blisters.


Norwegian scabies developing during treatment with fluorinated steroid therapy. A fit, normally intelligent young man developed Norwegian scabies after prolonged treatment with large quantities of clobetasol propionate ointment. The development of this overwhelming infestation from the normal eruption of scabies may be related to the local immunosuppressive effect of this potent topical steroid.


Fetal hemoglobin and alpha-fetoprotein in various malignancies. Fetal hemoglobin (HbF) concentrations were measured by a radial immunodiffusion assay in 233 patients with various malignancies. In 96 of these, alpha-fetoprotein (AFP) was also measured by radioimmunoassay. The concentration of HbF exceeded 2 SDs above the normal mean in 39 of 233 patients, most notably in patients with leukemia, lymphomas, multiple myeloma and testicular tumors. The proportion of HbF was not correlated with the total hemoglobin concentration or with serum AFP concentration.


Peripheral pathway of proprioceptive fibres from feline extra-ocular muscles. I. A histological study. The findings of the previous study (1976) involving orbital operations in 12 cats have been confirmed in this study involving intracranial operations in 20 more cats. The perikarya of origin of afferent fibres from feline extra-ocular msucles have been clearly localised to the trigeminal mesencephalic nucleus. The functional subdivision in the nucleus that was noted earlier has been reaffirmed. Thus the caudal or pontine part was the location of cell bodies from the lateral rectus muscle, the intermediate part contained those from the superior oblique, while the other muscles were represented by cell bodies in the rostral part, there being some degree of overlap in the last two zones. In every instance the representation was shown to be bilateral and the total ratio of cellular representation was in the region of 4:1 (ipsilateral-contralateral). The peripheral pathway of the proprioceptive fibres has been shown to be exclusively along the oculomotor, trochlear and abducent nerves which are therefore sensorimotor.


Studies on the histomorphology and histochemistry of the saccus vasculosus of Cyprinion macrostomus. The saccus vasculosus of Cyprinion macrostomus is made up of coronet and supporting cells. Neurones are not observed. The luminal surface of the coronet cells exhibits hair-like protrusions. The saccus vasculosus is mainly concerned with a secretory function. Plenty of secretory material is seen in the lumen. PAS and alcian blue tests are positive for the secretory material in the lumen and the apical protrusions of the coronet cells. Some cells also exhibit small PAS- and alcian blue-positive granules. The possibility of the elaboration of glycogen by the coronet cells is ruled out. The toluidine blue test is also positive for the secretory material in the lumen and the apical protrusions. Small metachromatic granules are also seen in some of the coronet cells. The acetone-Sudan black B and Sudan black B tests point to lipid moiety of the coronet cells, the apical protrusions and the secretory material in the lumen. The acrolein-Schiff and ninhydrin-Schiff tests point to a protein moiety of the coronet cells and the secretory material in the lumen. The performic acid-alcian blue test showed cystine to be present in small amount.


[Crystallization and dissolution of collagen fibrils during the histogenesis of the intervertebral disk]. We studied the modifications of collagen fibrils during the histogenesis of the intervertebral disc of cats. In connexion with these studies it is necessary to distinguish between the fibrillar (functional) structure, the arrangement of fibrils, and the nature of fibrils, their diameter, period and other properties. Collagen fibrils (40--50 nm) of the anulus fibrosus enter in hyaline cartilage and split off in thin fibrils (8--10 nm). In this area the cartilage fibrils have a diameter of 20--22 nm, in a greater distance the diameter is diminished to 7--8 nm. Analogous to the changing of the nature of fibrils, the number of the cells related to the sectional area is diminished. The cells of the anulus fibrosus resemble those of tendons. In the transition area their shape becomes roundish, the number of granular membranes is increased, a voluminous Golgi-Apparatus appears for a short time. Finally, the cells are once transformed in cartilage cells with a small reticulum or cells of fibrocartilage with a capsule and a decreased cytoplasm; some cells are disintegrated. In the capsule of the fibrocartilage cells, parallel orientated filaments exhibit a periodical arrangement. In the border of the capsule, filaments change into periodical fibrils. Therefore, we must regard cells and their surrounding intercellular substance as metabolic unity which in the cartilage may be characterized as the chondron.


Histochemistry of the duodenal glands of the cat and horse. The duodenal glands of cat and horse were studied using PAS, Alcian blue, dialysed iron, aldehyde fuchsin-Alcian blue and high iron diamine stains. It was found that the duodenal glands of the horse reacted positively to Alcian blue, dialysed iron stains and also took the Alcian blue stain in the combined aldehyde fuchsin-Alcian blue and high iron diamine-Alcian blue stains. Those of the cat gave negative results. These results suggest the presence of acidic groups in the mucosubstances secreted by the horse's duodenal glands. A suggestion is put forward on the strength of the high iron diamine-Alcian blue combined stains that the acidity is due to the presence of carboxyl groups. It is suggested that the acidity may be significant in either cellulose metabolism or the digestion of the bacterial microflora from the stomach of herbivores.


Lysosomal (leucocyte) proteinase and sulfatase levels in Dyggve-Melchior-Clausen (DMC) syndrome. Patients with the DMC syndrome have been suggested to possess a specific sulfatase abnormality and/or to be deficient in a proteinase cleaving glycoprotein-acid mucopolysaccharide (AMP) linkage. We have previously found in DMC patients an abnormal excretion of urinary AMPs of which hyaluronic acid and chondroitin sulfate (A + C) were oversulfated and keratosulfate and heparan sulfate were undersulfated. Lysosomal acid proteinase, i.e. cathepsin D (EC 3.4.23.5) and neutral proteinase : elastase (EC 3.4.21.11) and cathepsin G were found to be normal in DMC patients. However, alpha 2-macroglobulin in serum was raised. This increase may be associated with a complex formation of alpha 2-macroglobulin with a neutral proteinase released from the cells. Increased levels of chondroitin sulfate N-acetylgalactosamine-6-sulfate sulfatase and sulfamidase and decreased enzymic levels of arylsulfatase A and B (EC 3.1.6.1) were found in leucocytes of DMC patients. The sulfatase activities assayed in the present study support our theory that a specific sulfatase abnormality may exist in the DMC syndrome.


Treatment of keratoconjunctivitis sicca with liquid paraffin or polyvinyl alcohol in double-blind trial. Twenty-two eyes affected with keratoconjunctivitis sicca have been subjected to double trials using the double-blind randomized cross-over technique. Polyvinyl alcohol in a 5% concentration improved the condition whereas liquid paraffin aggravated it, as estimated subjectively, and by the measurement of the break up time of the corneal film, and, finally, by the scoring of rose bengal vital staining of exposed cornea and conjunctiva. The conclusion is drawn that oil is contraindicated in keratoconjunctivitis sicca, and that rose bengal scoring (modified Bijsterveld method) is a valuable aid in control of the sicca syndrome.


Azidomorphines and homopyrimidazols: a new approach to the ideal analgetic. Azidomorphines, new semi-synthetic isomorphine alkaloids and homopyrimidazols (1, 5-diazanaphtalenes), two new families of compounds favourably enlarging the scope of analgetics, were developed. Azidomorphine, a 40--50 times more potent analgetic in man than morphine, showed a remarkably great dissociation between analgetic potency and dependence capacity and proved to exert significantly less unfavourable effects than either morphine or pentazocine. Probon (Rymazolium), the first compound of the homopyrimidazol series, introduced to therapy as a new minor analgetic, potentiated the analgetic and antagonized the respiratory depressant effect of morphine and its derivatives. In patients with chronic intractable pain, a combination of azidomorphine (0.5 mg) and Probon (150 mg) achieved total pain relief without noticeable euphoria and none of the patients subjected to nalorphine-precipitation showed signs of abstinence according to the Himmelsbach scoring system. Since both the azidomorphines and the homopyrimidazols are unexploited new families, further progress in detail structure-activity relationship studies seems quite promising.


Retrograde axonal and transsynaptic transport of macromolecules: physiological and pathophysiological importance. Anterograde and retrograde transport within axons and dendrites of nerve cells represent an integral part of the nerve cell function and biochemistry. A few exogenous macromolecules with most different molecular weights and physico-chemical properties (Nerve Growth Factor, tetanus toxin, cholera toxin, various lectins, antibodies against dopamine-beta-hydroxylase) have been shown to be taken up and transported with the retrograde axonal transport in exceedingly high amounts if compared to most other macromolecules. Specific binding to membrane receptors seems to be the prerequisite for this highly efficient retrograde transport. Upon arrival at the cell body tetanus toxin is able to leave the neuron and to migrate transsynaptically to presynaptic nerve terminals of second-order neurons. For NGF, tetanus toxin and some neurotropic viruses retrograde axonal transport eventually followed by transsynaptic transport may be crucially involved in their mechanism of action. Indirect evidence suggests the existence of a variety of endogenous molecules carrying specific information from the target cell and the nerve terminal to the cell body and eventually transsynaptically into second- or third-order neurons.


Evaluation of radiation therapy for bone metastases: pain relief and quality of life. The records of 158 patients irradiated for bone metastases were reviewed to evaluate the effectiveness of pain relief and to judge the effect of treatment on overall quality of life. Within 3 months 73% of the sites treated had pain relief, with 55%-65% having sustained relief up to 1 year or death. Of patients surviving more than 3 months, 63% maintained a satisfactory quality of life and were able to take care of most personal needs. The median survival of all patients was 1 year from initial treatment for bone metastasis. Radiation dose and the primary tumor site do not seem to be significant prognostic factors for initial pain relief or quality of life.


Esterases in acute leukemias: a cytochemical and electrophoretic study. Specific and nonspecific esterases were extracted from various typical cytologic types of leukemic blasts and subjected to electrophoresis in polyacrylamide gel. Preparations rich in normal granulocytes and normal monocytes were analyzed in a similar manner. The results indicated the presence of specific esterase activity in normal monocytes and in myelomonocytic and histiomonocytic leukemia, and a lack of consistent differences in the electrophoretic patterns of both specific and nonspecific esterases in these leukemias. The results support the viewpoint that distinctions between myelomonocytic and histiomonocytic leukemias cannot be made with certainty, and that they may represent variants within a broad spectrum of monocytic leukemias rather than separate and distinct entities.


Lack of prognostic value of the periodic acid-Schiff reaction and blast cell size in childhood acute lymphocytic leukemia. Conflicting evidence has been published as to the prognostic significance of the periodic acid-Schiff (PAS) reaction and cell size in acute lymphocytic leukemia (ALL). Therefore, a large collaborative study was undertaken to evaluate the prognostic significance of the PAS reaction and cell size of bone marrow lymphoblasts obtained at the time of diagnosis in children with ALL. Known prognostic factors (age and white blood cell [WBC] counts) were also evaluated. Data from 80 newly diagnosed cases of ALL were analyzed. These patients were treated with similar therapy by members of the Pediatric Division of the Southwest Oncology Group. The PAS reaction was scored. Microlymphoblasts were defined as having a diameter of less than or equal to 12 micron; macrolymphoblasts, greater than 12 micron. Patients 10 years and older at the time of diagnosis had a significantly shorter duration of first remission and survival than those younger than 10 years. Those with pretreatment peripheral WBCs of less than or equal to 25,000/microliter had significantly longer duration of first remission and survival than those with a peripheral WBC greater than 25,000/microliter. There was no significant difference in duration of first remission or survival in patients having predominantly macrolymphoblastic or microlymphoblastic marrows. PAS reaction was of no value in predicting the duration of first remission or survival.


Drusen of the optic disk and aberrant axoplasmic transport. The XXXIV Edward Jackson memorial lecture. We believe axoplasmic transport alteration is the anatomic substrate for formation of drusen of the optic disk. In familial cases the cause of axoplasmic transport alteration may be related to the presence of a genetically determined, small, crowded optic nerve head. We believe these congenitally elevated nerve heads evolve over a period of many years through stages of atrophy and drusen formation. Vascular malformations in the familial cases are primarily developmental; however, secondary vascular alterations may occur as the drusen enlarge. In retinitis pigmentosa the drusen may be caused by diminished production of axoplasmic material by the ganglion cell. Chronic alterations in axonal transport from any cause produce aggregates of swollen nerve fibers. These give a yellow-white appearance to the disk tissue and account for the yellow, filled-in appearance of the disk in patients with drusen, chronic atrophic papilledema, melanocytomas, and, in part, for the waxy yellow appearance of the disk in retinitis pigmentosa.


[Formation of high-molecular aggregates between serum amylase and colloidal plasma substitutes (author's transl)]. The distribution of molecular weights of human serum amylase was studied by gel filtration of serum, obtained before and after infusion of the colloidal plasma substitutes hydroxyethyl starch, dextran and gelatin, respectively. Both in serum, drawn after intravenous infusion of hydroxyethyl starch, and in a solution of hydroxyethyl starch with serum we observed a significant increase in the molecular weight of serum amylase. The occurrence of this "macroamylase" may be explained by the formation of aggregates between hydroxyethyl starch and amylase. Because of its high molecular weight the elimination of this, presumably, enzyme-substrate-complex is retarded, thus leading to the observed increase of serum amylase activity. In contrast to these observations concerning hydroxyethyl starch no change in the apparent molecular weight of serum amylase was observed following the infusion of either gelatin or dextran or their solutions with serum.


[Significance and methods of the dye stuffs analysis under the specially consideration of the fluorochromes (author's transl)]. The analysis of the dye stuffs is the important way to standardize the histological and histochemical methods. This was clearly demonstrated for example by the fluorochromes.


[Histochemical investigations of the biomorphosis of the tube epithelium in the postmenopause and in the senium (author's transl)]. Probes of tube of 21 women in the age of 50-83 years old were investigated with histochemical techniques for detection of mucosubstances. It was found that the regressive changes in the tube epithelium run down by degrees. In the high age there is still evidenced some PAS-reactivity and alcianophilia.


[Prevention of complications of histamine liberation occurring after administration of anesthetic agents and adjuvants]. To protect the organism against histamine liberated during anesthesia specific premedication is used including:--hydroxyzine (Atarax) which blocks the H1 histamine receptors, and is an anxiolytic,--tritoqualine (Hypostamine) which inhibits histamine synthesis,--epsilon aminocaproic acid (Hemocaprol) which prevents the antigen-antibody reaction and blocks the alternate route of complement. Twenty five patients were thus premedicated, 25 others received no premedication. All were put to sleep with Alfatesine. The results were judged on the clinical symptoms and the variations of histamine in whole blood. This premedication seems very efficacious, in particular in subjects with a high risk of histamine liberation.


[Diagnostic, etiologic and therapeutic problems confronting the anesthesiologist in cases of bronchial spasm. Apropos of 4 cases]. The authors recall the symptoms of peroperative and early postoperative bronchospasm. They emphasise the etiology and the treatment. In fact, bronchospasm may be induced by several causes:--mechanical or chemical vagal stimulation;--direct or allergic-induced histamine liberation, induced by certain drugs (mainly curare);--taking beta-blockaders before operation, favoured by the use of morphine during operation;--finally, any irritation of the bronchi (inhalation of gastric juice, pulmonary embolism, pulmonary oedemal). The treatment is etiological but also symptomatic:--enrich the inspired air with oxygen;--inject I.V. 1/2 to 1mg of atropine;--in case of failure, one should use Salbutamol I.V. which is very effective during contraction of the bronchial muscles;--massive corticosteroid therapy will be effective in mucosal oedema.


[Mechanisms of anaphylactoid reactions to drugs used in anesthesiology]. Anaphylactic reactions to drugs used in general anesthesia have a complex mechanism: true anaphylaxis by antigen antibody reaction (IgG our IgE) histamine liberation by certain substances with a special chemical structure, activation of the alternative route of complement. The authors recall the immunological stages in each case and give examples.


[Endogenous histamine. Principles of prevention]. After recalling the machanisms of liberation of endogenous histamine and its fate; the author discusses the pharmacological methods of protection of the organism against histamine liberation.


[Comparative study of histamine liberation after administration of anesthetic substances, curare agents and plasma substitutes in man]. The authors studied in 270 volunteers histamine liberation after administration of drugs. Definite histamine liberation was noted after propanidide, pentothal, methohexital, Alfatesine, and also after muscle relaxants including pancuronium bromide. Until now, among all the substances studies, both clinically and in the laboratory, after 4 years, only etomidate, according to their personal experience is not a histamine liberator. Similar results were observed after ketamine, but also after administration of Atosil (Phenergan) fenestil (Dimethendène) and Trasylol (Zymofren). As far as plasma susbtitutes are concerned, the search for mediators of the anaphylactoid and anaphylactic reactions should be considered in a differential way.


[Factors favoring anaphylactic reactions to general anesthetics]. The prevention of anaphylactic reactions to general anesthetics depends on the definition of a high risk group owing to special risk factors in these subjects. This study based on a study of the world literature over 20 years and on the cases of anaphylactic reaction observed in Nancy (more than 30) led the authors to carry out a special study of 7 with an atopic background, a history of drug allergy of immediate type, the repetition of general anesthetics at short intervals, latent spasmophilia, aptitude to histamine liberation, and/or hyper-reactivity to histamine, type of anesthesia and association of various factors. This method of approach permits in turn a prevention of complications by appropriate premedication.


Bleomycin hypersensitivity pneumonitis.

Bleomycin hypersensitivity pneumonitis. Three patients developed radiologic and functional pulmonary changes after bleomycin therapy similar to ones previously associated with administration of this drug. However, biopsy specimens showed a pattern consistent with hypersensitivity pneumonitis rather than the interstitial pneumonia usually reported in bleomycin pulmonary toxicity. There was a patchy eosinophilic infiltrate surrounding small airways and distal air spaces, but no immune deposits were noted by ultrastructure or immunofluorescence using conventional techniques and a specific antibody against bleomycin. Two of the patients had peripheral eosinophilia of 12% and 16%. All three patients showed considerable improvement on chest roentgenogram after corticosteroid treatment. Our findings are consistant with the view that bleomycin hypersensitivity pneumonitis has a different pathogenesis than bleomycin interstitial pneumonitis. Its recognition as a separate entity seems warrnated because of the favorable response to steroid therapy.


Frequency of RFA colour polymorphisms of human acrocentric chromosomes in caucasians: interrelationship with QFQ polymorphisms. One hundred normal caucasians were studied by sequential QFQ and RFA in order to estimate the type and frequency of variation. Colour variants were classified into 1 of 6 colours by RFA and intensity variations into 1 of 5 levels by QFQ. The interrelationship between QFQ and RFA variants was also examined. It was found that there was no consistent relationship between negative or brilliant QFQ variants and the various colours observed with RFA. RFA colour polymorphisms for chromosomes 13, 14, 15, 21 and 22 were 33.0, 38.0, 28.0, 50.0 and 24.5% while QFQ frequencies were 56.5, 10.0, 10.0, 15.5 and 10.0% respectively. RFA is especially useful in studying the inheritance of chromosome 21.


Laryngeal amyloidosis: clinicopathologic study of seven cases. The larynx is usually involved with amyloid as an isolated phenomenon and infrequently in generalized amyloidosis. This study includes six females and one male with an average age of 54 years who complained chiefly of prolonged hoarseness. At direct laryngoscopy, the amyloid usually presented as firm, nonulcerated yellow, red, or white lesions most often involving the ventricle, true and false cords. Surgical biopsy and/or excision was the only form of treatment. One patient experienced recurrence of her amyloid seven years after her first operation while another patient developed extralaryngeal amyloid. Amyloid is deposited extracellularly as amorphous eosinophilic material in vascular walls and basement membranes of minor salivary glands, as random tissue masses, or as "rings" in adipose tissue. Under the electron microscope, all types of amyloid have the same basic structure. However, chemical analysis has revealed three different classes of amyloid: amyloid of immunoglobulin origin, amyloid of unknown origin, and apudamyloid. Evidence suggests an immunoglobulin origin of at least some cases of amyloid localized to the larynx. It is theorized that the secretions of a monoclonal plasmacytic infiltrate of the larynx are metabolized into immunoglobulin light chain fragments by adjacent histiocytes and deposited extracellularly as amyloid.


Current concepts of tumor immunology. II. Tumor immunodetection. A great deal of investigation is presently underway to develop methods of effectively assessing the status of an individual patient's immune system. Such methods might provide a means of early detection of tumor or of indicating prognosis so that treatment modalities may be tailored to individual patient needs. The cell-mediated response may be monitored using intradermal skin tests and in vitro lymphocyte stimulation and cytotoxicity tests. Humoral responses have been monitored using assays for antibodies against tumor specific as well as tumor associated antigens. Assays have been developed which are capable of detecting circulating fetal antigens in very small concentrations. Thus far no one assay technique has proven to be sufficiently sensitive nor specific to be clinically useful. However, by utilizing a battery of tests before, during and after treatment, it is possible to determine a great deal about individual patient response to treatment and prognosis. With so many investigators focusing upon this problem, it seems likely that more effective methods of immunodetection will soon be developed.


[The allotypic variants of the e14 pattern (author's transl)]. The e14 pattern, located on the Fc fragment of rabbit IgG molecules, can be detected by precipitating antiserum no 20633. The reaction in agar medium of this serum with a normal rabbit serum e14/e14 leads to the appearance of four precipitating zones. This result indicates the existence of at least four allotypic forms (or variants) belonging to the e14 pattern. Among these variants, one can be detected in the reaction of another anti-e14 serum no 822. All these observations imply the participation of a great number of e14 determinants in the e14 pattern. Carbohydrate structures might be involved in these determinants as those which belong to "Xg" pattern.


Is non-specific cross-reacting antigen a marker on the surface of human basophils? Leucocytes challenged with anti-NCA serum (non-specific cross-reacting antigen) can release histamine. This release is Ca++, glucose and temperature dependent as usually described for basophils. Only half of the subjects whose basophils can release histamine when challenged with anti-IgE serum are also able to release histamine with anti-NCA serum. There is no cross-reaction between IgE and anti-NCA serum or between NCA and anti-IgE serum. So it seems likely that NCA might be a marker on the surface of some human basophils.


Statistical analysis and quality control in radioimmunoassays for staphylococcal enterotoxins A, B, and C. The objective of these studies was to set up a reliable radioimmunoassay (RIA) for staphylococcal enterotoxins A, B, and C (SEA, SEB, and SEC) in a food system. Significant differences (95% confidence limits) were obtained between the 0- and 1-ng/ml enterotoxin standards, so the sensitivity of the RIAs was 1 ng/ml. Polystyrene tubes coated with anti-SEB and stored at 4 degrees C were unstable. The percentage of iodinated SEB bound to these tubes decreased at a rate of 0.33%/day, in contrast to the rate of 0.07%/day obtained with tubes prepared the day before the analyses. Satisfactory precision and maximum sensitivity were obtained by using six replicates for each sample and freshly coated tubes. The antisera used for coating the tubes were reused four times and were frozen between coatings. The process of drum drying mashed potatoes containing 1 mug of SEB per g of mashed potatoes inactivated 83% (wt/wt) of the SEB. Statistical quality control parameters were used to insure that RIAs were performing reliably with a sensitivity of 1 ng/ml. Over 450 samples of potato flakes and granules, which represented different production lots from 12 different manufacturers, were examined for SEA, SEB, and SEC. No enterotoxins were detected.


Cultural and physiological characteristics of Clostridium botulinum type G and the susceptibility of certain animals to its toxin. Strain 89 of Clostridium botulinum type G, isolated by Gimenez and Ciccarelli in 1969, was characterized culturally, biochemically, and toxigenically. It was motile, hemolytic asaccharolytic, weakly proteolytic, lipase and lecithinase negative, and it produced acetic, isobutyric, butyric, and isovaleric acids in peptone-yeast extract-glucose broth. No spores were seen in smears from solid or liquid media. Very low levels of toxin were produced in regular broth cultures, but dialysis cultures yielded 30,000 mouse 50% mean lethal doses (LD50 per kg, orally and subcutaneously, respectively; and for guinea pigs, 10,000 to 20,000 and 100 mouse LD50 per kig, intragastrically and intraperitoneally, respectively.


Pemphigus-like antibodies in bullous pemphigoid. A patient had clinical, histopathologic, and direct immunofluorescent findings compatible with a diagnosis of bullous pemphigoid. In addition, the patient's serum contained pemphigus-like antibodies with different antigenic specificities than true pemphigus antibodies. Absorption of the patient's serum with AB substance failed to block the intercellular substance staining but allowed the demonstration of a basement membrane zone reactive antibody as well. Atypical cases such as this should not cast doubt on the usefulness of immunofluorescence in the diagnosis of bullous skin diseases.


Intramembraneous particles and transmembraneous ionic channels in the epidermal cell membrane. A cytochemical study with the alcian blue-lanthanum technique. Normal skin was investigated with the Alcian blue-lanthanum technique. Nexus (gap junctions) were found in the stratum Malpighii. They were less numerous in the basal layer, increasing to the upper layers of the epidermis and lacking in the stratum corneum. They were five-layered, about 20 nm thick and showed a 5-7 nm broad lanthanum positive intercellular dense line. Transitional forms between the narrow intercellular space and the real nexus were observed. These "nearly nexus" were broader, the intercellular dense line measured 6-15 nm, and sometimes they were seven-layered. Both, nexus and "nearly nexus" revealed a specific distribution of lanthanum in their membranes. Lanthanum ions seemed to penetrate the membranes forming electron-dense transversal channels branching off from the central dense line with a periodicity of 3 nm. The tangential sections suggested that this distribution was based on the aggregation of intramembraneous particles 1.5-2.0 nm in diameter, which in some areas may be gathered to greater subunits. The nexus may play a role in the control of epidermal proliferation.


Splenectomy in myeloid metaplasia.

Splenectomy in myeloid metaplasia. A retrospective review of 19 patients with documented myeloid metaplasia undergoing, elective splenectomy during the past ten years at the Peter Bent Brigham Hospital is presented. The primary indications for splenectomy in 17 of these 19 were either hypersplenism or symptomatic splenomegaly. Eighteen of the 19 underwent both 59Fe-ferrokinetic studies and 51Cr-sequestration studies or, alternatively, 111In-marrow scintigraphy as a part of their routine preoperative evaluation. The death from sepsis of one patient six weeks post-operatively, whose marrow function was poor and whose level of splenic sequestration was minimal, confirms the efficacy of these studies in the preoperative prediction of hematologic response to splenectomy. Eighteen of the 19 patients benefited from the operation in terms of symptomatic relief and/or hematologic improvement, although surgery presumably did nothing to prolong survival in these patients. We conclude that splenectomy is indicated as a palliative maneuver for carefully selected patients with myeloid metaplasia without prohibitive operative risk, provided the criteria for selection of patients are adhered to and the surgeon and hematologist work together as a team.


Reverse transcriptase of foamy virus. Purification of the enzymes and immunological identification. Reverse transcriptase from foamy virus, strain H4188 was estimated and purified. The enzyme has the following characteristics: 1. The reaction utilized preferentially oligo (dT) poly (rA) as a primer-template; however, the synthetic primer-template oligo (dT) poly (dA) could also be used to some extent. 2. The reaction utilized oligo (dG) poly (rC) as a primer-template with very low efficiency. 3. The crude virus preparation had a detectable endogenous reaction using the four deoxyribonucleotides for DNA polymerization. 4. The cation requirement for the enzyme reaction was much more biased for Mn++ than for Mg++ ions. 5. The molecular weight of the partially-purified enzyme was estimated to be about 80,000. Aggregates of 240,000 daltons were also seen. The activity of this enzyme was not inhibited by antisera against the reverse transcriptases of various type C RNA viruses, namely, feline endogenous leukemia virus, RD 114, Woolly simian sarcoma virus (SSV-1) and avian myeloblastosis virus (AMV). Antiserum against Rauscher leukemia virus (RLV) enzyme was marginally active against foamy virus enzyme, perhaps indicating a slight cross-reaction. The biochemical characteristics of foamy virus reverse transcriptase seemed to be very close to those of the type C RNA viruses, but the immunological reaction proved that the foamy virus reverse transcriptase was distinct from the others.


Enhancement of antiviral protection against encephalomyocarditis virus by a combination of isoprinosine and interferon. The antiviral effect of interferon against encephalomyocarditis (EMC) virus infection in mice was enhanced by isoprinosine. However, the enhancement was only obtained when both interferon and the virus were inoculated into the peritoneum; the inoculation route of isoprinosone did not modify significantly the final results. In addition, the time sequence of injections was of great importance; generally the injection of isoprinosine had to precede that of interferon by a few hours.


The surgical management of total atrioventricular canal lesions. Between 1969 and 1976 sixteen children have had surgery for total atrioventricular canal lesions at the Royal Children's Hospital, Melbourne. Twelve infants had palliative banding of the main pulmonary artery to control heart failure and prevent the development of pulmonary hypertension, with two hospital deaths (17%) and one late death. One other patient has been lost to follow-up and may also have died. Nine patients have undergone complete repair, with three hospital deaths (33%), and one later death at reoperation for residual mitral incompetence. Five of these had previously had banding of the main pulmonary artery, and the mortality has occurred exclusively in this group. The techniques of repair are discussed, and reasons advanced in favour of early primary repair of the defect in preference to palliative banding and later secondary repair.


Inactivation of alpha- and beta-thrombin by antithrombin-III, alpha 2-macroglobulin and alpha 1-proteinase inhibitor. Inactivation of alpha- and beta-thrombin by alpha 2-macroglobulin, by alpha 1-proteinase inhibitor and by antithrombin-III and heparin was studied. The amount of alpha- and beta-thrombin inactivated by antithrombin-III was proportional to the concentration of the inhibitor, but the inactivation rates of the two forms of thrombin were different. Heparin facilitated complex-formation between alpha-thrombin and antithrombin-III, whereas inactivation of beta-thrombin by antithrombin was only slightly influenced, even at a heparin concentration two orders of magnitude higher. alpha 2-Macroglobulin inhibited both alpha- and beta-thrombin activity similarly, i.e. the amount of alpha- and beta-thrombin inactivated as well as the rates of their inhibition were the same. alpha 1-Proteinase inhibitor also formed a complex with alpha- and beta-thrombin, similarly to antithrombin-III, although the inactivation of the enzyme needed high inhibitor concentration and long incubation time. These results suggest that the inactivation of beta-thrombin, if it occurs in the plasma, is also controlled by plasma inhibitors.


The effects of ionophores on the fluorescence of the cation 3,3'-dipropyloxadicarbocyanine in the presence of pigeon erythrocytes, erythrocyte 'ghosts' or liposomes. 1. Pigeon erythrocytes, resealed lysed erythrocytes or liposomes derived from erythrocyte lipids were suspended in solutions containing up to 2 micrometer-3,3'-dipropyloxadicarbocyanine iodide. Gramicidin, valinomycin, nigericin or carbonyl cyanide p-trifluoromethoxy-phenylhydrazone, or combinations of these, were used to induce electrical diffusion potentials dependent on Na+, K+ or protons. In each instance hyperpolarization of the cell membrane lowered the fluorescence of the cell suspension, a process that was completed in about 1 min. Subsequent depolarization caused an increase in fluorescence. 2. Quenching of the fluorescence of the cell suspension appeared to be due to the reversible binding of the dye to the cells. Much larger amounts of dye were bound, both to the intact and to the resealed erythrocytes, than would be expected if partitioning of the dye cation followed the Nernst equation. The dependence of the binding on the extracellular dye concentration was studied in the presence and absence of valinomycin. The results were consistent with the suggestion of Sims, Waggoner, Wang & Hoffman [(1974) Biochemistry 13, 3315-3330] that the dye was bound at both membrane surfaces and that, at low dye concentrations, hyperpolarizing the cells promoted dye binding at the inner membrane surface. 3. The applications of the technique are limited by the circumstance that the direct effect of the electric field on the uptake of the dye into the cells is amplified by a binding process that may be affected by other physiological variables.


Enhancement by cytotoxic agents of artificial pulmonary metastasis. The formation of lung colonies by i.v. injected Lewis lung-tumour cells in syngeneic recipients was greatly enhanced by prior treatment of the mice with cyclophosphamide. The lung-cloning efficiency was linearly related to cyclophosphamide dose and the optimum time of treatment was 2-4 days before the injection of tumour cells. The resulting lung colonies had a similar size distribution to colonies in untreated recipients. Bleomycin, local thoraric irradiation and whole-body irradiation were much less effective in enhancing the lung-cloning efficiency. Cyclophosphamide also enhanced the take probability of i.m. implanted tumour cells.


Cellular immunity to encephalitogenic factor in man as measured by the macrophage migration inhibition test: the effects of serum. Sensitivity to human encephalitogenic factor (EF) was measured in 70 cancer patients, in 34 patients with various non-malignant diseases and in 18 healthy volunteers, using the macrophage migration inhibition (MMI) test. Sensitization was demonstrated in 44/70 (63%) of the cancer patients, in 11/34 (32%) of the patients with non-malignant conditions and in one (5%) of the healthy individuals. No significant difference was seen in the frequency of demonstrable sensitivity with clinical stage of disease in cancer patients.Autologous serum from cancer patients had the ability to abrogate EF-mediated migration inhibition in 22/30 sensitized individuals. This blocking occurred with a similar frequency in all 3 clinical stages of cancer. Autologous serum from patients with non-malignant disease caused abrogation of EF-mediated migration inhibition in 4/11 sensitized individuals, whilst none of the healthy control individuals showed any significant change in the migration index in the presence of autologous serum. Homologous serum from patients with carcinoma of the breast or lung with and without autologous blocking activity and serum from a healthy individual were tested against lymphocytes from patients with various tumour types with the MMI test. Of 11 patients tested in the absence of serum, 8 (73%) showed significant migration inhibition with EF, whilst serum from patients with carcinoma of the lung or breast with autologous blocking activity abolished migration inhibition with EF in all 8 individuals with the former and in 6 with the latter, regardless of the tumour type from which the lymphocytes under test were derived. Homologous serum from both a carcinoma of the lung and breast without autologous blocking activity did not abolish migration inhibition with EF, except with the latter in one patient with a carcinoma of the lung.


Measurement of the complexity and diversity of poly(adenylic acid) containing messenger RNA from rat liver. The complexity of rat liver poly (A)+ messenger RNA (mRNA) has been measured by analysis of the kinetics of hydridization with both complementary DNA (cDNA) and single copy DNA. The complementary DNA-poly(A)+ mRNA hybridization reaction demonstrates the existence of three abundance classes representing 18, 37, and 45% of the cDNA and 4, 290, and 24 000 different 1800-nucleotide sequences respectively. The poly(A)+ mRNA driven single copy DNA hybridization reaction reveals a single major transition accounting for 1.9% of the haploid rat genome. The kinetics of the poly(A)+ mRNA driven single copy DNA reaction suggest that approximately 45% of the mass of the mRNA population contains over 95% of the complexity. Although higher than previous estimates, the base sequence complexities of rat liver poly(A)+ mRNA measured in these two ways are in good agreement, suggesting that the technique of poly(A)+ mRNA-cDNA hybridization may be used in approximating the complexity as well as abundance of a messenger RNA population. DNA-driven cDNA reactions reveal that about 10% of rat liver poly(A)+ mRNA is transcribed from repetitive sequences in the rat genome.


Characterization and serum inhibition of neutral collagenase from cultured dog gingival tissue. 1. Explants of dog gingiva, maintained in culture for 9 days in the absence of serum, released a collagenase (EC 3.4.24.3) into the medium. The yield of active enzyme reached a maximum after 5-8 days with concomitant release of collagen degradation products from the explants. 2. The enzyme attacked undenatured collagen in solution at 25 degrees C resulting in a 58% loss of specific viscosity and producing the two characteristic products TCA(3/4) and TCB(1/4). Electron microscopy of segment-long-spacing crystallites of these reaction products showed the cleavage locus of the collagen molecule at interband 40. 3. Optimal enzyme activity was observed over the pH range 7.5-8.5 and a molecular weight of approximately 35,000 was derived from gel filtration studies. EDTA, 1,10-phenanthroline, cysteine and dithiothreitol all inhibited collagenase activity. Proteoglycan derived from porcine and human cartilage did not inhibit the enzyme. 4. The enzyme was inhibited by the dog serum proteins alpha2-macroglobulin and a smaller component of molecular weight approximately 40,000. This small component was purified by column chromatography utilising Sephadex G-200, DEAE A-50, and G-100 (superfine grade). Agarose electrophoresis of the purified component showed it to represent a beta-serum protein. alpha1-Antitrypsin did not inhibit the enzyme. 5. The physiological importance of the natural serum inhibitors and gingival collagenase are discussed in relation to latent enzyme and periodontal disease.


[Histamine and serotonin liberation and vascular permeability in a focus of acute aseptic inflammation]. Degranulation of mast cells of albino rat peritoneal fluid and mesentery of the small intestine and the release of histamine and serotonin in acute aseptic peritonitis began the first minute after the damage and reached their maximum by the 5-th minute; by the 15-th minute the level of free amines did not differ significantly from the initial one. The dynamics of the immediate phase of increased vascular permeability corresponded to the dynamics of the free amines. The greatest increase of vascular permeability was noted on the 10th--15-th minute; it decreased considerably by the 20th minute. It was concluded that histamine and serotonin caused an increase of vascular permeability in acute aseptic peritonitis mainly within 15 minutes after the damage.


[Effect of cyngal on gastric secretion in rats]. The authors studied the influence of gallic salt of cynoglossophin-heliosupin alkaloid (cyngal), extracted from Cynoglossum officinale L. on the gastric secretion of rats. Cyngal proved to stimulate the secretory function of the rat stomach, beginning from the dose of 0.25 mg/kg. This action is explained by the capacity of the preparation to release histamine from the labile depot.


Tumor immunology: a neurosurgical perspective. II. The immunology of glial neoplasms. The research thus far on the relation of the immune system to gliomas has shown that a glioma associated antigen does exist. Small quantities of glioma associated antibodies probably circulate within the patient's serum but there is definite evidence of depression of the cell-mediated vanguard of the immune response. This depression is caused by a blocking factor that may be present as an antigen, antibody, or antigen-antibody complex. Both active and passive immunotherapeutic techniques have been employed in a small number of patients with little success. Considerable understanding of the alteration of the immune system is necessary before a rational approach toward immunotherapy of gliomas may be undertaken. However, it is apparent that reductive therapy consisting of surgery, radiation, and chemotherapy will be necessary before the immune system will be effective against the tumor burden.


The effect of catecholamines on the in vivo and in vitro responses of the cat lung during anaphylaxis. 1. Anaphylaxis in the lung of cats actively sensitized to Ascaris antigen has been investigated in vivo and in vitro. 2. In vivo there was a 100% increase in airways resistance and a 50% decrease in dynamic lung compliance following intravenous challenge with Ascaris antigen. Prostaglandin F2alpha induced similar changes but with histamine only dynamic lung compliance was affected. (-)-Isoprenaline prevented these prostaglandin F2alpha- and histamine-induced changes and caused a delay of about 2 min in the onset of the mechanical changes following anaphylactic challenge. 3. In vitro the isolated lung strip contracted within seconds of challenge whereas there was a delay of 2 to 3 min in the onset of the tracheal anaphylactic response. (-)-Isoprenaline, (-)-adrenaline and (+/-)-noradrenaline reduced the magnitude of anaphylactic contractions of the isolated trachea but did not significantly affect those of the isolated lung strip. This indicated lack of inhibition of mediator release from the lung parenchyma. 4. Histamine was released from sensitized lung fragments following challenge with the Ascaris extract. This release constituted 6.3% of the total tissue histamine and was not inhibited by (-)-isoprenaline (1 micrometer). 5. (-)-Isoprenaline abolished 5-hydroxytryptamine (5-HT)-induced contractions of the isolated trachea but not those elicited in response to acetylcholine. The isolated lung strip responses to histamine, prostaglandin F2alpha and 5-HT were highly resistant to inhibition by (-)-isoprenaline.


Release of mediators of anaphylaxis: inhibition of prostaglandin synthesis and the modification of release of slow reacting substance of anaphylaxis and histamine. 1 When isolated perfused lungs from sensitized guinea-pigs were challenged with antigen, histamine, slow reacting substance of anaphylaxis (SRS-A) and prostaglandin-like substances were released into the effluent. 2 Treatment of the lungs before and during challenge with indomethacin (0.5--10 microgram/ml), sodium aspirin (1--10 microgram/ml), sodium meclofenamate (0.1--1 microgram/ml) or ketoprofen (0.5--5 microgram/ml) inhibited the release of prostaglandins while increasing the output of histamine and SRS-A between three- and five-fold. 3 Diethylcarbamazine (0.2--1 mg/ml) reduced the release of SRS-A and histamine but increased the amount of prostaglandin-like substances produced. 4 Eicosatetraynoic acid (10 microgram/ml) inhibited formation of prostaglandins but did not modify release of histamine and SRS-A. 5 The results with non-steroid anti-inflammatory drugs and diethylcarbamazine suggest that prostaglandins, or some other product of the cyclo-oxygenase system, depress the anaphylactic release of SRS-A and histamine.


Guanethidine-induced vasodilatation in the rabbit, mediated by endogenous histamine. 1 The effects of guanethidine (0.5-4 mg/kg i.v.) on arterial pressure, hindlimb blood flow and hindlimb vascular resistance (HVR) were studied in unanesthetized rabbits subjected to "total" autonomic block. 2 Evidence that this response was mediated by histamine release was that (a) 3H-labelled histamine levels in the hindlimb venous blood rose substantially after guanethidine; (b) infusion of exogenous histamine caused an inhibition of the guanethidine-induced vasodilatation; and (c) competitive antagonism of the response was obtained with the H2-antagonist burimamide. 3 There was good correlation between the [3H]-histamine ;elease and the time course of the vasodilator response. Glyceryl trinitrate infusions that lowered HVR substantially, did not cause release of histamine. 4 Reserpine, desipramine and indomethacin pretreatment did not alter the vasodilator response to guanethidine. 5 The guanethidine vasodilator response was not influenced by the H1-antagonist mepyramine or by the other H2-antagonists, metiamide or cimetidine. The vascular receptors stimulated by endogenous histamine may be distinctive from those stimulated by exogenous histamine, or the action of guanethidine may involve greater production of histamine at an intracellular site that is more readily reached by burimamide than by the other H2-antagonists.


The effect of antiandrogens and stilboestrol on the cytosol receptor in rat prostate. The effects of 4 antiandrogens and stilboestrol on the cytosol receptor of the rat ventral prostate have been compared. Equimolar doses of cyproterone acetate, chlormadinone acetate, SC 9022 and flutamide inhibited the binding of dihydrotestosterone to the receptor complex in vivo by 44 to 50% whereas stilboestrol had no effect. In the in vitro studies an equimolar concentration produced similar effects to those observed in vivo with the exception of flutamide which had no effect. This technique provides a method for assessing and comparing the effectiveness of antiandrogens on the androgen receptor complex of the prostate.


Carcinoma of the penis: a review of 42 cases. A retrospective survey was made of 42 cases of carcinoma of the penis presenting over 14 years. Cases for attempted cure of the primary lesion were treated by either radiotherapy or surgery. It is recommended that radiotherapy should be the primary treatment as it is non-mutilative, allows secondary surgical salvage where necessary and has no greater occurrence of post-treatment lymph node metastases than surgery.


Retinotopic organization within the thalamic reticular nucleus demonstrated by a double label autoradiographic technique. A 'visual receptive zone' of the thalamic reticular nucleus can be defined in rabbits by the transneuronal transport of [3H]proline from the retina through the lateral geniculate nucleus to the reticular nucleus. Small injections of [3H]proline into the striate cortex of rabbits produce localized patches of label within this visual receptive zone, smaller than the zone itself. The sum of these small patches corresponds approximately to the total extent of the visual receptive zone, suggesting that there is a retinotopic map within the corticoreticular pathway. This map has been studied by double injections, using [3H]proline and [35S]methionine to label two different parts of the striate cortex. After axoplasmic transport of the isotopes, the reticular distribution of these two labels can be demonstrated by a double emulsion technique. This allows a distinction to be made between the radiation emitted by each isotope and demonstrates that within the reticular nucleus there is an accurate retinotopic map. In accuracy and in the orientation of the major visual field axes, this map corresponds closely to the map established in the dorsal lateral geniculate nucleus. However, the reticular map shows an elongation in the dorsoventral axis, which corresponds to the orientation of dendritic arbors within the nucleus.


Guanosine 3',5'-monophosphate in bone: microscopic visualization by an immuno-histochemical technique. Guanosine 3',5'-monophosphate (cyclic GMP, cGMP) was localized in bone cells by the use of an immunoglobulin-enzyme bridge method. We observed that in cat alveolar bone most osteoblasts did not stain for cGMP, while adjacent periodontal cells displayed cytoplasmic as well as nuclear staining. Numerous osteocytes contained diffuse reaction products over most or all of the cellular area. The method used in this study may be helpful in identifying specific hard tissue cell types whose function(s) involve cGMP.


Cellular localization and concentration of bone cyclic nucleotides in response to acute PTE administration. The cyclic AMP and cyclic GMP concentrations of alveolar bone of control and PTE-treated cats were measured by chemical and immunohistochemical methods. In the PTE-treated animals, alveolar bone osteoblasts stained intensely for cAMP, but very weakly for cGMP; the periodontal ligament (PDL) cells stained for cAMP similarly to the controls, but some PDL cells stained more intensely for cGMP than their controls; osteocytes stained for cAMP with greater intensity than in the controls; osteoclasts stained intensely for both cyclic nucleotides. We found that bone samples taken from animals 20 and 60 min after administration of PTE contained twice the amount of cAMP, and almost three times the amount of cGMP observed in the controls. These results indicate that the cellular source of bone cyclic nucleotides in PTE-treated animals varies as to cell type, and therefore in bone and PDL the functions mediated by cAMP are not necessarily antagonistic to those mediated by cGMP.


Lipid and protein histochemistry of enamel--effects of fluoride. Staining reactions for a number of histochemical procedures for lipophilic staining and protein were studied in the enamel matrix along the length of rat incisors. Sudan Black gave a positive stain across the whole thickness of very early enamel (up to 30 micrometer) but this staining only continued as a narrow band close to the ameloblasts as the enamel matured. A variety of tests for protein produced almost identical staining patterns in enamel matrix up to 100 micrometer thick. Since the pattern of "lipid" staining persisted, after using a number of procedures which could normally be expected to remove lipid, it is suggested that Sudan Black positive staining may be due to lipophilic protein rather than lipid itself. Fluoride did not significantly alter the staining reactions for "lipid" and protein but did produce matrix which was much more effectively stained by cross-linking agents FFDNB and FF sulphone.


Comparative trial of combination chemotherapy in extensive squamous carcinoma of the lung: a Southwest Oncology Group Study. The Southwest Oncology Group carried out a comparative study of two combination chemotherapy regimens in 231 patients with extensive squamous carcinoma of the lung. One regimen consisted of bleomycin, adriamycin, CCNU, vincristine, and mechlorethamine (BACON). The other involved mechlorethamine, adriamycin, and CCNU (NAC) in the same dose and schedule but with the deletion of vincristine and bleomycin. The response rate was 21% for BACON and 16% for NAC. The median survival time (MST) was 16 weeks for all patients receiving each regimen. Pretreatment performance statues (PS) was significantly related to the response rates: these were 28% for BACON and 23% for NAC among fully ambulatory patients (PS, 8-10) versus 15% for BACON and 10% for NAC among those with a lesser PS (P less than 0.05). Survival was also influenced by PS; the MST was 28 weeks for PSs 8-10 with either regimen compared to an overall MST of 11.5 weeks for patients with PSs 5-7 and 2.8 weeks for PSs 1-4. The toxicity of the two regimens was comparable with a 4% incidence of treatment-related deaths. An additional 10% of the patients were hospitalized because of life-threatening but reversible toxic effects. The only patients for whom there may be an improvement in MST over that expected from supportive care alone are those with PSs 8-10. Patients who demonstrated response or improvement, regardless of PS, had a significantly longer MST: 39.5 versus 11.2 weeks for those who did not respond (P = 0.001).