[Experimental investigation of cardiac lymph vascular system (author's transl)]. Ligatures of the supracardiac lymph vessels and the cardiac lymph nodes have been performed in fifty mongrel dogs. Comparative electrocardiographical, light microscopical, scanning and transmission electron microscopical investigations were done one day to three months after surgery. The demonstrated findings confirmed former results concerning the topography and the microstructure of the cardiac lymph vascular drainage system. In addition, the comparative functional and morphological examinations made evident the pathogenetic importance of cardiac lymphostasis. Lymphostatic oedema has been discussed as a pathogenetic co-factor for human heart diseases. Therapeutic attempts on experimental cardiac lymphostasis with i.v. - application of Coumarin-Troxerutin were without effect.


[Long-term cardiac arrest by cardioplegic coronary perfusion (author's transl)]. The Mg++ aspartate-procaine-cardioplegia has been proven in animal experiments as well as from 1970 til 1975 in more than 1000 open-heart-procedures by a myocardial temperature of 32 degrees C and aortic crossclamping time up to 40 minutes superior to all other known procedures of cardiac preservations. To guarantee a safe myocardial protection of the arrested heart for a remarkable longer period of total ischemia, we further developed the cardioplegic technique in the animal lab, and use it now clinically. The arrest is induced by cardioplegia (Mg++ aspartate-procaine), than the arrested heart is cooled down to 15-20 degrees C by cardioplegic coronary perfusion maintaining the oxidative metabolism. The perfusion is stopped. The begin of ischemia is still under normal ATP-levels and continuous cardioplegia. 1. Crossclamping of the aorta; 2. cardioplegic induced cardiac arrest by Mg++ aspartate-procaine (Kirsch); 3. Surface cooling of the heart; 4. Coronary perfusion by hypothermic cardioplegic solution (8-10 min, flow 80-120 ml/min, perfusion pressure maximal 30 mmHg). Perfusate: O2-saturated, erythrocyte free, 6% hydroxyethyl starch solution added 2 mM Mg++ aspartate, 4 mM procaine, 50 mM Na+, 5 mM K+, 0,5 mM Ca++, 25 mM HCO3-, 10 mM glucose, 200 mM mannitol, 250 mg/l 6-methylprednisolone. 84 patients (29 ACVB; 55 valve replacements); crossclamping time: 71 min (SD 22); total time of ischemia: 57 min (SD 18; max 96, min. 27 min); reperfusion time restoring normal excitation-contraction of the heart: 3 min (SD 2); weaning off bypass: 23 min (SD 14). Hemodynamic 12 h postop.: SO2 venous 76% (SD 6). No sympathicomimetics were used. Only 30% of myocardial ATP is splitted after 120 min of cardiac arrest. Electron microscopic findings show only small, reversible alterations of fine structure.


[Controlling of artificial blood pumps after total heart replacement - an example of disregulation (author's transl)]. This is a report on the special regulation problem of the left blood pump after replacement of the natural heart by incorporated extracorporally driven blood pumps in an animal experiment. The consequence of the peripheral self-regulation on the transporting capacity of the bloodpumps considering the driving pressure and the systemic pressure losses has been investigated. Two possible controlling principles and the respective fields of application are discussed on the example of a lung oedema.


[Possibilities of pacing the heart by transmediastinal retrocardially inserted leads (author's transl)]. Based upon experiences with 14 patients the clinical feasibility of transmediastinal retrocardial stimulation of the heart, of the left atrium as well as in one case of the left ventricle, is reported. Principally both can be stimulated by thus introduced pacemaker electodes. Thus on the one hand thresholds and consequently pulse effectivity appear to be a function of the electrode distance from the myocardium, whilst on the other hand the transmediastinal retrocardial thresholds are initially rather high in analogy to the majority taken from the atrial endocardial surface. Nevertheless, the transmediastinal retrocardial technique is possibly applicable for permanent cardiac pacing. However, additional tests about this are still necessary.


[A simple method for tricuspid annuloplasty (author's transl)]. A new operative method for tricuspid annuloplasty is reported. In this method the antero-posterior portion of the tricuspid annulus is sutured to a semi-circular nonelastic strip of teflon by double needle sutures. Since the radius of this strip is shorter than the radius of the valve ring, the tricuspid annulus will be narrowed after the sutures are tied. Because of its simplicity, firmness and maintenance of the valvular ring elasticity, this method seems to be advantageous to all similar procedures. The results of the method in 5 patients with severe tricuspid incompetence have been excellent. This method can also be used for annuloplasty of the mitral valve.


[Congenital aneurysms of the membranous ventricular septum (author's transl)]. In 3 patients with a congenital aneurysm of the membranous portion of the ventricular septum diagnosis could be made by angiography. One of these patients was clinically asymptomatic, while the two other patients were transferred for surgery because of right ventricular outflow tract obstruction or intracardiac left-to-right shunt. These both patients underwent successful open heart corrections. Aneurysms with a different intracardiac localization could be found. One of the cases represents an unusual association with corrected transposition of the great vessels.


[Two stage surgical treatment of large ventricular septal defects (author's transl)]. Since March 1971, 51 infants were subjected to pulmonary artery banding (PAB) for a large ventricular septal defect (VSD) with pulmonary hypertension. 41 infants (80%) were under six months of age. Additional defects were present in 41%. Twelve babies died (24%). The lowest mortality was achieved in isolated VSD (6,7%). 28 patients subsequently underwent VSD closure and pulmonary artery debanding. Catheterization data revealed normal or slightly elevated pressures and normal vascular resistance in the pulmonary circuit in 22 children. The operative mortality rate was 10,7%.


[Aneurysm of pericardial right ventricular outflow tract patches (author's transl)]. Among 1022 patients who underwent total repair of tetralogy of Fallot, 252 patients received a pericardial patch of the right ventricular outflow tract (RVOT); and of these 10 subsequently developed an aneurysm of the RVOT. Cardiac catheterization and angiography revealed moderate pulmonary unsufficiency in all patients, a residual pressure gradient in the RVOT in seven and a residual ventricular septal defect in two patients. Surgery was indicated in eight patients because of progressive distension of the aneurysm. Reconstruction of the RVOT was accomplished by resection of the aneurysm and insertion of a woven Dacron patch in five patients, primary suture of the pulmonary artery in two and implantation of a woven Dacron conduit containing a Björk-Shiley valve in one patient. No early or late death occured. Although aneurysms of the RVOT with pericardial patches represent a rare complication after total correction of tetralogy of Fallot, we recommend primary reconstruction of the RVOT with a woven Dacron patch.


[Survival of 51cr-tagged red blood cells in patients with artificial heart valves (author's transl)]. Survival of 51Cr-tagged erythrocytes is determined in 10 patients approximately 1 week after insertion of an artificial heart valve ("early hemolysis") and in 9 patients approximately 2 years after heart valve replacement ("late hemolysis"). Red blood cell survival is found to be significantly reduced in all patients following insertion of an artificial heart valve as compared to a group of control patients. Hemolysis is significantly more pronounced in the early postoperative phase than two years postoperatively. LDH and plasma hemoglobin are relatively good indicators of hemolysis but less reliable than the determination of t/2 Cr.


Sinus histiocytosis with massive lymphadenopathy. Five cases of "sinus histiocytosis with massive lymphadenopathy" are reported. The clinical features and histopathological appearances are described. The majority were African children with massive cervical lymphadenopathy. Histologically, the lymphnode sinuses are widely dilated by mature histiocytes, with phagocytosis of lymphocytes and other hematopoietic cells by the proliferating histiocytes. The diagnostic difficulties are discussed. These are the first cases recognized in Zambia.


Electronic bladder stimulation in spinal cord paralysis. Authors performed electronic stimulation of the paralysed bladder that was attributed to various innervation troubles. For this purpose, they implanted 10 patients with stimulator Model PMS-3, each with 8 electrodes. In three cases, outside factors (like endocarditis, pyelonephritis aposthematosa, and progress of paralysis in the limbs) forced them to remove the stimulator. The other cases can be declared as successful, for complete bladder emptying has been obtained. The authors want to emphasize that patients with an implanted stimulator can dispense with an indwelling catheter thereby avoiding vesicoureteral reflux. The absence of recurrent pyelonephritis results in prolonged health. This new technique seems to be appropriate, especially in peripheric paralysis, while central paralysis connected with fibrosis of the bladder neck often requires additional surgical intervention, e.g. transurethral resection.


Evaluation of cellular immunologic responsiveness in the clinical management of patients with prostatic cancer. II. Effect of oestrogen, cryosurgery and transurethral resection on thymic-dependent lymphocytic blastogenesis. The effect of oestrogen, cryosurgery and transurethral resection (TUR) of the prostate on the blastogenic response of thymic-dependent peripheral blood lymphocytes (PBL) to the non-specific mitogen, phytohaemagglutinin (PHA) was evaluated as one in vitro criteria of each of these treatment modalities on the cellular immunologic responsiveness of 24 patients with prostatic cancer. A depression 5 days following receipt of oestrogen and 2-7 days following cryosurgery or TUR of the responsiveness of PHA-stimulated PBL was observed. Oestrogen-induced aberrations of responsiveness may not only be of relevance in prostatic cancer patients, but also suggested association between uterine cancer and prolonged administration of diethylstilboesterol and the development of vaginal tumours in offspring found in association with maternal ingestion during pregnancy. Particularly striking was that contrary to the reduced responsiveness of PBL cultured in autologous and homologous serum from patients receiving TUR, patients receiving cryosurgery, while also showing reduction in autologous serum, showed increased responsiveness when cultured in homologous serum. Although transient, depression of lymphocyte responsiveness, particularly if involving tumour-cloned T cells, may provide reduced surveillance to potential tumour cells leading to an alteration of tumour-host homeostasis. The potential of reduced tumour surveillance at least in the case of TUR, appears to be supported by observations that patients expiring from prostatic cancer at our institution had an antecedent TUR. The possibility of identifying those patients possessing aberrations of responsiveness prior to therapy, as well as those prone to develop or undergo further reduction in their responsiveness following the presently evaluated treatment modalities would appear to be of real and relevant concern in the management of the patient with prostatic, as well as other types of malignant neoplasms. The possibility of pre-operative and/or post-operative immunotherapy in such patients may be indicated pending further study.


[Necrosis of the prostate and the urinary bladder during kumarin therapy (author's transl)]. The very first case of part necrosis of the ruinary bladder and prostate during therapy with kumarin is presented. The pathogenesis of kumarin induced necrosis is discussed. Apart from other findings there was histologically proved thrombosis of arteries and veins.


Fatal cerebral embolism following aorto-coronary bypass graft surgery. In a case of fatal cerebral embolic infarction following aorto-coronary bypass graft (ACBG) surgery, postmortem examination revealed thrombosis of the vein grafts to the left circumflex and left anterior descending coronary arteries. Continguous with the thrombus in the graft to the circumflex artery was thrombotic material adherent to the aortic sutures and extending several millimeters into the lumen of the aorta. A nonadherent thrombus of similar histologic character was found in the right middle cerebral artery, associated with localized brain infarction. In addition to the risks of cerebral complication associated with other types of open-heart surgery, the location of the vein grafts in patients undergoing ACBG operations seems to offer a unique mechansim for the occurrence of systemic and cerebral embolism, which may be operational in other cases.


Complement levles in relation to certain antibodies in polytransfused thalassaemic patients. Polytransfused patients are exposed to a variety of antigenic stimuli which may eventually trigger autoimmune reactions. The relation of serum complement to the occurrence of various antibodies has been investigated in a group of 75 polytransfused thalassaemic patients. The incidence of the antibodies studied was as follows: anti-HBs 77%, anti-Gm 64%, rheumatoid factor 31%, antinuclear 13%, anti-smooth muscle 47%. Anti-perietal cell, anti-thyroid and anti-kidney were only rarely found and antimitochondrial antibodies were never detected. Total hemolytic complement was low in 6 and incidentally decreased in 21 patients. A positive correlation was found between low serum complement and presence of rheumatoid factor. The high incidence of anti-smooth muscle antibodies seems to be unrelated to liver disease.


False-positive Rose-Waaler rheumatoid factor titre given by anti-ruminant IgM antibody. An antibody against ruminant (goat, sheep, bovine) IgM is described which also cross-reacts with rabbit IgM. The antibody was found in the serum of a patient with adult coeliac disease and a selective IgA deficiency. This patient gave a false high Rose-Waaler rheumatoid factor titre due to the presence of the serum antibody to rabbit IgM that was capable of agglutinating rabbit antibody-sensitised erythrocytes.


[T-Lymphocyte shifts in patients with melanoma and bronchogenic carcinoma (author's transl)]. Lymphocyte subpopulations were investigated in 32 patients with malignant melanoma, 25 patients with bronchogenic carcinoma and 59 control subjects. Whereas the determination of membrane immunoglobulin-bearing lymphocytes and of complement receptor-bearing lymphocytes gave comparable results in the tumour patient and control group, significant differences were found in the T-lymphocyte population using the sheep red blood cell (SRBC) assay. The so-called "active" Wybran rosette test, which characterizes a  T-cell subpopulation with an especially avid receptor for SRBC, gave significantly lower results in patients with melanoma (25% control 35%, p less than 0.01) and bronchogenic carcinoma (21% control 35% p less than 0.01). Determination of the total T-cell population using the Jondal rosette assay gave significantly lower values in the patients with melanoma (52%, control 63%, p less than 0.01), but not in those with lung cancer (65%). Low rosette values were detected even at low histological invasion levels (classified according to Clark) in the patients with melanoma. No correlation was found between the invasion level and the percentage of rosette-forming cells. The significance of these findings and the value of the rosette assay in the assessment of the immunological reactivity of tumour patients is discussed.


Alpha-galactosyltransferase activity in the serum of frogs (Rana catesbeiana). Human blood group 0 cells were converted into B-active cells by incubation with uridine diphosphate D-galactose and unfractionated serum from bull frog (Rana catesbeiana). Under these conditions, "Bombay" (Oh) type red cells were not converted, and group 0 foetal cells possessing a few H antigenic sites were only weakly converted into B-active cells. In addition, the agglutination titer of the converted cells with anti-H serum decreased. These results therefore indicate that the conversion depends upon the presence of H-substance on the red cells. It was concluded from the results of this investigation that the blood group B specific alpha-galactosyltransferase was present in the serum of Rana catesbeiana as well as in the human group B serum.


[Bleeding from hiatal hernia (author's transl)]. Report on 7 cases of massive hemorrhage from hiatal hernias. In all cases diagnosis was made before operation by oesophago-gastroscopy and/or by selective angiography. Early operation is the only successful therapy. The procedure depends on the kind of lesion and the type of hernia. In sliding hernia a Nissen fundoplication, in the paraesophageal type a fundoplication combined with gastropexy is performed. In cases of hyperacidity a combination with vagotomy and pylorplasty is necessary. Ulcers should be excised or resected by a Billroth-I-type gastrectomy. All seven patients could be cured.


[Portosystemic anastomosis during pregnancy]. There is discussed the surgical treatment of massive otherwise uncontrolable haemorrhage from oesophageal varices during advanced pregnancy. The authors have performed in the above situation a splenorenal shunt in a women suffering from the prehepatic portal hypertension during her sixth month of pregnancy. The pregnancy was maintained but an unviable child was born. The authors were able to find only 5 quotations from the references available to them dealing with 5 similar cases in women who delivered healthy babies thanks to a surgical intervention (5 times a portal systemic shunt, once a direct operation). The most important prevention of those exceptional surgical indications is the careful evaluation of all circumstances for a pregnancy in women with portal hypertension.


Tumour-host relationship and its implications in the treatment and long-term prognosis of laryngeal cancer. Critical observations on the TNM system of tumour classification. The choice of surgical and/or X-ray treatment of a laryngeal cancer is usually established by taking into consideration the site of the tumor and its extension. The histologic type is considered only when this is easily identifiable, whereas the histologic grade of cellular differentiation and the tumour-host relationship are always erroneously disregarded. These latter factors are of a basic importance in establishing a "tailor-made" therapeutic programme for each patient and the long-term prognosis. The above factors have led to a new critical approach to laryngeal cancer and have also made it possible to obtain some practical results: 1 degrees the correct definition of the verrucous squamous cell carcinoma of the larynx, which is the result of the highest local defensive reaction to tumour growth (mediated by thymus-dependent lymphocytes); 2 degrees a criticism of the present trend to perform a more conservative surgery decided only opon the basis of the site and extension of the neoplasm; conservation surgery must be adopted for patients with an intense cellular immune response around the tumour and with a moderate histologic grade of malignancy; 3 degrees a criticism of the present criteria in establishing the long-term survival, which do not include the early immune response; 4 degrees the necessity of a systematic histologic study of the surgical specimen so as to evaluate the intensity of the immune reaction both around the tumour and in regional lymph nodes. In the light of these new data, the TNM system of tumour classification is now outdated, as witnessed by the constant efforts to adapt it to the unpredictable behaviour of malignant disease.


Intrathoracic pressure as a tourniquet technic to tamponade bleeding esophageal varices. The authors' report observations on 79 cases of esophagovariceal bleeding in which ten cases were subjected to an intrathoracic tourniquet maneuver of increasing intrathoracic pressure. All esophagovariceal bleeding ceased following the maneuver. An established maneuver safety limit (holding mean transmural CVP to no higher than 4.0 cm H2O) insured cardiac output maintenance and guaranteed against maneuver-generated morbidity. The authors conclude the cessation of the bleeding from esophageal varices observed is the combined result of tourniquet-tamponade by direct venous air compression on the bleeding varices as well as general esophageal compression.


Metastases to the esophagus causing gastrointestinal bleeding. A case of hypernephroma metastatic to the esophagus and presenting with massive upper gastrointestinal hemorrhage is described. The literature on metastatic esophageal neoplasm is reviewed and the methods of spread and prognosis summarized.


Alteration of colony-stimulating factor output, endotoxemia, and granulopoiesis in cyclic neutropenia. Cellular and humoral factors involved in the regulation of granulopoiesis were evaluated in two patients with cyclic neutropenia by utilizing the agar-gel marrow culture technique to serially study marrow granulocytic colony-forming capacity (CFC) and the urinary output of colony-stimulating factor (CSF). CSF output varied inversely with peripheral neutrophil counts and directly with monocyte counts and evidence for infection (endotoxemia and/or staphylococcal abscesses). Following autologous infusion of one patient's plasma obtained during a period of neutropenia, increased urinary excretion of CSF occurred concomitant with increments in both marrow CFC and the proportion of granulocytic progenitor cells in DNA synthesis. Neutrophil periodicity was not altered by the administration of the neutropenic plasma. These findings are consistent with the hypothesis that cyclic neutropenia is caused by a quantitatively decreased entry of stem cells or granulocytic progenitor cells into granulopoiesis.


The myeloproliferative disorders. Correlation between clinical evolution and alterations of granulopoiesis. Patients with myeloproliferative disorders were prospectively studied by in vitro agar-gel marrow culture technics to evaluate factors involved in the evolution of abnormal granulopoiesis. Marrow granulocytic colony-forming capacity was determined in 78 patients with chronic myeloid leukemia, subacute myeloid leukemia, preleukemia, Di Guglielmo's syndrome, polycythemia vera or essential thrombocythemia. A wide range of marrow colony-forming capacity values was noted early in disease courses; however, in 26 of 33 patients decreased colony-forming capacity was associated with disease transformation into acute myeloid leukemia or other clinically aggressive stages. An increased proportion of abnormally light buoyant density (less than 1.062 g/cm3) colony-forming cells was present in the marrow and peripheral blood of 15 of 16 patients with chronic myeloid leukemia, subacute myeloid leukemia, preleukemia or essential thrombocythemia; in seven of eight patients with greater than 35 per cent abnormally light colony-forming cells their disease subsequently underwent transformation. Elevated levels of urinary colony-stimulating factor output were noted in 17 of 31 patients, and in 10 of 12 patients whose disease subsequently underwent acute transformation within 10 months of study. In six of seven patients who simultaneously had an increased urinary output of colony-stimulating factor and low colony-forming capacity in marrow, transformation occurred within 10 months. These findings indicate that progressive abnormalities of both marrow clonal growth patterns and levels of possible humoral regulatory substances develop during evolution of these diseases. In contrast, patients with idiopathic sideroblastic ineffective erythropoiesis had normal values for marrow colony-forming capacity, proportion of light density colony-forming cells and urinary colony-stimulating factor output, and in none has their disease transformed into acute myeloid leukemia. These in vitro studies appear useful for clinical staging, evaluating prognosis and categorizing patients with myeloproliferative disorders.


Ionic pathways of secretory membrane of frog gastric mucosa in Cl--free media. Experiments were performed to determine the return ionic pathways of the secretory membrane of frog gastric mucosa associated with the electrogenic H+ pump in Cl--free media. The replacement of a 52 mM Na2SO4 secretory solution with a 52 mM K2SO4 secretory solution led to a decrease of resistance, an increase of the H+ secretory rate, and a reversal of the PD. The replacement of 52 mM Na2SO4 with 52 mM MgSO4 led to an increase of resistance and a decrease of the H+ rate. These results provided evidence for the existence of K+ and Na+ pathways, the former having a lower resistance than the latter. Short-circuiting the mucosa in Mg2+ solutions increased the H+ rate to the value in Na+ solutions, hence ruling out the possibility that Mg2+ might interfere with the H+ pump. The fact that the Mg2+ secretory solution, without K+ or Na+, did not abolish the H+ rate suggested the presence of at least a third ionic pathway. presumably SO42-, providing that Mg2+ does not penetrate the mucosa.


Transepithelial transport kinetics and Na entry in frog skin: effects of novobiocin. Na+ entry across the outer surface of frog skin and transepithelial Na transport were studied simultaneously at different [Na] in either the presence or absence of novobiocin by direct measurements of J12 (unidirectional uptake) and Io (short-circuit current). J12 consisted of two components: one linear, the other saturable. The kinetic parameters of the saturating components in controls were close to the kinetic parameters of overall transepithelial transport (Jm12 = 1.68+/-0.13 mleq cm-2h-1; Io =1.80+/-0.14 mueq cm-2h-1. K12 = 6.02+/-1.27 mM;Kio=6.12+/-1.33 mM). Novobiocin significantly augmented net transepithelial Na transport by increasing J13. J31 remained unaffected. A 1:1 relationship between the saturating component of J12 and Io was observed in both treated and untreated skins at all [Na] tested. (Jm12Iom, k12, and Kio were significantly larger in treated skins, but despite very drastic changes in transport rates, a close correlation between kinetic parameters of entry step and transepithelial transport was maintained. This suggests that the kinetics of transepithelial transport may simply reflect those of the rate-limiting step: the Na entry across the outer barrier of the skin. The results indicate that the linear component of J12 is not involved in transepithelial transport kinetics.


Quantitative determination of high molecular weight serum proteinase inhibitors in human semen. Immunochemical determinations of serum proteinase inhibitors in human semen showed the presence of alpha1-antitrypsin and alpha1,x-antichymotrypsin, whereas inter-alpha-trypsin inhibitor, antithrombin III, alpha2-neuramino-glycoprotein and alpha2-macroglobulin could not be detected. Both serum proteinase inhibitors were determined in the seminal vesicle secretions of two patients with prostatic cancer. Employing the Ouchterlony double immunodiffusion technique pattern of identity was found between alpha1-antitrypsin resp. alpha1,x-antichymotrypsin in seminal plasma, seminal vesicle secretions and serum. Mean alpha1-antitrypsin concentration in seminal plasma of 129 andrological patients was 97.7 mug/ml and that of alpha1,x-antichymotrypsin 32.8 mug/ml. There were no differences in the mean alpha1-antitrypsin concentrations of normozoospermic and oligozoospermic ejaculates and those with seminal plasma fructose deficiency. Azoospermic ejaculates, however, showed a significant decrease of the mean alpha1-antitrypsin concentration (p less than 0.05). Alpha1,x-antichymotrypsin concentrations of normozoospermic ejaculates were significantly higher compared to those of oligozoospermia and azoospermia (p less than 0.05). Alpha1,x-antichymotrypsin levels in semen samples were fructose deficiency were not different from those of the total ejaculate population. The cause and significance of the observed differences in the inhibitor concentrations within the different ejaculate types is not known. However, there are no indications for the involvement of both proteinase inhibitors in male reproductive processes.


The prevalence of alpha-antitrypsin heterozygotes (Pi MZ) in patients with obstructive pulmonary disease. An increased incidence of intermediate deficiency of serum alpha1-antitrypsin resulting from Pi phenotype MZ has been reported in patients with chronic obstructive pulmonary disease (COPD) by some laboratories but not confirmed by others. Prevalence of Pi MZ was determined in patients with COPD among 502 subjects referred to a pulmonary function testing laboratory in a region with low concentrations of air pollutants. Control prevalences were obtained from 930 randomly selected subjects in the same community as well as from patients without COPD referred to the laboratory. Depending on criteria used to define COPD, 155 to 306 subjects had COPD. Pi MZ prevalence in subjects with COPD varied from 1.5 to 4 times the prevalence in the community control group and in the patients without COPD. This difference approached significance or was significant. Because Pi MZ was present in only 3.5 to 4.5 per cent of patients with COPD, Pi MZ is not a major factor in the etiology of COPD in this community. The higher incidence of Pi MZ inpatients with COPD reported by other investigators may be explained by small sample size, bias in selection of study or control population groups, or the development of COPD from interaction between Pi MZ and air pollutants or other factors not present in this community.


Racial distribution of alpha1-antitrypsin variants among junior high school students. A survey of alpha1-antitrypsin phenotypes and serum trypsin inhibitory capacities was performed in 1,841 seventh grade junior high school students. Antitrypsin deficiency states were detected only in white subjects (3.04) per cent) and not in 461 subjects of other races or of Mexican origin. A screening level of serum trypsin inhibitory capacity at 75 per cent of normal or less included all of the deficient phenotypes, but phenotyping was necessary to eliminate a small percentage of normal and unimportant variant phenotypes from this group. It is suggested that future programs for detecting antitrypsin deficiency and for counseling students who are genetically prone to develop pulmonary emphysema be aimed primarily at white populations.


Localization of T and B lymphocytes in human adenoid, tonsil, appendix and Peyer's patches. T and B lymphocytes were detected in human adenoid, tonsil, appendix and Peyer's patches by adherence to sheep erythrocytes (E) and human erythrocytes sensitized with antibody and complement (HEAC). The percentages of T lymphocytes in adenoid and tonsil cell suspensions averaged 30.9 +/- 3.4 (S.D.) and 35.8 +/- 6.4 (S.D.). The percentages of B lymphocytes in the same tissues were 42.5 +/- 11.3 (S.D.) and 40.1 +/- 34 (S.D.) respectively. In adenoid and tonsil tissue sections, B lymphocytes were found in the follicles and T lymphocytes were detected around the follicular areas. The predominant cell population in Peyer's patches and appendix sections was constituted by B lymphocytes.


Clinical and immunological improvement in a patient with chronic mucocutaneous candidiasis treated with transfer factor. In a 19 year old patient suffering from CMC since the first months of life, clinical improvement accompanied by correction of the immunologic defect was achieved by Transfer Factor therapy. After 12 months from the last administration of Transfer Factor the improvement persisted. The positive outcome of the treatment in this disease is not constant. Possibly only patients with cellular immunologic defects are susceptible of a favourable response, moreover it is thinkable that the quality of Transfer Factor and the dosage administered must play a role.


[Focal infection on O.R.L. and its distant aseptic manifestations]. In connection with the cases of a group of patients hospitalised in Departments of Infectious Pathology, the authors consider the various general and visceral symptoms caused by the focal infection. In these statistics, fever occupies the first place and in its isolated form poses difficult diagnostic problems which can only be solved by a process of elimination. Repeated biological tests and careful attention to the clinical symptoms are necessary to link what has been observed to an infection which, it should be stressed, is descrete. Articular lesion, very different from acute articular rheumatism, cutaneous, ocular and renal symptoms are each in turn discussed and analyzed. From their personal observations, the authors recall the possibility of serous lesions and, in particular, of recurrent pericarditis. A summing-up of the theories concerning prescription completes this clinical survey which ends by recalling the function of the oto-rhino-laryngologist in the search for the causal infection and the difficulties involved in ascribing responsibility to an almost invariably latent focal infection.


Thymus: primary site of lymphopoiesis.

Thymus: primary site of lymphopoiesis. The thymus of the leopard frog is the primary, if not the sole, source of progenitor lymphocytic cells that normally colonize the spleen. Following embryonal parabiosis, a high level of cell chimerism exists in the thymus glands of each member of the parabiotic pair. Evidently, there can be an appreciable amount of cross-circulation of thymic cells between thymus glands.


Alternate sites of lymphopoiesis in the amphibian embryo. The presumptive ventral blood islands were reciprocally transplanted between chromosomally labelled 72-hour-old leopard frog embryos. At 10 days of development, the differentiating epithelial thymus glands were surgically removed. Following metamorphosis, the spleen and bone marrow from juvenile frogs were analysed cytophotometrically. During normal ontogeny, the vast majority of peripheral lymphocytes are derived from the thymus, not the ventral blood islands. In the absence of the thymus, the ventral blood islands made the major lymphocyte contribution to the peripheral lymphoid organs. Thus, removal of the thymus appears to initiate an alternate pathway of lymphocyte differentiation in the leopard frog.


Extrahepatic biliary atresia versus neonatal hepatitis. Review of 137 prospectively investigated infants. In a prospective regional survey of neonatal hepatitis syndrome 32 infants had extrahepatic biliary atresia (EHBA) and 103 had hepatitis. No cause for the lesion was found in infants with extrahepatic biliary atresia, but in 32 with hepatitis a specific cause was identified, 24 having genetic deficiency of the serum protein alpha1-antitrypsin. No differences were observed in parental age, mother's health in pregnancy, month of birth, birth order, or sex of the infants. Familial idiopathic hepatitis occurred in 3 of 67 sibs of patients with idiopathic hepatitis, but the 33 sibs of EHBA patients had no liver disease. Of the infants with hepatitis, 36 were of low birthweight, less than 2.5 kg, and 23 were born prematurely. Infants with biliary atresia were all of normal birthweight and only one was born prematurely. Consideration of clinical and biochemical abnormalities in the first 2 months of life showed no differences between the two groups except that infants with EHBA were more commonly jaundiced from birth (80%) and had more frequently acholic stools (83%). The frequency of these features in patients with hepatitis being 68% and 52%. Standard tests of liver function were not discriminatory. Percutaneous liver biopsies were diagnostic in 75% of those with EHBA and in 92% of those with hepatitis. The I131 Rose Bengal faecal excretion was less than 10% in 26 of 28 infants with EHBA and in only 5 of 18 with hepatitis. These latter two investigations together allowed a correct preoperativer diagnosis of EHBA in all instances. Bile drainage was achieved surgically in only 3 cases. A major reason for these poor results may have been the late referral of cases for diagnosis and laparotomy, which should be performed as soon as the diagnosis is suspected and always by 70 days of age.


B-cell ontogeny in the chicken.

B-cell ontogeny in the chicken. We conclude that our data are most consistent with the hypothesis that individual bursal stem cells give rise to multiple clones of B lymphocytes by a preprogrammed sequence of variable (V) region genes. The alternate hypothesis that each stem cell gives rise to one B cell expressing but one set of VH genes could only fit our data if the additional assumption is made that each stem cell is preprogrammed to give rise to an unique B-cell clonotype at a fixed time during development. Since we were unable to influence the pattern of expression of clonotypic diversity by modifying the exposure to antigens and since random somatic mutations would seem an inefficient mechanism for systematic generation of the diversity, we favor the possibility of a genetic mechanism involving an orderly pairing of germ-line VH and VL genes. The corollary of this hypothesis is that V-region diversity is generated first and Ig-class diversity is secondarily expressed within each clone by a switch mechanism for the sequential expression of CH genes.


In vitro studies on the ontogeny of lymphocyte populations. We have investigated the ontogency of lymphocyte populations in the mouse embryo using organ culture techniques. Our results indicate that B lymphocytes are generated independently in foetal liver, foetal spleen and foetal bone marrow, while T lymphocytes are generated in thymus. We have characterised the structural and functional properties of developing lymphocytes in the organs. Our results suggest that foetal lymphocytes may differ from adult lymphocytes in a number of important respects which may have a bearing on the generation of tolerance to self antigens.


Ontogeny of thymus factor secretion.

Ontogeny of thymus factor secretion. The circulating thymic factor (TF) detected by 0-conversion assay has been followed up in ontogeny. Serum TF evaluation in pregnant thymectomized mice and in new born mice indicates that TF secretion starts on day 12-13 of foetal life and has reached the adult's level at birth.


Maturation of thymus-dependent lymphocytes after confrontation with histo-incompatible cells. Antigen-induced differentiation of mature T lymphocytes after in vitro exposure to transplantation antigens has been reviewed. Upon confrontation with histo-incompatible cells the resting alloantigen-reactive T lymphocytes transform into blasts and divide several times. Concomitantly they acquire the capacity to kill relevant allogeneic target cells. Generation of killer cells requires DNA synthesis and cell division. It is also evident that at least two subsets of T cells participate in the generation of T killer cells. In vivo studies suggest that the activated T cells cooperate with B cells, and that this cooperation is necessary in IgG class alloantibody response. Other studies, performed in vitro, have demonstrated that the alloantigen-activated lymphocytes may also have an immulogically specific suppressive effect on an alloimmune response. At any rate, after the cell proliferation ceases, the T blasts return to resting state and revert back into small lymphocytes. The "secondary" T memory lymphocytes are restricted to the antigens of the first confrontation. Second stimulation by the original histocompatible (but not by unrelated) cells leads to a characteristic prompt secondary proliferative and cytotoxic response. The memory T lymphocytes do not respond to the T mitogens (PHA and ConA) but do respond to relevant histo-incompatible membrane preparations and to relevant UV-killed stimulator cells (non-primed T lymphocytes are unalbe to do so). Cell division is not absolutely necessary for the generation of killer cells in the anamnestic secondary response. The memory T lymphocytes are long-lived and are recovered up to 20 weeks after parking to T-deprived syngeneic hosts. While resting in the syngeneic host they grandually lose the ability to respond promptly, indicating that T-cell memory on the cellular level is limited.


Selective concentration and localization of gold in macrophages of synovial and other tissues during and after chrysotherapy in rheumatoid patients. Gold distribution was studied in the tissues of 7 rheumatoid patients who had died from 0 to 23 years after stopping chrysotherapy (sodium aurothiomalate) and in 23 samples of synovial tissue removed surgically at intervals during chrysotherapy in 5 patients. After the application of a highly specific staining technique, the cellular localization of gold was examined microscopically in various tissues: the amounts of gold in selected areas of the same specimens which had been examined microscopically were then measured by neutron activation analysis. During active chrysotherapy gold was abundant in synovial lining cells except where a fibrin layer was present on the surface; after stopping chrysotherapy, gold disappeared from the synovial lining cells. Gold accumulated progressively in the subsynovial connective tissues during chrysotherapy, but was not uniformly distributed, and bore no relationship to fluctuations in serum gold levels. Gold deposition was not confined to joint tissue, but was found within the macrophages of many organs, renal tubular epithelium, and, after recent chrysotherapy, in seminiferous tubules, hepatocytes, and adrenal cortical cells. Gold persisted in synovial and other tissues for up to 23 years after chrysotherapy was stopped. The overall findings indicated that gold is selectively concentrated within inflamed synovial tissues during chrysotherapy.


Histocompatibility antigens in psoriatic arthritis. Histocompatibility (HL-A) antigen typing was performed on 82 patients with psoriatic arthritis. The prevalance of HL-AB27 was increased (28%) compared with that in a control group (7-5%), and this was most marked in those with spinal changes. The prevalence in patients with sacroiliitis and syndesmophytes was 75%, with sacroiliitis alone 78%, but with syndesmophytes and normal sacroiliac joints only 36%. The overall prevalence in psoriatic spondylitis was 60%, with a prevalence of 71% in those fulfilling the New York criteria for anklosing spondylitis. The prevalence was not increased in those with only peripheral arthritis (11%). The prevalence of HLA-B13 was decreased in those with psoriatic spondylitis, though this was not statistically significant. The overall prevalence of HLA-BW17 was increased, this being particularly so in those with syndesmophytes, but values were not significant.


Bleeding mucosal lesions in the upper gastrointestinal tracts of patients with oesophageal varices and hepatic cirrhosis. Thirty panendoscopic examinations were carried out on 24 patients with oesophageal varices and hepatic cirrhosis who presented with gastrointestinal hemorrhage. A mucosal lesion, focal or diffuse, was found in the upper gastrointestinal tract in all but three instances. The findings confirmed previous reports that hemorrhage in patients with oesophageal varices frequently occurs from a source other than variceal. This study has also demonstrated that where hemorrhage occurs from oesophageal varices, erosions of the oesophageal mucosa may play a major role in its pathogenesis.


[Hairy-leukocyte leukemia (tricholeukocyte). Report of a case]. A case of a woman suffering of hairy cells leukemia (tricholeucocytes) is described. The diagnosis of this leukemia was set two years after a splemectomy, due to the enlargement of the spleen. The patient was treated for a period of two years as a refractory anaemia and leucopenia (neutropenia). After admission the diagnosis was confirmed by the examination of periferal blood, cytologic and histologic examination of the bone marrow and after a subsequent examination of the spleen tissue. All these examinations showed the presence of typical hairy cells--tricholeucocytes in the periferal blood, bone marrow and spleen. On account of their own cytochemical examinations, and especialy immunological examinations by other authors, the authors of this presentation suppose that the tricholeucocytes most probably belong to B lymphocytes and that, therefore, this leukemia should be placed in the group of malignant lymphocytoproliferative diseases.


Inactivation of human thrombin in the presence of human alpha1-proteinase inhibitor. Both the clotting and esterase activities of thrombin are inhibited by alpha1-proteinase inhibitor (alpha1-antitrypsin). The inhibition is a time-and temperature-dependent reaction which is proportional to the molar ratio of thrombin to inhibitor. Both the active-site serine residue of thrombin and the reactive-site lysine residue of alpha1-proteinase inhibitor are involved. alpha1-Proteinase inhibitor forms a 1:1 complex with thrombin that is comparable with the complex formed with trypsin and other proteinases. Incubation of the inhibitor with excess of thrombin, however, results in inactivation of nearly all the enzyme, even though only as much complex is formed as alpha1-proteinase inhibitor present. A portion of the remaining thrombin apparently aggregates. These results suggest that the mechanism for inhibition of thrombin may not be exactly the same as for trypsin, which is inhibited only to the extent to which complex is formed.


Comparison of amphibian whole-cell and cell-free activity towards different transferrins. 1. A cell-free preparation from immature-erythrocytes of the bullfrog (Rana catesbeiana) was about equally active towards iron bound to homologous, rabbit or human transferrin. 2. In contrast with the cell-free system, whole immature erythrocytes exhibited optimum, intermediate or low uptake of iron from the above and from other transferrins.


[Relations between serum apha-antitrypsin level and neoplasms]. Alpha1-antitrypsin levels were determined in patients with bronchopneumopathies and in others with various forms of neoplasia. No relationship between levels and disease was noted in the first group, whereas a marked increase in values was observed in the second, particularly in the case of subjects with lung cancer. The interestiang aspects of this finding are discussed.


[Immunosuppressive treatment of rheumatic diseases. Experimental bases of a rational concept of therapeutic approach (author's transl)]. For treatment of diseases such as rheumatoid arthritis or systemic lupus erythematodes, which are initiated or sustained by immune-pathological mechanisms, various "immunosuppressive" drugs are used. There are conflicting data as to the benefit of this type of therapy. In this paper it is attempted to define a base for a more differentiated application of available drugs, since the present therapeutic approach seems rather empiric or is deducted from analogy to selected animal experiments. The investigations presented focus primarily on the behaviour of the small and medium lymphocytes of the organism, the adopted carriers of immunological (as well as autoimmune) reactivity, under conventional conditions (and under the influence of suitable drugs) as a biological supposition for the activity of "immunosuppressives". In rabbits, and mice, number and rate of proliferation of lymphoid cells is determined in untreated controls and animals treated with 6-mercaptopurine (6-MP) and cyclophosphamide (Cy), two immunosuppressive agents representing different types of pharmacological action. The elucidation why in rabbits both substances are equally immunosuppressive, whereas in mice only Cy has significant immunosuppressive activity, yields the base for a therapeutic concept of clinical immunosuppression. This species dependent activity of 6-MP can be explained by different proliferation kinetics of lymphoid cells in mouse and rabbit. Lymphocytes of the rabbit, compared to those of mice, are short-lived and have a distinctly higher proliferation rate. Thus, 6-MP, as an antiproliferative agent, leads, in the rabbit (under long-term as well as single-dose therapy) to a significant reduction of the number of small lymphocytes, whereas it reduces the long-lived lymphocytes of the mouse only marginally, thus explaining the good immunosuppressive potency in the rabbit and failure in the mouse. Cy leads, in both species, to a marked reduction of small lymphocytes and affects the long-lived cells of the mouse as well, resulting in high immunosuppressive potency in both species. In the NZB mouse, a well-fitting model of human lupus erythomatodes, Cy is successful in prophylaxis and therapy. A similar therapeutic effect cannot be obtained with 6-MP. Neither of the two groups of substances revealed selective activity on circulating T- or B-cells. According to the literature available, lymphocytes in humans are predominantly long-lived, too. Accordingly, Cy possesses a good immunosuppressive potency in man, too. Its therapeutic success is paralleled by a reduction of small lymphocytes. In conclusion, a true basic immunosuppressive therapy of autoimmune diseases in humans will primarily be possible by aid of substances which act through a cytotoxic mechanism and are thus able to affect even the long-lived human lymphocytes. In contrast, a substance acting purely through interference with certain steps of cell proliferation will predominantly remain restricted to an antiphlogistic use.


Pharmacological and toxicological studies with 1-benzyl-3-(2,3-dihydroxypropoxy)indazole. 1-Benzyl-3-(2,3-dihydroxypropoxy)-indazole (benzidol) is a novel indazolane derivative with marked antiinflammatory, analgesic and antipyretic properties. Its acute toxicity is three times less than that of benzidamine and five times less than that of phenylbutazone. Rats, mice, guinea pigs and rabbits treated with benzidol during 6 months at doses of 5, 50 and 200 mg/kg did not present any pathological alteration. The anti-inflammatory activity of benzidol is similar to that of phenylbutazone and higher than that of benzidamine. The analgesic and antipyretic properties are also considerable. Benzidol is better tolerated than the mentioned drugs with similar activities.


Use of noninvasive methods in evaluation of left ventricular performance in coronary artery disease. II: Change in systolic time intervals after coronary artery bypass in patients with stable angina. Serial recording of systolic time intervals (STI) was used to assess changes in left ventricular (LV) function in 92 patients with stable angina undergoing coronary angiography and LV cineangiography. On the basis of angiography, patients were placed in the following study groups: mild or absent coronary artery disease group -21 patients with less than 70 per cent occlusion of all coronary arteries, considered to have non-significant coronary artery disease and not needing bypass surgery; surgical bypass group-52 patients with evidence of significant (less than 70%) obstruction of at least one coronary artery who underwent myocardial revascularization; and medical group-19 patients with evidence of significant coronary artery disease not undergoing bypass surgery. Measured STI, corrected for heart rate and sex, were expressed as indices. No significant differences were noted in the mean STI from the time of initial evaluation to second evaluation 3 to 6 months later in either the mold or absent coronary artery disease patients or the medical group. In the surgical bypass group, however, serial studies at initial angiographic evaulation and 3 to 6 months after bypass surgery showed a shortened pre-ejection period (PEP) from 150 +/- 20 to 142 +/- 16 mn (P less than 0-001), prolonged left ventricular ejection time (LVET) from 396 +/- 21 to 409 +/- 14 ms (P less than 0-02), and decreased PEP/LVET from 0-45 +/- 0-11 to 0-04 +/- 0-07 (P less than 0-02). Paired data analysis of the three groups also showed a significant change only within the surgical bypass group from initial to find study, with a shortened PEP (P less than 0-002), prolonged LVET (P less than 0-001), and decreased PEP/LVET (P less than 0-001). These data suggest improvement in LV function in patients with significant coronary artery disease within a few months of myocardial revascularization, without demonstrable change in STI in those patients with coronary artery disease not subjected to revascularization.


Characterization of serum factors modulating splenic cytotoxicity in a syngeneic rat tumour system. During the terminal stages of tumour growth (6-8 weeks) in Wistar rats bearing a syngeneic squamous cell carcinoma (Sp1), their sera can block in vitro anti-tumour cytotoxicity by immune splenic T lymphocytes. At an earlier stage of tumour growth (4-6 weeks) the sera do not block this cytotoxicity, but can induce anti-tumour cytotoxicity by non-immune spleen cells in the absence of complement. Sera taken at these 2 stages of tumour growth have been fractionated by ion-exchange chromatography, using DEAE-cellulose. The fractions have been examined by immunoelectrophoresis and tested for anti-tumour reactivity. Blocking activity was found in the Week-8 serum fraction eluted with 0-005M phosphate buffer, pH 7-4, whilst the "cytotoxic" activity of Week-4 serum was eluted with 0-02M phosphate buffer, pH 6-2. It is suggested that different IgG sub-classes are responsible for the 2 activities.


Acquired von Willebrand syndrome with inhibitors both to factor VIII clotting activity and ristocetin-induced platelet aggregation. A case of acquired von Willebrand's syndrome (vWs) is described which appeared to be due to antibodies directed against factor VIII clotting activity (FVIIIC), factor VIII-related antigen (FVIIIRAg) and von Willebrand factor. The antibodies directed against FVIIIRAg was demonstrated by the inhibitory effect of a platelet eluate on Ristocetin-induced aggregation of normal platelets. This effect was not shown by the patient's platelet-poor plasma alone, nor could it be demonstrated in platelet eluates from 13 other patients who had antibodies to FVIIIC but in whom there was no evidence of an acquired vWs.


[Aortic coarctation. Indications and results of surgical treatment. 16 years of experience]. Eighty-nine patients were treated surgically for coarctation of the aorta in a period of 16 years. In 79, the operative procedure consisted of excision of the coarcted segment and primary anastomosis; in 7 cases of hypoplastic arch and in 3 of aneurysm of the aorta, some form of aortoplasty utilizing the isthmus and the subclavian artery, or the use of a dacron prosthesis were required. In a group of 33 patients under 2 years, 76% had associated cardiac anomalies and 100% heart failure, which made immediate surgical treatment mandatory with a mortality of 42% and a recoarctation rate of 10.5%. Out of 56 cases over 2 years, 46% had other cardiac malformations; however, a less severe clinical conditions allowed for an elective operation, with a mortality of 1.8% and a recoarctation rate of 1.8%. This experience and the review of the literature support the concept of elective surgical treatment for coarctation of the aorta around the age of 4 years, prior to the occurrence of hypertension or its complications. In the neonate and infant, surgery is justified in the presence of heart failure non-responsive to medical treatment within 24 to 48 hours. A deeper understanding of the pathophysiology of the malformation in the very young and a better perioperative management of neonates, have led to a decline in mortality in recent years.


Practolol and ocular toxicity. Antibodies in serum and tears. Serological studies in 22 patients presenting with ocular disease attributable to dosage with the beta-blocking agent practolol revealed a raised incidence of antinuclear antibodies. There was also a marginal increase in the incidence of antibodies to smooth muscle in the more severely affected individuals but the incidence of ther autoantibodies and levels of IgG, IgA, and IgM were within normal limits. Semi-quantitative analysis of tears from 14 of the patients showed absence or near absence in the more severely affected patients of secretory IgA, which is indicative of damage to the lacrimal gland. Other immunological parameters in the tears were normal.


Intracameral injection of gentamicin. Report of a case. A case of bacterial endophthalmitis secondary to a penetrating injury was successfully treated with intracameral topical and subconjunctival injections of gentamicin. After treatment the patient had normal vision and there was no evidence of toxic side-effects on the anterior segment of the eye including the endothelium, angle structures, and lens. The potential pathogenicity of Staphylococcus epidermidis is again emphasized.


Purification and properties of rabbit trypsin. The purification of rabbit pancreatic trypsin (EC 3.4.21.4) by affinity chromatography on Trasylol-Sepharose is presented along with its physical, chemical and immunological relationship to other trypsins. The molecule is a single polypeptide chain, which immunologically cross-reacts with porcine trypsin, but not with rabbit acrosomal proteinase. Sequence homology with other mammalian trypsins is seen at the amino terminus.


[Mechanism of excitation and contraction uncoupling in frog and guinea pig myocardial fibers during block of slow sodium-calcium channels by compound D-600]. In the experiments performed on the strips of frog's atria and ventricle it was found that rhythmic stimulation facilitated the dissociation of excitation--contraction coupling caused by D-600 compound through the block of calcium channels, i.e. D-600 prevented the increase of tension in the series of contractions or even converted positive staircase into negative one. The first contraction was affected by D-600 to a lesser degree than the subsequent ones. Guinea pig's left auriculus depressing action of D-600 was found to be strongly dependent on the frequency of stimulation. The data obtained were analysed by the model of excitation--contraction coupling. It was concluded that in amphibians as well as in mammalians tension amplitude during rhythmic activity of myocardial cells is determined mainly by Ca inflow through the excitable calcium channels. On the other hand the amplitude of the first contraction depends on the storage content determined by Ca inflow through the Ca channels open at rest. These latter channels have low sensitivity to D-600 and are better presented in atrium than in ventriculum. An increase of contraction tension observed in low sodium medium took place also under the action of D-600; in this case Ca storage was replenished by the Na-Ca exchange diffusion.


Emergency abdominal surgery in the aged. The results of 375 emergency abdominal operations in elderly patients over the age of 75 years are presented and discussed in detail. There has been a fourfold increase in the population over the age of 75 years in England and Wales during the 60-year period from 1911 to 1971. The overall mortality of these patients of 31-7 per cent is unrelated to the age of the patient, but appears to be directly related to the severity of the surgical condition and to cardiorespiratory complications. Our approach to these problems is presented and discussed.


Sensitivity of Trichomonas vaginalis to metronidazole, tinidazole, and nifuratel in vitro. Prompted by the sensitivity of trichomonads to metronidazole and nifuratel in clinical practice, a study was conducted in 1971-1972 of 63 consecutive strains of Trichomonas vaginalis isolated from women with clinically refractory vaginal discharge. Their susceptibility to metronidazole, tinidazole, and nifuratel was tested, using a serial tube dilution technique. The minimum concentrations which in 48 hrs caused immobilization and lysis of trichomonads cultured in Diamond's medium was assessed. No differences in drug potency could be determined. The median trichomonistatic and trichomonicidal concentrations were 0-1 and 0-6 mug/ml. respectively when using an inoculum of 10,000 organisms per ml. An inoculum of 100,000 per ml. resulted in inhibitory concentrations of 1-0 and killing concentrations of 3-3 mug./ml. These levels are readily attained in blood and vaginal tissue after oral ingestion of the two imidazole derivatives. Thus, metronidazole has maintained its efficacy since it was first introduced more than a decade ago. The few therapeutic failures with metronidazole and tinidazole are considered to have been caused by pharmacokinetic deficiencies in the patients, or by re-infection.


Bimodal action of glycine on frog spinal motoneurones. In the presence of procaine the changes in electrical potential caused by glycine in the ventral root of the isolated hemisected spinal cord of the frog have been shown to be compounded of both hyperpolarizing and depolarizing responses to the amino acid. From a comparison of the effects of changes in the perfusion medium on the potentials produced by glycine, beta-alanine and L-glutamate in the presence and absence of strychnine, it was concluded that glycine acts on a similar receptor to beta-alanine and causes a hyperpolarizing response which is blocked by strychnine. However, glycine has an additional, depolarizing, action which is usually the major effect and masks the hyperpolarizing response. The depolarizations produced by L-glutamate and glycine could be differentiated by their different ionic dependencies. The glycine depolarization was selectively decreased by a lowered sodium ion concentration in the medium while L-glutamate depolarizations were selectively enhanced by lowered potassium ion concentration.


Heart disease indicators in patients with aortocoronary bypass operation. The incidence of cardiovascular disease risk factors and other indicators of cardiac impairment were studied in 478 patients prior to their aortocoronary vein bypass operation and 194 patients who had angiographic examination but did not undergo the operation because the clinical and coronary angiographic findings were not considered serious enough to warrant the bypass procedure. The patients referred for surgery had higher plasma cholesterol and triglyceride levels (259 and 219 vs 233 and 180 mg/100 ml), tended to be older (53 vs 49 years) and had more extensive occlusive disease (occlusion score 200 vs 70) than the group without the operation. There was little difference in the proportion of smokers (81 vs 83%) or prevalence of hypertension (33 vs 30%). In comparison with 9,964 participants of a local health screening program, both patient groups had markedly higher prevalence of smoking, hypertension, chest pain and previous myocardial infarcts.


[Kinetics and morphology of immune reactve cells in the spleen as observed uwing the immune adherence method. III. Spontaneous immunocytoadherence as influenced by total body irradiation]. The course of spontaneous immunocytoadherence as influenced by a total body 850 r irradiation was studied in the mouse spleen. Prior to the total body irradiation 0.87 RFC/100 cells occurring spontaneously, without any previous antigenic stimulus, were dislosed in the spleen. Twenty four hours after iraadiation 0.075 RFC/1000 cells were detected. This number dropped to 0.023 RFC/1000 cells at day 4 after irradiation. A qualitative morphological analysis showed the following values: 65,1% of the spontaneous RFC were small lymphocytes, 24.5% were medium-sized lymphocytes and 3% large lymphocytes; 1.1% were plasma cells and 5.4% macrophages. Twenty four hours after irradiation with a dose of 850 r the RFC contained 9.3% plasma cells, and 90.7% macrophages, the respective numbers on day 2 being 7.5% and 98.3%. At day 4, permitting to demonstrate the RFC in significant numbers there occurred macrophages only. The model experiment has shown that the formation of spontaneous rosettes represents a cirtually normal immune reaction.


Definitions and terminology in cancer (tumour) etiology. An analysis aiming at proposals for a current internationally standardized terminology. In an attempt to overcome the confusion that exists in the terminology of cancer (tumour) etiology, the author has analysed the current situation and proposed terms which, he hopes, will stimulate international discussion and lead eventually to an agreed standard terminology.


Poisoning caused by the consumption of organomercury-dressed seed in Iraq. In 1971-72, a large outbreak of poisoning caused by the consumption of seed dressed with organomercury compound occurred in Iraq. International assistance was requested by the Government of Iraq in investigating this outbreak. The results of the investigations to date were presented at the Conference on Intoxication due to Alkylmercury Treated Seed, held in Baghdad, Iraq on 9-13 November 1974. This paper summarizes the main findings and recommendations of the Conference.


Feasibility of undertaking cancer incidence studies in rural areas of India. In the rural areas of developing countries, modern medical facilities are well below optimum levels and death registration is not mandatory. In India, as a result of such a situation, very few studies have been undertaken on the incidence of cancer in the rural population, though 80% of the people live in villages. The paper presents cancer incidence rates observed in a rural area of India by means of a method involving the use of paramedical personnel for initial screening, to minimize the cost. A statistical evaluation of the results shows that the method can be used for registering common sites of cancer in an area where conventional cancer registration methods are not applicable.


Intra-ocular pressure in onchocerciasis. Some preliminary results of a field evaluation. Preliminary data are presented on the relationship between intra-ocular pressure and onchocerciasis. There was no significant difference in the mean ocular pressure between persons with no ocular onchocerciasis and those with microfilariae in the eye, but a significantly lower mean tension was observed in those with severe ocular onchocerciasis.


Immunization in India with trivalent and monovalent oral poliovirus vaccines of enhanced potency. In an attempt to improve the serological response of infants in warm climates to oral poliovirus vaccine (OPV), the authors administered to 79 children between 6 and 41 weeks of age trivalent and monovalent OPV containing a virus dose 10 times as high as that found in the standard vaccine. The seroconversion rates following one dose of this trivalent OPV were 42% to type 1 poliovirus, 85% to type 2, and 31% to type 3. These rates are only slightly better than those previously reported after one dose of standard trivalent OPV and much lower than those achieved after 3 doses. The seroconversion rates following one dose of the monovalent OPV of enhanced potency were 89%, 93%, and 76%, respectively. These rates are comparable to those achieved after 5 doses of the standard trivalent OPV. Thus the refractoriness of host response was only partly overcome by enhancing the virus inoculum 10-fold.


Yersinia enterocolitica : a review of its role in food hygiene. Since Yersinia enterocolitica, now classified as a member of the Enterobacteriaceae, was recognized as a distinct species in 1964 it has been isolated with increasing frequency from man and animals (including dogs and pigs) and from some human foods. Y. enterocolitica infections are now seen as a cause for some concern in both human and veterinary medicine. The organism is commonly found in specimens from swine slaughterhouses and has been isolated from samples of market meat, vacuum-packed beef, mussels, oysters, and ice-cream. It has also been found in nonchlorinated well water used for drinking purposes. Infections in man therefore probably have an alimentary origin. Only 23 human infections were recorded in 1966 but the number increased to over 4000 in 1974. However, reported incidence is affected by growing awareness about the role of the organism in human and animal disease and by intensive laboratory analyses. While knowledge about the geographical distribution of Y. enterocolitica is still fragmentary it is clear that infections are very frequent in some parts of the world and probably common but unrecognized in many countries. The most common symptoms of Y. enterocolitica infections in man are fever, abdominal pain, and diarrhoea. In the USA most isolations in human infections were made from blood and mesenteric lymph node samples. The pathogenic mechanism is not known. In one experiment involving a human volunteer subject a dose of 3.5 x 10(9) organisms was required to produce an infection. Only recently has some success been obtained in establishing experimental infections in mice, guinea-pigs, rats, and rabbits. Laboratory cultivation techniques for Y. enterocolitica are described together with a table of minimal tests for characterizing the organism and two biotyping schema. Little is known about methods for controlling this disease, but environmental hygiene and sanitation with regard to food and water should apply.


An international haematological survey.

An international haematological survey. Haematological surveys of adult population samples were conducted simultaneously in 12 countries, all but one of which are in Europe. Haematological estimations on samples from nine of the countries were made in one central laboratory. Differences between countries in the mean levels of haemoglobin (and haematocrit and red cell count) were found to be relatively small, and the prevalence of levels below the arbitrary WHO levels for anaemia were, on the whole, low. In males, the evidence suggests a fall in haemoglobin level throughout adult life, which increases slightly in advanced age. In females, there is no evidence of any important relationship between age and haemoglobin level.


The practice of endocrinology in a rural setting: suggested guidelines. For the purposes of medical practice, a ;rural setting' implies an environment with little or no facilities for the sophisticated laboratory investigations that may be needed for the diagnosis of certain endocrine disorders. Fortunately, however, most of the commoner endocrine disorders may be diagnosed from the patient's history and a physical examination, together if necessary with the observed response to therapy. A lack of facilities, therefore, need not hinder the effective practice of endocrinology in rural areas.


Plasma factors in delayed-type hypersensitivity. Augmentation of lymphocyte responses in borderline leprosy reactions. The phytohaemagglutinin-induced responses of lymphocytes were found to be inhibited by plasma from patients with leprosy when compared with their responses in pooled serum from healthy donors. When patients developed reversal reactions, the initial inhibitory effect of their plasma was replaced by an augmentary effect on the responses to phytohaemagglutinin. The period of augmentation coincided with that of the reversal reaction in patients with borderline tuberculoid leprosy, but was delayed in patients with borderline lepromatous leprosy. The plasma from each leprosy patient was also observed to have the same effect on lymphocytes from unrelated individuals, showing that the inhibition and augmentation were due to factors in the plasma and not to a change in lymphocyte receptors. It is possible that the normal stable state of leprosy results from the presence of factors in plasma which act as a control mechanism, and that delayed hypersensitivity reactions may be caused by a breakdown of this control.


Studies on the immune status of children with acute lymphocytic leukaemia. I. Early phase before and after first remission. Seventeen children of 2-15 years of age with newly diagnosed untreated acute lymphatic leukaemia (ALL) were evaluated with a number of immunological tests: for humoral immunity serum immunoglobulins and reactive antibody formation against three antigens (diphtheria, tetanus, KLH); for cell-mediated immunity in vitro response of blood lymphocytes against PHA; membrane characteristics of blood lymphocytes and lymphoid blasts for both B and T cells. The tests were repeated in thirteen patients who attained full remission. In the majority (twelve cases) no surface markers were detected (null-cell leukaemia), one patient fulfilled the criteria for a T-cell leukaemia with thymoma. Four patients had rather high absolute B-cell counts, but did not fulfill all the criteria for B-cell leukaemia; three of them died before remission. Immune globulin concentrations were only slightly changed, antibody formation, both primary and anamnestic, was possible. PHA response was extremely low in the initial phase, but normal immediately after remission. During remission all patients were markedly depleted in both their B- and T-cell compartment.


Studies on the immune status of children with acute lymphocytic leukaemia. II. In remission with and without cytostatic treatment. In eleven children with acute lymphocytic leukaemia (ALL), cytostatic treatment was stopped after sustained remission lasting for 9 months--6 1/2 years. Their immunological status was monitored every 6--12 weeks during the first year after cessation of therapy. Rebound of depressed parameters was observed for absolute lymphocyte, B-cell and T-cell counts and for immunoglobulins. A simple follow-up scheme for such patients is proposed.


Lymphocyte response to IgG in patients with ankylosing spondylitis and their families. Lymphocyte responsiveness to IgG was measured by an agarose method in nine patients with ankylosing spondylitis (AS), one patient with Reiter's Syndrome (RS), and thirty-six of their family members. Similar studies were also performed in five patients with rheumatoid arthritis (RA) and twenty-nine of their first degree relatives as well as in seven control families (twenty-seven subjects). Lymphocytes from the ten spondylitic patients and twenty-four of thirty-six family members responded in vitro to autologous IgG. Although most of these subjects had the histocompatibility antigen, B27, there was no association between B27 and response to IgG. Four of the five patients with RA and twenty of their twenty-nine first degree relatives responded in vitro to IgG, whereas only six of twenty-seven control family members gave a positive reaction. There was no difference in the incidence of antiglobulins (detected by agglutination tests) in the family members of patients with AS and RA or in control family members. These data indicate that lymphocyte responsiveness to IgG is the only aberrant immune response thus far described which is shared by patients with AS and RA and their family members.


Intramural hematoma of the esophagus: a complication of carbon tetrachloride intoxication with acute renal failure. Following a period of prolonged severe vomiting, an intramural esophageal hematoma could be demonstrated by endoscopy and by X-ray in a 21 year old patient with hepatic and renal failure after exposure to carbon tetrachloride. The hematoma resolved spontaneously. The intramural hematoma is thought to have developed from a microdissection of the esophageal wall in the presence of a hemorrhagic diathesis.


Time course of hypothalamic CRF activity after the administration of two different stresses. The time course of hypothalamic corticotropin-releasing factor (CRF) activity after the administration of ether stress was different from that after immobilization stress. The maximal response CRF activity was observed 2 min after ether stress, followed by a precipitous decrease 5 min after the stress. A gradual increase of CRF activity was subsequently observed for several minutes with fluctuated changes. Thus, response pattern was vibratory. But under immobilization stress, markedly fluctuant changes of CRF activity seen in the case of ether stress did not appear after the maximal response observed at 2 min, indicating that the response pattern was not vibratory. On the other hand, the concentration of plasma corticosterone increased significantly 5 min after the ether or immobilization stress with the peak value around 17 min.


Deoxyribonucleotide pools in mouse-fibroblast cell lines with altered ribonucleotide reductase. Mutant cells lines of 3T6 mouse fibroblasts, resistant to thymidine and deoxyadenosine, have an altered allosteric regulation of the enzyme ribonucleotide reductase (Meuth, M. and Green, H., Cell, 3, 367, 1974). Compared to 3T6, these lines contain larger pools of deoxynucleoside triphosphates, in particular deoxycytidine triphosphate, but show a normal rate of DNA synthesis. Addition of thymidine or deoxyadenosine to 3T6 cells results in large accumulations of the corresponding triphosphates and a dramatic decrease in the dCTP pool, concomitant with inhibition of DNA synthesis. Addition of thymidine to the mutant cell lines also leads to an increase in the dTTP pool but does not result in a depletion of dCTP or inhibition of DNA synthesis. Addition of deoxyadenosine only leads to a small increase of the dATP pool. In general the change in the allosteric regulation of bibonucleotide reductase is reflected in the deoxynucleotide pools.


Visual-vestibular interactions in the vestibular nuclei of the goldfish. The responses of vestibular nuclei neurons of relaxed unanaesthetized goldfish have been examined with trapezoid velocity stimuli under three conditions. Responses to horizontal body rotation in the dark (pure vestibular stimulation) resemble those observed in vestibular nerve afferents. Optokinetic responses to exclusive visual surround-motion are also direction-specific and, in contrast to vestibular responses, exhibit a tonic response to constant velocity. They show three different response profiles, classified A,B or C, based on the neuron's discharge rate: either increasing, decreasing or remaining constant once surround motion is maintained at constant velocity. Following these dynamic effects, optokinetic responses have a maintained modulation of resting discharge until deceleration commences. The time constants associated with the dynamic effects vary between 1 and 11 seconds. Steady-state modulation of optokinetic responses shows a weak relation to stimulus velocities exceeding 10 deg/sec. Responses to body rotation in the light were found to linearly combine the weighted vestibular and optokinetic responses so that accurate velocity information is available for sensory and motor functions independent of the neuron's vestibular (I,II) or optokinetic (A,B,C) response type. The principle of this visual-vestibular interaction is discussed with respect to multisensory processing within the vestibular nuclei.


Experimental allergic encephalomyelitis.-- The effect of dexamethasone on growth and proliferation in the draining lymph node. Dexamethasone, when administered from day 0 to day 9 following the sensitizing injection of encephalitogenic protein in complete Freund's adjuvant, suppressed both the characteristic enlargement of the paracortical area of the draining lymph node and the development of clinical and histopathological signs of experimental allergic encephalomyelitis. Division of cells within the node was not inhibited and therefore the effect of dexamethasone appeared to be a consequence of reduced migration of lymphocytes into the node.


[Driving phenomenon in neurons of the spinal center of frog lymph hearts]. Bioelectrical activity of motor axons of the lower lymphatic hearts was recorded in frogs. When the 5th and 6th dorsal roots were stimulated at a frequency lower than the spontaneous frequency, artificial bursts of motor impulses were usually produced together with spontaneous impulses. Latency of artificial impulses depended upon the time of stimulation in the interburst interval. When the same roots were stimulated at a frequency higher than the spontaneous rate, only motor impulses corresponding to the artificial frequency were observed. The latency of these artificial impulses was 100--160 msec.


[Possible participation of lactic acid in formation of a non-mediator agent stimulating the heart during exposure of the myocardium to sympathetic influences]. Release of A-factor, the physiologically active substance of a non--mediatory nature under sympathetic stimulation, depends upon the glycolytic process. To examine the assumption that A-factor may be a glycolytic product, lactic acid was studied in particular, and it was shown that A-factor is not identical to lactic acid. However it was found out that lactic acid participates in the release of A-factor in the heart. It was shown that under the effect of lactic acid a substance having high cardiostimulating activity was released in the frog heart muscle. This cardiostimulating substance as well as A-factor increases the amplitude of contractions of A-factor, was not abolished with beta-sympathicolytic inderal. The ability of both substances to stimulate heart activity was preserved after 20 min heating in a water bath. The cardiostimulating substance similar to A-factor increases heart sensitivity to sympathetic and decreases it to parasympathetic stimulations. It may be suggested that the cardiostimulating substance released in the heart under the effect of lactic acid is identical to A-factor released in the myocardium under the action of catecholamines and stimulation of the sympathetic nerve.


[Rsponses of the primary afferents of the frog lateral semicircular canal to caloric stimuli following section of the eighth nerve]. In curarized Rana temporaria, after transection of the 8th nerve, responses of 75 primary afferents of the LSC nerve to short local caloric stimule (0.5--12 degrees C over the canal temperature) creating theexcitatory current of LSC endolymph, were studied. In 41 per cent of the units (group A) the maximal (peak) frequencies (PF) of responses were shown to be associated either by linear or semilograithmic relations with the peak temperature (PT). In 23 per cent of the units (group B), PFPS revealed saturation at PT 8-12 degrees C. In 29  per cent of the units (group C), PFs were associated with PTs first by direct and then -- at increasing PTs-- by reverse proportionality. Duration of group A responses was related to PTs either in linear or semilogarithmic way. Comparison with previous data obtained in identical conditions but with intact 8th nerve indicates no noticeable difference in responses where efferent control was excluded.


[Effect of thrombin on chemoreceptors of the frog carotid labyrinth]. The frog's electrical activity of the carotid body chemoreceptors reacting to thrombin was studied. The chemoreceptor response was estimated by means of afferent impulsation in the n. glossopharingeus. The afferent impulsation frequency increases to a certain extent in proportion to the irritant concentration; too high a thrombin concentration is able to suppress the chemoreceptor activity. The direct dependence between the receptor response and the effector reaction diminishing the blood coagulation, was established. The receptors adapt slowly, their discharge is of an irregular character.


[Aorto-coronary by-pass. Personal experience based on 342 cases operated on between April 1971 and December 1974 (author's transl)]. The authors report on the casuistry of aorto-coronary by-pass operations they performed between April 1971 and December 1974, discussing the criteria which indicate the necessity of operating, the principles of the operative techniques, and the results obtained. Out of a total of 342 operated cases, there was an operative mortality (within 30 days) of 3% in isolated by-pass cases, and 4% if one includes associated operations. In 3,5% of patients, postoperative necrosis was present. Almost the same values were found in the smaller group (66 cases) which underwent urgent by-pass operations. The authors consider that the aorto-coronary by-pass operation is a very useful treatment, both for stable and unstable angina, as long as the anatomo-functional conditions exist.


[Operative and long term results in 52 patients operated on for chronic postinfarction left ventricular aneurysm (author's transl)]. Operative and late post-operative results in 52 patients undergoing operation for chronic postinfarction left ventricular aneurysm are described. Aneurysm resection was performed in 33 patients. This procedure was combined with myocardial revascularization by means of insertion of a venous aorto-coronary by-pass graft in 14 cases. Hospital mortality for the total group was 3,8% (2 deaths). Surviving patients were followed-up 3 to 66 months. Two late deaths occurred. Clinical and functinal improvement occurred in the majority of surviving patients. The impact of simultaneous aorto-coronary by-pass grafting on operative results is discussed.


Mitotic variations in the lens epithelium of the frog IV. Studies with isolated anuran pituitary factors. Proteins corresponding to growth hormone and prolactin have been electrophoretically separated from the pituitary gland of the frog (Rana pipiens berlandieri and Rana catesbeiana). These substances can independently stimulate mitosis in the lenses of animals where it had previously been inhibited by means of hypophysectomy. DNA synthesis is greatly augmented six days after the start of hormone administration to intact animals. Nine days are required before this occurs in hypophysectomized ones. No other anterior pituitary hormone has been found to achieve the effect described. Initial attempts at amino acid analysis, though incomplete, indicate that the two frog hormones are different from each other as well as from their bovine counterparts. Pituitary factors do not affect mitotic activity in either corneal epi or endothelium of the frog.


Cytologie and cytochemistry of colony cells in soft agar gel culture from normal and leukemic bone marrow. In order to judge differentiation of cells in soft agar colonies, cytological and cytochemical classification of single cells within these colonies is necessary. In this study, 1,026 colonies from 15 normal and 95 leukemic bone marrows have been evaluated using cytological, cytochemical, and immunocytochemical techniques. In 180 colonies from 15 normal controls no segmented neutrophils have been observed. The colonies mostly consisted of monocytes and macrophages, rarely pure eosinophil colonies were observed. The number of monocyte/macrophage colonies in untreated AML and the percentage of pure eosinophil colonies in AML and ALL in remission are reduced, as compared to normal controls. In 174 colonies from a total of 926 colonies derived from bone marrows of leukemic patients, plasma cells and in 20 colonies, blast cells have been observed. In contrast to normal colonies, growth of colonies containing blast cells does not depend upon the conditioned medium of the leukocyte feederlayer. This investigation has demonstrated the necessity of cytological and cytochemical classification in addition to quantiative evaluation of soft agar colonies when studying the effect of factors on proliferation and differentiation of normal and leukemic stem cells.


Immunological characterization of blast cells in patients with acute lymphoblastic leukemia. Evaluation of its clinical significance. A panel of lymphocyte surface markers was used to identify blast cells from 111 patients with acute lymphoblastic leukemia (ALL). Three groups of patients were found. 1) 14 patients with B derived ALL. Only three patients had a common ALL; in the other cases the blastic proliferation was featured by Burkitt's tumor cells or supervened in patients affected with chronic lymphocytic leukemia (CLL). 2) The blast cells from 28% of the patients with common ALL had T cell properties. 3) The cells from the largest group of patients did not bear B or T cell markers but were featured by the presence of a leukemia-associated antigen revealed by a rabbit antiserum to CLL B cells. Studies with another antiserum to CLL B cells as well as with an antiserum to foetal thymocytes revealed also leukemia-associated antigens but these antigenic determinants were present on all acute leukemia cells which had been tested and were therefore of no help to classify various leukemias. A number of clinical and hematological findings were more frequent in the group of patients with T cell ALL: high white blood cell counts, tumoral disease, thymic enlargement, meningeal involvement, strong acid phosphatase activity in blast cells. However no difference in the survival curve is yet apparent at 30 months.


Immunological membrane markers of Hodgkin's cells. Reed-Sternberg and other Hodgkin's giant cells derived from involved spleens and lymph nodes of patients with Hodgkin's disease were examined for surface markers of T and B cells and macrophages. Attachment and phagocytosis of untreated (E) or sensitized (EA and EAC) sheep red blood cells and yeast by Reed-Sternberg cells did not occur. IgG frequently detected at the membrane of Reed-Sternberg cells was partially removed by incubation and washing at 37 degrees C. Fluorescence with a specific anti-T cell serum was not seen on Reed-Sternberg and other Hodgkin's giant cells lack most detectable normal human lymphoid cell markers, but do exhibit membrane bound immunoglobulin possibly of exogenous origin.


The phenotypic abnormality in leukemia: a defective cell-factor interaction? Differentiation of hemopoietic cells appears to depend upon specific interactions of certain cell-factors. The phenotypic abnormality in leukemia may involve an impairment in these interactions. In this report we present some of our views of leukemogenesis with respect to cell-factor interaction and the feasibility of experimental approaches to this problem. In culture, the interaction of myelogenous cells with factor(s) leading to differentiation can be measured either with a suspension mass culture method or by a solid (semi-soft) clonal method. The protein factors that support the growth of hemopoietic cells in suspension culture are termed growth stimulating factors (GSA) and in semi-solid culture, colony stimulating factors (CSA). Studies using conditioned medium prepared from phytohemagglutinin stimulated human lymphocytes (PHA-LyCM) and whole human embryo cells (WHE) revealed that GSA and CSA were not identical for growth of either normal human or leukemic leukocytes. In some cases maturation of leukemic leukocytes was observed. Fractionation of PHA-LyCM showed that there are three peaks for CSA. Each peak contains different fractions for supporting cellular proliferation, differentiation, and self-renewal of precursor cells in suspension culture. Apparently, each contains heterogenous species of protein factors some of which functionally overlap, while others do not.


Prognostic criteria and staging in ALL in childhood. On the basis of a retrospective review of 100 children with acute non-myeloid leukaemia the authors examined the effect on the prognosis of some initial features such as age, nodal and organ enlargement, initial white blood cell count, blast morphology and cytochemical characteristics, and platelet count. A remarkable correlation was found between age at diagnosis, initial white blood cell count and platelet count, and total survival and duration of remission. There was no significant correlation between PAS score and prognosis. The beta-glucoronidase reaction did not prove a useful index of prognosis. Adverse prognostic factors were an age below 2 or one above 10 years, a high initial white blood cell count and a low platelet count. The usefulness of attempts at staging in acute lymphoblastic leukaemia in childhood are discussed together with the predictive value of some features present at disgnosis.


alpha1-antitrypsin: common subtypes of Pi M. More than 20 different alleles are so far known at the Pi locus, corresponding to a total variant phenotype frequency of about 10% in most western Europeans. The common phenotype Pi M constitutes the remaining major group. Now it has been possible to identify three subtypes M1, M1M2 and M2, corresponding to the gene products of two common alleles PiM1 and PiM2, segregating as autosomal codominant alleles. Preliminary gene frequencies are reported for eight populations, the PiM2 frequency varying from 0.20 in Maris (USSR) to 0.02 in Bantus (Kenya).


Cellular changes in cultured lenses.

Cellular changes in cultured lenses. Observations were made on the frog lens epithelium after culture of the entire lens or of capsular explants. General deviations from normal lens structure as well as specific changes in two media were studied. DNA synthesis and mitosis were induced in the central epithelial cells. Disruption of the orderly, single, epithelial layer that is characteristic of normal lenses was accompanied by the appearance of multilayered plaques of epithelial cells and invasion of vacuolated regions of the lens fibers by epithelial cells. Cells that are fibroblast-like in appearance were observed in regions of the capsule depleted of cells and at the free edges of epithelial sheets in cell culture. Epithelial cells were surrounded by capsule-like material even situated in the lens interior. Nuclie derived from central epithelial cells of lenses cultured in L-15 medium and medium 199 had served as donors in previous nuclear transfer experiments in this laboratory. In our current observation of L-15-cultured lenses, cells were sparsely distributed on the capsule and nuclei were abnormally shaped; in 199-cultured lenses, cells were more densely distributed and nuclei resembled those of normal lenses. Medium 199 without serum could better maintain normal lens structure than L-15 medium without serum. In addition, the percentage of epithelial explants demonstrating cellular outgrowth was greater in medium 199. The differences in cellular behavior were shown not to be the result of different sugars, pH, or the presence of CO2. The nuclear transfer results may reflect the structural changes in the epithelium after lens culture in the two media.


Some biochemical changes in lenses of riboflavin deficient rats. In order to better understand the role of riboflavin in the lens, we investigated the lenses of rats fed on a riboflavin deficient diet for 7 weeks to determine changes in the inactivation of cortisol, the glucose-6-phosphate dehydrogenase (G-6-PD) activity and the histidine or 5-hydroxytryptophan decarboxylase activity. The cortisol-binding capacity and G-6-PD activity in the lenses of rats fed on a riboflavin deficient diet were found to be decreased as compared with a control. Histidine decarboxylase activity was found twice as high in the riboflavin deficient rats as in the normal lenses however, 5-hydroxytryptophan decarboxylase was somewhat decreased. These findings show that catabolical changes in the metabolism of rat lenses are induced comprehensively by feeding on a riboflavin deficient diet in the same manner as changes are seen in the cataractous lens.


Epidemiologic characteristics of women infected with Corynebacterium vaginale (Haemophilus vainalis). In a group of 184 women infected with Corynebacterium vaginale (Haemophilus vaginalis), 34% over age 30 were divorced or separated and 8% gave a history of induced abortion. Fifty-one percent were taking an oral contraceptive drug, as compared to 36% of 140 women in a control group. Various sexually transmitted diseases were diagnosed either concomitantly or at another time in 52% of women in the study group and 38% of those in the control group. The rate of cervical neoplasia (invasive carcinoma, carcinoma in situ, and dysplasia) was 13.6% in the study group and 5.7% in the control group, the rate in the study group being several times that in the general population. These and other available epidemiologic data support the conclusion that C vainale is transmitted sexually.


Studies on urinary kallikreins. I. Purification and characterization of human urinary kallikreins. Human urinary kallikrein [EC 3.4.21.8] (HUK) was purified about 200-fold with an overall yield of 40 percent from crude powder by DEAE-cellulose chromatography, acetone fractionation, Sephadex G-100 gel filtration and DEAE-Sephadex A-50 chromatography. Its activity was 200 kallikrein units (KU) per A280. HUK from active fractions obtained by DEAE-Sephadex A-50 chromatography was separated into three active components showing isoelectric points of 3.9 (HUK-1), 4.0 (HUK-2), and 4.2 (HUK-3) by isoelectric focusing: each HUK component was homogeneous on disc electrophoresis. The approximate molecular weights of HUK-1, -2 and -3 were estimated to be 2.7 X 10(4), 2.7 X 10(4), and 2.9 X 10(4), respectively, by gel filtration on a Sephadex G-100 column. The optimum pH's of HUK-1, -2, and -3 in esterolytic action were found to be 8.0, 8.3, and 7.5, respectively, and they were fairly heat stable in comparison with other glandular kallikreins. The three components of HUK were weakly inhibited by Trasylol, but were not affected by soybean and ovomucoid trypsin inhibitors. They were strongly resistant to treatment with urea and weakly resistant to treatment with guanidine. The activation energies of HUK-1, -2, and -3 were found to by 1.17 X 10(4), 5.1 X 10(3), and 1.45 X 10(4) cal per mole, respectively. The Km values were estimated toward N-alpha-tosyl-L-arginine methyl ester (TAME), N-alpha-benozyl-L-arginine ethyl ester (BAEE), and N-alpha-benozyl-L-arginine methyl ester (BAME).


Laboratory diagnosis of rheumatoid arthritis: a solid phase radioassay for IgG and IgM antiglobulins. A technique suitable for the routine estimation of IgM and IgG antiglobulins has been devised. The assay involves the binding of antiglobulins to plastic tubes coated with rabbit immunoglobulin: the amount of antiglobulin bound is then determined by adding radiolabelled antihuman IgG or IgM. The conditions for the assay have been examined and optimal incubation times and amounts of reagents established. Verification of the antibody nature of antiglobulin activity has been obtained. Both IgG and IgM antiglobulins were raised in virtually all seropositive rheumatoid arthritics, and most seronegative patients gave elevated values for either IgM or IgG rheumatoid factors. The use of an anti-light chain reagent as a screening test for total antiglobulins was investigated. These tests should prove valuable in diagnosis and permit quantitative evaluation of research studies.