Solid-phase radioimmunoassay for detection of staphylococcal antigen in serum of rabbits with endocraditis due to Staphylococcus aureus. To aid in the rapid diagnosis of staphylococcal infection, a solid-phase radioimmunoassay for Staphylococcus aureus antigen was developed and evaluated in rabbits with staphylococcal endocarditis. Test specimens containing antigen were added to polystyrene tubes coated with antibody to S. aureus. Antigens immobilized on the tube were detected by adding radiolabeled antibody to S. aureus. Sensitivity for antigen was 0.312 microgram/ml in buffer and 1.25 microgram/ml in 50% rabbit serum. Cross-reactions were not observed with antigens extracted from streptococci; however, antigen extracted from Staphylococcus epidermidis (which contained ribitol-teichoic acid) could also be detected at low concentrations. Antigen was detected in each of 12 rabbits with S. aureus endocarditis but not in control rabbits. This assay is sensitive, specific, reproducible, and capable of detecting antigens in the serum of rabbits with endocarditis.


In vitro inhibition of subacute sclerosing panencephalitis virus by the antiviral agent ribavirin. The multiplication in tissue cultures of three isolates of subacute sclerosing panencephalitis virus as well as the Edmonston strain of measles virus was observed to be inhibited by various concentrations of the antiviral agent ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide). The blockage of viral replication by ribavirin could be reversed by the simultaneous addition of equimolar concentrations of either guanosine or adenosine. Expression of virus-specific antigens was greatly reduced in the presence of the antiviral drug.


Preparation of the major plasma fractions by solid-phase polyelectrolytes. The solid-phase ethylene/maleic anhydride PE's E-5 and E-100 were used to developed a flexible integrated system of batch methods for the fractionation of albumin and gamma globulin as well as the clinically important coagulation factors. Each method for the isolation and purification of the fractions or a modification of it could also be used independently or could be added onto another method or methods. Each fraction was prepared in three steps: adsorption on solid-phase PE's elution from the PE's, and concentration by ultrafiltration or by use of PEG or both. Since the methods required no organic solvent but relied primarily on electrostatic bonding, they were essentially nondenaturing. Solid-liquid phase separation was easily accomplished by centrifugation or filtration. The yield and purity of each fraction was as follows: (1) coagulation factors II, VII, IX, and X concentrates 63% and 200-fold purified; (2) AHF 43% and 52-fold; (3) vWF 43% and 71-fold; (4) PPF, as albumin, 93% yield and 92% pure; (5) albumin 92% yield and 98.5% pure; and (6) gamma globulin 92% yield and 97.5 pure. During the preparation of gamma globulin the E-100 also tended to adsorb and remove the HBSAg and infectivity, when present.


Demonstration of a cytoplasmic receptor protein for oestrogen in the canine prostate gland. A receptor protein that selectively binds oestrogens has been demonstrated in the cytosol of the canine prostate gland. The steroid--receptor complex was found to have a sedimentation coefficient of 4--5 S with respect to bovine serum albumin after sucrose density-gradient centrifugation. The high affinity and low capacity of the protein for oestrogens was indicated by displacement studies, which gave a value of 3.8 +/- 1.53 (S.D.) X 10(-10) mol/l for the dissociation constant. A metastasizing prostatic tumour was also shown to possess this receptor, with binding properties similar to those exhibited by the receptor in normal prostatic cytosol. The implications of these findings are discussed with regard to normal prostatic function in the dog and the virtually inevitable advent of prostatic hyperplasia with age in this species.


Relationship between the pituitary gland and gonadal steroids: involvement of a hypophysial factor in reduced alpha 2u-globulin and increased transcortin concentrations in rat serum. Evidence is presented that the level of alpha 2u-globulin in the serum of male rats depends, at least in part, on neonatal androgens. After castration of adult animals the concentration of this protein falls but remains measurable, whereas in intact or ovariectomized female rats alpha 2u-globulin cannot be detected. Moreover, alpha 2u-globulin is found in adult male and female rats gonadectomized at birth and treated with a single injection of testosterone propionate immediately thereafter. The mechanism by which neonatal androgens increase the concentration of alpha 2u-globulin has been investigated. Transplantation of a supplementary pituitary gland under the renal capsule of male rats resulted in reduced levels of alpha 2u-globulin and increased levels of transcortin. The changes discussed here were observed only in those animals in which the transplant was functional and they were amplified or reversed by modulators of prolactin secretion such as oestrogens or bromocriptine respectively. The hypothesis is advanced that neonatal androgens stimulate the production of a hypothalamic inhibitory factor that controls the secretion of prolactin, or another hypophysial hormone subjected to similar neuroendocrine control. Measurements in gonadectomized animals and in rats receiving both oestradiol benzoate and bromocriptine indicate that, besides these pituitary-mediated effects, both oestrogens and androgens exert direct effects on the level of alpha 2u-globulin.


Endogenous steroid levels in the human prostate from birth to old age: a comparison of normal and diseased tissues. The levels of steroids in prostatic tissues were determined by radioimmunoassay after solvent extraction of a single (300--600 mg wet tissue) sample and chromatography of extracts on hydroxyalkoxypropyl Sephandex microcolumns. In normal adult prostates (n = 18) the concentrations of steroids (mean +/- S.E.M. ng/g wet tissue) were: testosterone, 0.25 +/- 0.04; androstenedione, 0.13 +/- 0.03; 5alpha-androstane-3,17-dione (5alpha-androstanedione), 1.31 +/- 0.30; 17beta-hydroxy-5alpha-androstan-3-one (5alpha-dihydrotestosterone, DHT), 1.22 +/- 0.14; 5alpha-androstane-3alpha, 17 beta-diol (3alpha-androstanediol), 4.32 +/- 0.49; androsterone, 4.15 +/- 1.07; progestrone, 0.39 +/- 0.07; 17alpha-hydroxyprogestrone, 0.42 +/- 0.06. Concentrations of of steroids tissues from outer-gland regions were within the ranges found in the periurethral regions. In the prostates of newborn boys, the concentrations of all steroids were high, including progesterone and 17alpha-hydroxyprogesterone. Apart from 3alpha-androstanediol, the levels of which tend to increase after this age, the concentrations of all steroids were lower in the infant and pubertal prostates, but most were re-established to a variable extend in the adult tissues. This was particularly evident with respect to 5alpha-androstanedione and androsterone, and it is suggested that these two androgens may have a functional role in the mature prostate. The concentrations of testosterone, androstenedione, 5alpha-androstanedione, progesterone and 17alpha-hydroxyprogesterone in tissue taken from ten patients with benign prostatic hypertrophy (BPH) were similar to those in normal adult adult tissue. The concentration of DHT was markedly raised (5.33 +/- 0.46 ng/g) and the level of 3alpha-androstanediol and androsterone were reduced (1.40 +/- 0.12 ng/g respectively) in adenomatous compared with normal tissue. The concentrations of various androgens displayed remarkable interelationships which characterize normal and BPH tissues. The concentrations of testosterone, androstenedione, DHT and 3alpha-androstanediol were particularly high in the untreated prostatic carcinomatous tissue sample investigated, whereas the concentrations of 5alpha-androstanedione and androsterone were very low. After oestrogen treatment, testosterone and androstenedione virtually disappeared, while reduced but significant concentrations of their metabolites remained in similar proportions to those observed in the untreated carcinomatous tissue. Under the conditions of therapy, oestrogens are suggested to influence the uptake of androgens.


IgG2a-producing variants of an IgG2b-producing mouse myeloma cell line. 12 variant cell lines producing an IgG2a (kappa) immunoglobulin derived via different routes from the IgG2b (kappa) synthesizing MPC 11 were studied. These variants all have the parental MPC 11 idiotype as shown by a radioimmunoassay. A comparison of the variants by charge, peptide maps, and assembly patterns has shown that most of them differ from one another, and some can be grouped. One group consists of three primary variants generated with two mutagenic agents: these three have almost indistinguishable peptide maps. Two other primary variants which arose in a similar fashion differ markedly from each other and from this group. A second group is comprised of the four secondary variants which arose from two short heavy chain producing primary variants. Other secondary variants and the one spontaneously arising variant cannot be grouped. Possible genetic mechanisms such as translocation, expression of previously silent genes and recombination are discussed.


Cytotoxic T-cell responses show more restricted specificity for self than for non-self H-2D-coded antigens. The specificity of recognition of H-2 antigens by various subsets of Tc cells was investigated with respect to the two separate molecules known to be coded in the H-2D(d) region (a) D which carries the private specificity H-2.4 and (b) D'which carries the public specificity H-2.28. BALB/c.H-2(db) mutant mice express D but not D' on their cell surfaces, whereas wild-type BALB/c mice express both D and D'. H-2 restricted Tc cells specific for viral-plus- H-2D(d)-coded antigens on infected self cells, or minor H-plus-H-2D(d)-coded antigens on H-2-compatible cells apparently recognize D, but do not detectably recognize D. In contrast, BALB/c-H-2(db) anti-BALB/c Tc cell responses do recognize D' (the only known antigen which is not shared by mutant and wild-type); furthermore, D' is also detectably recognized by a significant proportion of the Tc cells that respond in MLR to H-2D(d)-coded antigens. In these latter responses, D' was recognized separately from D, i.e., the response was not "H-2 restricted". These results indicate that H-2 restricted Tc cell responses to modified-self cells are more specific for self H-2D(d)-coded antigens then are allogeneic Tc cell responses directed at the same antigens, in that haplotype-unique (private) specificity recognition (of the D molecule) exclusively occurs only in the former, not the latter case. The implications of this specificity of H-2 restricted responses for possible processes of somatic selection of anti-self recognition structures on progenitor Tc cells are briefly discussed.


The immune response of allophenic mice to 2,4-dinitrophenyl (DNP)-bovine gamma globulin. I. Allotype analysis of anti-DNP antibody. The question of whether or not lymphoid cells can cooperate across a histocompatibility difference barrier has been studied in several laboratories. Using an adoptive transfer system, Katz et al. (1) first showed that T cells from (low responder x high responder) F(1) mice, primed to the terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT), could collaborate with 2,4-dinitrophenyl (DNP)-primed B cells from a high responder, but not a low responder strain, in response to DNP-GLT. The response to GLT is under H- 2-1inked Ir gene control. In contrast, studies with mouse bone marrow chimeras have shown that T cells can interact with H-2-histoincompatible B cells in response to antigens not under Ir gene control (2-4). Another type of chimera, the allophenic mouse, has been used to study possible histoincompatible cell interactions to a number of antigens, including DNP-L- glutamic acid, L-lysine, L-alanine; L-glutamic acid, L-alanine, L-tyrosine; L-glutamic acid, L-lysine, L-phenylalanine; and poly-L (Tyr, Glu)-poly D,L- Ala-poly-L-Lys[T,G)-A-L] (5-9). The response to each of these antigens is under H-2-1inked Ir gene control. It was initially reported (8, 9) that in allophenic mice containing both high and low responder cells, the antibody to (T,G)-A-L was of both the high and low responder allotype. This was interpreted to mean that high responder T cells had cooperated with low responder B cells across a histocompatibility difference barrier in the environment of the allophenic mice. However, Press and McDevitt (10) have recently reported that additional and more accurate analyses of these allophenic mouse sera failed to detect any anti-(T,G)-A-L antibody of the low responder allotype. Moreover, in an experiment using bone marrow chimeras, there was no low responder allotype antibody produced in response to (T,G)-A- L(10). The present study was undertaken to test the immune response of allophonic mice to an antigen, DNP-bovine gamma globulin (DNP(56)BGG), known to be controlled by genes both inside and outside the H-2 complex (11, 12).(1) When high and low responder cells to DNP(56)BGG are present in allophenic mice, only antibody of the high responder allotype is produced. The results suggest that cell cooperation in allophenic mice cannot occur across a histocompatibility difference barrier in response to an antigen whose genetic control is at least partially within the H-2 complex.


New technique for measuring dynamic axonal transport and its application to temperature effects. A new technique was devised for the dynamic detection of the axoplasmic transport of beta-radioactively labeled materials in which a semiconductor radiation detector was used as the beta-ray counter. The detector element is a silicon p-n junction diode and has a diameter of 2.0 mm. With this detector, the beta-radioactive distribution of axoplasmic transport could be measured in a axon maintained physiologically without cutting nerves. This method makes possible determination of the transport rate using one bundle of peripheral nerves. The rate in the bullfrog was 6.4 mm per hour at 24.0 degrees D. Temperature effects on the bullfrog axoplasmic transport were also observed at different temperatures, ranging from 5.0 to 24.0 degrees C. At these temperatures the rate increased as an exponential function of temperature from 1.1 to 6.4 mm per hour. Within this temperature range, the Q10 is 2.5 and an Arrhenius plot of the natural logarithm of velocity versus the reciprocal of absolute temperature yielded an apparent activation energy of 14.8 Kcal. this technique offers great advantages in permitting direct study of the axoplasmic flow of the axon in a physiological condition.


Two-dimensional immunoelectrophoresis of unconcentrated cerebrospinal fluid. The two-dimensional immunoelectrophoresis on cellulose acetate, already utilized for serum proteins, has been applied to CSF proteins. The technical modifications which allow the use of unconcentrated CSF are described. By utilizing a particularly suitable supporting medium, a good separation of proteins is achieved; consequently narrow-based peaks are obtained and the isoantigens can be displayed as distinct components in spite of closely similar migration velocities. The preliminary results of this method are given. Particulary interesting appears a beta-migrating protein and the gamma-migrating oligoclonal bands. The first may present an anodic cleavage suggesting that it may be the beta1C/beta1A-globulin. If this hypothesis is confirmed, the relative concentrations of the two components can be investigated. No clear-cut peaks corresponding to the gamma-migrating oligoclonal bands have been observed, their place being taken by a low precipitation line continuous with the IgG peak. The reasons for this phenomenon may be tentatively ascribed to a local specificity of these IgG.


Muscular carnitine synthesis and palmitate metabolism in vitro. The carnitine content of the culture media for normal and pathological human muscles, including a case of systemic carnitine deficiency (SCD) was measured and the carnitine concentration was the same in all normal and pathological muscle culture media. Carnitine was never detected in growth medium. Some fibroblasts and myoblasts were filled with neutral lipids in SCD. 14C-palmitate added to the medium was incorporated by SCD fibroblasts or myoblasts to the same concentration as in normal or pathological cells. Factors other than carnitine seem to account for the lipid accumulation of SCD in cell culture.


Doppler flow velocity measurements in patients with intracranial hypertension. In patients with severe brain lesions monitoring of the intracranial pressure as well as monitoring of cerebral blood flow can be of clinical value. While at the moment there is no atraumatic method for measuring cerebral blood flow in man, it is recommended to measure blood flow velocity with the ultrasound Doppler technic in the common carotid artery. On theoretical grounds a positive correlation between cerebral blood flow and blood flow velocity can be expected and the observations presented show that such a correlation exists in normal controls and in neurological patients. In many neurological patients the flow velocity in the common carotid artery decreases with increasing intracranial pressure. This suggests that the autoregulation is disturbed. The demonstration of such a disturbance can have clinical implications.


Further histochemical studies characterizing the lipofuscin component of human neuromelanin. The residuum of bleached substantia nigra neuromelanin and the nonoxidized and oxidized intraneuronal masses of inferior olive lipofuscin gave sudanophilic staining reactions with oil red O, Sudan black B, and a Sudan III and IV combination stain. The pigments also exhibited oxidation basophilia, each having been stained by Gomori's paraldehyde fuchsin method after bleaching or oxidation with potassium permanganate and by the modified carbol fuchsin method of Barbeito-Lopez after bleaching or oxidation with hydrogen peroxide or potassium permanganate. Confirmation of the presence of lipid substances in bleached neuromelanin was obtained by repeatedly staining, decolorizing, and restaining the residuum of the pigment when utilizing the chemically nonreactive beta naphthol type Sudan combination stain, Sudan III and IV. Not only were tinctorial properties characteristic of lipofuscin clearly demonstrated in the bleached residuum of neuromelanin, but additionally, a partial separation was achieved between the relatively soluble beta naphthol type Sudan-staining lipid component and an insoluble component, possibly lipoprotein, staining with Sudan black B and both basic fuchsin dye-containing mixtures. Consideration was given to the idea that the oxidation basophilia  of these neuronal pigments was due to the oxidative formation or exposure of one or more kinds of acidic groups consisting of carboxyls or those containing sulfur or phosphorus.


The diagnostic value of the short sleep EEG and other provocative methods following sleep deprivation. One hundred and eighty-five EEGs recorded after deprivation of sleep for 24 h were evaluated. Valuable diagnostic information was found in 59% of the EEG recordings; 24% of the EEGs contained seizure activity. The duration of the stages of sleep and the frequency of seizure activity, paroxysmal sharp wave groups and localizing findings were analyzed. The sleep stages A to C (based on the Loomis scale) were reached for about equal duration by an EEG recording of 30--40 min; sleep stage D was reached only shortly and stage E was not observed. Pathological EEG findings appeared for the most part in the sleep stages A and B. Localized findings were pronounced in stage C. No significant differences pertaining to the occurrence and form of EEG patterns were found between patient groups with primary generalized seizures, psychomotor seizures or those with unclarified disturbances of consciousness. The combination of the short sleep EEG following 24 h of sleep deprivation with subsequent use of the additional provocative methods of hyperventilation, photostimulation and hydration, yielded, in all, new information in 50% of the patients. Each of these additional methods contributed nearly equally to this information.


Supplementary cytodiagnostic analyses of mononuclear cells of the cerebrospinal fluid using cytological markers. Various methods of CSF cell differentiation are discussed. These methods provide additional information regarding the origin and, therefore, the types of pathological alterations occurring in the leptomeninges. They include the application of immunological and cytochemical markers to differentiate and identify B and T lymphocytes as well as cells from the monocyte-macrophage series and precursor cells of polymorphnuclear leukocytes. Application of these methods to CSF cells and the differentiation of CSF cells from 16 patients with inflammatory or neoplastic alterations were discussed. B cell or T cell type lymphocytes predominate with multiple sclerosis, T lymphocytes with tubercular meningitis. Varying quantities of B and T lymphocytes are found with viral meningitis. In one case the tumor cells of a reticulum cell sarcoma were identified in the CSF as T cells; in one case of plasmacytoma, tumor cells in the CSF were identified as B lymphocytes. In selected cases of leukemic or carcinomatous infiltration of the meninges and of medulloblastoma, CSF cells did not react to treatment with immunological markers.


Quantitative analysis of neurophysiological processes of the aging CNS. Electrophysiological studies were performed on 65 aged subjects (62--91 years) and 48 control subjects (18--38 years). The power spectrum of the EEG in the aging persons shows different types, from spectra with a marked peak of alpha activity to spectra of a desynchronized type. Progressive deterioration of the periodicity of the occipital alpha rhythm and also a progressive time shift between the activities of both occipital lobes were found in the aging subjects. The SEP and VEP have prolonged latencies of all components. The amplitudes of all components of the SEP are significantly increased and those of the VEP are within normal limits. There is a more significant involvement of the dominant hemisphere. Transcallosal transmission of the SEP is qualitatively not involved. Quantitatively there is a marked prolongation of the duration of the transmission of certain SEP components. Transmission of the SEP from the specific cortical response area to different areas of the ipsilateral hemisphere is significantly increased. It is assumed that during aging there is an involvement of the cortical neuronal transmitter mechanisms and a progressive decrease of the specific cortical inhibitory processes.


Dystrophia myotonica and hypothyroidism. Two cases of dystrophia myotonia associated with hypothyroidism are reported. This association is not frequent. In both cases the hypothyroidism precipitated an otherwise mild muscular weakness due to dystrophia myotonia. Treatment with dried thyroid improved the muscular power, while the myotonia remained unchanged. Since dystrophia myotonica and hypothyroidism have many presenting symptoms in common, a complete assessment of the thyroid function in every case of dystrophia myotonica seems worthwhile.


Alpha fetoprotein in the differentiation of neonatal hepatitis and biliary atresia: current status and implications for the pathogenesis of these disorders. Neonatal hepatitis (NH) and biliary atresia (BA) are disorders of early infancy that may be difficult to differentiate. Since surgical therapy can be curative if performed early in the disease course of BA, accurate diagnosis is of great importance. Elevated levels of serum alpha fetoprotein (AFP) do occur in many cases of NH and may be helpful in differentiating this condition from BA. Evidence is presented which suggests that initially BA and NH may be the same disease. The individual host response determines the final clinical outcome and AFP could be the immunoregulatory substance which affects pathological progression from NH to BA.


Early effects of cobalt chloride treatment on certain blood parameters and on urine composition. The authors studied the variations of some blood parameters and urine composition during the first hours after CoCl2 treatment in rats and rabbits. These showed an increase in hematocrit with a decrease in plasma volume and, at the same time, a decrease in total proteinemia as well as in the albumin (rabbits) and gamma-globulin fractions. On the basis of observations carried out in rabbits, these phenomena are not seen if the cobalt is complexed with cysteine before treatment; moreover, they are at least partly reversed by cysteine administration soon after cobalt. Plasma Na+ and K+ concentrations do not show significant changes in CoCl2-treated rabbits; on the contrary, the excretion of such electrolytes, as well as urinary protein content, decreases. In addition, the urine of CoCl2-treated rabbits contains at least two pigmented substances with different molecular weights, which are separable by dialysis and DEAE-cellulose chromatography and both contain cobalt in different percentages. The authors believe that CoCl2 treatment leads to an early and profound increase in vascular permeability with depletion of plasmatic material in the tissues and hemoconcentration; moreover, the above stated phenomena seem to be correlated with the forming of cobalt complexes.


Further studies on the mode of action of Clostridium welchii type-D epsilon toxin. Intradermal injection of Clostridium welchii type-D epsilon toxin increased the permeability of blood vessels in guinea-pig skin to Evans blue dye by a mechanism not dependent on the release of histamine. The toxin was also found to raise the plasma concentration of cyclic adenosine 3', 5'-monophosphate in mice. It is concluded that epsilon toxin is an enterotoxin capable of causing widespread damage, after binding to receptor sites on the surface of certain cells, through a mechanism mediated by an adenyl cyclase-cAMP system.


Identification of Gomori-positive glia in autoradiographs. Unstained Gomori or paraldehyde fuchsin or chrome-haematoxylin-alum positive granules in the perikaria of so-called Gomori-positive glia of the periventricular zone of the rat hypothalamus, fixed with Bouin's or Carnoy's fluids, have been found to produce a positive chemographic (blackening) effect on autoradiographic emulsion. Similar action was produced by some granules in ependymal cells localized in the ventral part of the third ventricle between optical chiasma and median eminence. It is suggested that this positive chemographic effect can be employed for the identification and characterization of Gomori-positive glia in autoradiographic studies.


Morphology and cytochemistry of acinar secretory granules in normal and isoproterenol-treated rat submandibular glands. Several fixation procedures have been utilized in a fine-structural study of rat submandibular glands with the aim of correlating the morphology of granule substructure with its composition. Procedures included fixation with aldehyde in a variety of buffers, with or without fixation additives such as tannic acid or calcium chloride. Both immersion and perfusion fixation studies were performed. Osmium tetroxide postfixed tissue was compared with non-postfixed tissue. Thin sections were stained for carbohydrate-containing constituents by either periodic acid-thiocarbohydrazide-silver proteinate or tannic acid-ferric chloride sequences. The morphology and cytochemistry of acinar secretory granules were highly dependent upon the fixation procedure utilized. In postfixed tissue, fine filaments and vesicles were the major granule constituents. Filaments often aggregated into fibrils in fixatives containing phosphate buffer or calcium, whereas vesicles were prominent with fixatives containing collidine buffer. Tannic acid, as a fixation additive, imparted enhanced density to the peripheral rim of aggregated filaments. If post fixation was eliminated, an amorphous meshlike material was the major granule component. This stained readily with methods for carbohydrate whereas the granules of post-osmicated tissue did not. Following chronic isoproterenol treatment the degree of filament aggregation in postfixed tissue was augmented, and this corresponded to an increase in amount of material stainable for carbohydrate in non-post-osmicated tissue.


Lung carcinoma-reactive antibodies isolated from tumor tissues and pleural effusions of lung cancer patients. Low pH elution techniques were used on lung cancer tissues and pleural effusions of lung cancer patients to dissociate antigen-antibody complexes. The immunoglobulins obtained were assayed by indirect immunofluorescence against tissue cultures and fresh cell suspensions of various target cells; they reacted positively, in significant titers, with cells of squamous cell carcinomas and adenocarcinomas of the lung but not with cells of normal adult and fetal lung or of nonpulmonary tumors. Immunoglobulins, similarly dissociated from tumor effusions of other organs, showed no reactivity in indirect immunofluorescence tests against lung carcinoma cells.


Comparison of Mason-Pfizer monkey virus and squirrel monkey (Saimiri sciureus) retrovirus by immunoelectron microscopy. Comparison of Mason-Pfizer monkey virus and squirrel monkey retrovirus (both candidate type D oncornaviruses) by immunoelectron microscopy revealed that these two viruses do not share common surface antigens.


Transmission electron microscopy surveillance of retroviruses in tissue culture cells prepared by the critical-point drying method. Tissue culture cells grown on grids were processed by the critical-point drying whole-cell method. With the use of a conventional transmission electron microscope operating at 100 kV, this technique permitted visualization of intracytoplasmic organelles of unsectioned whole cells. The morphology of type C virus in the process of budding and also in extracellular locations closely resembled that revealed in thin sections. Prelimininary results of virus surveillance of tissue culture cells prepared by this technique was corroborated by the levels of reverse transcriptase activity in culture media and by immunofluorescence staining of viral antigens on the cell surface.


[Triiodothyronine, reverse-triiodothyronine, thyroxine, resin-triiodothyronine-uptake and protein bound jodide in the fluid of thyroid cysts (author's transl)]. T3, rT3, T4, PBI and the saturation of T3-T4-binding proteins in yellow and brown cyst fluids of nontoxic goiters differ from the values in sera. In the brown cyst fluids, resulting from a hemorrhage, T3, rT3, T4, PBI and T3 U are significantly higher than in sera and no correlation could be found with the values in sera. In the yellow cyst fluids T3 and T3 U are significantly higher then in sera, T4 is lower, PBI and rT3 do not differ from the values in sera. Only T3 and rT3 are not correlated. Various reasons for higher concentrations of hormones in the cyst fluid such as destruction of thyroid follicles and lymphvessels, a high protein concentration and direct secretion of hormones and iodoproteins from thyroid tissue in the cyst wall into the cyst fluid are taken into consideration. As these hormones in the cyst fluid may be absorbed, the results are also of clinical value.


Evidence for an association between cholelithiasis and hiatus hernia. A prospective, controlled study was carried out to determine if there was an association between hiatus hernia and cholelithiasis. The prevalence of gallstones was calculated in 100 patients (50 men and 50 women) with radiological evidence of hiatus hernia. 100 subjects (50 men and 50 women) without hiatus hernia, matched for age, body-weight, and number of pregnancies, acted as controls. Gallstones were twice as common in the former group (34%) as in the control group (17%) (P less than 0.01). Moreover, a comparison of the lipid composition of the gallbladder bile in 15 subjects operated on for hiatus hernia with that in 17 patients operated on for another digestive disease showed that the molar percentage of choelsterol in the bile and the cholesterol saturation index were significantly higher in the patients with hiatus hernia (9.3 +/- 1.1, mean +/- S.E.M., 1.41) than in the control subjects (5.9 +/- 0.5; 0.97) (P less than 0.01). These results suggest an association between hiatus hernia and cholelithiasis. It is likely that common factors, probably related to a low-residue diet, predispose to the two diseases.


Vascular-laboratory diagnosis of clinically suspected acute deep-vein thrombosis. Doppler ultrasound, impedance plethysmography, and contrast venography were performed in 207 lower limbs suspected of harbouring deep-venous thrombosis, to clarify the diagnostic value and limitations of the non-invasive methods. Doppler ultrasound and impedance plethysmography were accurate in 96% and 95% of normal limbs, respectively. In limbs with venographic evidence of thrombosis requiring treatment, Dopper ultrasound and impedance plethysmography correctly detected thrombosis in 60% and 97%, respectively. Doppler ultrasound was 97% accurate in recognising chronic venous insufficiency. Impedance plethysmography was incorrectly positive in 74% of limbs with chronic venous insufficienv cy which had no venographically detected thrombosis. These findings suggest that, for the accurate diagnosis of clinically suspected deep-vein thrombosis, venography is necessary only in patients with chronic venous insufficiency who have normal Doppler ultrasound tests and abnormal impedance plethysmograms and in patients with abnormal cardiac haemodynamics. In this series, 86% of limbs would have been spared venography had non-invasive tests been used. Venography, however, remains the standard test for the detection of minor calf-vein thrombosis. A diagnostic and therapeutic schema is proposed.


Controlled clinical trial of five short-course (4-month) chemotherapy regimens in pulmonary tuberculosis. First report of 4th study. East African and British Medical Research Councils. Five 4-mo regimens of chemotherapy for tuberculosis are compared. The two regimens in which rifampicin was given throughout the 4 mo were associated with bacteriological-relapse rates of 8% in the first 6 mo after stopping chemotherapy, but the three regimens in which rifampicin was given for only the first 2 mo had relapse-rates of 24-32%. There was no evidence that the addition of pyrazinamide in the second 2 mo of chemotherapy reduced the bacteriological-relapse rate. Removal of the streptomycin from the first 2 mo appeared to reduce the bactericidal and sterilising activity of the regimen, although the differences were not statistically significant. The incidence of adverse reactions was very low with all five regimens.


Megaloblastic haemopoiesis in patients receiving nitrous oxide. In a prospective study the incidence of megaloblastic change after ventilation with nitrous oxide for periods of up to 24 h has been determined and the cause of the altered D.N.A. synthesis studied with the deoxyuridine (dU) suppression test in 22 patients undergoing cardiac bypass surgery. 8 patients who received nitrous oxide and oxygen for 24 h had megaloblastic bone-marrow aspirates and abnormal dU suppression tests at the end of ventilation. 5 patients who received no nitrous oxide had normoblastic aspirates and normal dU suppression test. Of the remaining 9 patients, who received nitrous oxide during the operation only, 3 had abnormal dU suppression tests at 24 h. The abnormality revealed by the dU suppression tests was identical with that found in vitamin-B12 deficiency, but the patients' serum-B12 concentrations were normal. These results suggest that nitrous oxide interferes with the function of vitamin B12. Nitrous oxide oxidises vitamin B12 in vitro, and probably also in vivo when premixed 50% nitrous oxide and 50% oxygen mixture ('Entonox') is given.


Enterotoxigenicity of colonising coliform bacteria in tropical sprue and blind-loop syndrome. The enterotoxigenicity of strains of Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli, which represented the predominant coliform species isolated from the jejunum of 12 patients with tropical sprue and 5 with the blind-loop syndrome, was quantitatively assessed in terms of the ability of toxin preparations to induce water secretion as assayed by in-vivo perfusion in the rat jejunum. All 12 patients with sprue harboured 1 or more highly toxigenic strains--14 of the 16 strains isolated from this group produced heat-labile and/or heat-stable toxins which were as potent as toxins derived from strains isolated from persons with acute diarrhoea and documented as toxigenic. None of the 9 strains isolated from patients with the blind-loop syndrome produced potent toxins. This difference between the coliform bacteria in sprue and the blind-loop syndrome probably accounts, at least partly, for the different intestinal response in these two disorders to contamination by these organisms.


Differentiation of thyrotoxicosis induced by thyroid destruction from Graves' disease. Thyroid function was tested in untreated patients with Graves' disease or thyrotoxic subacute thyroiditis, and in patients with autoimmune thyroiditis who showed postpartum or spontaneous transient thyrotoxicosis. The serum triiodothyronine/thyroxine ratio (T3/T4) was greater than 20 ng/microgram in Graves' disease but less than 20 in all patients with subacute thyroiditis and 9 of 11 patients with autoimmune thyroiditis. Thus, like radioactive iodine uptake, the serum T3/T4 ratio is useful for differentiating destruction-induced thyrotoxicosis from the stimulation-induced hyperthyroidism of Graves' disease.


Clinical relevance of coagulation and renal changes in pre-eclampsia. Changes in coagulation tests (fibrin/fibrinogen degradation products, factor-VIII activity, and platelet-count) and in renal function (creatinine clearance and serum concentration, clearance, and fractional reabsorption of urate) were measured in late pregnancy. 10 patients with severe preeclampsia showed changes in both coagulation and renal function when compared with 13 normotensive controls. 18 patients with mild pre-eclampsia had changes in renal function only. Results from 5 patients with essential hypertension did not differ from those of the normotensive group. When results from the patients with severe pre-eclampsia were arranged in order of decreasing protein excretion, only renal-function tests correlated significantly with this ranking. It is suggested that, in the management of patients with established preeclampsia, assessment of renal function may be of greater practical value than measurement of the degree of coagulopathy.


Loss of nitroglycerin from intravenous infusion sets. During initial studies with nitroglycerin infusion in patients with acute myocardial infarction, higher doses than previously reported were required to achieve the desired haemodynamic effect. A flow-rate-dependent loss of drug from the plastic infusion set was demonstrated during simulated infusion. This loss was considerably reduced when nitroglycerin was infused from glass syringes through high-density polyethylene tubing.


Value of immune-complex assays in diagnosis and management. Two complement-dependent assays for circulating immune complexes, the C1q-binding assay and the conglutinin binding, were used to study patients with suspected immune-complex disease. Complexes were detected most frequently in multisystem disease such as infective endocarditis (69%) and systemic lupus erythematosus (60%), and less frequently in isolated nephritis (26% of membrano-proliferative nephritis). Sequential estimations in 32 patients showed that concentrations of circulating immune complexes correlated with disease activity and were useful in monitoring therapy.


Isolation of an infectious agent from bone-marrows of patients with multiple sclerosis. Bone-marrow aspirates from 5 patients with recent episodes of multiple sclerosis (M.S.) contained increased numbers of plasma cells, and aspirates from 3 of these patients contained atypical reticulum cells. When bone-marrow from 4 of the patients was inoculated into cell cultures a cytopathic effect (C.P.E.) was observed, and this effect could be serially passaged to further cultures. The C.P.E. was not observed when ether-treated extracts of cells showing C.P.E. were used for passage or when the passage material was filtered through a 100 nm filter. Appearance of C.P.E. was delayed in cultures inoculated with 220 nm filtrates of inoculum was passed through filters of greater pore size. No C.P.E. was observed after culture of bone-marrow aspirated from each of 7 patients under clinical investigation for disorders other than M.S.


Plasma-triglycerides in regulation of H.D.L.-cholesterol levels. Plasma-high-density-lipoprotein (H.D.L.) cholesterol concentrations are lower in patients with coronary-artery disease than in control subjects. In an investigation of the relationship of H.D.L. cholesterol to other lipid and lipoprotein parameters in normal and hyperlipoproteinaemic subjects inverse correlations were found between H.D.L. cholesterol and very-low-density-lipoprotein (V.L.D.L.) cholesterol, and between H.D.L. cholesterol and plasma-triglyceride levels. Mean H.D.L.-cholesterol concentrations in normal subjects were 50 mg/dl, and in hyperlipoproteinaemic patients they were: type I, 17 mg/dl; type II, 44 mg/dl; type III, 38 mg/dl; type IV, 37 mg/dl; and type V, 27 mg/dl. H.D.L.-cholesterol levels were lowest in patients with fasting chylomicronaemia and were diminished in hypertriglyceridaemic subjects, suggesting a relationship between the metabolism of triglyceride-rich lipoproteins and H.D.L.


Anti-prostglandin therapy in prevention of side-effects of intrauterine contraceptive devices. The efficacy of an anti-prostaglandin, tolfenamic acid (T.A.), in the prevention of side-effects after insertion of a copper-T200 intrauterine contraceptive device (I.U.D.) was evaluated in a double-blind trial in 160 women. T.A. relieved pain and reduced bleeding after insertion and during three subsequent menstruations without serious side-effects. A scoring system for the assessment of I.U.D. side-effects showed that the acceptability of I.U.D. was significantly better in women treated with T.A. than in those given placebo.


Co-trimoxazole for prevention of infection in acute leukaemia. 30 patients with acute leukaemia being treated with cytotoxic drugs were investigated in a randomised trial to determine whether oral administration of co-trimoxazole in addition to non-absorbable antibiotics would reduce the rate of infection. Three significant differences were observed between the co-trmoxazole and the control groups: (i) 15 of the 16 (94%) control patients but only 8 of the 14 (57%) patients on co-trimoxazole developed infections and required additional antibiotics intravenously; (ii) although the duration of severe neutropenia (neutrophils less than 0.1 times 10(9)/1) was similar in the two groups, control patients required intravenous antibiotics on average after  2 days of neutropenia, whereas patients receiving co-trimoxazole required these only after 12 days; and (iii) the only 2 patients who died of infection were in the control group. Prophylaxis with co-trimoxazole is important in preventing or delaying the development of infection in neutropenic patients receiving therapy for acute leukaemia.


HLA antigens in severe pre-eclampsia.

HLA antigens in severe pre-eclampsia. When the HLA types of 80 pre-eclamptic women and their husbands and 83 control couples were compared significantly more pre-eclamptic women had only one identifiable HLA B antigen, and were presumed to be homozygous at this locus. Those who were homozygous for HLA B were more likely to be homozygous for HLA A as well, and more likely to be homozygous for HLA A as well, and to have more severe pre-eclampsia. There was neither increased HLA incompatibility nor greater antigen-sharing between pre-eclamptic women and their husbands, but maternal HLA A and B homozygosity reduced the number of antigenic disparities between pre-eclamptic women and their husbands. The data are consistent with the hypothesis that maternal recessive immune-response genes may contribute to the development of pre-eclampsia. Alternatively maternal HLA homozygosity may predispose to fetal changes comparable to runting.


Coma in the Wernicke-Korsakoff syndrome. Four comatose patients were found to have the Wernicke-Krosakoff syndrome. All had a history of alcoholism, previous alcoholic neurological disease, and poor nutrition. Intravenous or nasogastric tube feeding without vitamin supplements precipitated coma in three. Examination showed a diffuse encephalopathy with intact pupillary light reflexes, no focal neurological signs, and absent doll's eye and caloric responses. The tendon reflexes were uniformly absent. Two patients were hypothermic and one was hypotensive. Although the level of consciousness improved in all after parenteral thiamine, three died and one was left disabled. The Wernicke-Korsakoff syndrome merits wider recognition as a cause of coma and empirical treatment with thiamine in cases of coma of unknown cause is recommended.


Low mortality in burned patients in a Pseudomonas vaccine trial. In a controlled clinical trial of a polyvalent pseudomonas vaccine in burned patients infected with Pseudomonas aeruginosa all 18 vaccinated patients survived, whereas 8 of 20 unvaccinated patients died.


Is group-specific meningococcal vaccination resulting in epidemics caused by groups of virulent meningococci? In 1976 routine vaccination against Neisseria meningitidis serogroups A and C was started in the Finnish Armed Forces. A case of fulminant, complicated pneumonia caused by group-Y meningococcus in a vaccinated recruit, prompted a study of the distribution of the meningococcal groups isolated from the recruits in the same unit. 14 (46%) of the 31 isolates from 84 recruits were group Y. Group-Y meningococcus was rarely isolated from unvaccinated controls. These results suggest that widespread vaccination against serogroups A and C may have led to an increase in the frequency of meningococcus group Y.


Exocrine-gland function and the basic biochemical defect in cystic fibrosis. A biochemical link is proposed between secretion and reabsorption in exocrine glands, in the form of a factor (kinin E) which initiates ion reabsorption. Activation of this factor involves arginine esterases, and in cystic fibrosis these may be defective, preventing the formation of kinin E. In cystic fibrosis stimulation of exocrine glands produces abnormal reabsorption of ions, leading to the physiological abnormalities and clinical manifestations of the disease.


Does that child really have cystic fibrosis? A diagnosis of cystic fibrosis was incorrectly made after false-positive sweat tests in 14 children. 13 of these children had been tested at hospitals where it seems likely that sweat tests were not done very often. All the children had normal sweat-electrolyte values when the test was repeated at a regional paediatric centre where approximately 250 sweat tests are done each year. In 5 cases, detailed testing of pancreatic function was normal. None of the children had typical chest disease and only 2 had gastrointestinal symptoms. In the absence of the typical clinical features of the disease a diagnosis of cystic fibrosis should be made with extreme caution and only after meticulous testing of both sweat electrolytes and pancreatic function.


Cow's milk as a cause of infantile colic in breast-fed infants. 18 mothers of 19 breast-fed infants with infantile colic were put on a diet free of cow's-milk protein. The colic disappeared promptly from 13; in 12, it reappeared on at least two further indirect challenges (in the form of a diet containing cow's milk to the mother). Most infants became symptom-free at age 2 to 4 months; at 4 months, only 4 reacted with colic when the mother took cow's milk. 5 infants were directly challenged with cow's milk; 4 reacted promptly with colic. Other signs of intolerance to cow's-milk protein developed in 3 infants during weaning. The treatment of infantile colic in breast-fed infants by a diet free of cow's milk for the mother appears worthwhile.


Testicular histology after combination chemotherapy in childhood for acute lymphoblastic leukaemia. A study of testicular histology has been made in 44 boys treated with combination chemotherapy for acute lymphoblastic leukaemia. At the time of testicular biopsy 21 boys were still receiving cytotoxic drugs and 23 had completed their chemotherapy some time earlier. Evidence of leukaemic infiltration was seen in 5 (11%), interstitial fibrosis in 24 (55%), and basement-membrane thickening in 6 (14%). The mean tubular fertility index in the 44 biopsies was 50% of that in age-matched controls, and 18 of the biopsies had a severely depressed tubular fertility index (40% or less). Three variables had a highly significant effect on the tubular fertility index: previous therapy with cyclophosphamide or cytosine arabinoside (greater than 1 g/m2) depressed the tubular fertility index, whereas with increasing time after completion of chemotherapy the tubular fertility index improved. The prognosis for fertility in these subjects is not known. Long-term surveilance is necessary.


Renin and blood-pressure in children with renal scarring and vesicoureteric reflux. Plasma-renin-activity (P.R.A.) was raised in 9 of 15 hypertensive children with pyelonephritic scarring secondary to urinary-tract infection and vesicoureteric reflux and also in 8 of 100 normotensive children with such scars. P.R.A. was much less likely to fall with age in normotensive children with renal scarring than in normal children. The identification of hyperreninaemic normotensive children with renal scarring is important, since P.R.A. may prove to be of value in early identification of children at risk of developing hypertension. A longitudinal follow-up is proposed to establish this hypothesis.


Chronic lymphocytic leukaemia: Clonal origin in a committed B-lymphocyte progenitor. The glucose-6-phosphate dehydrogenase (G.-6-P.D.) types of isolated blood-cell populations and normal skin were determined in two patients with chronic lymphocytic leukaemia (C.L.L.) who were heterozygous at the G.-6-P.D. locus. Normal tissues from each patient manifested both A and B G.-6-P.D. types, but the C.L.L. B-lymphocyte preparation from one patient showed only a single enzyme type, and from the other patient it showed 95% activity of one G.-6-P.D. type. These observations confirm the supposition based on immunoglobulin-marker data that at the time of study C.L.L. has a clonal origin. In contrast to the B lymphocytes, granulocytes, erythrocytes, platelets, and T lymphocytes displayed both enzyme types in proportions similar to those found in skin. These findings indicate that C.L.L. involves committed B-lymphocyte progenitors. Thus, the disease stands in contrast to chronic myelocytic leukaemia and other myeloproliferative syndromes, all of which involve multipotent haemopoietic stem cells.


Absence of a newly described cytochrome b from neutrophils of patients with chronic granulomatous disease. A unique cytochrome b which becomes incorporated into phagocytic vacuoles has been described in human neutrophils. This cytochrome b appears to be situated in the plasma membrane of these cells, and acts as a component of the microbicidal oxidase system. Absence or gross abnormality of this cytochrome b was demonstrated in all four patients with chronic granulomatous disease who were investigated, and reduced concentrations in two mothers known to be carriers of the disease.


"Body-brace" oesophagitis, a complication of kyphoscoliosis therapy. Oesophagitis developed in 4 patients, 3 of whom had scoliosis braces and 1 a body cast after surgery for kyphoscoliosis. Symptoms varied from chronic epigastric pain to gastrointestinal haemorrhage. Prophylaxis of oesophageal disease in children undergoing correction of scoliosis may prevent severe oesophagitis.


A possible role for propranolol in the treatment of renal osteodystrophy. The effect of propranolol upon parathyroid hormone (P.T.H) concentrations was investigated in patients undergoing chronic haemodialysis. 9 patients receiving propranolol for the treatment of hypertension or angina pectoris were compared with 25 similar patients not taking the drug. P.T.H. and alkaline phosphatase concentrations were lower in patients receiving propranolol and there was less radiological evidence of renal osteodystrophy in these patients. Prospective studies are needed to determine whether propranolol may be helpful as an adjunct to other therapy in reversing or preventing renal osteodystrophy.


Women with positive cervical smears but without surgical intervention. A follow-up study. By a collaborative effort among British cytopathologists, 101 women were identified who had had unsuspected "positive" cervical smears but who, after at least 2 years, had still escaped biopsy through refusal, default, or failure to trace. Of these, 31 still could not be traced; 10 were traced but could not be further examined (8 because they refused); 7 had clinically diagnosed carcinoma of the cervix; and the remaining 53 had further smears and/or biopsies after a mean interval of 5.2 years. In 19 of the 53 the smear had become negative or biopsy showed no lesion. Regression was confined to women aged under 40 at the time of the initial positive smear. In 20 cases biopsy showed dysplasia or carcinoma-in-situ, in 3 microinvasive carcinoma, and in 3 occult invasive carcinoma. Of the 7 women who presented clinically with carcinoma of the cervix, this caused death in 5.


Prenatal detection of the 47, XYY karyotype. The ethical decisions involved before and after the prenatal diagnosis of a 47, XYY karyotype in the fetus of a 32-year-old woman are discussed. It was decided that the parents should be presented with all the known facts about XYY-associated abnormalities and allowed to choose whether pregnancy should continue; the physician's role would be to support them in their decision and help them carry it out.


Raised plasma oestradiol and oestrone levels in young survivors of myocardial infarction. Of 35 male survivors of myocardial infarction, aged 24-48 years, 34 had higher plasma-oestradiol levels than age-matched controls. 29 of the 35 had higher oestrone levels than controls.


Natural oestrogen as an effective treatment for type-II hyperlipoproteinaemia in postmenopausal women. Seventeen postmenopausal women with raised serum total and low-density-lipoprotein (L.D.L.) cholesterol concentrations were treated with oestradiol valerinate for 6 months. Serum-L.D.L.-cholesterol decreased in sixteen patients--the average change at 6 months was -18%. Serum-high-density-lipoprotein (H.D.L.) cholesterol increased by 30% during treatment and the mean H.D.L./L.D.L. cholesterol molar ratio rose significantly from 0.21 to 0.34. There was a significant positive correlation between the size of the decrease in L.D.L. cholesterol and initial L.D.L.-cholesterol concentration. Serum triglyceride and very-low-density-lipoprotein (V.L.D.L.) concentrations were not significantly changed by the treatment. The results suggest that type II hypercholesterolaemia may be taken as another indication for oestrogen therapy in postmenopausal women.


Prevention of acute porphyric attacks by intravenous haematin. A thirty-three-year-old female with acute intermittent porphyria (A.I.P.) was having regular attacks of the disease with her menstrual periods. During several of these attacks she received intravenous haematin, which was followed by chemical and clinical remissions. Hormones failed to prevent the regular attacks, which were completely prevented by 200 mg of haematin, given approximately once a week for six months. There were no changes in menstruation. The monthly attacks recurred on withdrawal of haematin.


Ingested mutagens from opium and tobacco pyrolysis products and cancer of the oesophagus. Substances which are commonly sucked or chewed in two areas where the incidence of oesophageal cancer is high, the Transkei and north-east Iran, were tested in bacterial mutagenicity assays. Pyrolysed substances, opium dross in north-east Iran and tobacco pipe residues in the Transkei, displayed mutagenic activity in Salmonella typhimurium strains TA98 and TA100 in the presence of rat liver microsomes.


Evidence for sacroiliac disease as a common cause of low backache in women. 99M Tc stannous pyrophosphate bone scanning with quantitative sacroiliac scintigraphy (Q.S.S.) has been used in 50 females with low backache and in 66 symptomless female controls. Mean uptake of radionuclide at the sacroiliac joints was significantly increased in the patients when compared with controls. Q.S.S. gave objective evidence of unilateral sacroiliac disease in 2 of the 66 controls compared with that of unilateral and bilateral sacroiliac disease in 8 and 14 of the 50 patients respectively. Of the 22 patients with abnormal scans, 20 had normal radiographs. An abnormal scan did not correlate with the presence of HLA B27. It is concluded that sacroiliac disease is a common cause of low backache in women, and that it can be objectively diagnosed by Q.S.S. when radiographs are normal.


Abscesses of the frontal lobe of the brain secondary to covert dental sepsis. The bacterial species found in pus aspirated from brain abscesses in two patients were typical of those found in dental sepsis. Subsequently apical-root abscesses were demonstrated in the upper jaws of both patients. This evidence strongly suggests that these cerebral abscesses were secondary to dental sepsis which could have spread from the teeth to the frontal lobes by several possible antaomical pathways.


Myoglobinaemia in Duchenne muscular dystrophy patients and carriers: A new adjunct to carrier detection. Myoglobinaemia was detected in 14 of 18 patients with Duchenne muscular dystrophy (D.M.D.) with a sensitive specific complement-fixation assay. Myoglobinaemia was also detected in 10 of 16 known D.M.D. carriers, including 4 with normal serum-creatine-phosphokinase activity. 9 of 27 possible carriers also had myoglobinaemia. It is suggested that this assay is a useful adjunct to present methods of carrier detection in D.M.D.


Migraine: A blood disorder?

Migraine: A blood disorder? It is suggested that a primary abnormality of platelet function can account for the diverse clinical, biochemical, and pathological findings reported in migraine.


Medical student concentration during lectures. A simple procedure, based on a questionnaire, was used for the assessment of student concentration during lectures. Analysis of 1353 questionnaires from 12 lectures showed that student concentration rose sharply to reach a maximum in 10-15 min, and fell steadily thereafter. The data suggest that the optimum length of a lecture may be 30 instead of 60 min. This method by which student feedback is obtained may also be used to improve lecturing performance.


Dare we count the cost of cancer chemotherapy? During 1972-1976, when the incidence of cancer rose only slightly in the United Kingdom and the number of cancer patients seen at a large metropolitan teaching hospital and oncological centre remained largely unchanged, the use of cytotoxic drugs rose from 5.1% to 14% of the hospital's total drug budget. Most of the rise in cost can be ascribed to the increased use and increased unit cost of four effective but expensive drugs. Although the cost of drugs is but a small proportion of the cost of care of the cancer patient, it is argued that cytotoxic chemotherapy cannot offer a "cheap alternative" to surgery and radiotherapy. In a health service with cash spending limits the use of the more expensive cytotoxic drugs should be limited to the treatment of patients in whom "cure" or long-term ablation of disease is being attempted or to protocol studies in which their effectiveness is compared with that of other, possibly less expensive, drugs. Further studies are required of the use of the less expensive cytotoxic drugs in order to maximise their usefulness in the palliative treatment of advanced disease.


Remission of relapsed leukaemia during a graft-versus-host reaction. A "graft-versus-leukaemia reaction" in man? Acute lymphoblastic leukaemic in two boys relapsed after engraftment of marrow from siblings identical at HLA A, B, and D loci but went into remission during subsequent graft-versus-host reactions without specific anti-leukaemia therapy. Later leukaemic relapse was primarily in extramedullary sites, with little or no involvement of bone-marrow, liver, or spleen. Cytogenetic studies in both cases showed that the relapsed leukaemic blasts were those of the recipients while marrow cells and blood lymphocytes detected during marrow remission originated from the female donors. Blood lymphocytes from one of the recepients kiled. 51Cr-labelled autologous lymphoblast. The prolonged bone-marrow remission in the face of active and even massive extramedullary leukaemia suggests a graft-versus-leukaemia reaction in these two patients.


Bacterial adherence to periurethral epithelial cells in girls prone to urinary-tract infections. Bacterial adherence to epithelial cells from the periurethral region of 48 healthy girls aged over 2 years and of 76 girls with repeated urinary-tract infections was investigated. The infection-prone girls had a significantly higher mean number of adhering bacteria than the healthy controls ( P less than 0.01). This difference was valid irrespective of whether or not the infection-prone girls had urinary-tract infections at the time of investigation. Furthermore, statistically significantly higher numbers of a pyelonephritic strain of Escherichia coli (075:H-:K-non-typable) were found to adhere to washed periurethral cells from infection-prone girls than to cells from healthy controls. These characteristics of the periurethral epithelial cells may facilitate the primary periurethral colonisation which precedes infection of the urinary tract.


In-vitro lymphoproliferative response to Mycobacterium leprae of HLA-D-identical siblings of lepromatous leprosy patients. Lymphoproliferative responses to Mycobacterium leprae and P.P.D. were measured in 23 lepromatous and borderline lepromatous leprosy patients and in 27 of their normal siblings. At the same time siblings HLA-D-identical with the patients were identified by the absence of a mixed-lymphocyte reaction. The 7 siblings who were HLA-identical to lepromatous patients responded as well to M. leprae as did the 20 HLA-non-identical normal siblings. In contrast, 22 of the 23 lepromatous patients failed to respond to M. leprae but responded normally to P.P.D. The specific unresponsiveness of lepromatous patients thus does not result from an HLA-linked genetic defect and the defective cell-mediated immune response to M. leprae seems to be acquired, not inherited. Lepromatous patients may be high responders to antigens shared by M. leprae and other microorganisms in whom a strong antibody response has blocked the induction of an M. leprae-specific-cell-mediated immune response.


Haemoglobin A1, blood glucose, and high-density lipoprotein cholesterol in insulin-requiring diabetics. In forty insulin-requiring diabetics there was a significant correlation between haemoglobin A1 (HbA1) and blood-glucose measured at the same time and mean clinic blood-glucose measured over the previous year. There was no significant correlation between high-density lipoprotein (H.D.L.) cholesterol concentration and HbA1 or blood-glucose. HbA1 is not a good predictor of H.D.L. cholesterol concentration in insulin-requiring diabetics.


Does hypokalaemia precede delirium tremens? Serum-potassium was determined daily in 37 chronic alcoholics when alcohol was withdrawn on admission to hospital. Serum-potassium was normal in all patients at admission but in 26 patients in whom delirium tremens developed a contiuing decrease in serum-potassium led to hypokalaemia, (mean 2.9 mmol/l) when delirium tremens started. At the end of the attack serum-potassium rapidly returned to normal. The change in serum-potassium was not associated with any variation in serum electrolytes or acidbase balance. In the 11 patients in whom delirium tremens did not develop serum-potassium concentration remained unchanged.


Non-specific ileojejunitis in Arequipa, Peru. Non-specific ileojejunitis, characterised by mild to moderate structural changes in the intestinal mucosa and often associated with asymptomatic malabsorption, is known to occur in the tropics and in countries with hot climates. This acquired condition is probably related to environmental factors, and some consider it to be a subclinical form of tropical sprue. Changes in the intestinal mucosa typical of non-specific ileojejunitis were found in 10 indigenous Indians as well as 5 people of Latin stock living in the Southern Peruvian sierra, where tropical sprue has not as yet been demonstrated and which has a temperate climate.


Protective effect of dietary fibre against chemically induced bowel tumours in rats. 101 rats were fed one of four diets containing graded amounts of dietary fibre. Subcutaeous dimethylhydrazine (D.M.H.) was given to half the rats in each of the diet groups. Stool mass was found to be directly related to the amount of dietary fibre consumed, and the incidence of D.M.H.-induced colon carcinoma was reduced as dietary fibre increased.


Renal prostaglandins in systemic lupus erythematosus. Inhibition of prostaglandin synthesis at the prostaglandin synthetase and phospholipase steps could account for acute changes in renal function which are sometimes induced in patients with systemic lupus erythematosus (S.L.E.) by nonsteroidal anti-inflammatory drugs and high-dose corticosteriids, respectively. Renal function in S.L.E. patients seems to be more susceptible to inhibition of prostaglandin synthesis than in normal subjects. This susceptibility, in conjunction with increased urinary excretion of prostaglandin compounds, indicates that renal function in  S.L.E. patients may depend on enhanced renal prostaglandin production for the maintenance of renal haemodynamics.


Drug-induced myopathies in man.

Drug-induced myopathies in man. Drug-induced diseases constitute up to 5% of hospital admissions,a figure which almost certainly understates the total morbidity due to drugs1. Sever drug-induced myopathies are uncommon, but milder forms may be more prevalent than is generally appreciated, since skeletal muscle constitutes some 45% of total body-weight and has a major metabolic role in addition to its mechanical function2. Knowledge of possible effects of drugs on the neuromuscular system is of increasing importance both because the range of therapeutic agents continues to expand and because the resulting syndromes, through usually reversible at the outset, may progress and lead to grave consequences if the drug responsible is not stopped. Drug-induced neuropathies3 will not be considered here, but it will be appreciated that muscle weakness may also be feature of such disorders and that some drugs may cause both a neuropathy and a myopathy. The features of the main drug-induced syndromes are summarised in the table. To these one could justifiably add the unwanted effects of srugs given for the treatment of central-nervous-system or neuromuscular  disorders per se-e.g., the cholinergic block which may be produced by anticholinesterases alone or with corticosteroids in the myasthenic,4 and the profound weakness which may supervene after relief of spasticity with dantrolene sodium5.


Critical assessment of dilatation and curettage in 1029 women. Of 1029 dilatation-and-curettage operations carried out in a 12-month period, more than half were in women aged under 40, and 38% were for menstrual disturbances. The yield of intrauterine disease in these groups was low--curettage for post-menopausal bleeding or discharge in 150 women detected 15 endomettrial carcinomas and a similar number of other endometrial lesions. The complication-rate resulting from curettage was 1.7%--i.e., equivalent to the overall rate of detection of endometrial carcinoma. Selection of patients submitted to uterine curettage could be better, but postmenopausal bleeding remains an indication for mandatory uterine curettage.


Existence of 28R-antigen in a certain strain of group F streptococcus. An inter-Group common antigen was detected between Group A type 28 (Small)- and Group F (21/58/O'Mahoney, Colindale)-streptococcal cells by the T-typing agglutination reaction. The characteristics of this antigen coincide with those of the 28R-antigen, which was first detected in the Group A type 28 (Small) cells by Lancefield in 1943, in the following points: 1) It can be extracted from the cells with HC1 at pH 2.0 at 100 C in a stable state; 2) It can be kept in a stable state by heating in an alkaline solution at pH 7.8; 3) The antigen on the heat-killed cells was not affected by trypsin digestion at pH 7.8 but was destroyed by pepsin digestion at pH 2.0.


Correlation of clinical findings with quinacrine-banded chromosomes in 90 adults with acute nonlymphocytic leukemia: an eight-year study (1970-1977). We observed chromosome-banding abnormalities in leukemic cells of 46 of 90 (51 per cent) adults with acute nonlymphocytic leukemia at initial hospital admission. The difference in survival between 37 treated patients with an initially normal karyotype (10 months) and 43 with an initially abnormal karyotype (four months) was significant (P less than 0.01). When patients were classified as having acute myelogenous leukemia or acute myelomonocytic leukemia, this difference in survival was even more pronounced. Of 16 treated patients with acute myelogenous leukemia and a normal karyotype, 11 (69 per cent) had a complete remission and a median survival of 13 months. Of eight patients with acute myelogenous leukemia in whom only abnormal metaphases were observed, none had a complete remission, and the median survival was only two months (P approximately 0.50). Remission rate and median survival were not significantly different in patients with acute myelomonocytic leukemia grouped according to initial karyotypes.


Immune response to Rauscher virus-induced leukemia in DBA mice. II. Correlation between antigenic expression and pathogenesis. Previous studies have demonstrated that the Rauscher virus induces a biphasic erythroleukemia in DBA mice, and the regression of the disease is connected with the appearance of antibody-dependent cellular cytotoxicity. In the present work, attempts were made to reveal the mechanism leading to the lethal exacerbation of the leukemia. In the sera of leukemic mice soluble tumor-specific antigen could be demonstrated in the stages of early progression and regression but not in the stage of exacerbation. The antigen was present in form of immune complexes with free antibodies in excess. The emergence of a new population of leukemia cells has been observed during the stage of regression. On the surface of these cells the antigen receptor sites were masked by sialic acid which resulted in the loss of immunosensitivity and immunogenicity.


[Antigenic structure of bacteriophage lambda. Identification of the chief antigens of bacteriophage lambda]. The antigenic composition of the bacteriophages lambdaC1857 and lambdagt-lambdaC was investigated by modified immunoelectrophoresis in a 1,2% agarose gel involving 1% Triton X-100 and 0,25% sodium desoxycholate. The phages lambdaC1857 and lambdagt-lambdaC were shown to have identical antigenic compositions and to comprise three basic antigens, such as a1, a2, a3. The main structural proteins of the phage such as pE, pV and pD were isolated by preparative electrophoresis in 13% polyacrilamide gel. The immunophoresis of individual proteins indicated the antigens a1, a2 and a3 to be proteins pV, pD and pE, respectively.


Complement-fixing soluble antigen from rat lymphoma (C58NT)D. Preliminary characterization of the antigen and some positive human sera. A soluble complement-fixing antigen prepared from the Gross virus-induced rat lymphoma (C58NT)D reacted in complement-fixation with the sera of some patients with different malignancies (particularly acute leukemia) and with the sera of some healthy individuals. Results of gel filtration of crude (C58NT)D antigen on Sephadex G 200 indicate that the antigenic activity is eluted with the void volume of the column, i. e. in fractions corresponding to proteins of low molecular weight. Gel filtration of some positive patient sera indicate that complement-fixing activity of tested sera is associated with fractions corresponding to IgM and/or IgG.


Lower gastric secretion and higher incorporation of orotic acid into liver RNA in rats treated with 5-azacytidine and cycloheximide. Out of different azapyrimidines tested for their ability to affect metabolism of orotic acid in the liver of rats kept on food only 5-azacytidine resulted in the enhanced incorporation of orotate into liver RNA following 24 hr pretreatment. Similar effect was observed also in cycloheximide-treated animals. No stimulation of orotic acid utilization following 5-azacytidine or cycloheximidine treatment was observed in the liver of starved animals. Both drugs (but not other pyrimidine analogues tested) depressed markedly gastric secretion in rats and caused decreased evacuation of the stomach. The decreased secretion of pepsin and lower gastric acidity resulting in drug-simulated starvation of the treated animals are discussed in relation to the enhanced uptake of orotic acid into liver RNA.


Myelin basic protein-stimulated rosette-forming T cells in multiple sclerosis. A subpopulation of T lymphocytes sensitized to human myelin basic protein in peripheral blood of patients with multiple sclerosis, central nervous system (CNS) tumors, and cerebrovascular accidents was demonstrated by the antigen-stimulated, rosette-forming T-cell assay. A significant increase in the percent of active rosette-forming T cells was detected after in vitro exposure of peripheral blood lymphocytes to human myelin basic protein but not to histones. In contrast, peripheral blood lymphocytes from healthy controls and from patients with benign and malignant breast diseases were unresponsive to stimulation by either antigen. These results demonstrate a functionally active T-lymphocyte subpopulation sensitized to myelin basic protein in patients with multiple sclerosis and in patients with certain other CNS diseases.


[Treatment of algodystrophic syndromes with calcitonin]. A general account of algodystrophic syndromes is followed by the presentation of results obtained with 160 MRC U/day extracted pig or 100 MRC U/day synthetic salmon calcitonin in 95 patients with the most common form (Sudeck's syndrome). Clinical, biohumoral and radiographic data are reported. There was no difference in the response to the two products. Excellent results were noted, first clinically and then radiographically. Some radiographs are presented.


[Study of nucleic acid structure by immunochemical methods. I. Antibodies specific for 6-sulfo-5,6-dihydro-4-methoxyaminopyrimidinone-2]. Immunization of animals with DNA modified by a mixture of bisulphite and O-methylhydroxylamine and methylated bovine serum albumin results in production of antibodies mainly reacting with modified DNA. Antibodies that react with denatured DNA were produced in minute quantity. It was shown that elicited antibodies possess a high specificity and have the ability to recognize only nucleotides with a double modification. The immune sera were fractionated by Sephadex G-200 column chromatography and the antibody activity was demonstrable in the 19S and 7S fractions. The attempts to induce synthesis of antibodies by injection of DNA modified by O-methylhydroxylamine failed.


Mitomycin C, vincristine, and bleomycin therapy for advanced cervical cancer. The Southwest Oncology Group has treated 130 patients with advanced disseminated uterine cervical carcinoma no longer amenable to therapy with further radiation or surgery. Patients received one of three different schedules of mitomycin C, vincristine and bleomycin. A twice weekly schedule of bleomycin and vincristine produced response in 60% of patients. An infusion bleomycin schedule produced response in 39% of patients and a once weekly vincristine bleomycin schedule produced a 25% response rate (45% overall). Responding patients lived significantly longer than nonresponders (30 vs 18 weeks). Toxicities encountered included leukopenia, thrombocytopenia, peripheral neuropathy, gastrointestinal upset, dermatitis, and alopecia. We believe two of the schedules utilized represent an improvement in producing tumor remission induction in this previously recognized refractory carcinoma.


Inhibition of oncornavirus functions by poly (2-methylthioinosinic acid). Poly (2-methylthioinosinic acid) [poly(ms2I)] was found to markedly inhibit the RNA directed DNA polymerase (reverse transcriptase) activity of murine (Moloney, Rauscher) leukemia virus and murine (Moloney) sarcoma virus, while under the same conditions the unsubstituted parent compound poly(I) showed little, if any, inhibitory effect. Copolymers of inosinic acid (I) and 2-methylthioinosinic acid2(ms2I) showed an intermediary effect, depending on the I:ms2I ratio. Poly(ms2I) also inhibited the transformation of normal cells by murine (Moloney) sarcoma virus, as assessed by an infectious center assay.


E. coli tRNAs as inhibitors of viral reverse transcription in vitro. Reverse transcription of 70S AMV RNA by AMV reverse transcriptase has been studied in the presence of E. coli tRNAs. We have shown that inhibition of DNA synthesis occurs and that the tRNAs bind to the enzyme and not to the 70S RNA. The results have implications for the control of reverse transcription in vivo.


Continuity of care for patients with malignant disease. The first year of running a new continuing Care Unit for patients with malignant disease demonstrated the importance of continuity of care in their management after curative measures have ceased to be appropriate. This was achieved by regular home visiting by Unit ataff, liaison with home care services and the promise of readmission whenever necessary. As a consequence good relationships with patients, relatives and community services were built up, the average duration of in-patient stay was reduced to 19.6 days and more effective episode care was possible, this being integrated with an understanding of the overall problem.


Tumor-specific transplantation antigen: use of the Ad2+ND1 hybrid virus to identify the protein responsible for simian virus 40 tumor rejection and its genetic origin. Cells transformed by simian virus 40 (SV40) possess a tumor-specific transplantation antigen (TSTA) that has the property of immunizing animals against syngeneic tumor challenge. We find that the early SV40 DNA segment present in the human adenovirus 2 (Ad2)-SV40 hybrid, Ad2+ND1, is sufficient to induce this SV40-specific TSTA in BALB/c mice. Moreover, studies on the intracellular distribution of TSTA activity in Ad2+ND1-infected cells, as determined by the ability of various subcellular fractions to immunize mice against syngeneic tumor challenge, have suggested a correlation between this biological activity and the presence of the SV40-specific 28,000Mr protein in coded by this hybrid virus. Both the TSTA activity and the 28,000 Mr protein are found in the plasma membrane fraction and in the perinuclear region of infected cells but are virtually undetectable in the cytoplasmic fraction. Using a hamster antitumor antiserum that can specifically immunoprecipitate the 28,000 Mr protein, we are able to demonstrate a loss of TSTA activity concomitant with the removal of this SV40-coded protein. Thus, it appears that antigenic determinants responsible for SV40-specific tumor rejection in mice are contained within the 28,000 Mr protein coded for by the early SV40 DNA segment that extends from 0.17 to 0.28 map unit.


[Modification of the Heidenhain's method of staining with iron hematoxylin for detection of the A-cells of the islands of Langerhans]. The authors suggest to use iron hematoxylin according to Haidenhain's prescription, with the subsequent passage of stained and differentiated histological sections through the ammonia solution for detection of A-cells in the pancreatic islets. The A-cells cytoplasm stained dark blue intensively; as to the nuclear structures--they acquired bluish-black tints. The method can be used for the study of morphology, topography and the number of A-cells in the islets.


Use of computerized multidimensional scaling to compare immunoelectron microscopy data with protein near-neighbor information: application to the 30S ribosome from Escherichia coli. A three-dimensional model of the protein arrangement in the Escherichia coli 30S ribosome was constructed by using computerized multidimensional scaling of immunoelectron microscope data. This enabled data comparison between the new electron microscope technique and other methods such as crosslinking, chemical protection, affinity labeling, energy transfer, and assembly interactions. The immunoelectron microscopy data are reasonably consistent with those from other sources. Reasons for some inconsistent data are discussed and our calculation of the dimensions of the proteins, both globular and elongated, are summarized.


[Effect of corticosterone on serotonin metabolism in the rat brain]. The authors studied the influence of a single intraperitoneal administration of corticosterone to rats on the content of serotonin, 5-hydroxyindolacetic acid (5-HIAA), serotonin turnover in the hypothalamus, mesencephalon, dorsal hyppocampus, frontal and parietal cortex. In a dose of 1 mg per 1 kg of body weight corticosterone increased the content and the turnover of serotonin in the hypothalamus and the mesencephalon 30 min after its administration. 120 min after the administration of the hormone the content of serotonin was restored to control values. Corticosterone produced no influence on serotonin content and its turnover in other regions of the brain. Corticosterone in a dose of 10 mg/kg 30 min after its administration decreased the serotonin content and its turnover in the hypothalamus and the mesencephalon. The 5-HIAA content decreased considerably in the hypothalamus, but rose in the mesencephalon and the hyppocampus. The results obtained indicated that the influence of corticosterone on serotonin metabolism depended on the region of the brain under study, on the dose used and the time lapse after its administration.


Repeating covalent structure of streptococcal M protein. We have attempted to identify the covalent structure of the M protein molecule of group A streptococci that is responsible for inducing type-specific, protective immunity. M protein was extracted from type 24 streptococci, purified, and cleaved with cyanogen bromide. Seven cyanogen bromide peptides were purified and further characterized. Together, the peptides account for the entire amino acid content of the M protein molecule. Each of the purified peptides possessed the type-specific determinant that inhibits opsonic antibodies for group A streptococci. The primary structures of the amino-terminal regions of each of the purified peptides was studied by automated Edman degradation. The partial sequences of two of the peptides were found to be identical to each other and to that of the uncleaved M protein molecule through at least the first 27 residues. The amino-terminal sequences of the remaining five peptides were identical to each other through the twentieth residue but completely different from the amino-terminal region of the other two peptides. However, the type-specific immunoreactivity and the incomplete analysis of the primary structure of the seven peptides suggest that the antiphagocytic determinant resides in a repeating amino acid sequence in the M protein molecule.


Study of antibodies against human melanoma produced by somatic cell hybrids. We fused spleen lymphocytes obtained from mice immunized against a human melanoma cell line and melanoma-mouse hybrid cells with the P3 X 63 Ag8 mouse myeloma in order to produce hybrids secreting antibodies against a human melanoma. Antibodies secreted by individual hybrids were tested for their reaction with a panel of human melanoma, colorectal carcinoma, and normal cells in an indirect radioimmunoassay, and they displayed different specificities and crossreactivities. Some reacted only with melanomas, whereas others crossreacted with normal human or human colorectal carcinoma cells. By analysis of competitive binding of mixtures of monoclonal antibodies, it was possible to delineate different epitopes on melanomas. Hybrids growing in nude mice and producing antimelanoma antibody suppressed growth of melanoma tumors.


Effects of zinc sulphate pretreatment on gastric acid secretion and lesion formation in rats infused intravenously with graded doses of methacholine. The effects of intraperitoneal pretreatment with zinc sulphate (22, 44 or 88 mg/kg) were studied on gastric acid secretion and lesion formation induced by methacholine (125, 250 or 500 microgram/kg/h) infused intravenously in rats with stomachs perfused in situ. Graded infusions of methacholine produced dose-dependent increases in gastric acid secretion and lesion incidence in saline-pretreated control rats. These effects were progressively reduced by increasing pretreatment doses of zinc sulphate. The relationship between these findings and the action of zinc on gastric mast cells is discussed.


[Management of bone metastases. Indication for radiotherapy and surgical internal fixation (author's transl)]. Radiotherapy of bone metastases can achieve in up to 78% of patients complete relief of pain. Recalcification avoids pathological fractures and beginning compression of the spinal cord. Depending on size and site of the osteolytic process a prophylactic surgical stabilisation will be necessary. Bone metastases are a sign of generalized disease. Systemic therapy should be provided in addition to local therapy.


[Histological technique for intramural ganglia in thick tissue preparation (author's transl)]. A simple staining technique for gastrointestinal tract neurons in Auerbach's plexus is proposed in thick tissue preparation. The ganglion cells between two muscular layers are easily seen by optical microscope examination in "spread" preparations up to 300 micron in thickness, following dehidratation. Routine paraffin sections can be used. Neurons in thicker preparations (over 300 micron) like in human small intestine can also be seen but only by using small to medium magnifications. A special fixation procedure was developed for this technique.


Separation of anti-dinitrophenyl antibodies according to affinity by fractionated elution from immunoadsorbent using thiocyanate. The possibility of fractionating anti-DNP-antibodies according to their affinity by successive elution from a DNP-immunoadsorbent with increasing concentrations of thiocyanate (KSCN) was investigated. Using KSCN at molarities of 0.5 M, 2.0 M and 3.0 M in a stepwise elution procedure, the mean affinity of the eluted antibody fractions was found to increase with increasing molarity of the eluent. The method described is a simple, reliable means of separating antibodies on an affinity basis which is of special value in systems where haptens are not available.


Urinary excretion of albumin and beta 2-microglobulin in a population from an area where Balkan nephropathy is endemic. The urinary excretion of albumin and beta 2-microglobulin in a population of 294 persons, living in an area where Balkan nephropathy is endemic, has been studied. In fifty-six (about 19%) of the subjects the beta 2-microglobulin concentration was above the +2 SD level for a reference group of healthy individuals from non-endemic areas. Albumin elevation was found in forty-four (about 15%) of the cases. In twenty-one of the subjects the urinary concentration of both beta 2-microglobulin and albumin were increased, in sixteen of these cases the relationship between the two proteins was consistent with tubular proteinuria. An increased beta 2-microglobulin excretion is considered to be a sign of Balkan nephropathy. Radioimmunoassay of the protein is sensitive enough to detect tubular proteinuria at an early stage and is suggested as a suitable screening test for the disease.


Pre-treatment of serum samples for immunonephelometric analysis by precipitation with polyethylene glycol. A pre-treatment schedule for plasma samples to be analysed with immunonephelometry has been worked out using polyethylene glycol 6000 for precipitating the lipoproteins. The pre-treatment conditions have been studied in detail. By decreasing the blanks in immunonephelometric analysis a greater sensitivity of the method was gained. this was shown by performing analyses of S-beta2-microglobulin to concentrations below 1 mg/l. Another advantage with such a pretreatment is that blank determinations can be omitted for S-transferrin analysis and probably other analyses since the blanks in different samples are reduced to almost the same level.


[Antigens from Giardia lamblia trophozoites and cysts. Detection and immunoallergic evaluation]. A suitable technique for the preparation of antigen extracts from Giardia lamblia trophozoites and cysts is described. The immunoallergic characteristics of the antibodies obtained with these extracts were studied using in vivo and in vitro tests in experimental animals and 50 healthy individuals. It was proved that the human is able to produce antibodies to Giardia lamblia trophozoites and cysts and also that these antibodies are directed to several antigenic determinants.


Analysis of mechanisms of maintenance of neonatally induced tolerance to foreign alloantigens. Mice made tolerant to allogeneic tissues in neonatal life have been examined at different times for their ability to respond to the tolerizing determinants in a variety of assays (in vitro CML, MCL and in vivo GvH assays). All animals were tolerant in terms of their inability to produce CTL to the relevant determinants, and to induce GvH in lethally irradiated F1 recipients. Nevertheless, some mice also showed a normal MLC proliferative response and contained antigen-specific serum inhibitory factors, while other mice contained apparently antigen-specific suppressor cells. The pool of the latter, futhermore, was expanded considerably upon adoptive transfer of tolerant cells (with tolerizing antigens) to lethally irradiated syngeneic recipients. The data are compatible with the notion that suppression of clonal expansion represents the primary mechanism of tolerance maintenance (induction), and that the infrequently observed serum reactivity in such tolerant mice represents a vestige of the means whereby-cell mediated suppression was induced.


Partial characterization of cell surface idiotypes on alloantigen-activated T lymphoblasts. T lymphoblasts of specificity Lewis anti-DA, Lewis anti-BN, BN anti-DA and L.BN anti-DA were purified on Ficoll-Paque from mixed leucocyte cultures on day 5. Blasts were radiolabelled with iodine-125 by the lactoperoxidase method and lysed by the aid of Nonidet P40. Idiotypic molecules were puried from the lysates by the use of anti-idiotypic antiserum of specificity anti-(Lewis anti-DA) and Staphylococcus aureus bearing protein-A. In this way, molecules with a molecular weight of 150,000 and 75,000 daltons could be isolated from Lewis anti-DA and L.BN anti-DA T lymphoblasts but no significant radioactivity was brought down by the same procedure from Lewis Lewis anti-BN or BN anti-DA T lymphoblasts. No additional molecules were detected on the lower molecular weight regions where light chains of Ig type as well as conventional products of the MHC genes would appear. The 150,000 dalton molecules are composed of two single polypeptide chains with a molecular weight of around 75,000 daltons. These data are in complete agreement with earlier results on antigen-binding, idiotypic receptors obtained from normal rat T lymphocytes.


Studies on the structure of T lymphocyte receptors using xenogeneic anti-idiotype antibodies. The present study is an attempt to produce xenogeneic anti-idiotype antibodies (Id) against mouse anti-H2 antibodies. The purpose is to obtain such anti-Id antibodies with reactivity against both B and T cells in quantities which will allow thorough investigation of the biochemical nature of the T cell receptor for alloantigen. Data are presented from experiments performed with an antiserum 5936 which was obtained after immunization with C57B1/6 anti-CBA antibodies.


Induction of specific unresponsiveness to transplantation antigens. Transplantation of tissue between non-identical human beings does normally require heavy, non-specific immunosuppressive treatment to be successful. Complications of severe nature are frequently induced by such therapy. Here, procedures allowing a selective immunosuppression of the recipient with regard to the donor's alloantigens would be of paramount importance as to reduce the need for non-specific immunosuppressive agents. Classical pathways to achieve specific reduction of reactivity against transplantation antigens include "transplantation tolerance" and "enhancement". Although occasional successful when using adult, immunocompetent individuals in experimental animal systems these approaches have so far failed to leave impressive impacts with regard to the human transplantation immunologists. In the present article an entirely new concept will be introduced, namely that of auto-anti-idiotypic immunity leading to specific lack of reactivity towards transplantation antigens. The principle and the underlying results supporting the concept wil be presented and the practical implications will be discussed.


Urinary beta2 microglobulin related to chronic low level exposure to metallic cadmium dust in Finnish cadmium processing workers. The determination of urinary beta2 microglobulin is a sensitive method for screening groups which run the risk of developing renal tubular damage due to cadmium exposure. In this study, the urinary beta2 microglobulin excretion of 78 male workers who had been exposed to cadmium dust levels of 6.3-11.0 microgram/m3 from 0.5 to 4 h daily for an average of four years was compared to 35 nonexposed male workers. Possible effects of smoking on renal beta2 micorglobulin excretion were controlled. The results indicate that the levels of cadmium to which the workers were exposed have no measurable renal effects on the health of workers.


[Treatment of gynecologic neoplasms in internal medicine]. In the treatment of gynecological malignancies, chemotherapy is used with increasing frequency. The palliation in advanced stages is limited, but a marked prolongation of survival is proven in patients who achieve remissions. The remission rates of the commonly used agents and their combinations are listed. The use of cytotoxic chemotherapy is recommended in advanced stages of gynecological malignancies. Hormonal therapy offers a nearly nontoxic but less effective alternative to cytotoxic therapy.


[Disorders of supra-ventricular rhythm and of atrioventricular conduction in the aged patient]. Incidence and features of the disorders of the supraventricular rhythm and of the atrioventricular conduction seen in 429 patients with a 20-months follow-up, the patients being aged 60 to 99. Nature of the associations was described and compared with other similar series.


Lymphoma of the prostate presenting as benign prostatic hypertrophy. A case of lymphocytic lymphoma involving the prostate is reported. Lymphomatous infiltration of the prostate had been mentioned infrequently in the literature, so that the incidence, prognosis, and treatment are not well known. Lymphomatous or leukemic infiltrate should be considered as a causative agent of prostatism, particularly in patients with hematologic abnormalities where chemotherapy may relieve the symptoms.


Evaluation of human chorionic gonadotropin and alpha fetoprotein in benign and malignant testicular disorders. The marker proteins alpha fetoprotein and human chorionic gonadotropin are useful adjuncts to clinical evaluation of patients with non-seminomatous testicular germ cell malignant growths during and after therapeutic interventions. Measuring both markers is better than measuring either one alone. An elevated marker assay indicates the presence of active disease. A normal marker assay does not exclude active disease being present. Lastly, these markers are of limited usefulness in the evaluation of undiagnosed testicular masses.


[Some aspects of the control of atrophic rhinitis (author's transl)]. The results obtained by a number of methods adopted in the control of atrophic rhinitis in herds in which this disease occurred, are reviewed. The long-term results may be described as disappointing. A number of possible causes of these disappointments are discussed.


[Lymph node metastases and ureteral obstructions as prognostic parameters for the percutaneous radiotherapy of the bladder carcinoma (author's transl)]. The results of a percutaneous radiotherapy of 136 patients with bladder carcinomas who were treated between 1966 and 1972 are presented in a retrospective study. Before the beginning of the treatment, the diagnosis of these patients had been verified by a lympho-cavo-urography. 21% of the patients had a pathological lymphogram and 40% a pathological urogram. The survival time of patients with normal and those with pathological lympho-cavo-urography showed a difference which was statistically significant (p less than 0.001). There was no patient with inhibited urinary defluxion and demonstrated lymph node metastases who lived longer than 21 months after the treatment. Exclusive percutaneous radiotherapy and primary total cystectomy cannot be considered as curative therapeutic methods. If metastases in the lymph nodes of the regio iliaca communis and paraaortal are demonstrated by lymphography, the prognosis is unfavourable and only palliative methods are justified.