Phytohemagglutinin effects on cultured human neural crest tumors. Two human melanoma lines, RPMI-7931 and HS-294, respond to mitogenic stimulation by PHA. A dose-response curve for these lines can be demonstrated with maximal stimulation at 16 and 32 micrograms per ml and inhibition at 75 to 250 micrograms per ml PHA. The mitogenic effects of PHA were inhibited by N-acetyl-D-galactosamine. Neuroblastoma cells also exhibits a similar but less important dose-response to PHA. These data indicate that human melanomas and neuroblastomas may have PHA receptors or mechanisms for mitogenic stimulation which are analogous to those observed with normal lymphocytes.


Culture of adult rat lung cells: benzo(a)pyrene metabolism and mutagenesis. A method is described for obtaining and culturing large numbers of lung cells from normal adult male rats. The lungs were perfused in situ to remove blood cells and then perfused via the trachea with a trypsin-collagenase solution to initiate tissue digestion. The tissue was further digested in the enzyme solution and approximately 2 X 10(8) viable lung cells were obtained per animal. Primary cultures contained a mixed cell population. Through eight subcultures about 70% of the cell population possessed an epithelial-like morphology, whereas the remaining 30% was fibroblast-like. Three clones of epithelial-like cells were isolated at the fourth subculture. The mass culture lung cells and the epithelial-like clone that was studied retained a normal karyotype and did not grow in soft agar. Both the mass culture cells and the epithelial clone metabolized the lung carcinogen benzo(a)pyrene (BP) to water-soluble products. Furthermore, the mass culture lung cells metabolized BP to intermediate(s) which mutated Chinese hamster V79 cells from ouabain sensitivity to ouabain resistance. These lung cell cultures have potential use in cell transformation, mutation and carcinogen metabolism studies.


Proliferation and morphology of chick embryo cells cultured in the presence of horse serum and hemoglobin. We have shown previously that hemoglobin greatly stimulates chick embryo cell proliferation in Eagle's minimal essential medium supplemented with horse serum. In the present study we compared the effects of horse serum plus 10 micrometers hemoglobin to those of fetal bovine serum on subcultures of chick embryo cells serially propagated at high cell densities. The cells became elongated in the presence of fetal bovine serum and their rate of proliferation progressively decreased, whereas they became polygonal in the presence of horse serum plus hemoglobin and proliferated well in successive cell passages. The polygonal cells obtained in the presence of horse serum plus hemoglobin rapidly elongated if cultured at low cell densities in the presence of fetal bovine serum, but, in contrast, elongated cells did not yield polygonal cells if cultured at low densities in the presence of horse serum plus hemoglobin. It is possible that the polygonal and elongated cells are undifferentiated cells and differentiating myogenic cells, respectively.


Isolation and characterization of fibroblasts obtained by pulmonary lavage of human subjects. Cells that possess the morphology and collagen synthetic capacity of fibroblasts were recovered by bronchofiberscopic subsegmental pulmonary lavage from patients with pulmonary fibrosis, from patients with miscellaneous nonfibrotic lung diseases and from healthy volunteers. Lavage cells were placed in tissue culture, observed for 2 to 6 weeks, and compared with human lavage pulmonary alveolar macrophages (PAM), WI-38 and IMR-90 human fetal lung fibroblasts, and adult lung tissue fibroblasts (CLAC-76). Lavage fibroblsts (LF) were identified as proliferating clones in monolayers of nonproliferating PAM and could be subcultured repeatedly. Fibroglasts were propagated from 28 of the 92 lavage specimens cultured. Time-lapse cinematography showed similar distributions of interdivision times for LF, CLAC-76 and WI-38, but the LF and CLAC-76 lines had slower mean migration rates than the fetal line. Light, scanning, and transmission electron microscopy of LF showed attenuated spindle-shaped cells with interdigitating filopodia, flat surfaces with few microvilli, and containing numerous cytoplasmic polyribosomes and rough endoplasmic reticulum. Extracellular fibrils with the appearance of collagen were seen. Collagen synthesis by LF was measured as 3.9% to 4.9% of the cell-associated protein sensitive to bacterial collagenase. This protein was rich in hydroxyproline, and had an electrophoretic migration pattern identical to known collagen. LF did not contain lysozyme although this enzyme was abundant in fresh and 1-week cultured PAM. Thus LF were similar to human fetal and adult lung tissue fibroblasts in their morphology, tissue culture characteristics, constitutive enzymes and collagen synthetic properties but were distinctly different from PAM.


Growth characteristics of skin fibroblasts and 3T3 cells entrapped by polymerizing fibrin. Skin fibroblasts as well as 3T3 cells were cultured after entrapping freshly prepared cells in medium containing polymerizing fibrin. In contrast to cells grown on plastic substratum, fibrin-clot-cultured cells became highly elongated forming strands of cells. The strands interconnected by lateral cellular protrusions so that horizontal networks of cells were present throughout the clots. Cell growth as well as stretching were dependent upon the concentrations of fibrin. Highest growth rates were obtained with low fibrin concentrations (0.3 mg fibrinogen per ml). As shown by deprivation experiments nutritional limitations appear to be responsible for differences in growth rates observed in fibrin clots of higher density. In this system the fibrin meshwork serves as substratum for adhesion, elongation and multiplication of fibroblasts. The method makes it possible to study single cells in culture and the effects of persistent microenvironmental influences.


Localization of vtiamin A by autofluorescence during induced metaplastic changes in cultures of skin. A technique was devised for following the uptake and location of vitamin A in organ cultures. Explants of 12- and 13-day embryonic mouse upper lip skin were grown for 3, 6 or 9 days in biological medium to which was added 0, 4.1 or 6.9 micrograms per ml of retinyl acetate. This form of vitamin A caused glandular morphogenesis of vibrissa follicles, and keratinization in epidermis and follicles was completely suppressed in 12-day explants and partially suppressed in 13-day explants. Frozen sections at 16 microns showed the white, nonfading fluorescence of keratin and the green, rapidly-fading fluorescence due to vitamin A which was captured by high-speed photography. Although more concentrated within lipid droplets in the dermis, the vitamin penetrated both the epidermis and the hair follicles. The ability to obtain permanent photographic records of the fading fluorescence makes this a useful method for analyzing vitamin A distribution as well as keratin distribution.


Effect of horse serum on neural cell differentiation in tissue culture. The effects of various concentrations of horse serum on dissociated mouse glial precursor cells in colony cultures were evaluated. High concentrations (20% or more) favored cell attachment but inhibited cell proliferation and differentiation, whereas lower concentrations (5% to 10%) favored cell proliferation and differentiation. In fetal bovine serum the cells did not attach to culture surfaces to the same degree nor did they achieve the same level of differentiation as in corresponding concentrations of horse serum.


Inhibition of complement-dependent rosette formation after lymphocyte incubation with fatty acids. Overnight incubation of lymphocytes with certain fatty acids bound to albumin has previously been shown to modify the fatty acid composition of cellular phosphoglycerides without impairing viability, and also to inhibit mitogen and antigen-induced lymphocyte transformation. In the present study, incubation of human lymphocytes with palmitic acid or with linoleic acid impaired their capacity to form complement-dependent rosettes but had no effect on either spontaneous rosette formation with sheep erythrocytes or Fc(gamma)-dependent rosette formation. With mouse lymphocytes, complement-dependent rosette formation was suppressed only following incubation with linoleic acid and there was no effect on Fc(gamma)-dependent rosette formation. Although the mechanism of these effects remains to be elucidated the results suggest that control of membrane lipid composition may modify the important in vivo immunological functions which involve complement receptors.


Radioassays of blood group M, N and T (Thomsen-Friedenreich) antigens. Radioassays employing the double-antibody or Farr techniques were developed for the M, N and T antigens. Blood group glycoproteins were isolated by butanol extraction of red cell stroma and iodinated by the chloramine-T technique. The final purity of glycoprotein was over 75% as judged by radioimmunoassay (RIA). T activation of glycoprotein was obtained with neuraminidase. A specific RIA was obtained for the M antigen and was sensitive to approximately 10 ng of glycoprotein or glycopeptide. In the RIA system rabbit anti-M displayed a higher affinity for M glycoprotein than for M glycopeptide. A RIA that was entirely specific for the N antigen, could not be obtained. A radioassay, obtained for the T antigen with peanut agglutinin in the Farr technique, was sensitive to approximately 100 ng of T antigen and was readily inhibitable by monosaccharides. A RIA, obtained for the T antigen with rabbit anti-T, was entirely specific and sensitive to approximately 1 ng of T activated glycoprotein or glycopeptide but was not inhibitable by monosaccharides.


Post-translational modification of rat immunoglobulins synthesized in the Xenopus oocyte translation system. The post-translational modification of rat immunoglobulin synthesised in Xenopus laevis oocytes was studied. The major products of translation of rat spleen poly-(A) containing mRNA were found to be assembled 7S immunoglobulin molecules indicating extensive modification of primary translation products. The possibility that these immunoglobulin molecules might include antibodies of defined specificity was investigated using spleen mRNA from rats hyperimmunized with ferritin and keyhole limpet haemocyanin. The presence of antibodies to immunizing antigen in oocyte translation products was determined by affinity chromatography on Sepharose-antigen columns and the synthesis of Sepharose-antigen binding antibodies was observed, equivalent to 2.5-3% of total immunoglobulins. The oocyte produced antibodies were of the same immunoglobulin class as the circulating antibodies from the immunized rats.


Suppression of delayed hypersensitivity by the depletion of circulating monocytes. The intraperitoneal injection of Marcol oil was previously reported to result in the depletion of circulating monocytes. The way in which this depletion affected guinea-pigs' ability to respond to challenge with antigen was tested by challenging with tuberculin after sensitization and examining the ability to respond to DNCB. It was found that the ability to respond to tuberculin was completely abrogated by the injection of Marcol and could be restored by removing the oil from the peritoneal cavity. The ability to respond to a secondary challenge with DNCB was not affected, while the ability to become sensitized was impaired. A normal inflammatory response was seen. The role of the circulating monocyte is discussed.


Effect of protein A of Staphylococcus aureus on the binding of monomeric and polymeric IgG to Fc receptor-bearing cells. The effect of protein A of Staphylococcus aureus (SpA) on the binding of rabbit IgG to the Fc receptors of mouse lymphocytes and macrophages was found to correlate with the aggregation of the IgG ligands. After binding anti-erythrocyte IgG complexed with SpA, the cells were able to attach to and kill erythrocyte indicator cells with a higher efficiency than lymphoid cells treated with anti-erythrocyte IgG alone. The amount of anti-peroxidase IgG which can be bound to effector cells was not changed by reaction with SpA. In contrast, the binding to cells of IgG-coated erythrocytes and of anti-peroxidase IgG complexed with peroxidase was substantially reduced by reaction with SpA. The results are compatible with the presence of two distinct Fc receptors, one for cytophilic monomeric IgG and another for polymeric (antigen-complexed) IgG.


Kinetics of humoral responsiveness and antigenic distribution in operated rats. Wistar R/A rats were injected intravenously with 10(9) sheep red blood cells (SRBC) prior to, during or after a standard laparotomy. Stimulation of anti-SRBC antibody synthesis was already observed when the antigen was given 4 h prior to surgery and was maximal if SRBC were administered at the time of operation. The enhancing effect on the immune response lasted for 2 days after surgery. From the third post-operative day on, the injection of SRBC induced a normal humoral response. No subsequent depression was detected. Inter-organ distribution studies of 51Cr-labelled SRBC injected at various times prior, during or after the surgical procedure, showed a maximum decrease of liver uptake during operation; the depression was still present 2 h later but on the first post-operative day, no significant difference from the controls could be demonstrated. When the labelled antigen was given before surgery, organ distribution was normal. Consequently, there is no time relationship between the stimulation of antibody production and the alteration of total phagocytosis induced by surgery. Therefore, the enhanced humoral response cannot be explained only by spillover of the antigen from the liver into lymphoid organs.


Functional properties of bovine IgG1 and IgG2: interaction with complement, macrophages, neutrophils and skin. Bovine immunoglobulin G subclass (IgG1 and IgG2) antibodies were found to fix bovine complement while only IgG1 fixed guinea-pig complement in vitro. Similar results were noted when IgG1 and IgG2 antibodies were tested by passive cutaneous anaphylaxis (PCA) in that both IgG1 and IgG2 caused PCA in bovine skin while only IgG1 mediated the reaction in rat skin. In precipitation reactions IgG1 antibodies to DNP failed to cause precipitation of DNP19-ovalbumin while IgG2 antibodies to DNP precipitated DNP19-ovalbumin. Both IgG1 and IgG2 antibodies to ovalbumin precipitated ovalbumin. Surprisingly, IgG2 antibodies to equine erythrocytes caused phagocytosis by bovine neutrophils and peripheral blood monocytes while IgG1 antibodies failed to cause either phagocytosis or adherence. Results with peripheral blood monocytes cultured for 7 days demonstrated that both IgG1 and IgG2 could mediate phagocytosis.


The responsiveness of efferent lymph cells to phytohaemagglutinin during the response of the popliteal node to dinitrophenylated bovine serum albumin. Cells, recovered from the efferent lymphatics of the popliteal nodes of sheep during in vivo responses to dinitrophenylated bovine serum albumin (DNP-BSA), were examined for their responsiveness to phytohaemagglutinin (PHA) in vitro during the first 4--5 days of the immune response. The response was almost totally depressed when cells collected throughout the response were cultured with supra-optimal doses of the mitogen. Optimal and suboptimal doses of PHA resulted in greatly enhanced responses in cells collected in the first two periods (0--6 h; 6--12h) of the response; the presence of high doses of DNP-BSA in the culture media prevented the enhancement in the second period but had no adverse effects on the cells collected during the first 6 h. Efferent cells collected after 12 h generally showed decreased responses, this depression being maximal in cells collected 2--3 days after antigenic stimulation. Later in the response the cells again exhibited enhanced responses. The possible interpretations of these results in terms of regulation of the response are discussed.


In vitro transfer of cellular immunity in experimental allergic orchitis by means of immune RNA. Ribonucleic acid (RNA) extracts were obtained from lymph nodes of guinea-pigs that had previously been immunized with a purified testicular antigen emulsified in Freund's complete adjuvant. The RNA extracts were incubated with normal guinea-pig peritoneal exudate cells (NGP-PEC). After treatment, the NGP-PEC cells showed specific inhibition of migration when tested with the specific antigen. No inhibition of migration was observed when cells were tested with an unrelated antigen or when the cells were incubated with RNA obtained from animals immunized with adjuvant alone. Failure of inhibition of migration was also observed when the 'immune' RNA was degraded with RNAse. The appearance of this I-RNA in the immunized guinea-pigs correlates with the appearance of delayed hypersensitivity in vivo.


The respiratory response of sensitized rats to challenge with antigen aerosols. An experimental procedure was developed to evaluate the effects of challenging sensitized conscious rats with antigen aerosols. The challenge resulted in changes in the respiratory patterns which were antigen specific and mediated by IgE antibodies. The response was inducible in non-sensitized rats by passive administration of IgE-rich serum. Sprague-Dawley rats were heterogeneous with respect to the respiratory response. A proportion (20--70%) of each group had continuous dyspnoea and other symptoms similar to asthma; the other had only episodes of apnoea. Wistar and Long-Evans rats resembled Sprague-Dawley rats; Fischer 344 rats had apnoea only, even though they produced IgE antibodies. The type of response did not correlate with serum IgE levels. The respiratory responses were reduced by dexamethasone, disodium cromoglycate, epinephrine and theophylline. Rats that respond with dyspnoea may provide a useful experimental model of allergic asthma.


Complement response after experimental bacterial infection in various nutritional states. In malnourished rats, nutritionally rehabilitated rats at various stages, and in well nourished rats, levels of serum complement after bacterial infection caused by Staphylococcus aureus, as well as tuberculin reactivity, were examined. The elevation of complement showed a peak 2--3 days after infection, herein called the first complement response. A reelevation occurred at a later stage, 7--14 days after infection, and is referred to as the second complement response. The first complement response was observed in all the rats after Staphylococcus aureus infection but it was greater in well nourished rats. In malnourished rats, only the first complement response was observed and the tuberculin reaction and second complement response were lacking. After 1 week of nutritional rehabilitation, 40% of the rats showed recovery of tuberculin responses and both the first and second complement responses were observed. Nutritionally rehabilitated rats treated longer than 2 weeks, together with the well nourished control rats, showed positive tuberculin reactivity. The second complement response was also observed in such rats when bacterial infection was severe but not with mild infection.


Hydrocortisone and the antibody response in mice. I. Correlations between serum cortisol levels and cell numbers in thymus, spleen, marrow and lymph nodes. Mice injected with a single well tolerated dose of hydrocortisone acetate were observed over 2--3 weeks for serum cortisol levels and for cell depletion in thymus, spleen, femoral marrow, mesenteric, inguinal and popliteal lymph nodes. Serum cortisol peaked within 24 h and declined to normal after 4 days. Total marrow cell numbers were relatively unaffected, but in all other tissues studied, cell depletion was severe and prolonged. B lymphocytes were affected more severely than T lymphocytes. There was a transient increase in the percentage of marrow T lymphocytes but otherwise little change. The percentage of node T lymphocytes increased while that of B lymphocytes decreased. The percentage of spleen B lymphocytes was reduced severely but transiently during the period of serum cortisol elevation. Spleen T lymphocyte percentages rose steadily between the fourth and seventh days after treatment, then returned to normal. Representatives of most types of lymphoid tissue were studied. As cell losses in any one were not compensated by gains in any other, most were probably due to destruction rather than redistribution. The slow rates of recovery were also more consistent with regeneration than with reappearance after redistribution.


Experimental inflammation and tumor growth: chemical carcinogenesis in adjuvant arthritic rats. Development and growth of primary (methylcholantrene or benzpyrene-induced) sarcomas in adjuvant arthritic rats were investigated and compared with the chemical carcinogenesis in normal healthy animals. When carcinogen and adjuvant were applied in the same time, tumor development and growth rate did not differ significantly from nonarthritic controls. When carcinogen was applied to rats with fully established arthritic disease, development and growth of tumors were significantly enhanced. In the latter case local and systemic adjuvant disease was more severe in tumor-bearing rats. Enhanced chemical carcinogenesis in arthritic rats can be explained by a defective immune responsiveness in the chronic stage of arthritis.


Inflammatory lesions and bone resorption induced in the rat periodontium by lipoteichoic acid of Streptococcus mutans. Severe inflammatory lesions were induced in the periodontal tissues of the rat following the intragingival injection of lipoteichoic acid (LTA) from Streptococcus mutans. There was no difference in the severity and distribution of the lesions between nonimmunized rats and animals immunized against LTA after antigenic challenge. The lesions are characterized by the occurrence of granulation tissue, massive infiltration of PMNs, abscess formation, bone resorption, and new bone formation. Deacylated LTA and saline caused relatively mild inflammation, and no significant bone resorption or new bone formation was evident. The peak response was reached after 3 intragingival infections. The mechanisms by which LTA caused the pathological alterations in the rat periodontium and the possible relations of this experimental model to periodontal disease in the human are discussed.


Arachidonic acid aggregates neutrophils. Arachidonic acid, but not several structurally similar fatty acids, stimulated neutrophils in suspension to aggregate; this effect was blocked by 5, 8, 11, 14-eicosatetraynoic acid, an inhibitor of arachidonic acid metabolism. Analagous to platelets, arachidonate may be a precursor of active metabolites which mediate neutrophil responses.


Permeability factor contaminating hyaluronidase preparations. Both crude and highly purified testicular hyaluronidase preparations have been shown to contain a component which increases the permeability of the microcirculation in rat skin. This permeability activity had an isoelectric point of 7.4 while hyaluronidase was 9.4. It also could be separated from hyaluronidase by acrylamide gel electrophoresis. The permeability factor was not inhibited by serum and may explain previous observations that hyaluronidase preparations decrease the ischemia and necrosis appropriate to experimental myocardial infarction in vivo.


Macromolecular, anionic pulmonary permeability factor. Aqueous extracts of fresh or acetone-powdered calf lung have been found to contain a factor which increases the permeability of the microcirculation when injected into the skin of rats. This permeability factor, which is not found in similar extracts of muscle or kidney, was concentrated by Amicon ultrafiltration at a molecular weight range of between 50,000 and 100,000 daltons and via isoelectric focusing at an IEP of pH 4.2. After preparative acrylamide gel electrophoresis, this permeability factor was homogeneous by electrophoretic criteria and in SDS acrylamide gel electrophoresis had a molecular weight of approximately 82,000 daltons. This apparently homogeneous permeability factor from lung was inhibited by pepstatin, and yet possessed no acid proteolytic activity against any substrate. Its activity was completely inhibited by pretreatment of the animals with antihistamines. This pepstatin-inhibitable permeability factor was found largely in the lysosomal fraction of fresh lung and could also be obtained by extraction of large amounts of alveolar "washout" macrophages. Since macrophages, during phagocytosis, are known to leak significant quantities of their lysosomal contents, the fact that one of these components is a material which could release histamine from mast cells and thereby increase locally the permeability of the microcirculation may be of importance in the defense system of the lung.


Concentrations of nystatin in faeces after oral administration of various doses of nystatin. Nystatin was administered in ten healthy adult volunteers in increasing doses of 3 X 10(6) I U, 6 X 10(6) I U, 9 X 10(6) I U and 12 X 10(6) I U per day, each dose being given for a five-day period. Faecal samples were collected daily for the determination of their concentration of biologically active nystatin. Nystatin concentrations were determined biologically; the sensitivity of this method was less than or equal to 20 mcg/g of faeces. During the four treatment periods with increasing doses, 38%, 31%, 26% and 20% respectively of the faecal samples contained biologically undetectable amounts of nystatin. This means that nystatin is either inactivated or unevenly distributed through the intestinal contents, or both. The practical consequences of this may be that in a significant portion of the colon there is no inhibitory nystatin concentration against Candida albicans, despite treatment with as much as 12 X 10(6) I U of nystatin per day.


Infectious episodes in severely granulocytopenic patients. In a prospective study, 40 episodes of granulocytopenia (granulocytes less than 500/mm3) in 34 patients were analyzed. During 52.5% of these episodes there was proven infection; these infections were present for only 24.4% of the 1,435 granulocytopenic days. The risk of infection and mortality were closely linked with extreme granulocytopenia (granulocytes less than 100/mm3). Of the episodes with severe granulocytopenia (granulocytes 100-500/mm3) only a small number were associated with infections, and mortality was virtually absent in this category. These results implicated a restricted use of supportive measures (e.g. granulocyte transfusions) especially when granulcotye counts are higher than 100 mm3.


Pharmacokinetics of tobramycin in the newborn. Following an intramuscular dose of 5.0 mg of tobramycin in eight full-term newborn infants, peak levels averaging 2.69 +/- 0.70 microgram/ml were attained after 30 to 60 minutes. The serum half-life thereafter correlated inversely to postnatal age during the first seven days after birth. Pharmacokinetic analysis revealed that in newborn infants the elimination rate was markedly declined, but the absorption rate was nearly the same as that in older children. Average urinary recovery within eight hours was as low as 26.8%, which suggested accumulation of this antibiotic in the renal tissue.


Antibacterial active components in human urine after administration of penicillins. Four-hourly urine from volunteers and patients who had received penicillins orally or intravenously was investigated by means of thin layer chromatography and bioautography. Antibacterially active metabolites were not detected with only two of 12 penicillins, namely amoxicillin and mezlocillin. In the case of the other penicillins the metabolites possessed variable antibacterial activity as could be demonstrated using different test microorganisms. After administration of carbenicillin esters three antibacterially active spots were detected, one of which corresponded to penicillin G; the other two were active against Pseudomonas aeruginosa. The bioautogram after treatment with azlocillin showed two components which were active against Bacillus subtilis, Staphylococcus aureus and Escherichia coli; only the rapid moving component was active against P. aeruginosa, however. The formation and chemical nature of these additional active components is still to a large extent not understood. It is quite possible, however, that they affect the bio-availability of an antibiotic.


Accidental amikacin overdose in man: emergency therapy by extrarenal dialysis. Three accidental overdoses of amikacin (6, 6.5 and 8 times the normal dose) are reported. Emergency haemodialysis therapy was given and the serum levels monitored. No toxic effects were encountered. The need for such emergency haemodialysis seems to be limited to patients with impaired renal function or to cases where little time has elapsed between intake and detection of overdose.


Quantitative correlation between the Dane particle-associated DNA polymerase and the hepatitis B e antigen. In order to evaluate the potential infectivity of blood of hepatitis B patients, the Dane particle associated DNA polymerase was determined, which is a reliable marker for the presence of complete viral particles. Enzyme activities were compared with hepatitis B e antigen (HBeAg) titers determined by radioimmunoassay. Detectable DNA polymerase activity was only present in HBeAg positive blood, preferentially in samples with high antigen titers (1 : 1000 and above). These samples therefore have to be considered as highly infectious. However, blood with low HBeAg levels and free of detectable polymerase activity can still be infectious, since the polymerase reaction is rather insensitive compared to the radioimmunological HBeAg determination.


Immunoglobulin prophylaxis against hepatitis A among Swedish UN soldiers in an endemic region. Six hundred and fifteen Swedish soldiers (X = 24.9 years) serving with the UN forces in Cyprus were tested for antibody against hepatitis A (anti-HAV) before and after six months' service. Before the service, a high susceptibility to hepatitis A was found, as only 2.3% (14/615) had anti-HAV. In comparison, the prevalence of anti-HAV among 124 native Cypriots (X = 23.9 years) was 97% (120/124), which showed Cyprus to be a region where hepatitis A is endemic. The soliders were given immunoglobulin (IG) prophylaxis (2 ml of 16.5% IG) against hepatitis A very third month. The incidence of subclinical seroconversion against hepatitis A among the Swedish soliders was 0.2% (1/615). It was concluded that the IG-prophylaxis scheme used seems to be highly effective and probably completely prevents even subclinical seroconversion against hepatitis A in non-immune persons in regions where hepatitis A is endemic.


Bacteroides fragilis in acute salpingitis. The bacteriology of acute salpingitis was studied in 87 patients. Gonococci were recovered from 18 patients. Lower yields of bacteria were isolated in the peritoneal fluid than from the vaginal cultures, and a poor correlation was observed between the peritoneal fluid and vaginal cultures. Anaerobic bacteria dominated in both sites. Staphylococci, streptococci, enterobacteria, peptostreptococci, peptococci, lactobacilli and bacteroides normally present in the vagina were the predominant isolates recovered from the culdocentesis. Paired acute and convalescent-phase sera obtained from patients with isolates of Bacteroides fragilis were assayed for antibody response to the polysaccharide antigen of B. fragilis. Significant titer increases were observed in sera from only two out of eight patients with non-gonococcal salpingitis and no titer changes were noticed in two patients with gonococcal. These findings suggest that B. fragilis only infrequently plays an etiologic role in acute salpingitis.


[Variations in resistance of viruses from different groups to chemico-physical decontamination methods]. The resistance of a total of 13 different viruses to some important chemico-physical influences was studied under uniform experimental conditions. Stability in tape water, thermostability and sensitivity to anodic oxidation, gamma radiation, some virucidal substances and several commercial disinfectants were tested. In evaluating the results, an attempt is made to rank the viruses investigated according to their sensitivity. On average a bovine parvovirus, and also a reovirus and three enteroviruses, proved most stable. These were followed by infectious canine hepatitis (adenoviruses). Newcastle disease (paramyxoviruses) and vaccinia (poxviruses) demonstrating less resistance. In all the tests an orthomyxovirus (influenza A), a rhabdovirus (vesicular stomatitis), and particularly a herpesvirus (pseudorabies) and a togavirus (sindbis) proved to have relatively low resistance.


[Serum and tissue concentrations after a single dose of cefaclor]. Serum and tissue concentrations of cefaclor were determined a total of 155 and 96 times respectively in 16 volunteers after a single dose of 1 g. At this dosage peak concentrations of 13.5, 14.5 and 13.4 mcg/ml were measured after 60, 90 and 120 minutes respectively. Tissues in which concentrations were measured included cortical bone, spongy bone, muscle, fascia, cutis and subcutis. By measuring blood concentrations of the tissue samples, a division could be made for purposes of calculation into intravascular and extravascular active components. Low amounts of extravascular cefaclor could be established merely in the fascia and in the cutis. The cefaclor concentrations found in spongy bone, muscles and subcutis proved to be determined to a large extent by the intravascular antibiotic. No cefaclor could be detected in cortical bone at the given dosage.


Post-varicella acute transverse myelitis. This report of a case of acute transverse myelitis, after otherwise uneventful varicella, further stresses the importance that the possibility of this relatively rare complication should be kept in mind in patients developing a paraplegic syndrome late in the course of the disease.


Co-trimazine distribution in the canine prostate. Constant infusion experiments were performed on dogs to determine the concentration levels of co-trimazine (a combination of trimethoprim and sulphadiazine) in the dogs' prostatic secretion, prostatic interstitial fluid, prostatic tissue, urine, and other tissues. Trimethoprim concentrations in prostatic secretion, interstitial fluid and tissue were higher than corresponding serum values, whereas the concentrations of sulphadiazine were far below these values. These results were compared to those of a similar study which combined trimethoprim and sulphamethoxazole (co-trimoxazole). The prostatic secretion to serum ratios of sulphadiazine were lower than those for sulphamethoxazole. Urine concentrations of sulphadiazine, however, were much higher than those of sulphamethoxazole. In serum and urine, only co-trimazine had a trimethoprim/sulphonamide ratio approximating the optimal synergy ratio of 1:20. Neither trimethoprim/sulphonamide combination appears to have any theoretical advantage over the other in the treatment of prostatitis. However, co-trimazine may be more effective in the treatment of urinary tract infections in general because of the high concentrations of sulphadiazine in urine.


Renal lymph and interstitial fluid concentration of co-trimazine: an experimental study in dogs. Renal clearance and renal hilar lymph and interstitial fluid concentrations of co-trimazine were investigated in dogs during constant intravenous infusion. The lymph was obtained by direct cannulation of the lymphatics, and the interstitial fluid from small plastic tissue chambers, implanted 4--6 weeks before the experiments. The clearance values for trimethoprim and sulphadiazine, compared to the glomerular filtration rate, as measured by 125I-iothalamate clearance, showed a net tubular secretion of trimethoprim and tubular re-absorption of sulphadiazine. Renal lymph and interstitial fluid concentrations were found to be lower than the plasma concentrations, corresponding well with earlier findings for several other antimicrobial agents. We found a statistically significant difference between lymph/plasma and interstitial fluid/plasma ratios, indicating different composition and origin of lymph and interstitial fluid.


Studies on the optimal dosage of co-trimazine in children. There are many difficulties in creating a simple and useful dosage schedule for co-trimazine treatment in children. However, it has been possible to propose a schedule based on age. No advantage can be seen in choosing doses according to weight or other measures of body size. The schedule referred to as schedule B leads to levels of both sulphadiazine and trimethoprim that are as near the optimal as possible with respect to efficacy and side-effects.


Development of sulphonamide-trimethoprim combinations for urinary tract infections. Part 2: Comparative pharmacokinetics of five sulphonamides. The pharmacokinetics and renal excretion of the sulphonamides sulphachloropyridazine, sulphadiazine, sulphaisodimidine, sulphamerazine, and sulphamethoxazole were investigated in a cross-over study with doses of 800 mg each. The serum half-life, urine levels, distribution volume, protein binding and potential antibacterial activity in the urine renders sulphadiazine the preferred component in a combination tablet together with trimethoprim for the treatment of urinary tract infections.


Development of sulphonamide-trimethoprim combinations for urinary tract infections. Part 3: Pharmacokinetic characterization of sulphadiazine and sulphamethoxazole given with trimethoprim. Plasma levels and renal excretion of sulphonamide and trimethoprim following oral administration of co-trimazine (140 mg sulphadiazine + 90 mg trimethoprim) and co-trimoxazole (800 mg sulphamethoxazole + 180 mg trimethoprim) were monitored in healthy volunteers after a single dose and in the steady state after 12-hourly dosage. The plasma levels of free, non-protein bound components after co-trimazine were approximately half those after co-trimoxazole and thus correlated with the doses given. Urine recovery of trimethoprim was better after co-trimazine (70%) than after co-trimoxazole (58%). Sixty-six percent of the sulphadiazine was recovered as unchanged, active sulphonamide in the urine compared with only 13% of the sulphamethoxazole. Consequently, the sulphonamide levels of sulphadiazine were 2.5 times those of sulphamethoxazole. With respect to plasma half-life after the first dose, sulphadiazine with 8.0 hours was closer to trimethoprim with a half-life of 8.8 hours after cotrimazine and 9.6 hours after co-trimoxazole than to the half-life of sulphamethoxazole which was 7.7 hours. The distribution volume of sulphadiazine was closer to that of trimethoprim than was that of sulphamethoxazole. On the basis of these characteristics, it has been concluded that sulphadiazine is more suitable for a fixed combination tablet with trimethoprim than sulphamethoxazole, particularly for the treatment of urinary tract infections. Some renal tubular reabsorption occurs with both unchanged sulphonamides but is more pronounced with sulphamethoxazole. The solubilities of the sulphonamides and their acetylated metabolites at acid urinary pH indicate that therapy with co-trimazine is at least as safe as with co-trimoxazole. With the former drug, the result of scrutiny for crystals after dosage until the steady state was negative, whereas crystals of acetylated sulphamethoxazole were detected and verified chemically in two of eight subjects.


Pharmacokinetics of sulphadiazine, sulphamethoxazole and trimethoprim in patients with varying renal function. The pharmacokinetics of tablets containing combinations of sulphadiazine (SDZ) and trimethoprim (TMP) (cotrimazine) and tablets with sulphamethoxazole (SMZ) and TMP (co-trimoxazole) were compared in patients with different renal functions. In normal renal function, SMZ is more similar to TMP than in renal impairment. In renal impairment although the serum half-life (t1/2) of both active and total SDZ remains similar to that of TMP, the t1/2 of total SMZ becomes several times higher than the t1/2 of TMP. The unchanged SMZ maintains approximately the same elimination velocity in reduced as in normal renal function. Consequently, for co-trimoxazole there is a buildup of SMZ metabolites which can only contribute to toxicity for co-trimoxazole, whereas the co-trimazine components have t1/2 values of the same order, also in renal dysfunction. The distribution volumes of SDZ, SMZ or TMP are the same regardless of renal function. However, the distribution volume of SDZ is closer to that of TMP, i.e. higher than the SMZ values. More active SDZ is excreted in the urine than SMZ both in normal and in reduced renal function. Thus co-trimazine, in addition to having some advantages in the normal individual, is in many respects distinctly more suitable in patients with renal functional impairment. On the basis of the patients with renal functional impairment. On the basis of the pharmacokinetic properties, dosage schedules are suggested that will give approximately the same plasma levels regardless of renal function.


Effect of bacampicillin on human mouth, throat and colon flora. Bacampicillin was given as tablets or syrup in doses of 400 mg three times per day for seven days to twelve subjects. Saliva, throat and faecal specimens were taken during fourteen days for cultivation of aerobic and anaerobic bacteria. No changes in the oral, throat and faecal flora were seen in the subjects receiving tablets while there was a decrease in the number of aerobic and anaerobic bacteria in those subjects receiving syrup. No increased resistance to ampicillin were found in the isolated bacterial strains. Bacampicillin was well-tolerated and no gastrointestinal disturbances were experienced.


Dose dependence in human absorption of aminopenicillins. The concentration of antibiotic in a focus of infection depends both on the peak serum concentration and on the area under the serum concentration time curve (AUC). A knowledge of the relationship between increased doses and the corresponding response in serum concentration would be relevant as a basis for determining an adequate clinical dosage. Dose-related changes in the two pharmacokinetic variables, peak serum concentration and AUC, after single doses of bacampicillin are compared with data on different aminopenicillins from other studies. With ampicillin there is a nonlinear relationship between both dose-peak and dose-AUC. The results indicate that the poor absorption of oral ampicillin can only be partially compensated for by increasing the oral dose. But with amoxycillin and the ampicillin esters the absorbed amount (AUC) is a linear function of the dose in the dosage range investigated. The increase in peak serum level with high doses of oral ampicillin is far less than proportional, while this tendency was less pronounced for amoxycillin and still less for pivampicillin, talampicillin and bacampicillin.


Penetration of ampicillin into human bronchial secretions. Ampicillin concentrations in serum and bronchial secretions after oral administration of bacampicillin were evaluated. Twenty-eight hospitalized patients with acute bronchopulmonary infections received a single dose of 800 mg of bacampicillin. Samples of bronchial secretions were obtained during diagnostic bronchoscopy and blood samples were drawn simultaneously. Significant concentrations of ampicillin were found in bronchial secretions, the peak level, reached after approximately two hours, being 0.27 micrograms/ml on an average. The penetration of ampicillin into the bronchial secretions after the administration of bacampicillin could be correlated with the degree of bronchial inflammation, as illustrated either by macroscopic purulence or protein concentration in the secretions. The results suggest that bacampicillin is a useful drug in acute bronchopulmonary infections.


Ampicillin concentration in normal and pathological lung tissues after oral administration of bacampicillin. Following oral administration of 800 mg bacampicillin, the concentrations of ampicillin were determined in normal (n = 16) and pathological (n = 12) lung tissue after 3.6 and 9 hours in a total of 28 patients. The serum concentration was determined simultaneously. The mean peak serum concentration (+/- SD) after one hour was 9.7 +/- 7.2 micrograms/ml. The mean concentration (+/- SD) in normal lung tissues were, after 3, 6 and 9 hours, 3.73 +/- 1.10 micrograms/ml, 1.06 +/- 0.99 micrograms/ml, 0.15 +/- 0.30 microgram/ml respectively, and in pathological lung tissues 0.95 +/- 0.31 microliters/ml, 0.86 +/- 1.11 micrograms/ml and 0.40 +/- 0.24 micrograms/ml respectively. Thus bacampicillin produced concentrations well above the MIC of the most important pathogen, Haemophilus influenzae, in both pathological and normal lung tissue.


Ampicillin concentrations in middle ear effusions in acute otitis media after administration of bacampicillin. The penetration of ampicillin into middle ear effusions after oral administration of 800 mg bacampicillin to patients with acute otitis media was studied and compared with the serum levels. One hour after administration a mean (+/- SEM) concentration of 2.4 +/- 0.4 micrograms/ml ampicillin was found in the effusions and the mean serum level was 7.7 +/- 0.8 micrograms/ml. After twelve hours a mean concentration of 0.6 +/- 0.2 micrograms/ml was found in the middle ear effusions and 0.1 +/- 0.03 micrograms/ml in the serum. The high concentration of ampicillin in middle ear effusions after twelve hours suggests that a twice daily dosage of bacampicillin should be given in acute otitis media.


A pharmacokinetic study of bacampicillin in patients with chronic maxillary sinusitis. The penetration of ampicillin into sinus mucosa and secretion after oral bacampicillin was studied in 30 patients subjected to radical maxillary sinus surgery. Bacampicillin in a dose of 1200 mg was administered orally before the operation and the concentrations in serum, sinus mucosa and secretion were assayed. The mean serum concentration (+/- SEM) reached its maximum of 13.4 +/- 1.2 micrograms/ml in about one hour. The mean concentrations in the secretion and mucosa after two to five hours were 1.6 +/- 0.5 micrograms/ml and 1.6 +/- 0.4 micrograms/ml respectively. The clinical course of the patients was mostly uneventful. Adverse effects probably caused by the drug were found in two cases.


Penetration of ampicillin into urethral and cervical secretions after oral administration of bacampicillin. The study comprised 24 male and 24 female patients treated either for uncomplicated gonorrhoea or as a prophylaxis. A single dose of 800 mg of bacampicillin + 1.0 g probenecid was administered orally to each patient. The concentrations of ampicillin in urethra and cervix were assayed by means of alginate swabs that were used as diffusion centres on agar diffusion plates. The inhibition zones were compared with a standard series of swabs containing known amounts of ampicillin. The amounts of secretions absorbed into the swabs were determined by weighing each swab before and after taking the specimen. The median ampicillin concentration in the male urethra one hour after the single dose of bacampicillin plus probenecid was 2.0 micrograms/ml of urethral secretion and increased to 3.2 micrograms/ml two hours after administration of the antibiotic. In the female urethra, the median concentrations of ampicillin were 1.5 micrograms/ml and 2.3 micrograms/ml of urethral secretion one and two hours, respectively, after the same dosage as above. The corresponding ampicillin concentrations in the cervical secretion were 1.6 micrograms/ml and 2.9 micrograms/ml, respectively.


Experimental evidence of a decreased incidence of penicillin allergy through use of pure penicillins. The results revealed the presence of high molecular weight impurities in commercially available penicillins, measured with a radioimmuno assay. The impurities had penicilloyl specificity and induced antibody formation in mice when the contaminated penicillin was administered in 50 mg/kg body weight daily for ten day periods with a 20 to 30 day interval. Penicillin of high purity similarly administered produced very few antibodies. Furthermore, experimentally contaminated penicillin given according to the same schedule caused IgE antibody formation against the penicilloyl moiety, while pure penicillin did not. These findings were explained by the weak immunogenicity of isologous penicilloylated serum albumin in rabbits both regarding the IgE and the IgG/IgM antibody formation compared to the immunogenicity of heterologous bovine serum albumin similarly penicilloylated.


Review of side-effects of aminopenicillins. Side-effects of aminopenicillin therapy are reviewed on the basis of nine comparative studies of ampicillin and bacampicillin, and available literature data from investigations with talampicillin, pivampicillin, bacampicillin and amoxycillin. Diarrhoea is more common with ampicillin than with newer aminopenicillins. Exanthema do not appear more frequently with newer aminopenicillins. The frequency of upper gastrointestinal complaints in association with some of the newer aminopenicillins (amoxycillin, bacampicillin) is not more frequent than with ampicillin. All current evidence speaks in favour of a change from ampicillin to modern aminopenicillins for oral therapy.


25-hydroxycholecalciferol in the treatment of renal osteodystrophy in haemodialysed patients. The effects of 25-OHD3 on renal osteodystrophy have been studied in 6 patients on maintenance haemodialysis. Administration of 25-OHD3, 50 microgram/day, did not improve biochemical data and intestinal absorption of calcium. With a dose of 100 microgram/day in all patients an increase in blood calcium levels eventually reaching hypercalcemic values was observed. In two cases a fall in alkaline phosphatase toward normal values was noted. In the same cases the treatment-induced hyperphosphatemia, uncontrolled by AI(OH)3 supplementation and similarly high iPTH levels were observed. In two cases repeated bone biopsy following 8 months treatment and not show substantial improvement of bone lesions. In one case addition of 1,25-(OH)2D3 to the treatment with 25-OHD3 led to a more rapid improvement in biochemical parameters and iPTH serum levels. Doses of 25-OHD3 capable to correct blood calcium levels and intestinal absorption of calcium, may have minimal benefit on the osteitis fibrosa component of the bone lesion.


Comparative value of different dialysis membranes, including a carbon coated membrane for removal of noxious substances in hepatic coma. Three dialysis membranes, including a polyacrilonitrile membrane, a polycarbonate membrane and a cuprophan membrane coated with charcoal, have been compared with cuprophan in order to assess their ability to clear from aqueous solution and plasma, substances thought to be of pathogenetic importance in hepatic coma (ammonia, short chain fatty acids and mercaptans), some protein bound (glycocholate and bromsulphthalein) and some middle molecular weight molecules (ethylenediaminetetracetic acid, cyanocobalamin and inulin). High clearance of ammonia, short chain fatty acids and mercaptans were found with membrane tested but dialysis was relatively ineffective for removal of protein bound molecules. Cyanocobalamin, glycocholate and ethanethiol were removed best by the carbon coated membrane and by combining dialysis with adsorption, this membrane may offer advantages over other treatments for liver failure.


Blood purification by haemoperfusion.

Blood purification by haemoperfusion. Blood purification by haemoperfusion is considered, principally in terms of the European effort. The development of the different approaches which have emerged and the assessment of adsorbents and devices are described. The application of haemoperfusion is examined in the areas of acute poisoning, liver failure and uraemia.


Amberlite hemoperfusion in the treatment of acute drug intoxication. Hemoperfusion is more effective than hemodialysis in clearing drugs from the blood of patients with acute overdose. In addition, the clinical improvement in the depth of coma is dramatic during hemoperfusion. There is normalization of the respiratory and circulatory systems usually within one hour, and response to verbal command within a few hours of initiating treatment. Amberlite XAD-4 is an unchanged polystyrene resin with a particular adsorptive attraction for lipid-soluble drugs. It is a more effective adsorbent than some of the coated or uncoated carbons in clearing blood of most of the drugs commonly involved in life-threatening acute overdose.


Evaluation of a new coated charcoal for hemoperfusion in uremia. A new coated charcoal for hemoperfusion in uremia was investigated in 14 patients with end stage renal disease who underwent hemoperfusion or combined hemodialysis-hemoperfusion (39 seances). Investigations concerned removal of small molecules, coagulation and hematological status and amino acids and some hormones equilibrium. Clinical observations were also made in all patients. The methacrylate-coated charcoal enabled the removal of "toxins" up to 5000 daltons and the total solute removal did not significantly differ from previous hemoperfusion systems. However, the new coating membrane showed improved biocompatibility, in terms of clinical side effects and/or platelet and fibrinogen alterations.


Microprocessor-based EEG spike detection and quantification. A microprocessor-based system for the detection and quantification of sharp EEG waveforms is described. The hierarchical approach utilises initial transient detection based on computation of a second-derivative measure of curvature, followed by pattern-recognition and artifact-rejection routines based on consideration of specific waveform parameters. Initials results demonstrate an ability to approximate human-analysis results, while providing precise measures of amplitude, duration, and sharpness. The decreasing cost of microprocessors makes multichannel configurations economically feasible.


Simulation of disturbed cell renewal systems by means of a microprocessor system. In this contribution a computer model is presented which enables a simulation of disturbed cell growth and cell renewal systems by means of a microprocessor system. The results consist of a time course study of the number of cells and of the local configuration of cells in a cell matrix at any arbitrary discrete moment. A similarity to morphological cuts and cell kinetic curves obtained by experiments is obvious.


[Model of the function of the nephron].

[Model of the function of the nephron]. After a short review of the functional anatomy of the kidney, we express the usual hypotheses about the phenomena of reabsorption and filtration in the loop of Henle and the collecting duct. Starting from these hypotheses and the laws of biophysics, we formulate the equations of the model. This model accounts for the great increase in concentration of electrolyte and urea in the loop of Henle, the collecting duct and the interstitium, as we "go down" from the outer medullary area towards the inner areas, the active transportation of sodium in the loop of Henle being limited to the thick ascending limb.


Numerical analysis of binding studies: a direct procedure avoiding the pitfalls of a Scatchard analysis of equilibrium data for unknown binding models. It is shown on theoretical grounds that the straightforward analysis of binding data according to Scatchard may lead to erroneous results, especially when more complicated binding schemes are involved. We have demonstrated this point by presenting Scatchard plots with slight variation of experimental parameters. These inherent difficulties of Scatchard analyses can be avoided by applying a direct procedure. We have developed a program, which compares the measured quantity and the theoretical value directly and which considers the following binding models: (i) independent equivalent binding of n ligands; (ii) independent unequivalent binding of 2 ligands; (iii) positive or negative cooperative binding of 2 ligands. Other binding schemes can easily be implemented. We have used this procedure for the evaluation of equilibrium data on the complex formation of tRNA-Tyr and tyrolyl tRNA synthetase from E. coli in terms of different binding models.


Bifurcation in non-negotiable games: a paradigm for self-organisation in cognitive systems. The interaction between two self-organising systems, each possessing two hierarchical levels, is dealt with. The communication process is pursued as a bidirectional information transfer. The criterion for the selection of the intrasystem control algorithm(s) is based on the maximisation of the 'Joint Figure of Merit' related to the long-term average of an appropriately weighted sum of conflicting terms: Probabilities of homeostases versus adequate matching with the partner.


Jittermeter--a microcomputer-based system for single fibre electromyography. In single fibre electromyography (SFEMG) an exact measurement and computation of a number of time parameters is required. This paper describes a low-cost microprocessor-based measurement system for SFEMG data acquisition, computation of the parameters and display, as an alternative to a general purpose-computer based system. Time measurement is performed at dual resolution: 0.1 microsecond and 0.1 msec. Erroneous data due to disturbing voltages are automatically eliminated. A variety of SFEMG applications is covered by 3 basic modes of data handling. The microprocessor unit is based on the 6800 family and contains 3K of program memory, input-output modules and 4K data memory. The instructions are entered through a keyboard and output is provided by an LED display, line-printer and X-Y storage display.


Multiexponential and multicompartmental approaches for analysis of tracer washout data from animal. A comparison is made between multiexponential and multicompartmental analyses of tracer washout data from biological tissues. Various analytical and computer methods are used to explore the relations between kinetic parameters of three-compartment models and parameters of three-exponential functions fitted to typical observed tracer washout records and also to examine relations between kinetic parameters of the same three-compartment models determined analytically and numerically. It is concluded that exponential factors and coefficients cannot always be equated respectively with conpartmental transport rate constants or compartment sizes. Sufficient analytical and computer methodologies exist so that selection of meaningful biological models should not be hampered by a lack of appropriate solution procedures.


Computation as a thermodynamic process applied to biological systems. A physical quantity, 'information,' can be defined and must be included in the second law of thermodynamics. This quantity is different from entropy, though closely related to it. Acquisition and use of information is characteristic of most systems, especially those of biological orgin. Treatment of information as a physical quantity permits many types of machines (in the most general sense) to be understood in respect of a thermodynamic function, and as well an investigation of the extent to which the laws governing information are or may limit their behavior. This limitation is most important at the molecular level, such as in the process of DNA and RNA synthesis. However, it may ultimately have a significant impact on all areas of biology including the theory of evolution, which in light of the concept of information can now be addressed in an important new way.


An iterative algorithm for analysis of variance. In this paper, an iterative algorithm is proposed for computing estimates of parameters and sums of squares in non-orthogonal multivariate analysis of variance, without inverting any matrix. It is useful in the case of a large design matrix for it saves memory and computation time. It was first proposed by Stevens (1948) for 3 factors and is here generalised to any number of factors and interactions of any order. Convergence properties are studied. The more orthogonal is the design, the faster is the convergence. Several examples are provided.


[Selective diffusion and osmosis: application to the problem of the functioning of the nephron]. In this article, we propose a new hypothesis concerning biological semipermeable membranes, the walls of vessels or tubules of the human organism. As regards the properties of diffusion of the membranes, this hypothesis includes the phenomena of active and passive transport; as far as the properties of diffusion and osmosis are concerned, it takes into account the orientation of the phenomena, which explains its name: hypothesis of selectivity. By applying this theory to the problem of the transport of salts and urea in the nephrons, we demonstrate that this property is a necessary and sufficient condition to explain the part and working of the functional unit of the kidney, i.e., the nephron, and to validate its operating model, subject of our study. No contradiction has appeared within the present experimental results.


Computing in the bio-sciences with hypernumbers: a survey. A survey of higher types of number, with more sophisticated arithmetics than square root -1, is presented. Such powerful embodiments of the number concept are capable of representing entities and operations in the bio-sciences, where phenomena are characteristically more recondite than in naively reductionist, mechanistic physics or chemistry, which today even quantum theory (which itself deploys two kinds of hypernumber) has shown to be inadequate to explain observed phenomena. When the bio-sciences enter the picture, four other kinds of hypernumber are needed, one of them (w) relating also to the frontiers of quantum theory, in terms of the resolution of problems such as the breakdown of parity conservation and of time reversal, and the concomitant elimination of unwanted divergences (infinities). A brief statement of the relevance of each of the additional kinds of hypernumbers in bio-scientific computing is furnished, as an introduction to an approach that is not only viable in terms of digital computing, but is fraught with new implications for bio-scientific research.


Alcoholism and substance sniffing among the Cheyenne and Arapaho Indians of Oklahoma. Common determinants of alcoholism and substance sniffing are identified among the Cheyenne and Arapaho Indians of Oklahoma. Computer correlations, interviews, and questionnaires provided data. Findings indicate chronic sniffing is prealcoholic behavior. Confusing family interpersonal relationships, alcoholism in the immediate family, and severe parent-child emotional deprivation predispose to alcoholism.


Arrest record and retention in methadone maintenance treatment. It was found that when compared with those who stay in methadone maintenance treatment for less than 18 months, those who remain at least 18 months have a lower pretreatment and a lower in-treatment arrest record. It is questioned, however, if this group entered with a favorable bias and would have responded better to any form of treatment, including simple dispensation of methadone.


The failure of therapeutic communities, drug treatment, and rehabilitation programs. A positive behavioral modification program is described. This program has been useful in dealing with "Borderline Personality Organization" in residential treatment centers. It is pointed out that behavioral modification programs are more effective if designed around an analytically-based understanding of the developmental dynamics which contributed to the behavior.


Delta 9-tetrahydrocannibinol: acute efects on defensive and primary-process language. This study examined the effects of delta 9-tetrahydrocannibinol (THC) on defensive, primary-process, and secondary-process language. Four male volunteers provided 5-minute monologues in three conditions: Round 1,placebo; Round 2, 15 mg THC; Round 3, recovery. THC was found to attenuate defensive language behavior (retractors, qualifiers, direct references) and to increase the use of secondary-process (intellectualizing) vocabulary.


Crime and treatment of heroin users.

Crime and treatment of heroin users. In San Antonio serious reported crime increased every year from 1965 through 1969. Then, in 1970, coincident with a marked increase of heroin users in treatment, the crime rate decreased. In three succeeding years while the treatment rate increased, crime decreased. Then in 1974, due to loss of program funds, the treatment rate decreased and the crime rate increased. The changes in the crime rate were due primarily to changes in the theft rate. For the years 1970-1974, treatment and theft had a significant negative correlation. We tentatively attribute part of the changes in the theft rate to changes in the treatment rate.


Parental and peer influences as correlates of problem drinking among high school students. This study was concerned with the relative importance of parental, peer, and demographic variables in predicting problem drinking among young people. A survey of drinking and drinking problems was conducted among 1,439 students in two schools in Ontario. A Multiple Classification Analysis was employed to identify variables with a significant and unique predictive power. It was found that problem drinking is best predicted with situational factors and those directly connected with drinking. Parental and peer variables had little unique predictive power. Problem drinkers were more often male, had their first drinks away from home, and usually drank in cars.


Children of heroin addicts.

Children of heroin addicts. Fourteen Black male, opiate addicts, their wives, and their children were studied intensively using psychiatric interviews and psychological tests. Their 32 children were compared to 37 pediatric clinic children. The children raised in a home where father is an opiate addict function cognitively less well than their father, and the teenagers show earlier and stronger antisocial trends than pediatric clinic peers. On the other hand, there is a surprising absence of other psychopathology that one might expect, taking into consideration the deviant environment from which they come.


The policy culture of drugs: Ritalin, methadone, and the control of deviant behavior. Various concepts are introduced which may be new to most readers of sociological journals. The concepts include policy culture and the medicalization of deviant behavior. Treatment drugs such as methadone and Ritalin are discussed within a framework which utilizes these concepts. It is concluded that the policy culture surrounding the introduction and use of these drugs is highly particularistic. This process in turn tends to produce certain unintended consequences.


Inhalant, marijuana, and alcohol abuse among barrio children and adolescents. Prevalence of inhalant, marijuana, and alcohol abuse was studied in a sample of 457 male and female Mexican-American children and adolescents between the ages of 9 and 17 years. Subjects interviewed resided in four housing projects located in East Los Angeles. All interviews were conducted by adolescents who resided in the same housing projects. Results indicated that compared to a national sample, Mexican-American adolescents were at least 14 times more likely to be currently abusing inhalants. The prevalence rate of marijuana was double the national rate, but the prevalence of alcohol was equal to that found nationally. Reasons for elevated substance abuse rates are explored.


Alcohol abuse by heroin addicts: review of research findings and issues. Although most studies suggest that alcohol abuse by heroin addicts is an important problem, the estimated extent of problem drinking ranges from less than 10 to 50%. The difficulties in assessing the extent of alcohol abuse and comparing results from different studies arise from several methodological issues: the definition of alcohol abuse, population characteristics, type of survey, time frame used, and the reliability and validity of self-reported data. However, data do generally suggest that a reasonable estimate is that at least 20 to 30% of heroin addicts have a past or current drinking problem.


Beliefs among college students on settings and emotions conducive to alcohol and marijuana use. Two hundred college student alcohol and marijuana users rated their desire to drink alcohol and desire to smoke marijuana in or after different settings shown via color photographic slides. Contrary to the compensation hypothesis (that these drugs are used to escape from unpleasant circumstances), desire for both alcohol and marijuana was greater both in and after more pleasant settings than unpleasant ones. These results were more consistent with an amplification hypothesis, that alcohol and marijuana intensify emotions already present.


Attitudinal differences affecting participation in group counseling in outpatient drug treatment centers. Despite the fact that group counseling is emphasized in most drug treatment programs, client resistance to participation in groups is a common problem. Attitudinal differences between inner-city drug treatment clients and a graduate student sample were investigated as a possible factor contributing to resistance. Drug treatment clients were found to have less experience with counseling and therapy, and less understanding of the nature and purpose of the process.


The validity and reliability of self-reported data from heroin addicts: mailed questionnaires compared with face-to-face interviews. Immediately following receipt of their 1-year follow-up mailed questionnaire, 55 former patients from an addiction treatment program were interviewed personally, and a urine sample was collected. Results indicate a high degree of correspondence of self-reported drug use with the urinalysis reports, and moderately high correspondence between the information on employment, school attendance, legal status,and length of heroin run given in the mailed questionnaire with that provided in the personal interview.


Amikacin: in vitro bacteriological studies, levels in human serum, lung and heart tissue, and clinical results. The amikacin sensitivity of bacteria cultured from 3282 clinical cases of mixed type was determined. Gentamicin and amikacin were equally effective against E. coli strains. Amikacin inhibited the growth of more Pseudomonas aeruginosa strains than did gentamicin. Against Gram-positive bacteria gentamicin proved to be more effective. Many of the gentamicin-resistant strains were sensitive to amikacin. Amikacin levels were measured during 21 pulmonary and 14 heart operations, subsequent to a intramuscular administration of 500 mg amikacin. The serum contained 17-20 microgram/ml amikacin, in the intact, inflamed and tumourous parts of removed lung tissue 9, 6 and 6 microgram/g concentrations were detected, respectively, whereas the cardiac auricle and the pericardial fluid contained 3-4 and 2-4 microgram/ml, respectively. These amikacin levels reach or in most cases even exceed the minimal inhibiting concentrations against the bacteria. Therefore, amikacin is excellent for the treatment of respiratory infections, pericarditis and endocarditis caused by Gram-negative, gentamicin-resistant bacteria. Amikacin treatment of 8 patients with grave diseases as well as the successful local administration of amikacin based on the therapy of 55 cases of surgical suppurations is reported.


Effects of intravenous administration of brain phospholipids on gonadotropin release in man. Administration of 600 mg of brain phospholipids i.v. in normal adult volunteers results in a significant decrease of the testosterone circulating levels. This phenomenon is not accompanied by a modification in gonadotropin quantitative levels, but by a reduction in LH pulsatility. This seems to be important for the peripheral biological activity of LH.


The effect of intramuscular pirenzepine on esophageal contractile activity and lower esophageal sphincter pressure under fasting conditions and after a standard meal. A double blind study. In two studies, each on 16 healthy volunteers, the effects of pirenzepine on esophageal and lower esophageal sphincter (LES) contractile activity were studied under double blind conditions. One study was carried out on subjects who had fasted, the other on subjects who had ingested a standard meal. Each subject underwent two experiments, one with i.m. injection of 0.2 mg/kg body weight pirenzepine, the other with an injection of solvent. Heart rate, respiratory rate, electroencephalogram, and reaction time to acoustical stimuli were recorded to control for cardiovascular, respiratory and central nervous effects respectively. Pirenzepine under both fasting and nonfasting conditions caused significant decreases in number, amplitude, and duration of swallow-contractions. LES pressures under both conditions were significantly lower after pirenzepine than after the solvent. Pirenzepine furthermore caused a significant heart rate deceleration and respiratory acceleration, as well as an increased power in the faster Beta- and decreased power in the Alpha-range of the EEG. In conclusion, pirenzepine inhibits esophageal and LES contractile activity and also affects the central nervous system by a direct or indirect mechanism. An application of pirenzepine in hypertensive states of the LES and the esophagus seems possible and deserves further investigation.


Changes of electrolyte excretion, renin activity, angiotensin-II and aldosterone concentrations during administration of 3-amino-1-(3,4-dichloro-a-methyl-benzyl)-2-pyrazolin-5-one (Bay g 2821). After the administration of 40 mg Bay g 2821, a new potent diuretic substance, a significant increase of sodium and water diuresis occurred. There was only a short rise in potassium excretion. In contrast to the sodium and water diuresis no significant increase of renin-activity, angiotensin-II or aldosterone concentration was seen. In spite of the insignificant stimulation of the renin-angiotensin-aldosterone system, a significant increase of correlation occurred between the three components of the renin-angiotensin-aldosterone system.


Oral florid papillomatosis (verrucous carcinoma). 1. Florid Papillomatosis (FP) seems to be another form of verrucous carcinoma. 2. Besides the mouth, FP can be found in the larynx, nose, genitalia, skin, etc. 3. FP would appear to be a carcinoma with a low degree of malignancy, and is locally aggressive. They do not cause generalized metastases and rarely metastasize locally. 4. In the mouth, the lesions, either single or multiple, usually occur in adult men. The most frequent sites are the buccal mucosa and the alveolar-gingival area. They develop on a healthy mucosa, or on preexisting lesions, namely, leukoplakia, atypical lichen, abrasive cheilitis and traumatic ulcers. FP may cause fistulas and jaw destruction. 5. Histologically, three stages can be recognized: type I, with acanthosis and papillomatosis, etc., type II, with the aspect of an in situ carcinoma, and type III, carcinoma-like in aspect but with some characteristics of FP. 6. Ten percent of the cases may develop an anaplastic carcinoma or may become associated with other types of carcinomas in other organs and near the area where the FP appeared. 7. Predisposing factors are the same as those for classical carcinomas (especially smoking and chewing tobacco or betel). FP may develop on preexisting lesions similar to those described for regular carcinomas. No virus has been isolated. Some authors believe FP is a precancerous condition; we think it is a cancer with a low degree of malignancy. 8. Treatment should be initiated with cytostatic drugs, especially methotrexate, followed by electrocoagulation, radium implantation and surgery. If the lesions are small in size, methotrexate is not required. If the lesions are large or there is bone destruction, surgery is the treatment of choice after methotrexate and sometimes high-voltage therapy with 60Co. 9. A cure rate of 75% can be obtained in properly treated cases.


Transient neonatal pustular melanosis.

Transient neonatal pustular melanosis. A Mexican-American boy presented at birth with an extensive eruption consisting of 0.5 to 1.0 cm hyperpigmented macules with a distinct peripheral scale involving primarily the forearms, abdomen and lower back (Fig. 1). Rare intact vesicopustules were also identified. There was an unremarkable prenatal history, and the infant was a product of a normal vaginal delivery. With the exception of the skin lesions and moderate hepatosplenomegaly, the physical examination was normal. Gram stains of the pustules showed numerous neutrophils but no bacteria. Bacterial cultures, of the skin and blood, TORCH screen (toxoplasmosis, rubella, cytomegalic virus, and herpes virus) and a VDRL were negative. On the second day of life, the patient developed several pustules with surrounding erythema consistent with erythema toxicum neonatorum. Wright-stained smears of these lesions showed abundant eosinophils. Hepatosplenomegaly resolved by the third day of life and at the time of discharge only hyperpigmented macules persisted. Follow-up visit six weeks later showed no evidence of skin lesions.


Pemphigus in El Salvador. An eight-year study (1970-1977). Of 23 patients with pemphigus seen between 1970 and 1977, 18 had foliaceus and five had vulgaris (ratio of 3.73:1). The characteristics of pemphigus foliaceus (age of onset, disease among sisters, presence of lesions resistant to corticotherapy) suggest Brazilian pemphigus foliaceus (fogo selvagem).


Kaposi's sarcoma with extensive silent internal involvement. A case of Kaposi's sarcoma is presented in which extensive diagnostic studies failed to detect the cardiac, pulmonary, intestinal and nodal involvement that was found to be present at autopsy.


Patterns and intensity of autofluorescence and its relation to melanin in human epidermis and hair. The skin of 41 patients including 16 blacks, 15 Caucasians, and 10 Hispanics, was observed using a fluorescent microscope. Three patterns of autofluorescence were observed: intercellular, cytoplasmic, and a combination of intercellular and cytoplasmic. The hair of 75 subjects, including 18 Negroes and 55 Caucasians, was observed. Two patterns were found: medullar and at the cortex. Skin form black patients was associated with the cytoplasmic pattern of autofluorescence. Compared to lighter skin, black skin was also significantly associated with increased intensity of autofluorescence, indicating that autofluorescence of the epidermis parallels the clinical degree of pigmentation. In the hair of 75 subjects, similar results were obtained: Negro hair exhibited more fluorescence than Caucasian hair, and darker hair (brown to black) exhibited more fluorescence than lighter hair (blond). This may be related to melanin and it breakdown products.


Ultraviolet phototherapy of uremic pruritus. Repeated exposure to mid-range ultraviolet light (UVB) can dramatically relieve the pruritus associated with uremia. The efficacy of UVB phototherapy in uremic pruritus has been established in a controlled trial; experience with 38 patients suggests that 80 to 90% of those receiving 6 to 8 exposures respond favorably within the treatment period (2 to 5 weeks). Treatment frequency appears not to influence the remission rate, although patients on more intensive schedules experience relief sooner than those treated once weekly. Remissions are long-lasting in many patients, sometimes longer than 2 years. Patients with recurrent pruritus respond to phototherapy at least as well as previously untreated patients and tend to improve more rapidly. UVB phototherapy appears to exert its beneficial effect systemically rather than locally, but its mechanism of action is otherwise unknown.


Tinea pedis masking a Kaposi's sarcoma.

Tinea pedis masking a Kaposi's sarcoma. A 67-year-old white man presented with bilateral blancing erythema and scale of the second through fifth toes extending on to the dorsa and moccasin areas of the feet for two years. The right great toe had subungual debris. No cultures or KOH studies were recorded. A course of tolnaftate cream therapy was initiated. Two years later, the patient returned and complained of no change in his condition. Previously recorded descriptions and diagrams in the medical record confirmed his report. At this time, KOH preparations from the skin and nail were positive for hyphae. He refused to accept medical recommendations for a fungal culture and griseofulvin therapy. He, therefore, was instructed to use miconazole cream twice daily as alternative treatment. One year later, physical examination was unchanged. KOH preparations and fungal cultures of the skin were twice negative. A 4-mm punch skin biopsy specimen of the erythematous patch on the dorsum of the foot was performed. Hematoxylin and eosin-stained sections revealed a proliferating vascular process in the cutis. Many spindle-shaped cells formed vascular slits and endothelial-lined spaces in which there were erythrocytes. No hyphae were seen. One year after the biopsy specimen was taken, the erythema of his feet persists, and a few nonblanching nodules are visible. He declined further studies.


Metronidazole in the treatment of tropical phagedenic ulcers. In an uncontrolled preliminary trial, metronidazole administered orally to 30 patients was effective in resoving tropical phagedenic ulcers within a period of one to two weeks. The efficacy of this drug indicates the important role played by fusospirochetes in causing tropical ulcers.


Treatment of psoriasis with topical nitrogen mustard. With the advent of various new methods of treating psoriasis, it is necessary to remind physicians to consider an agent that is easy to administer, locally effective, relatively inexpensive, not time-consuming and without systemic toxic effects. Nineteen patients were treated with topical nitrogen mustard between 1972 and 1976, and only five developed sufficient contact sensitization to warrant stopping medication.


Leptospirosis in dogs and cats on the Island of Trinidad: West Indies. Confirming previous observations on dog populations in other parts of the world, notably Japan, the Philippine Islands, and some countries in South America, we found that a high percentage of dogs in Trinidad are infected with organisms from many serogroups of Leptospira. Serogroups Canicola and Icterohaemorrhagiae were most commonly found. Ten isolates obtained from 50 kidneys from stray dogs (20% infectivity rate) were typed as portland-vere (six) and canicola (two) of the Canicola serogroup, copenhageni of the Icterohaemorrhagiae serogroup (one), and georgia in the Hebdomadis serogroup (one). To the best of our knowledge, this is the first record of a serotype in the Hebdomadis serogroup being isolated from a dog. A cat isolation was identified as canicola. Serological results showed that 55% or more of stray dogs had been exposed as opposed to only 12.5% of the cats examined. Serogroups Canicola, Icterohaemorrhagiae and Hebdomadis are found most frequently in dogs, cats, mongooses, and man in Trinidad.


Manifestations of sexual and aggressive drives in prelatency, latency, and postlatency children. The purpose of this study was to test Freud's proposition that the sexual drive is dormant during the latency stage. The null hypotheses were that there are no differences in the manifestations of sexual and aggressive drives during the prelatency and latency as well as the latency and postlatency stage groups. Subjects consisted of prelatency (3-5 years), latency (7-9 years), and postlatency (14-16 years) children. There were 180 subjects; 30 boys and 30 girls in each stage group. TAT cards 4, 10, 13MF chosen for sexual content; 3BM, 8BM, and 18GF for aggressive content; and 1, 2, 13B chosen for neutral content were used. Subjects rank ordered these nine cards in order of preference. Chi squares and t-values of Ss' preferences supported the Freudian concept of the latency age. In addition, the data also revealed that the older a child becomes, the less likely he is to show interest in aggressive content material. There was only one significant sex difference. This involved the preference for sexual content material among postlatency boys and girls.


Resocialization problems in a chronic psychiatric department. In this paper we discuss the problems we encountered in our effort of resocialization in a chronic psychiatric Department. Resocialization of chronic mental patients is a complicated and time-consuming task. Good staff relationships are absolutely necessary, otherwise the whole resocialization program could be jeopardized. Changes must take place slowly and be fully absorbed by the ward's life before new ones are introduced. There is always the possibility that the nursing staff will resist any change. This is due to the notion that the more independent a patient is the more dangerous he becomes, and to the very fact that resocialization means some loss of the nurses' authority.


Ethnic differences in expressions of shame feeling by mothers of severely handicapped children. Shame on the part of parents of mentally handicapped children has pronounced effects on child-rearing practices. The aim of this study was to compare expressions of shame of different ethnic groups in Israel. The attitudes of 23 Western mothers and 26 Eastern mothers towards their moderately and severely retarded children were studied. Significant differences (p less than 0.05-p less than 0.01) were found, suggesting that the Eastern mothers strongly expressed their shame, whereas the Western mothers 'felt ashamed' to express it at all. The Western mothers felt that the social norms that reject feelings of shame and their own personal feelings of embarrassment were in conflict.


University students and mental health. Canada, Britain and Singapore. There are many crucial determinants of the individual outcome and benefit of a university education including the stressful interplay of cultural and socioeconomic factors which are of growing importance in the inflationary 1970's. An epidemiological study of university students from 1969-1972 in Canada, 1973-1974 in Britain, and 1975 in Singapore, attempted to identify stresses leading to mental ill-health in these students. Singapore was chosen as an example of a culture bridging the developed Northern and developing Southern nations of the world. Cultural differences affecting the results of the study are discussed as is the role of social change.


Factors in the drug involvement of inner city junior high school youths: a discriminant analysis. Data from a survey of youths attending an inner city junior high school were examined to learn how their demographic characteristics, socio-cultural experiences and the drug use existing among their neighbourhood peers related to their involvement with substances. Discriminant analysis uncovered two important factors that were associated with the youths' drug taking: (1) a street scene, social/recreational drug use factor and (2) a cluster reflecting friends' use of alcohol/marijuana and other drugs. The implications of these results for drug abuse prevention programming are explored.


Lens gap junctions: a structural hypothesis for nonregulated low-resistance intercellular pathways. Structural evidence is presented which suggests that gap junctions between lens fibers are adapted to remain in a low-resistance physiological state, under conditions which switch gap junctions in other tissues to a high-resistance state. The lens gap junction subunits (connexons) do not crystallize in the membrane plane in response to fixation, anoxia, lens damage, or homogenization and isolation. Rapid freezing experiments (Raviola et al.) suggest connexon resistance. Freshly homogenized liver cytoplasm does not contain an assayable factor which can crystallize connexons in lens gap junctions. Polyacrylamide gel electrophoresis of enrighed preparations of isolated lens junctions reveals a 27 +/- 2 kilodalton principal polypeptide which is similar in electrophoretic mobility to one of the principal polypeptides resolved in gels of isolated hepatocyte gap junctions. These results indicate that the whole lens may be extremely vulnerable to surface injury, perhaps even to injury of a single lens fiber.


Histological and electron microscopic studies of experimental herpetic keratitis in the rabbit. Histological and electron microscopic observations, together with virus cultures, were made in the eyes of 50 New Zealand white rabbits which received bilateral intrastromal inoculation with the RE strain of herpes simplex virus. Virus cultures of whole corneas were positive for the first 2 weeks following inoculation, but were consisently negative thereafter. An inflammatory response to HSV infection, consisting of polymorphonuclear leukocytes and lymphocytes, was seen in the limbus within 7 hours after inoculation of the cornea. A massive accumulation of lymphocytes and plasma cells appeared in the limbus, suggesting that the limbus may behave as a lymphoid tissue, where differentiation and maturation of lymphoid cells occur as they acquire immunocompetence. Neovascularization of the cornea was associated with a heavy infiltration of the surrounding stroma with polymorphonuclear leukocytes, as well as numerous plasma cells and a few lymphocytes and macrophages. Numerous abnormal, pleomorphic keratocytes were found in the stroma. Lymphocytes were frequently found closely adhering to these abnormal keratocytes, suggesting a T-cell attack on a target cell. A model which describes the mechanism by which herpes virus infection leads to corneal scarring is suggested.


Experimental traumatic cataract. I. A quantitative microradiographic study. Traumatic cataract was induced in rat and rabbit. The progression of the posterior subcapsular cataract and the wound healing were followed by quantitative microradiography. This method makes it possible to determine the dry mass content and to calculate the refractive indices in the lens. In the injured rat lens a reduced dry mass concentration was determined in both the wound region and the posterior subcapsular region immediately after trauma. During the first week a subcapsular opacity was observed to enlarge. This opacification always corresponded to a reduction in the subcapsular concentration of dry mass. This reduced content of dry material, mainly consisting of protein, is interpreted as a hydration of the subcapsular cortex. In the rabbit lens a much larger injury had to be made in order to cause any posterior cataract. The same reduction in the content of dry material was determined in regions corresponding to opacitices but the reduction was less pronounced than in the rat lens. The border zones between different concentrations of dry mass are suggested to be the main sources of scattered light in the traumatic cataract.


Experimental traumatic cataract. II. A transmission electron microscopy and extracellular tracer study. Lens changes caused by injury to the anterior part of the lens were studied with Procion yellow as an extracellular tracer and by transmission electron microscopy at different time intervals after trauma. Both rats and rabbits were used. The findings were related to the slit-lamp appearance of the wounded lenses. In the rat lens a posterior subcapsular cataract developed within the first hour after trauma. Within 1 hr after injury the fluorescent tracer was seen at the wound but was also conspicuous at the posterior pole. Swelling of lens fiber cells and the formation of large syncytical aggregates were found as the posterior opacity enlarged. These changes reached the anterior subcapsular cortex via the equatorial cortex after about 1 month. In the rabbit lens a slight cellular swelling was seen in the subcapsular cortex. Only in one of 15 lenses a posterior subcapsular opacity developed after about 1 week in spite of a large wound. The uptake of Procion yellow was most prominent in the wound area and was never observed at the posterior pole. In both species, no further penetration of the dye occurred through the wound after the epithelium, by regeneration, had sealed the wound. The importance of epithelial wound sealing and that of a restored cellular barrier at the posterior pole are discussed as well as the significance of these factors in the cataract progression.


Immunopathology of Toxocara canis and Ascaris suum infections of the eye: the role of the eosinophil. Intravitreal infection of guinea pigs with second-stage larvae of Toxocara canis and second- and fourth-stage larvae of Ascaris suum induced intraocular IgE antibodies and a dense eosinophil infiltration in the anterior chamber and throughout the uveal tract. The eosinophil infiltrate began within 1 day after infection and persisted for as long as 51 days. By day 12 after intravitreal infection, the injected ascarid larvae were surrounded by granulomas which consisted almost entirely of eosinophils. Firm adherence of eosinophils to the parasite cuticle, morphologic alterations and degranulation of eosinophils with the deposition of free eosinophil granules on the parasite surfaces, and ingestion of eosinophils and eosinophil granules by the parasite larvae also were observed. Intravitreal injectionof a soluble antigen derived from third-stage A. suum molting to the fourth-stage in defined media in vitro also induced intraocular IgE antibody and a diffuse ocular eosinophil infiltrate. Dense eosinophil infiltration of the choroid, not immediately adjacent to a parasite larva, was accompanied by destruction of the lverlying outer retina, with cystic changes in the retina and between the retina and the choroid. Few eosinophils were observed within the retina, and the retinal destruction may be the result of direct toxic action of constituents of the choroidal eosinophils. Evidence which indicates that the eosinophil is the principal effector cell in immunity to helminth infections and is cytotoxic for the parasites, possible mechanisms for the induction of the ocular eosinophil infiltrates, and evidence for autotoxicity by eosinophils are briefly reviewed, and the potential roles of the eosinophil in the ocular response to helminth parasites are discussed.


Retinal vessels: proliferation of endothelium in vitro. Tissue culture of retinal vessels from fetal calf eyes produced colonies of endothelium, pericytes, and smooth muscle. Identification of endothelial cells was based upon culture morphology, [3H]thymidine labeling of isolated vessels, and factor VIII immunofluorescence. Thimerosal added to the culture medium destroyed pericytes and muscle cells, leaving only endothelial cell colonies in the primary cultures. This tissue culture system may be useful in the study of retinal vascular cell biochemistry and pathophysiology.


In vitro proliferation of endothelial cells from kitten retinal capillaries. When microvessel (predominantly capillary) fragments freshly isolated from the retinas of young kittens are incubated in tissue culture medium, we observe the slow outgrowth of cells that appear to be derived from the capillary endothelium. The cells grow as a monolayer with a tightly packed, mosaic-like array. Electron microscopy of these cells reveals "tight junctions" (zonulae occludentes) resembling those found in the endothelium of intact capillaries. The availability of in vitro preparations of retinal capillary endothelial cells should facilitate investigations of the causes of abnormal endothelial cell proliferation in various diseases and of factors that modify cell junctions and capillary permeability in the retina. Since we have previously demonstrated proliferation in culture of intramural pericytes ("mural cells") from retinal capillaries, it should now be possible to carry out compratative studies of biochemical and functional properties of retinal capillary pericytes and endothelial cells.


Tapetum disorganization in taurine-depleted cats. A severe disorganization of the lattice arrangement of tapetal rods occurs in cats nutritionally deprived of taurine. This is the first reported example of a nutritionally related degeneration of tapetal cells. The tapetal cell degeneration, along with the previously noted photoreceptor degeneration in taurine-depleted cats, suggests that taurine plays a vital role in maintaining the structural integrity of some biological structures. The visual evoked potentials were severely reduced in taurine-depleted cats as were the electroretinogram responses, as previously noted, indicating that they are deficient in light processing. These results also emphasize the importance of dietary taurine for the maintenance of normal structure and function of the eye, at least in the cat.


Protein in rabbit lacrimal gland fluid.

Protein in rabbit lacrimal gland fluid. A variety of proteins have been identified in tears, which are composed of secretions from all the orbital glands. It has been assumed that the lacrimal gland was the source of these proteins because there is indirect evidence that the lacrimal gland can secrete protein in response to cholinergic stimulation. In the present study, the concentration of protein was determined in lacrimal gland fluid, i.e., the fluid collected directly from the main excretory duct of the lacrimal gland, uncontaminated by secretions from the other orbital glands. The concentration of protein in the lacrimal gland fluid was higher than that in plasma at lacrimal gland fluid flow rates between 2 and 10 microliter/min, but it was the same as plasma at flow rates slower than 2 microliter/min and faster than 10 microliter/min.