Diagnostic value of female genital malignant tumors by using 111In-bleomycin scintigraphy. In order to know if it is possible to objectively decide the extent of infiltration of female genital malignant tumors into parametrium by using 111In-bleomycin scintigraphy, a fundamental and clinical investigation was made. The result was as follows; 1) The radiochemical purity and stability of 111In-BLM were comparatively unchangeable. When this complex was kept at room temperature for a week, there was not more than 2% of the free 111In. 2) As to blood clearance, when the blood radioactivity of 111In-BLM 5 minutes after the injection was counted as 100%, about 80% of the radioactivity was cleared from the blood in 48 hours. Over 50% of the radioactivity was excreted into the urine in 48 hours. 3) Of 29 cases of female genital malignant tumors, 23 cases (79%) showed positive images. Therefore 111In-BLM was found to be one of the suitable radiopharmaceuticals for the diagnosis of female genital malignant tumors. 4) 111In-BLM scintigraphy was of great use for deciding the extent of the invasion of carcinoma cervicis uteri into parametrium and for the search of metastasis.


Autofluorescence and fluorochrome-staining of Hassall's bodies in rabbits. The phenomenon of autofluorescence is reported in the thymus of rabbits; besides reticular epithelial cells, Hassall's bodies also emit autofluorescence. The staining of thymic corpuscle by fluorescein isothiocyanate is also described. This staining is important not only because FITC is commonly used in immunofluorescence and may lead to misinterpretations due to false-positive results, but also for it permits a good precision in the observation of the relationship between Hassall's bodies and reticular epithelial cells. Some hypothesis are set up to explain the autofluorescence, and the fluorochromization of Hassall's bodies by acid fluorochromes.


Binding activity regulation of rabbit skeletal muscle adenosine 3'-5'-monophosphate-dependent protein kinases. A cAMP-dependent protein kinase has been isolated from rabbit muscle and purified. The affinity constant of the enzyme for the nucleotide is Ka = 9.3 X 10(-9) M, with a Vmax = 0.013 X 10(12) moles bound cAMP/1 microgram protein. The influence exerted by different factors is studied: a) Inhibitor (I) of kinase activity: increases the binding capacity for cAMP, by percentages which depend on the amount of I. In the presence of inhibitor (120 microgram/100 microliter) the affinity constant is Ka = 4.1 X 10(-9) M, without change in Vmax. b) Effect of pH: it has a complex influence over binding, being also regulated by cAMP concentration. The positive effect on binding of ionic and bovine serum albumin concentrations, and the negative effect of enzyme preincubation before additions of (H3) cAMP, have also been studied. The importance of these effectors to obtain a high degree of sensitivity in the binding protein method has been assertained.


Staining of glycosaminoglycans of intervertebral disc tissue. Intervertebral discs of six species were stained with Alcian blue and PAS methods to identify glycosaminoglycans. The polyanions are most concentrated in 'ring-like' pericellular areas and in material lying between individual lamellae and bundles of collagen. A slight increase occurs early in life and towards the disc centre. The concentration of glycosaminoglycans cannot be correlated with species which are known to suffer from clinical disc disease, though there appears to be a higher concentration in the discs of the cat and dog than in other species studied.


[Insensitivity to pain: electrophysiological study of the nociceptive reflex. Influence of naloxone (author's transl)]. Electrophysiological studies of the nociceptive reflex (R3) were carried out in eight normal subjects, and one patient with congenital insensitivity to pain, in order to compare the effects of naloxone and a placebo. No significant variation in the reflex threshold was seen in the normal subjects. Two electrophysiological abnormalities were observed in the patient: a 350 per cent spontaneous elevation in the R3 threshold compared to the control group; a rapid and large drop (67 per cent) in the threshold lasting for about ten minutes after the injection of Naloxone. These results suggest that in this particular case the insensitivity to pain could be related to the permanent hyperactivity of a morphine-like inhibitory system.


Gluten-sensitive enteropathy: genetic analysis and organ culture study in 35 families. The genetic marker histocompatibility antigen HLA-B8 is present in 80% of patients with gluten-sensitive enteropathy (GSE). We studied 35 families with at least one affected member to determine whether an HLA-region gene alone could determine susceptibility to GSE. The incidence of HLA-B8 in the patients was 69% vs 22% for normals (P less than 0.001). The incidence of GSE in HLA-genotype-identical siblings of patients was only 8%, and in HLA-B8-haplotype-identical siblings and parents of patients was only 14% and 5%, respectively. In addition, intestinal biopsies of HLA-identical or partially identical relatives of patients were studied in an in vitro organ culture system capable of detecting gluten sensitivity in subjects ingesting a normal diet. The results confirmed the low incidence of gluten sensitivity in these individuals. The organ culture system could not differentiate mucosa obtained from unaffected parents or siblings of patients with GSE (who presumably carry the HLA-associated genetic information) from mucosa obtained from normals. We conclude that the genetic material inherited with HLA-B8 alone is not sufficient to produce clinical or subclinical disease. Other genetic and environmental factors appear to be important for disease pathogenesis.


The recovery of mice from influenza A virus infection: adoptive transfer of immunity with influenza virus-specific cytotoxic T lymphocytes recognizing a common virion antigen. Mice inoculated intranasally with infectious influenza virus of a given A strain were adoptively transferred 24 h later with preparations of secondary influenza virus-immune T cells generated either in vitro or entirely in vivo. The immune cells were raised during infection with homologous or heterologous A strain influenza viruses or with a type B virus. The greatest antiviral effect, measured by reduction in lung virus level of recipient mice, occurred if homologous viruses were used. Sharing of haemagglutinin specificity was shown to be important, but significant antiviral activity was still expressed if neither haemagglutinin nor neuraminidase antigenic specificities were shared. The antiviral effect was type-specific. Adoptive transfer of type A influenza immune T cells did not express antiviral activity against type B virus, and vice versa. On the basis of earlier work, the effector population in the transferred cells was cytotoxic T cells (Tc). Intranasal reinfection of mice with a heterologous type A virus sharing neither haemagglutinin nor neuraminidase antigenic specificity with the first infecting virus induced enhanced and earlier production of cross-reactive Tc against type A influenza viruses. This was paralleled by significantly lower virus levels in the lungs. The results of this work demonstrate heterotypic cell-mediated immunity in influenza virus infection in mice.


The specificity of radiostaining in crossed radioimmunoelectrophoresis. The major allergen from codfish (DS 22) was used to study specific and non-specific radiostaining in crossed radioimmunoelectrophoresis (CRIE). Various modifications of CRIE experiments were performed including experiments where immunoprecipitates in agarose were transferred to test tubes and the radioactivity was measured in a gammacounter. The degree of non-specific binding of IgE and 125 I-anti-IgE  to the percipitates was low. A linear relation was found between the amount of human serum IgE antibody used in CRIE and the degree of radiostaining obtained. Increasing the amount of DS 22 in the precipitates from 0.31 to 2.5 microgram resulted in a moderate increase in the uptake of 125 I-anti-IgE, whereas further increase of the amount of DS 22 (5--10 microgram) resulted in reduced uptake of isotope. Serum from a patient containing IgE antibodies to rabbit serum gave rise to radiostaining over the entire antibody-containing gel area, and it is suggested that such human sera be avoided when using CRIE.


Are doctors able to assess prostatic size? The between-observer variation was evaluated through three independent estimates of preoperative prostatic weight in each of 40 patients. Error in the estimates was of considerable magnitude irrespective of size of prostates. Experienced urologists did not attain a more reliable estimate than unexperienced doctors. Only about 2/3 of estimates were correct within a range of +/- 25 g. However, there was a statistically significant correlation between estimated and actual operative prostatic weight.


Intravesical pressure during transurethral resection using Iglesias resectoscope with continuous irrigation and suction. Intravesical pressure was studied in 20 patients during transurethral resection (TUR) of the prostate using the Iglesias resectoscope with continuous irrigation and suction. The suction pressure (50 cm H20) was considerably lower than that suggested by Iglesias. The amount of irrigant was thereby appreciably diminished and blocking of the outlet system was avoided. The intravesical pressure averaged 35 cm H20 during resection, which is less than in conventional resection, and 15 cm during evacuation of tissue chips. Signs of TUR syndrome were not seen. We consider the new resectoscope to be a considerable improvement for TUR.


N-acetyl gramicidin: single-channel properties and implications for channel structure. Substitution of a methyl group for the N-terminal hydrogen of gramicidin greatly increased the rate of dissociation of conductive channels in lipid bilayer membranes. The finding of short lifetimes for conductive channels, comparable to those seen for the neuromuscular junction, lends support to the head-to-head dimer structure for the conductive channel.


Membrane glycolipids: regional synthesis and axonal transport in a single identified neuron of Aplysia californica. Glycolipids moving along an identified axon Aplysia californica were synthesized and incorporated into intracytoplasmic membranes solely in the perikaryon: direct injection of tritiated sugar into the axon revealed no local synthesis or exchange. There was no indication for transfer into axoplasm from glia. Insertion of glycolipids into nascent membranes occurs coordinately with insertion of protein components in the cell body.


Teaching psychiatry in a new medical school: a multimedia approach. As a developing department in a new medical school, we were able to improve our curriculum by using a multimedia approach to teaching psychiatry. We relied heavily on a programmed self-instructional text with videotaped clinical examples (PLS), learning objectives, formal classroom presentations, small group discussions, self-assessment exercises, an affective approach to the patient-doctor relationship using role-playing and videotaped patient vignettes, and finally live patient interviews. We believe we have been able to present the widely agreed upon content in the basic science years, using a wide variety of teaching materials and technics which maintain the interest of most students.


Erroneous diagnosis of meningitis due to false-positive gram stains. During a two-month period, 6% of Gram stains of predominantly CSF specimens revealed gram-negative bacilli with no growth. The source of the false-positive Gram stain results was an alcohol storage bath from which slides were taken and flamed to remove residual alcohol. All 11 patients in the outbreak had further diagnostic tests or changes in therapy. In the laboratory, false-positive slides could be created by contaminating a slide bath with 10(5) bacilli/ml, flame drying, and staining. In addition, contaminated crystal violet caused a false-positive result when applied to a warm but not to a cool slide. To prevent false-positive Gram stain results, the storage of slides in alcohol baths should be abandoned, slides should not be flamed to remove alcohol, and specimens should be Gram-stained only when the heat-fixed slide has thoroughly cooled.


Open-heart palliative surgery for pulmonary atresia with ventricular septal defect and hypoplastic pulmonary arteries. The surgical management of pulmonary atresia with ventricular septal defect (VSD) and hypoplastic pulmonary arteries poses difficult problems. Adequate palliation was achieved in two such patients by restoring continuity between the right ventricle and the pulmonary arteries by means of a woven Dacron patch. The VSD was left unrepaired. Angiography performed one month after operation showed the reconstructed pulmonary outflow tract to be widely patent and the pulmonary arteries to be enlarged. This approach may allow subsequent total correction by closure of the VSD in these hopeless patients.


Transitivity of response in the mixed lymphocyte culture test. We present a model of mixed lymphocyte culture (MLC) response which assumes one specificity per locus. It also assumes that an animal A will fail to stimulate animal B if, and only if, the set of specificities possessed by A is a subset of the set of specificities in B. The last assumption implies that non-stimulation is transitive; that is, if A does not stimulate B, and B does not stimulate C, then A will not stimulate C. The inclusion of antigenic sets can be used to partially order the animals in a hierarchy. Partial ordering can detect multiple lymphocyte-defined (LD) loci with relative ease; it indicates the number of antigens present in particular individuals; and it detects exceptions to the rule of transitivity which may expose immune response genes, minor loci, or other mechanisms that affect MLC response. This analytical procedure is most useful when testing half-sib families or hybrids sharing a common parental strain. We have applied this procedure to the MLC in cattle half-sib families and found that the data strongly support the existence of at least four LD loci.


HLA--D typing with homozygous cells identified in an American indigenous isolate. I. Population studies. Lymphocytes from six individuals homozygous for their HLA--A, --B, --C and --D loci belonging to an American indigenous group, the Warao, have been used as typing cells to detect HLA--D determinants in 121 donors from the same indigenous isolate and in 71 donors of mixed ethnic origin living in Venezuela. Two determinants responsible for strong proliferation in mixed lymphocyte cultures have thus been identified. Four HLA--A2, B5 cells (r values between 0l72 and 0.57) identify a determinant provisionally called LD5a showing a gene frequency of 0.30 among the Warao and of 0.09 among the population of mixed ethnic origin. The nearest B locus antigen to this new specificity among the Warao is HLA--B5 (r value = 0.20). A second determinant identified by two HLA--A2, B15 sisters (r values of 0.71) shows a gene frequency of 0.15 among the Warao and of 0.03 among the mixed population. The latter is related to Dw8 as shown by results of the VI and VII Histocompatibility Workshops, and is weakly associated (r value of 0.28) to HLA--B15 among the American indigenous population tested.


HLA antigens in patients with psoriasis. Tissue typing was performed on lymphocytes of 46 Jewish patients with psoriasis vulgaris. HLA B13, B17, B37 and Cw6 were found increased. It is suggested that the increase in the B and C locus antigens is inter-related and may determine the genetic predisposition for the development of this disease.


HLA-antigen frequencies in patients with a Plummer-Vinson stricture. Factors of individual susceptibility seem to be involved in the occurrence of Plummer-Vinson stricture, which is a permanent stricture of the cervical esophagus associated with long continued iron deficiency. Fifty female patients with Plummer-Vinson stricture were HLA typed and the antigen frequencies were compared with those of 75 female blood donors from the same geographic area and of the same race. A comparison was also made with the HLA antigen frequencies of a group of 200 blood donors (75 female and 125 male). There were no statistically significant differences in the HLA antigen distributions of the three groups.


The operation of immunological networks in Graves' disease. Association between Graves' disease and HLA--B8 has been previously documented, as have been associations between 1 gG heavy chain allotype markers (Gm). We found a significant increase in the phenotype fnb/fb (ie. positivity for fb) in patients with Graves' disease compared to controls, raising the possibility of allotypic restriction of thyroid stimulating antibodies thought to be causally related to the disease. The influence of fb on the susceptibility to Graves' disease was found to be independent of HLA--B8 status suggesting that the immunological network operated by the Histocompatibility-linked genes is independent of that centered around IgG allotypes. It is postulated that, whereas the former genes determine the level of helper T lymphocyte function in the production of thyroid stimulating antibodies in Graves' disease, a person who also happens to carry the Gm marker fb would be assured of the production of IgG antibodies with thyroid stimulatory activity.


The association of HLA with juvenile diabetes mellitus in Newfoundland. In view of the reported variation in the association between HLA antigens and Juvenile Diabetes Mellitus (J.D.M.) among different Caucasian populations, we have undertaken a study of these antigens among 44 Caucasian Newfoundlanders and 135 matched controls. We have also studied the allotypic markers for Immunoglobulin G (Gm) and variants of C3 among 36 of these patients. We found that both HLA--B8 and B15 were increased among the patient group, resulting in a relative risk of 3.9 and 4.4 respectively. While these values are the highest to be described for J.D.M. among Caucasians, and fell outside the 95% confidence intervals for the combined relative risk calculated from published series, it is still possible that they can be accounted for by sampling. The combination of the two antigens increased the relative risk for J.D.M. in an additive fashion. Additionally, we also found that the combination of HLA B8 and B18, but not B15 and B18, also appear to act in an additive manner. The incidence of Gm allotypes and variants of C3 were not different in the J.D.M. group from those observed among controls.


HLA phenotype frequencies in individuals with cleft lip and/or cleft palate. The HLA types of 133 patients with cleft lip and/or cleft palate were determined. Caucasian patients with isolated cleft palate showed a possible association with HLA. Ten of 11 male patients had HLA--A2 as compared to one out of eight female patients (P less than 0.005). Caucasian males with cleft lip and cleft palate had a slight increased frequency of HLA--Aw24 (P = 0.07) and Mexican-American males with cleft lip and/or cleft palate showed an increase of antigen HLA-A28 (P = 0.07), though neither were statistically significant. Females with cleft lip and/or cleft palate from either racial group had no differences from the controls. The serum from 90 mothers of patients with cleft lip and/or cleft palate were reacted against their child's lymphocytes. Of these crossmatch tests, 12% were found to be positive. These preliminary results suggest that male patients with isolated cleft palate are worthy of further studies with respect of HLA associations.


Absorption, elution and blocking studies with the complex antiserum ST. Quantitative absorptions and elutions were performed with the broadly reactive serum ST. The major component of this serum is directed towards the B-locus antigens Bw35, B5, and B18, which comprise the 4c CREG. A second component contains lower titered antibodies which react with members of the 4c CREG, but also appear to detect qualitative and quantitative variations associated with B-locus specificities, B15, B17 and B8. Blocking studies indicate that these antibodies do not bind to the same sites on B8 cells as well-defined anti-B8 sera. These findings are discussed in terms of public specificities at the B-locus or a new specificity at a closely linked locus.


Use of microimmobilization and microagglutination assays for attempted detection of HLA antigens and beta2 microglobulin on human sperm. Microtechniques for detecting sperm agglutinating and immobilizing antibodies are described. These assays are proved to be useful in the study of anti-sperm antibodies in the sera of vaseectomized men and the serum of a rhesus monkey immunized with human sperm. However, using various antisera against beta2 microglobulin and HLA region antigens, including Ia antigens, in these assays, very little, if any, activity was found against sperm. Absorption and inhibition tests also could not show a significant amount of these antigens on sperm. Although no HLA region antigens could be detected in the seminal plasma by inhibition tests, a large amount of beta2 microglobulin was found. It is suggested that some beta2 microglobulin could be adsorbed onto sperm, since mouse sperm was shown to pick up beta2 microglobulin after incubation with human seminal plasma. The maximum amounts of HLA region antigens and beta2 microglobulin in the seminal plasma are estimated.


Increased HLA-B heterozygosity with age. 427 healthy individuals ranging in age from 16 to 101 years were tested for HLA-A and -B antigens. No significant differences were found for any particular antigen according to the age of the individual. However, a significant trend of increasing frequency with age was found for individuals possessing two detectable HLA-B antigens. An apparent trend of increasing frequencies for individuals possessing four HLA-A and -B antigens was not significant. These results concur with those of some previously published studies.


RhLA complex of Rhesus monkeys. X. Implications of the association between D and Ia1 locus antigens. A high association has been found between D-locus determinants defined by cellular methods (typing cells) and the serologically defined B cell or Ia antigens controlled by the Ia1 locus. Data from recombinant offspring in two rhesus families place the Ia1 locus within RhLA, in the close vicinity of the D or major MLC locus. In fact, identity between the products of those two loci cannot be excluded. Further, it was shown that cells proven to be homozygous for Ia1 antigens, are nearly always typing cells (and therefore homozygous for D-locus determinants) and, conversely, that proven typing cells carry only a single Ia1 antigen and are thus probably homozygous for Ia1 products. In addition, it could be demonstrated that matching for Ia1 antigens greatly facilitates the detection of unrelated individuvals who are mutually non-reactive in MLC. This "predictive value" of Ia1 matching has important implications for the selection of optimal donors for organ transplantation.


A haplotype study of HLA complex with special reference to the HLA-DR series and to Bf. C2 and glyoxalase I polymorphisms. Fifty-three French families were typed for alleles at seven loci of the HLA complex (HLA-A, -B, -C, -DR, -Bf, -C2 and -GLO) and 212 haplotypes were demonstrated. Eleven recombinations were observed (two A/B, two A/C, two B/Bf, one Bf/D and four D/GLO). The linkage disequilibrium was calculated not only between two alleles (delta) but between three, four...seven alleles (D). In order to compare the intensity of D values in the various haplotypes, the influence of the differences in gene frequencies was eliminated by the introduction of the standardized Ds (Ds = D/D max). The number of haplotypes in disequilibrium is relatively limited since most of the significant Ds involved about 17 haplotypes. For some haplotypes, the disequilibrium covered the whole distance from A to GLO but the stronger disequilibrium concerns the C to Bf or C to DR segment. Three hypotheses (isolation, admixture of population and selection) concerning the formation and maintenance of the disequilibria are discussed.


Isolation and culture of pulmonary artery endothelial cells. It has become increasingly evident that endothelial cells function as far more than a mechanical barrier between blood and parenchyma. Endothelial cells from one vesicular bed are known to differ structurally from those of another, and it has been suggested that they may differ functionally. Further to test the hypothesis that endothelial cells from one site may differ in terms of function from those of another site, it is necessary to test endothelium from various source after having obtained these cells in pure, well-characterized cultures. To facilitate such studies, we herein describe in detail means for the isolation, culture and characterization of endothelial cells from calf pulmonary artery. These cells may be of major interest in terms of specific metabolic activities as it has become evident that the lungs play a prominent role in determining the hormonal composition of systemic arterial blood.


A new preparation method for several histopathological examinations on a single block. A new method of specimen preparation is described permitting several studies such as routine staining, histochemistry, enzyme histochemistry, immunohistochemistry, and electron microscopy on a single block of biopsy specimens. Tissues are immersed in the fixative, which primarily stabilizes carbohydrate moieties, and embedded in the mixture of JB-4, methylmethacrylate and divinylbenzene. The resin is polymerized at 4 C. Thin sections (1-2 microns) are obtained with a sliding microtome, and ultrathin sections (60-90 millimicrons) with a ultramicrotome. The sections are stained directly with various conventional procedures without removing the embedding resin. This preparation method offers a potentially useful tool for histopathological studies on biopsy specimens.


Myelin impregnation: an improved Golgi-Cox modification. Optic tecta of goldfish were coated with egg yolk and immersed for only one week in one of the following impregnation fluids: a) Solution A + B; A = 1 g K2Cr2O7 and 1 g HgCl2 boiled for 15 min in 85 ml distilled water and allowed to cool; B = 0.8 g K2Cr2O4 and 0.5 g KWO4 dissolved in 20 ml distilled water. b) Solution A + B two volumes diluted with boiled distilled water. c) Solution A + B four volumes diluted with boiled distilled water. Each tectum was immersed 6 hr in 100 ml distilled water containing 0.5 g LiOH and 15 g KNO3, washed 18 hr in 500 ml 0.2% acetic acid, dehydrated with ethanol, and embedded in low viscosity nitro cellulose. Sections were cut at 100 micron with a rotary microtome after clearing with cedarwood oil. Methods b) and c) have two advantages compared with method a), the original Golgi-Cox method. First, more cells are impregnated, especially in the layers extending 200-400 micron below the surface, and dendrites as well as unmyelinated axons are well impregnated. Second, myelin sheaths are impregnated and can be recognized by their peculiar chain-like appearance. The described Golgi-Cox modification offers an appropriate method to study the morphology of superficially located nervous tissue.


Methods for removing uranyl acetate precipitate from ultrathin sections. Precipitate resulting from en bloc staining with uranyl acetate was removed by treating sections with 15% oxalic acid in 50% methanol for 30 minutes at 40 C. Precipitate resulting from poststaining sections with hot uranyl acetate was removed by rinsing sections in 0.25-0.50% aqueous oxalic acid for 10-15 seconds at room temperature. Rinsing sections for longer than 30 seconds removed uranyl precipitate and also destained the sections. These procedures did not damage the embedding medium or cellular detail.


Aldehyde fuchsin staining, direct or after oxidation: problems and remedies, with special reference to human pancreatic B cells, pituitaries, and elastic fibers. Successful production of aldehyde fuchsin (AF) having the unique properties described by Gomori depends on each of many critical variables. AF made from basic fuchsins which contain mainly rosanilin (C.I. 42510) do not stain properly-fixed pancreatic B cells, pituitary basophils, or elastic fibers in unoxidized sections. AF made from basic fuchsins containing mainly pararosanilin (C.I. 42500) stains these entities strongly. Substances stained by AF without oxidation fall into two classes: 1) nonacidic peptides and proteins, most of which contain half-cystines, and 2) polyanions, particularly when sulfated. Group 2 substances stain rapidly, Group 1 substances stain slowly. Many modifications of aldehyde fuchsin have been described. Modified aldehyde fuchsins (MAFs) differ in the kind of aldehyde and in the amount of aldehyde and hydrochloric acid used in their formulation; they differ also in the temperature and duration of the ripening necessary before they can be used. If microsections are first oxidized by acid permanganate or other oxidant, MAF staining of pancreatic B cells, pituitary basophils and other substances containing cystines is speeded and intensified. Most modified methods prescribe oxidation, but the author's does not. The chemical basis, final result and potential side-reactions of oxidation methods (OXMAF) differ from those of direct methods (DIMAF) such as the author's. DIMAF staining is slower but inherently simpler and less destructive. The time required for optimal staining with DIMAF depends on the potency of the stain, which in turn depends on how the stain was made and its age. Detection of DIMAF--reactive peptides and proteins may be hampered by the strong staining of polyanions. This can be remedied if the polyanions are first stained with Alcian blue (AB) or other durable basic dye of contrasting color resistant to acid ethanol. Experiences with the AB-DIMAF staining of pancreatic B cells, pituitaries and elastic fibers in formalin-fixed human tissues are detailed. Proper control of the variables which affect MAF will insure useful and reliable results either directly or after oxidation. Authors and editors are urged to be more careful hereafter to distinguish the results of DIMAF from those of OXMAF methods. Published reports should always specify the parameters that affect the properties of MAF. In OXMAF methods the steps intervening between oxidation and staining should be spelled out. Such care should help dispel the confusion and uncertainty which cloud the use and reputation of aldehyde fuchsin at present. This unique dye deserves wider and wiser use.


A carmine-Giemsa staining technic for meiotic prophase chromosomes of the genus Beta L. For a detailed study of chromosome morphology in meiotic prophase stages of Beta species, a special double staining technic has been developed. It consists of combined maceration-staining in an ethanol-hydrochloric acid-carmine mixture followed by poststaining of the squashed material in a diluted Giemsa solution. The technic yields well-spread prophase meiotic nuclei showing detailed structures both in weaker stained chromosome segments and in threadlike chromatin structures. This technic proved to be especially favorable for stages which are difficult to interpret, such as pachytene, schizotene and diffuse stages.


The staining of acid fast bacilli in sections of glycol methacrylate embedded tissues. Acid-fast bacilli can be stained in tissue embedded in glycol methacrylate. Modification of the Ziehl-Neelsen technique, along with changes in the formula of the plastic embedding medium, allow production of 1 to 2 micron sections which retain their integrity throughout the procedure, and within which the bacilli are clearly visible.


Alpha-foetoprotein during chemically induced hepatocellular carcinoma in rats. During induction of hepatocellular carcinoma (HCC) in rats with 3'MeDAB (3'methyl-dimethyl-aminoazobenzene) and Aflatoxin B1 alpha-foetoprotein (AFP) could already be demonstrated in the serum in the early phase of carcinogen administration. In this period the liver showed livercell necrosis but no tumour formation. The AFP level in the induction phase was correlated with the degree of livercell necrosis. The detection of AFP during the induction period is of importance as it is followed by a high frequency of liver tumours in later phases. The AFP concentration in the tumour phase was not related in any histological feature of the tumour; however, the mean AFP concentration in cases of HCC combined with cirrhosis was much higher than in cases of HCC without cirrhosis. Some rats with HCC showed AFP-negative sera, but AFP-positive bile.


Eperythrozoon ovis. I. Serological diagnosis of infection by the indirect immunoflurescent antibody test. The indirect immunofluorescent antibody test (IFAT) was evaluated for the detection of Eperythrozoon ovis infection in sheep. The test first became positive, on the average, 10 days following exposure to E. ovis and remained positive for 24 months, the longest period checked. Reciprocal titres in the first three days after becoming positive in the IFAT were between 4 and 80, but rose to 640 within 9 weeks; in general titres were between 4 and 640, exceptionally titres of 1280 were obtained. Negative sera produced no fluorescence at serum dilutions of 1:4. Paired serum samples collected before and after experimental infection demonstrated the specificity of the test. Further support for the specificity and reliability of the IFAT was provided by lack of cross-reactivity between E. ovis antigen and antisera to Anaplasma ovis and Theileria ovis, the two common blood parasites of sheep and goats in Nigeria, and the results of a longitudinal survey in a flock of sheep on the research farm where E. ovis was first detected.


[Dendritic spinules detected by the peroxidase method]. The structure of marked associative pyramidal neurons, their dendrites, and spines in layer III of somato-sensory cortex in cats after HRP-injection into the motor cortex has been described. Secondary and tertiary branches of basal dendrites are revealed more often than the apical ones. But the spines, especially their heads, were more obvious on the apical dendrites. The marked associative neurons are displaced sparsely, making no accumulations.


Confirmation of Bg-HLA relationships by antiglobulin microcytotoxicity testing. Antiglobulin reagents have been reported to increase the sensitivity of lymphocytotoxicity procedures for the detection of HLA antibodies that may affect the survival of transplanted kidneys or cause nonhemolytic transfusion reactions. This paper describes how such a procedure may also be used to demonstrate the presence of specific HLA antibodies in sera containing anti-Bg antibodies but lacking HLA antibodies that can be detected by conventional procedures. With the use of more sensitive procedures for the detection of both anti-Bg and HLA antibodies, studies of the relationship between specific HLA and Bg antigens can be extended, and the genetics of the expression of the Bg antigens can more easily be studied.


Distribution of di- and mono-(2-ethylhexyl) phthalate in human plasma. The distributions of di-(2-ethylexyl) phthalate and mono-(2-ethylhexyl) phthalate among the protein constituents of human plasma were studied by selective precipitation and chromatographic procedures. The distributions resulting from the leaching of phthalates from blood bags were simulated conveniently by allowing plasma to extract phthalates from coated Celite. More than 80 per cent of the diester was associated with lipoproteins, in the order: LDL greater than VLDL greater than HDL greater than chylomicrons. The remaining diester was apparently adsorbed weakly and nonspecifically to other proteins, including albumin. Mono-(2-ethylhexyl) phthalate was in equilibrium between free in solution and adsorbed to albumin; none was bound to lipoproteins. Extraction of phthalate from Celite into plasma should provide a convenient preparation for toxicity or pharmacokinetic studies.


[Biochemical study of serum from sheep infected with Brucella ovis]. Blood serum was used of 49 rams and 20 ewew infected with Brucell ovis. The study on the total protein and the protein fractions of rams revealed that there existed gamma-globulinemia, the percent of the gamma-globulin rise showing a positive correlation with the morphologic changes in the testes. The alfa-globulins were found to rise immediately following the experimental infecting of the sheep for about a month, after which they came back to normal. In experimental infection the activity of the alkaline phosphatase, aldolase, glutamate-oxalacetate-transaminase, and glutamate-pyruvate-transaminase of the blood serum showed transient characteristic changes, having, however, no diagnostic value.


Elastin VIII. A correlative study of the aging elastica of arteries and skin. Nigrosin base in an acid alcohol solution and Gomori's aldehyde fuchsin gave excellent staining of the elastic fibers in the arteries and skin regardless of age. Neutral hydroalcohol solutions of alcohol soluble nigrosin stained the elastic fibers in the arteries and skin of humans above age 20. Clara's neutral hematoxylin stained the arterial elastica of children less than 10 years of age, but did not color the elastic fibers of the skin. By these staining procedures, it may be possible to obtain information about arterial elastica by a skin biopsy.


Analysis of sister chromatid exchange and chromosome replication kinetics using Brd-U-dye techniques. The basis of BrdU-dye techniques for detecting DNA synthesis in cytological preparations is reviewed. General procedural modifications are described for applying this approach for the study of chromosome replication kinetics and sister chromatid exchange formation. Implications of sister chromatid exchange analysis for detecting mutagen-carcinogens and for differentiating human chromosome fragility diseases predisposing to neoplasia are discussed.


[Activity of acid protease in subcellular fractions of dog brain with intracysternal administration of antibodies]. The intracysternal administration of the immunoglobulins G fraction containing mainly antiboides to myelin basic protein activites acid protease in the lysosomic, soluble fractions and in myelin of the brain white matter and spinal cord of dogs. Administration of the fraction of immunoglobulins G obtained from the intact dog blood serum does not change (with some exception) the protease activity. Therefore, a definite specificity is observed in the reaction of the acid protease activation when the brain is affected by antibodies to the myelin basic protein.


Bleomycin: effect on satellite DNA in mouse fibroblasts. The effect of Bleomycin on the semiconservative replication of mouse nuclear DNA has been studied. When asynchronously dividing mouse fibroblasts (L-cells) were grown in the presence of 5-bromodeoxyuridine (25 mg/l medium) for 18 h, three hybrid DNA bands with densities of 1.722, 1.752, and 1.761 kg/l appeared after caesium chloride density gradient centrifugation of nuclear DNA. In cells exposed to Bleomycin (100 mg/l) however, replication of satellite DNA is more strongly inhibited than is the replication of the main band DNA; preferentially the thymidinerich hybrid duplex at 1.761 kg/l could no longer be detected.


[Monitoring the effectiveness of conservative treatment of benign prostatic hypertrophy by means of uroflowmetry]. 96 patients with benign hyperplasia of the prostate and dysuric complaints in stage I and beginning stage II were treated conservatively and medicamentously up to 12 months. In the collective of patients subdivided into 4 groups the conservative therapy was carried out in 3 groups with different phyto-preparations and in one group with gestonorone capromate. The voiding of the bladder was examined by means of uroflowmetry in intervals of four weeks before and after therapy. A clear success of the effect appeared only in the group of patients treated with gestonorone capromate. With phyto-preparations uroflowmetrically no significant effect on the disturbed voiding of the bladder could be established. The conservative treatment of the benign hyperplasia of the prostate should be carried out under uroflowmetrical control, in order not to miss the time of a necessary operative intervention.


[Controversial and unsolved problems in the prevention of infectious hepatitis]. Data are presented indicating that 1 ml of 10% and 1% immunoglobulin possessed similar epidemiological activity in the prophylaxis of infectious hepatitis. It was shown that redical action of infectious hepatitis on the epidemic process was possible only in case of embracement by immunoglobulin vaccination of not less than 80% of children aged from 1 to 11 years. The economic effect of the introduction of 1% immunoglobulin constituted about 40 000 roubles per 100 000 persons vaccinated. Besides, a possibility of side-effects were nilin case of placental immunoglobulin since in the 1% preparation nonspecific biologically active substances could penetrate in much lesser amounts.


[Quantitative assessment of EB strain cell death in an aerosol and following rehydration]. The authors assessed quantitatively inactivation of lyophilized cells of EB strain by the action of aerosol stress and rehydration using the method of bacterial nucleoide staining. With the advance of dust aerosol "ages" microbial sensitivity to rehydration increased and to the action of aerosol stress--decreased. The method can be used to calculate the aspiration dose in aerogenic vaccination and also to assess the efficacy of lyophilized bacteria restoration.


[Role of thyroid gland dysfunction in the pathogenesis and course of cerebral circulatory disorders]. The functional state of the thyroid gland was studied in 160 patients with different forms of disturbed cerebral circulation. The observations included studies of the iodine content and its fractions in the blood serum and a scanning of the thyroid gland. The author established the significance of thyroid gland dysfunction in the pathogenesis of hypertensive disease and cerebro-vascular insufficiency. In patients with hypertensive crises these studies detected the existence of a hyperthyroid syndrome. It was also found that in patients with cerebrovascular insufficiency accompanied by thyroid gland dysfunctions the clinical picture becomes more aggravated.


[Relationship between the dynamics of mental disorders in patients with primary hypogonadism and surgical intervention (testicular transplantation)]. Clinico-catamnestical, experimental-psychological and EEG studies were made of 60 patients with primary hypogonadism. Variants of protracted pathological reactions to the disease and pathological personality development are described. The studies indicate an intercorrelation of the dynamics of mental disorders and the character of the main disease. Recommendations as to the prophylaxis and treatment of mental disorders in different stages of surgical treatment are given. Some deontological problems of transplantation are discussed as well.


Giant melanin granules in vitiliginous achromia with malignant melanoma. Histological and ultrastructural examination of normal and perilesional skin of a patient with vitiliginous depigmentation associated with a malignant melanoma revealed the presence of giant melanin granules in keratinocytes and melanocytes. These structures are compared to macromelanosomes which have been observed in numerous pigmentary diseases. The formation and significance of the giant melanin granules is discussed.


The nature and role of epidermal regressive changes in the development of the psoriatic lesion. Damaged epidermal cells present in psoriatic lesions were investigated using histochemical and histomorphological methods including ultrathick sections. In early lesions these cells were found throughout the epidermis, being particularly numerous in the upper part of the latter and around the adnexa. In a later developmental stage the damage to the keratinocytes in the suprapapillary region was found to precede the damage to the basement membrane. These findings, together with the difference between the damaged keratinocytes lining the ascending side and the venous limb of the papilla respectively with regard to degree of severity of the damage, suggest that blood stasis is the cause of the regressive changes in the suprapapillary epidermis. The enzymatic activity of non-specific esterases and acid phosphatases was increased and that of succindehydrogenases and DPN-diaphorase was decreased in damage keratinocytes. The significance of these findings in relation to the genesis and development of psoriasis is discussed. The view is expressed that there is a causal relationship between damage to the epidermal cells and proliferation of epidermis.


Adrenergic nerve innervation of the human cutaneous glomus. Adrenergic (monoaminergic) nerve innervation of cutaneous glomus from the human thumb was examined by the fluorescence method of Falck and Hillarp for the demonstration of monoamines. The main anastomotic vessel (Suquet-Hoyer canal) was found to possess a pattern specific for nerve innervation. The Suquet-Hoyer canal was surrounded like a sheath by numerous thin adrenergic fibers, which were distributed like threads around a bobbin. These nerve fibers are superimposed directly on the outer surface of the glomus cell layer, not penetrating between these cells. They show varicose axon ramifications.


Finger skin perfusion pressure in generalized scleroderma. Skin perfusion pressure in fingers in 6 normal persons and 12 patients suffering from generalized scleroderma was estimated as the minimum external counterpressure required to stop 133Xenon wash-out. The isotope was introduced atraumatically into the skin, and local counter-pressure was exerted by a miniature blood pressure cuff. Local perfusion blood pressure in normal fingers was 100.5 mmHg +/- 3.3 SEM, while in the patients the value was 72.5 mmHg 1.8 SEM (p less than 0.001).


Neutrophil granulocyte function in pustulosis palmoplantaris. The phagocytic bactericidal capacity of circulating neutrophilic granulocytes was estimated in 22 patients with pustulosis palmoplantaris (PPP). The control group comprised 100 healthy individuals. Leukocytes from the patients had a statistically significant reduced capacity to kill Staph. aureus in autologous as well as in AB serum. Leukocyte killing of E. coli was not reduced. Serum levels of total hemolytic complement, C3, C4 and neutrophil myeloperoxidase activity were normal. The findings suggest an intrinsic or cellular defect of circulating neutrophil granulocytes in patients with PPP.


Plasminogen activator in vaginal smears during the menstrual cycle. A cytologic staining technique in which the reaction produces an insoluble colored precipitate at the site of trypsin-like proteolysis was applied to human vaginal smears, taken daily over six menstrual cycles. The day of urinary LH surge for each cycle was determined. The enzyme action, namely hydrolysis by plasminogen activator, is confined mainly to intermediate squamous cells. The number of cells stained by the enzyme method reaches a maximum three days prior to the LH surge, whereas the maximum in karyopyknosis occurs close to or at the day of LH surge. The enzyme staining method can thus be used when anticipation of ovulation by about 4 days is needed. No immediate fixation is required prior to the enzyme staining.


Failure of transfer factor therapy in atopic dermatitis. A controlled clinical study was conducted on 6 patients with atopic dermatitis to assess the efficacy of transfer factor. After the code was broken the 3 patients treated with placebo preparation were treated with transfer factor for a further period of 10 weeks. No definite therapeutic effects could be demonstrated. The immunological in vivo and in vitro tests failed to reveal any effects except for a change to positive in the tuberculin skin test in those patients who had previously been skin test negative. The treatment had to be discontinued in one patient due to a suspected allergic reaction against transfer factor.


Quantification of anaerobic diphtheroids on the skin. The widely used technique for sampling skin bacteria employs a detergent (Triton X-100) in buffer solution to remove and suspend the microorganisms. The fraction of the total population of anaerobes on the forehead removed by scrubbing with this solution was estimated. We calculated that approximately 10% of the resident anaerobes were removed by one minute of scrubbing with the detergent solution and two 1-min washes remove approximately 19.5% of the resident anaerobes (8.8 X 10(5)/CM2).


Dermatitis herpetiformis in Finland.

Dermatitis herpetiformis in Finland. During a 3 1/2-year period, 492 patients with dermatitis herpetiformis (DH) visited the dermatological departments of Finnish hospitals. The prevalence of DH in Finland was 10.4 patients/100,000 inhabitants, or 1/10,000. About 60 patients contracted DH each year, giving an incidence of 1.3 patients/100,000 inhabitants/year. These figures show that DH is a rather common disease in Finland--much more so in Finland than in Britain. Its incidence does not differ much from that approximated for coeliac disease in Finland. DH occured in all parts of the country. The birth-places of the patients were distributed evenly over the whole country, in contrast to the distribution pattern of rare hereditary diseases in Finland. No significant difference was found in the occurrence of DH in areas with differing levels of wheat consumption or iodine intake.


Psoriasis and arthritic lesions in relation to the inheritance of HLA genotypes: a family study. This family consists of forty-eight subjects, all of whom have been examined with regard to the presence of psoriasis and nearly all for the presence of arthritic lesions (sacroiliitis and peripheral arthritis). All the members have been tissue-typed not only for HLA-A, B and C locus products but also for D locus products. This has enabled us to study the entire HLA chromosomal region. In the family concerned we have found that those subjects haploidentical with the proband have, to a very large degree, either one or all clinical manifestations, which demonstrates a close genetic relationship between joint (especially sacroiliitis) and cutaneous manifestations. These findings prompt us to repeat our previously made proposal about different phenotypic expressions of the same genotype. In this family study the disease-associated haplotypes did not contain the genes for B13, 17 or 37 antigens which are known to occur frequently in psoriatic patients. However, not all psoriasis patients have these antigens. Despite that, we believe that the gene(s) which increase the likelihood of developing psoriasis are identical in all patients and therefore family studies where the proband does not carry the particular psoriasis associated B-alleles are equally illuminating as to the inheritance pattern of disease.


A clinical and histological study of cutaneous leishmaniasis. Sixty-five cases of proved cutaneous Leishmaniasis have been studied on clinical, histological and laboratory grounds. A new histological classification is proposed and emphasis is given to specific histological changes and their correspondence to distinct clinical signs.


Systemic lupus erythematosus with multiple myeloma. A 44-year-old white man presented with an erythemato-squamous rash in the supra-orbital and preauricular regions of the face. The diagnosis systemic lupus erythematosus was confirmed by histopathology, immunofluorescence (circulating antinuclear antibodies and a positive lupus band test), and by immunoelectron microscopy. Further examinations disclosed a multiple myeloma of the IgG type without cutaneous involvement. The coexistence of these two disorders has not been reported previously.


Juvenile plantar dermatosis.

Juvenile plantar dermatosis. Juvenile plantar dermatosis seems to be a new skin disease found mainly in children between 3 and 14 years old. The main symptoms are: redness, shiny hyperkeratosis, lamellar scaling and painful fissure formation in weight-bearing parts of the soles and toes. Sometimes the hands also seem to be affected. External factors, occlusive socks and footwear, possibly together with an atopic constitution, are believed to be the cause of the disease, which is very difficult to treat. The findings in 157 published and 23 own cases are discussed.


Progressive depigmentation of the coat of C3H mice after neonatal thymectomy. Progressive depigmentation of the coat has been observed in C3H mice thymectomized at birth and reared in a germ-free environment. The origin of the pigmentary anomalies is discussed. It is probable that a causative relationship exists between thymectomy and the acquired depigmentation observed.


Phylogenetic studies with pemphigus and pemphigoid antibodies. Indirect immunofluorescence (IF) studies were performed on skin from a variety of vertebrate specimens and IgG fractions from pemphigoid and pemphigus sera. Pemphigoid antigen was present in fish, amphibian, reptilian, avian and mammalian skin, whereas pemphigus antigen was observed in avian and mammalian skin only.


Distribution of complement and immunoglobulin in oral pemphigus lesions. The present report describes four cases of oral pemphigus vulgaris lesions in which complement, in contrast to the situation as reported for skin, was found only in the basal and parabasal layer, whereas IgG was present in all layers of the epithelium.


Werner's syndrome and the cellular immune reactions. A case of Werner's syndrome in a 39-year-old man is described. PPD and trichophytin intradermally proved negative; the percentage of T-lymphocytes and the lymphocyte response to PHA were reduced. Cellular immune reactions seem to have been impaired in this case.


Pulsating fixed drug eruption due to tetracycline. A 29-year-old woman developed a pulsating, fixed drug eruption following a year's course of both oral and parenteral administration of tetracycline for pharyngitis. Patch testing of tetracycline powder under occlusion at the site confirmed the diagnosis.


Sutton's summer prurigo of the elbows.

Sutton's summer prurigo of the elbows. Seasonal variations in skin diseases are most noticeable in those parts of the country with significant changes of seasons. For the past 5 years, I have noticed an unusual recurrent prurigo of the elbows which was originally described by Sutton. This disease, which I feel is related to atopic eczema, usually occurs on the elbows of children during the first few weeks of good spring weather. The disease appears as a papular eczematous dermatitis which is usually limited to the elbows but may also affect the knees, hands and chest. It responds well to topical corticosteroids but has a tendency to recur each spring for several years.


A pustular eruption of the chin (a variant of pyoderma faciale?). Two cases are reported of patients who developed a dramatic pustulo-nodular rash on the chin. The onset was explosively sudden and cosmetically disabling. Ultimately, resolution occurred with minimal scarring.


The painful, non-indurated chancre.

The painful, non-indurated chancre. After reviewing 20 consecutive male patients with primary syphilis and 23 textbooks on venereology, it can be emphasized that the syphilitic chancre may be painful, and not indurated, and that the textbooks in some cases give a misleading description of the disorder.


Treatment of acne vulgaris with topically applied erythromycin and tretinoin. A twice daily application of 2% erythromycin base in hydroalcoholic solution accompanied by once daily use of 0.05% tretinoin (retinoic acid) solution was substantially more effective than tretinoin or erythromycin alone for treatment of inflammatory acne of moderate severity. Therapeutic enhancement by this combination can be attributed to the different modes of action, erythromycin acting chiefly by suppressing Propionibacterium acnes, while tretinoin is comedolytic. In addition, by altering the horny layer barrier, tretinoin doubtless increases the penetration of erythromycin.


Pediculosis capitis treated with quassia tincture. 454 patients were treated with quassia tincture for head lice. At examination one week later only three patients had hatched lice. There was firm evidence that these patients had been reinfested. The treatment procedure was acceptable both to patients and to staff and no side-effects were observed. As resistance to clophenothane has appeared, alternative cures are needed. This study confirms earlier reports on the effectiveness of quassia tincture, which seems to be a useful alternative to clophenothane. At present the recommended treatment is two applications with an interval of one week.


Studies on an inhibitory factor to phytohemagglutinin-induced lymphocyte transformation found in the serum of patients with various liver diseases. When normal lymphocytes were stimulated with PHA in the presence of serum taken from patients with various liver diseases, lower lymphocyte transformation was seen in many cases. The occurrence of a serum inhibitory factor in liver diseases tends to increase with the progress of the disease from acute hepatitis to cirrhosis of the liver. No such inhibitory factor was detected in two asymptomatic HBs-antigen carriers. When the inhibitory factor was fractionated by DE-52 column chromatography, an active component was obtained and shown to have mobilities from alpha2-globulin to beta-globulin in cellulose acetate membrane electrophoresis. However, two active fractions were separated by DEAE-cellulose column chromatography with stepwise increases of the concentration of the acetate buffer and their mobilities were consistent with those of alpha1-globulin and alpha2-globulin, respectively. In 11 cases of acute hepatitis which were followed for at least 6 months, three out of four inhibitory factor positive cases developed into the chronic form and the other became a protracted case. On the other hand, six out of seven inhibitory factor negative cases completely recovered and the remaining case followed a protracted course.


Residual nitrous oxide in operating room personnel. The concentrations of nitrous oxide in the blood and end-tidal air of 10 operating-room nurses were assayed by gas chromatography immediately and 1, 2, 5, and 21 h after 3 hours of exposure to an average of 380 ppm of nitrous oxide in operating-room air. In the second trial the nurses' end-tidal air concentrations of nitrous oxide were assayed on Monday, Wednesday, Friday and Sunday morning, and on Sunday afternoon and evening to reveal a possible accumulation of nitrous oxide during a routine week. After cessation of exposure there was a rapid decrease in the blood concentrations of nitrous oxide during the first hour (from 153 +/- 110 microgram/1 to 48 +/- 20 microgram/l at 1 h; means +/- s.d.), followed by a slower decrease. Small amounts (mean +/- s.d.: 18 +/- 6 microgram/l) of nitrous oxide were still measurable on the following morning 21 h after exposure. At 2 or 5 h after exposure there was an increase in blood and end-tidal air concentrations of nitrous oxide in seven and nine nurses, respectively. The end-tidal air concentrations of nitrous oxide were greater on Wednesday (22 +/- 7 microgram/l) than on Monday morning (8.4 +/- 1.5 microgram/l), but on Friday they were similar to those measured on Monday morning. The concentrations measured on Sunday, i.e. 2 days after exposure, were similar (average 15 microgram/l) to those measured during the week. It is concluded that, after cessation of exposure to nitrous oxide, there is a rapid decrease in the concentrations in blood and end-tidal air, but small amounts of nitrous oxide remain in the body for at least 3 days after cessation of exposure.


Fingerprints in congenital rubella following maternal gamma globulin. The fingertip skin ridge patterns of ten children with the congenital rubella syndrome whose mothers had received gamma globulin following exposure to german measles during pregnancy were compared with those of 29 patients whose mothers had not received gamma globulin and with those of 162 control children. Statistical evaluation of the pattern profiles by the Mann-Whitney U-test showed that the dermatoglyphics of the two groups of patients differed significantly from each other. Each group also differed from the control children: there was a significant (p less than 0.001) increase in whorls in patients whose mothers had not had gamma globulin, but an increase (p = 0.001) in ulnar loops in those whose mothers had received gamma globulin.


Induction of leukochemotaxis by peptidoglycan of Staphylococcus aureus. Leukochemotactic activity of staphylococcal peptidoglycan and isolated, specified fragments has been studied. The D-Ala-D-Ala group of the pentapeptide was found to be the major cytotaxigen, and C5a to be the dominant cytotaxin. A molecular weight of about 2,000 appeared to be a critical lower limit for inducing chemotactic response, the highest effect being observed with a fragment having a molecular weight of 3,000. The effect seems to depend on the kind of available antigenic determinants in the fragments and the proportion of specific antibodies in the complement source.


Lymphocyte subpopulations in man. Expression of HLA-DR determinants on human T cells in infectious mononucleosis. In a study of lymphocyte subpopulations in peripheral blood during infectious mononucleosis the lymphocytosis was found to be of T-cell origin (i.e. E-RFC), while the number of non T lymphocytes (i.e. EA-, EAC-RFC and SmIg + ve cells) was normal in 7 out of 8 patients. Ten patients were tested for the presence of HLA-DR determinants on their B and T cells and not only B lymphocytes but also a great part (31--75%) of T cells were lysed by the anti HLA-DR testsera, indicating that HLA-DR determinants are expressed on a population of T cells in IM patients. After recovery all patients were retested and showed a normal pattern of HLA-DR typing. This indicates an increase of HLA-DR antigens on T cells or a vigorous proliferation of a small DR-positive T-cell subpopulation during the acute stage of IM.


Selection of new human foreskin fibroblast cell strains for interferon production. The aim of this work has been to isolate and characterize new diploid cell strains, suitable for large-scale production of human fibroblast interferon. Twenty cell strains were isolated from individual neonatal foreskins obtained with the informed consent of the donors' parents. The techniques employed for the isolation of the cell strains were aimed at obtaining the highest possible yield of normal diploid cells, free of contaminating microorganism and viruses. The bulk of the cell yield has been frozen at a low population doubling level. Each of the isolated cultures was tested for interferon producing characteristics with poly(I)-poly(C) under a number of different conditions including "superinduction" with metabolic inhibitors. Most of the newly established cell strains produced lower interferon yields than the reference FS-4 cell strain. However, some new cell strains produced similar interferon yields as the FS-4 cells on superinduction. Five cell strains, designated FS-30, FS-35, FS-44, FS-48 and FS-49, identified as the highest interferon producers among the new cells, were selected for further testing. Of these, three cell strains (FS-35, FS-48 AND FS-49) produced similar interferon yields as FS-4 cells after superinduction. Cell strains FS-48 and FS-49 were found to have stable interferon producing characteristics over a wide span of population doubling levels. The interferon produced in these new cell strains had the antigenic and biological characteristics of human fibroblast interferon.


Antigenic properties and heterospecific antiviral activities of human leukocyte interferon species. Human interferon obtained in peripheral leukocytes was purified approximately 1000-fold by affinity chromatography on anti-leukocyte interferon globulins coupled to Sepharose 4B, and by filtration on SDS-Sephadex G-100. The interferon was subsequently resolved into two molecular species by adsorption chromatography on SDS-hydroxylapatite. The two species which were eluted at different phosphate molarities from hydroxylapatite, could also be distinguished on the basis of electric charge properties and they migrated at different rates in SDS-polyacrylamide gels. Crossneutralization tests with monospecific rabbit anti-leukocyte and anti-fibroblast interferon sera revealed that the two species possessed leukocyte interferon-specific antigenic determinants. Both were immunogenic in mice and they were neutralized to a comparable degree by antisera against either component. A variable degree of antiviral activity was expressed by both interferon components in bovine, porcine and murine cells. However, the two interferon species were equally active in this respect, and the protective effects exhibited in homologous and heterologous cell cultures were similarly susceptible to reduction by beta-mercapto-ethanol. We conclude that the two molecular species of human leukocyte interferon are biologically similar.


Defaecation syncope.

Defaecation syncope. Defaecation syncope is recorded in seven female and two male patients aged between 63 and 78 years seen over a period of nine years. The tendency for defaecation syncope to occur at night contrasts with the rarity of nocturnal defaecation in most old people. The close similarity with micturition syncope is noted.


Ventricular extrasystoles and intracellular electrolytes before and after potassium and magnesium infusions in patients on diuretic treatment. Thirty-four patients suspected of being magnesium deficient were given intravenous infusions of potassium and magnesium. The muscle contents of sodium, potassium, magnesium, and chloride were determined by atomic absorption spectrophotometry on skeletal muscle samples obtained by percutaneous biopsies. The frequency of ventricular etopic beats (VEBs) was assessed from a 3-hour ECG tape recording before the infusions and after the completion of each infusion. The potassium infusions did not result in any changes in the cellular potassium content, nor in the frequency of VEBs. After the magnesium infusions, however, a significant increase was noted in the cellular potassium content and likewise a significant decrease in the frequency of VEBs. This emphasizes the importance of magnesium in potassium metabolism.


Planning helps industrial hygienists provide effective audiovisual presentations. The use of audiovisual aids can improve presentations and facilitate the comprehension and retention of information by an audience. In this article, the author discusses the basic steps in planning, producing, and presenting a simple yet effective audiovisual program. Topics discussed include the use of planning boards, simple slide production techniques and the use of slide dissolve and sound synchronizer units.


Value of a noninvasively induced ventricular extrasystole during echocardiographic and phonocardiographic assessment of patients with idiopathic hypertrophic subaortic stenosis. Fifteen patients with idiopathic hypertrophic subaortic stenosis had a ventricular extrasystole induced with a new external mechanical cardiac stimulator during noninvasive evaluation of left ventricular outflow tract obstruction. Ten patients were monitored with simultaneous echocardiogram, phonocardiogram and indirect carotid pulse tracing; five were monitored with the phonocardiogram and indirect carotid pulse tracing alone. Nine of the 15 patients showed obstruction in the beat after the ventricular extrasystole, as defined by appearance of the characteristic bifid carotid pulse contour and, where recorded, an increase in systolic anterior motion of the mitral valve on echocardiography. Six patients did not show obstruction. All nine patients with obstruction had greater than 20 msec prolongation of uncorrected systolic ejection time in the post-extrasystolic beat of the carotid pulse tracing. Change in the uncorrected ejection time was + 0.038 +/- 0.15 second (mean +/- standard deviation) in these nine patients compared with -0.003 +/- 0.005 second in the six not showing obstruction (P less than 0.01). Six patients underwent cardiac catheterization: Three patients without obstruction after a noninvasively induced ventricular extrasystole had no obstruction at catheterization and three patients with obstruction after noninvasively induced ventricular premature beats demonstrated obstruction at rest or after provocative maneuvers during catheterization. These results indicate that the noninvasive induction of a ventricular extrasystole is a useful and easily performed procedure for both diagnosing and evaluating the dynamic left ventricular outflow tract obstruction of idiopathic hypertrophic subaortic stenosis.


Co-circulation of two influenza A (H3N2) antigenic variants detected by virus surveillance in individual communities. From March through June 1977 a total of 31 influenza A (H3N2) viruses were isolated from students with respiratory disease who were seen at the student health service on the Berkeley campus of the University of California, and 32 influenza A (H3N2) viruses were isolated from persons who participated in a city-wide febrile respiratory disease surveillance program in Seattle. The antigenic specificity of the hemagglutinin was determined for each isolate by hemagglutination inhibition testing with sera from ferrets infected with prototype strains A/Victoria/3/75 and A/Texas/1/77. In each of the three months, April, May and June, A/Victoria/3/75-like and A/Texas/1/77-like viruses were identified among isolates from both communities, and the numbers of isolates of the two antigenic variants from patients seen with influenza-like illnesses were similar. The findings emphasize the need to examine multiple isolates even from within single communities to determine the antigenic specificity of current strains of influenza virus.


Theophylline education: development and evaluation of teaching methods. A study was conducted on three adult medicine units in a 300-bed teaching hospital to (1) evaluate the effect of a slide-tape program in increasing patients' short-term knowledge of theophylline treatment and (2) evaluate the effect on this knowledge of a pharmacist's presence during the educational session. Thirty-four patients were assigned randomly to one of two treatment groups. Patients in both groups viewed a 10-minute program, Group 1 patients with the pharmacist present and Group 2 patients alone. Patient knowledge was measured before and after the educational program with identical 20-item objective tests. The posttest scores of both groups were significantly higher than their pretest scores (p less than 0.05). No significant difference was found in the mean improvement in scores between the two groups. Pharmacist-designed audiovisual patient education programs can be used effectively in the pharmacist's absence.


Pulsating forces in orthodontic treatment. A controlled pulsating-force system for the orthodontic movement of teeth was designed and its biologic effects were examined, with the dog serving as an experimental model. This system was applied to the maxillary right second premolar while a continuous force was delivered to the maxillary left second premolar. After a 12-day experimental period in which pulsating forces were used, the amount of tooth movement and the radiographic and histologic changes were comparable to those produced by continuous force. These preliminary data indicate that forces of greater magnitude and duration will be necessary to more fully characterize the potential advantages of a pulsating orthodontic force.


Trypanosoma cruzi-sensitized T-lymphocyte mediated 51CR release from human heart cells in Chagas' disease. Cytotoxicity of T-lymphocytes from patients with Chagas' disease to parasitized and non-parasitized human heart cells labelled with 51Cr was demonstrated. The highest ratio of 51Cr released from the normal, non-parasitized heart cells was observed when the T-lymphocytes were collected from patients with acute Chagas' disease. The quantity of 51Cr released from the normal heart cells that were destroyed by T-lymphocytes collected from patients with chronic Chagas' disease was also significantly higher than the quantity of 51Cr released from normal heart cells incubated with lymphocytes from normal donors. The specific release of 51Cr from the heart cell cultures destroyed by the immune T-lymphocytes from patients with acute Chagas' disease and from patients with chronic disease was 38.1% and 25.8%, respectively, compared to the release of 51Cr observed in control studies. A small particle human heart cell antigen was shown to inhibit the migration of Trypanosoma cruzi-immune peripheral blood leukocytes. The findings appear to indicate that T-lymphocytes from patients with Chagas' disease are susceptible to activation by a cross-reactive heart cell antigen and suggest that an autoimmune mechanism can be established in some cases of acute Chagas' disease and can be perpetuated in the chronic phase of this disease by the continuous antigenic stimulation. Further, these experimental data indicate that the autoimmune destruction of heart cells in Chagas' disease is produced by delayed-type hypersensitivity mediated by T. cruzi-sensitized T-lymphocytes.


Reappraisal of esophagogastrectomy for esophageal malignancy. Esophagogastrectomy performed in eighty-three patients with a thirty day mortality of 7 per cent, a resectability rate of 93 per cent, and no anastomotic leakage, provided dependable relief of malignant obstruction and restored oral alimentation in all surviving patients. Long-term survival was unchanged. The successful resection of all midthird lesions with a 3.9 per cent mortality reflects the capability of current surgery and suggests that surgical palliation of midthird esophageal tumors is preferable to radiotherapy alone.


The cerebellar projection from locus coeruleus as studied with retrograde transport of horseradish peroxidase in the cat. The cerebellar afferent projection from locus coeruleus has been studied in the cat by means of retrograde axonal transport of horseradish peroxidase. Labelled cells are present bilaterally in locus coeruleus only following injections in the cerebellar vermis (especially its anterior and posterior parts), the ventral paraflocculus and the flocculus. The labelled cells are restricted to the caudal half of the nucleus. A few labelled cells are also present in locus coeruleus following injections in the fastigial nucleus, and in nucleus interpositus anterior. The findings are discussed in relation to other studies on the efferent and afferent connections of the locus coeruleus.


Immuno-histochemical localization of cyclic nucleotides in the periodontium: mechanically-stressed cells in vivo. Cyclic AMP and cyclic GMP, considered to be cell proliferation regulators, have been reported to fluctuate in proliferating fibroblasts in vitro. The objectives of this experiment were to study the localization, distribution and staining patterns of these cyclic nucleotides in mechanically-stressed, proliferating periodontal fibroblasts in vivo. Cat canines were tipped by force applications for 0 to 48 hours and serial sagittal sections of fresh frozen, unfixed, undecalcified jaws were processed immuno-histochemically for the localization of cAMP and cGMP. Periodontal tension sites were studied microscopically. Fibroblastic staining for cAMP, which was localized mainly in the cell periphery, did not change appreciably as a result of tension. However, staining intensity increased one hour after the application of force, decreased after 6 hours and increased again at 24 hours. Staining for cGMP, initially covering the entire cell area, was concentrated over nuclei three hours after onset of tension, and diffused over cell periphery and cytoplasm thereafter. Intensity of staining for cGMP was maximal at 3 hours and low at 12 and 48 hours. These results demonstrate that stress-induced fibroblastic responses in vivo involve alterations in staining intensity for both cyclic nucleotides which may correspond with fluctuations of these regulators, reported to occur in vitro in various stages of the mitotic cycle. Moreover, this technique enables the identification of the involved cells in a stimulated, non-synchronized cell population.


Immuno-histochemical localization of cyclic nucleotides in mineralized tissues: mechanically-stressed osteoblasts in vivo. Previous experiments indicate that bone cells respond to external stimuli with fluctuations of cyclic nucleotide levels. The objective of this experiment was to study the response of alveolar bone to the application of tensile forces through an examination of the osteoblastic staining pattern for cAMP and cGMP. Cat canines were tipped by 80-g force for 0 to 48 hours. Fresh frozen, unfixed, undecalcified jaws were sectioned sagittally and stained immuno-histochemically for cAMP and cGMP. In tension sites, osteoblastic staining intensity for cAMP decreased gradually from one to three hours, and then increased by 24 hours. Intense staining for cGMP, visible in osteoblasts of all treated cats, peaked after three hours of treatment and then again at 24 hours. Generally, groups of cGMP-stained osteoblasts were found adjacent to unstained osteoblasts. The observed fluctuations in the osteoblasts staining pattern for cAMP and cGMP indicates involvement of these substances in the early response of osteoblasts to mechanical stimuli in vivo.


Proteolytic enzyme activity of blood leukocytes and cerebrospinal fluid in multiple sclerosis. Upon stimulation by immune complexes, the polymorphonuclear (PMN) blood secretes lysosomal hydrolases, including neutral proteinase, which is concentrated in the PMN cell. Neutral and acid proteinase activity were increased and decreased, respectively, in the circulating white cells of patients with multiple sclerosis during an exacerbation of the disease, but there was no correlation with serum immune complex levels. Neutral proteolytic activity in the cellular fraction of the cerebrospinal fluid was also found to be elevated in acute multiple sclerosis, as monitored by digestion of myelin basic protein.


[Optimization of the nutrient medium makeup for the biosynthesis of bleomycine antibiotic using a mathematical method of experimental design]. The fermentation medium for bleomycin biosynthesis was optimized with the help of a mathematical method for experiment modelling. With the use of the schemes of orthogonal latin squares the optimal concentrations of the sources of nitrogen, carbon and mineral salts were determined and the negative effect of cupric sulphate on the antibiotic biosynthesis was shown. The antibiotic production on the developed medium was 3.7 times higher than that on the initial medium.


Mesencephalotomy for intractable pain due to malignant disease. 40 mesencephalotomies were carried out on 38 patients with intractable pain secondary to malignant disease. In 2 patients with bilateral pain, a bilateral mesencephalotomy was required. Most of the patients had pain in the head, neck or upper trunk secondary to carcinoma of the nasopharynx, jaw, tongue, or neck.


Chicken egg yolk stabilizes the reverse transcriptase activity in type C particles produced by cultured MOPC-315 murine myeloma cells. Type C particles released from cultured murine myeloma MOPC-315 cells were significantly protected when the purification steps were all conducted in the presence of 10% chicken egg yolk fluid. The yolk fluid also slowed down the inactivation of viral particles during incubation at 37 degrees C and enabled full recovery of viral particles through several cycles of freezing and thawing. The purification of viral particles in the presence of yolk fluid did not affect the capability of the viral DNA polymerase to reverse-transcribe the virion RNA in vitro, nor that of the viral RNA to act as a functional template.


Autoradiography and epifluorescence microscopy combined for the determination of number and spectrum of actively metabolizing bacteria in natural water. A technique is described for the determination of bacterial numbers and the spectrum of actively metabolizing cells on the same microscopic preparation by a combined autoradiography/epifluorescence microscopy technique. Natural bacterial populations incubated with [(3)H]glucose were filtered onto 0.2-mum Nuclepore polycarbonate membranes. The filters were cut into quarters and fixed on the surface of glass slides, coated with NTB-2 nuclear track emulsion (Kodak), and exposed to the radiation. After processing, the autoradiographs were stained with acridine orange. A combination of overstaining on the slightly alkaline side and gradual destaining on the acid side of neutrality gave the best results. Epifluorescence microscopy revealed bright-orange fluorescent cells with dark-silver grains associated against a greenish-to-grayish background. Based on the standardization curves, detection of actually metabolizing cells was optimal when cells were incubated with 1 to 5 muCi of [(3)H]glucose per ml of sample for 4 h and the autoradiographs were exposed to NTB-2 emulsion at 7 degrees C for 3 days. In water samples taken immediately above sandy sediments at beaches of the Kiel Fjord and the Kiel Bight (Baltic Sea, FRG), between 2.3 and 56.2% (average, 31.3%) of the total number of bacteria were actually metabolizing cells. Spearman rank correlation analysis revealed significant interrelationships between the number of active bacteria and the actual uptake rate of glucose.


[Morphological virus diagnosis--electron microscopy study of animal viruses with negative contrast procedure]. Reported in this paper are results obtained in morphological virus diagnosis by using the negative contrast technique on the basis of electron microscopy. The availability of high-efficiency electron microscopy as well as of perfectly improved techniques of preparation, knowledge of the latest virus model concepts, and indivudual skills in diagnosis are essential conditions for the above approach. Parvoviridae, picornaviridae, and togaviridae are identifiable only in high particle concentrations and by group representation. Papovaviridae, adenoviridae, herpetoviridae, poxviridae, and reoviridae, on the other hand, can be safely identified even as single particles. The diagnosis of orthomyxoviridae, paramyxoviridae, rhabdoviridae, and retroviridae is facilitated by their own dimensions and their characteristic helico-symmmetrical nucleocapside. Coronaviridae are of highly conspicuous morphology but, nevertheless, pose problems in differential diagnosis. Substantive improvement of morphological virus diagnosis, in terms of minute details, may be achieved by means of the negative contrast method on the basis of immune electron microscopy. Advantages implied in that morphological method include less time-consuming and quite uninvolved practicability and good dependability of diagnosis for more efficient decision-making in research and practice.


[Differentiation of matrix proteins of influenza A viruses using enzyme immunoassay]. Matrix protein is known as a type-specific structural protein of influenza viruses. An attempt has been made to find out whether or not strain-specific components could be detected from matrix protein, in addition to its type-specific antigen determinants. The technique of enzyme immune assay was chosen as the optional method to differentiate between matrix proteins of various influenza-A viruses. Antigen titration was undertaken of several matrix proteins, using two specific anti-matrix-protein sera in each case. Information regarding serological relationships between the tested matrix proteins of various influenza-A viruses was obtained from a quotient between the titres of one antigen, on the one hand, and the two anti-matrix-protein sera used in titration, on the other. Two matrix protein sub-types were established in the context of the influenza-A viruses tested. Sub-type M1 was attributable to older strains (A/PR/8 and A/FM/1), whereas the matrix protein of sub-type M2 was found to be present in more recent strains (A/Hongkong and A/Port Chalmers).


[The effect of pesticide combinations on laboratory rats. I. Determination of the acute oral toxicity (LD50) of pesticide combinations]. The growing use of a diversity of pesticides in agricultural practice calls for studies into the toxicity of pesticides when used in combinations. Fundamental studies were conducted into the acute toxicity of pesticide combinations in rat and showed that double or triple combinations of parathion-methyl, carbaryl, and Lindan could aggravate or mitigate toxicity, depending on the active ingredients involved. The above findings were obtained from acute animal experiments, but it may well be necessary to develop proper screening models for optimum information and to study subchronic toxicity as well.


[The effect of pesticide combinations on laboratory rats. II. Modification of selected hematological parameters and blood glucose]. Reference is made to the first communication made under this heading. The haematological parameters did not undergo any visible change in response to the chosen experimental arrangement. Further studies should be undertaken, with the view to elucidating the possibility of bone marrow change. The blood glucose levels were strongly increased two hours from application of parathion-methyl, carbaryl/Lindan, and carbaryl/Lindan/parathion-methyl and strongly decreased 24 hours after application. Complementary experiments should cover chronic and subchronic situations.


[The effect of pesticide combinations in laboratory rats. III. Modification of selected enzymes]. After oral administration of pesticides Parathion-methyl, Carbaryl, Lindane and their combinations were investigated the activities of enzyme SGOT, SGPT, Alkaline Phosphatase and Cholinesterase. Results concerning SGOT-activity demonstrated a significant increase in all groups. The cause of this rise can be found in its effect on liver, muscle and/or heart. The activity of cholinesterase is significantly lower in the combinations of Parathion-methyl/Lindane, Lindane/Carbaryl and Carbaryl/Parathion-methyl. In future the extent of these investigations concerning the subacute toxicity, chronical toxicity, the additive or cumulative effects of pesticide--combinations, combinations of pesticides with drugs and/or xenobiotics etc. must be enhanced in any case.


Surgical treatment of adenocarcinoma. Location: junction of the right, left, and common hepatic biliary ducts. Thirty-eight patients with primary adenocarcinoma arising at the junction of the right, left, and common hepatic biliary ducts were seen at the Mayo Clinic, Rochester, Minn, between 1950 and 1976. Prompt and lasting relief of jaundice and cholangitis occurred in four patients undergoing resection of the tumor combined with left hepatic lobectomy, and their mean survival was 33 months. Relief of symptoms was only temporary in 26 patients treated with drainage of the biliary tree, and their mean survival was only ten months. Eight patients undergoing exploration only had no relief of symptoms, and none survived beyond four months. We conclude that resection of these tumors in selected patients gives good palliation and offers the chance of long-term cure. If resection is not possible, biliary decompression results in satisfactory palliation, whereas exploration only does not.


The nonoperative approach to esophageal perforation due to celestin tube placement. Perforation of the esophagus during placement of esophageal tubes for palliation of obstructing inoperable cancer is a well-known complication that may preclude satisfactory amelioration of symptoms. Experience with two such patients suggests that the complication can best be treated by proper placement of the tube so that it seals the leak and bypasses the obstruction. Judicious use of antibiotics is beneficial. Drainage of the mediastinum may also be necessary. Resectional or extensive operative therapy is probably not wise in these ill and debilitated patients, particularly if the cancer is incurable.


A new coronavirus-like particle associated with diarrhea in swine. Coronavirus-like particles were detected by electron microscopy in the intestinal contents of pigs during a diarrhea outbreak on 4 swine breeding farms. Diarrhea was reproduced in experimental pigs with one of the isolates, designated CV777, which was found to be distinct from the 2 known porcine coronaviruses, transmissible gastroenteritis virus and hemagglutinating encephalomyelitis virus.


[Immunomorphological study of the liver in clinical and experimental postnecrotic cirrhosis]. Immunomorphological study of the liver was carried out in 5 dead patients with postnecrotic cirrhosis of the liver and in 50 white rats with experimental cirrhosis of the liver for the purpose of detection of fixed immunoglobulins localization. Saturation with gamma-globulins of the vessel walls, forming connective-tissue septae and hepatocytes undergoing degeneration was established in rats. In man, gamma-globulins were found in the connective tissue strands, in vessel walls, and in the cytoplasm of mesenchymal cells and hepatocytes. The analysis of the results suggests different origin and dissimilar importance of gamma-globulins in different structures of the liver.


[Method of staining of semi-thin sections with hematoxylin-eosin]. A method for staining semi-thin sections with standard hematoxylin and eosin solutions is proposed. The staining is achieved by pre-treatment of the sections with an alkali and staining them with hot solutions. The method permits morphological examinations of sections 1-2 micron thick.


A clinical analysis of pseudopapilledema. I. Population, laterality, acuity, refractive error, ophthalmoscopic characteristics, and coincident disease. To clarify clinical features of pseudopapilledema, 142 cases (250 eyes) were analyzed regarding sex, age, race, bilaterality, acuity, refractive error, fundus characteristics, and coincident disease. Ninety-eight cases of identifiable hyaline bodies ([HB] group 1) were compared with 44 cases of pseudopapilledema without HB (group 2). The following results were notable: marked predominance of whites; one third in group 1 were unilateral, and 14% of all pseudopapilledema was unilateral; in only one eye did HB apparently account for diminished acuity; refractive error distribution paralleled that in the general population; anomalous vascular patterns occurred in 20% of group 1 and in 31% of group 2; pigment epithelial changes were found in 33% of group 1 and in 20% of group 2; and a statistically significant association was found with retinitis pigmentosa only. Analysis of field defects is the subject of a companion report.


A clinical analysis of pseudopapilledema. II. Visual field defects. Goldmann perimetry was performed on patients with pseudopapilledema. The cases were subdivided into those with ophthalmoscopically visible hyaline bodies (HB), (group 1) and those without (group 2). In group 1, 37 of 52 eyes (71%) demonstrated field abnormalities, including enlargement of the blind spot (68%) and various nerve fiber bundle defects (70%); inferior nasal defects were the single most frequent defect. In group 2, ten of 47 eyes (21%) showed only enlarged blind spots and two fields were generally constricted. No nerve fiber generally constricted. No nerve fiber bundle defects were found in this group. It is noted that field defects related to other ocular or intracranial diseases may be found in patients with intrapapillary HBs.


The clinical and pathogenetic significance of rheumatoid factors. Rheumatoid factors are immunoglobulins with antibody specificity for antigenic sites on the Fc part of the heavy chain of IgG. The heterogeneity of RF in terms of antigenic specificity and class of immunoglobulin is indicative of the complexity of the provoking immune response. There is little doubt that in many patients rheumatoid factors are autoantibodies which form part of immune complexes, and that complexes containing IgG rheumatoid factor appear to be of pathogenetic importance. Although IgM rheumatoid factors are not specific for RA, their detection aids in the diagnosis and categorisation of rheumatoid arthritis. On the other hand, IgG rheumatoid factors occur in a variety of rheumatic diseases and are of little diagnostic value.


Clinico-laboratory aspects of anti-nuclear and anti-native DNA antibody tests. Available techniques for detection of anti-nuclear antibodies are here briefly reviewed. The relatively insensitive LE cell test has been largely supplanted by the indirect immunofluorescent ANA test which should be reported in terms of titre and pattern. Specific measurement of nDNA antibodies is now a regular technique in SLE diagnosis and management.


Biochemical and genetic characterization of kynurenine formamidase from Drosophila melanogaster. The molecular weight forms of kynurenine formamidase were studied both gentically and biochemically. Formamidase I (native molecular weight 60,000) was purified using (NH4)2SO4 and pH fractionation, DEAE-cellulose chromatography at two different pH's, hydroxylapatite chromatography, and Sephadex G-100 gel filtration. Its subunit molecular weight, as determined by SDS gel electrophoresis, is 34,000, indicating that formamidase I is a dimer. Its Km is 1.87 X 10(-3) M. Its isoelectric point is pH 5.3. Its amino acid composition is reported. Formamidase II (native molecular weight 31,000) was partially purified using techniques similar to those above. Its Km is 2.31 X 10(-3) M. The response of formamidase activity to change in gene dosage was measured in segmental aneuploids generated in the second, third, and X chromosomes. Two separate chromosomal regions were identified which when present in extra dosage result in an elevation of the level of formamidase activity close to that predicted for the addition of a structural gene in a two-gene system. These tentative map positions were substantiated by demonstration that addition of one of the regions, 25A-27E, causes a 50% elevation in the relative amount of formamidase II. Addition of the other region, 91B-93F, causes a similar elevation in the relative amount of formamidase I. A model of the evolutionary origin of the two forms is presented, and the significance of these results to this model is discussed.


Effect of glutamine on the degradation of glutamine synthetase in hepatoma tissue-culture cells. In certain lines of hepatoma tissue-culture cells, the extracellular glutamine concentration regulates the specific activity of glutamine synthetase. By quantifying the radioactivity in immunoprecipitated glutamine synthetase on polyacrylamide gels, we found that the rate of degradation, but not of synthesis, of glutamine synthetase is a sensitive function of extracellular glutamine. The activiy that degrades this enzyme appears to be labile.


Demonstration of beta 1H globulin together with C3 in the dermal-epidermal junction of patients with systemic lupus erythematosus. Skin lesions and clinically normal skin from 10 patients with systemic lupus erythematosus (SLE) were examined by immunofluorescence for the presence of C3 and its control protein, beta 1H globulin. beta 1Hwas always found in association with deposited C3; in the instance where C3 deposits were not found beta 1H was also not found. Granular deposits of C3 and beta 1H were found in the dermal-epidermal junction (DEJ) in all of the 5 nonlesional skins studied. In the lesional skin, C3 was found in 4 of 5; in 2 of these 4, beta 1H was also found. As previously demonstrated for in vitro systems, beta 1H also binds in vivo to fragments of C3, presumably C3b, generated during activation of the complement system.


Bleomycin lung damage: the pathology and nature of the lesion. The pathology of two cases of pulmonary damage due to bleomycin is described. The drug damages the alveolar walls. A sequence of pathological changes could be traced commencing with oedema, intra-alveolar fibrin and haemorrhage, followed by type II pneumocyte hyperplasia associated with bronchial epithelial squamous metaplasia. This led to intra-alveolar and alveolar wall collagen formation producing diffuse interstitial fibrosis with microcyst formation associated with cuboidalization of the epithelium. These changes are similar to those seen in experimental bleomycin damage in mice, where it has been shown that the changes are the result of vascular damage and type I pneumocyte necrosis. It is inferred that human diffuse alveolar damage develops in the same way.


A case of atypical polyagglutinability due to Tk-transformation. A case of acquired transient polyagglutinability in a group O, Rh(D) positive female patient, Wa, is described. An unusual finding in the preliminary serological investigation was the non-reaction of the cells with peanut (Arachis hypogaea) extract. The patient's red cells were strongly agglutinated by normal human and rabbit sera from which anti-T had been removed. Electrophoretic mobility studies and tests with polybrene indicated that their sialic acid content was normal. The use of a specific antiserum raised in a rabbit to Wa cells and cross-absorption tests showed that the patient's erythrocytes shared similar antigenic determinants to red cells treated with supernatants from pure cultures of Bacteroides fragilis. The in vitro-modified red cells reacted strongly with BS II lectin prepared from Bandeiraea simplicifolia seeds thus providing confirmatory evidence for Tk transformation on Wa cells. It is concluded that the Tk receptor is probably a more frequent feature of acquired transient polyagglutinability than has hitherto been recognized.