The ontogeny of B lymphocytes. V. Lipopolysaccharide-induced changes of IgD expression on murine B lymphocytes. Murine splenocytes contain two minor subpopulations of B cells, one inducible by lipopolysaccharide to convert within 2 h from IgD- to IgD+ and the other to change from IgD+ TO IgD-. These two subpopulations can be separated by density centrifugation. Their relative proportions show a marked age dependency: IgD- leads to IgD+ cells are more frequent in suckling mice, while IgD+ leads to IgD- inducible cells become predominant in mice older than 3 weeks. The age dependency observed in the relative proportions between the two cell types suggest that they are ontogenetically related as progenitor-successor. This hypothesis is corroborated by phenotype analysis of the two subsets, revealing IgD- leads to IgD+ cells as IgM+, Ia+, complement receptor- (CR-) and IgD+ leads to IgD- cells as IgM+, Ia+, CR+. Our data show that IgD and CR are expressed concomitantly during B cell differentiation. On further differentiation, induced by lipopolysaccharide, both markers are lost from the cell surface at different rates: IgD decreases significantly in a very short period (less than 2.5 h) while induction of a decline in CR requires longer culture periods (greater than 8 h). Th: loss of IgD may thus herald an early differentiation event toward antibody-producing cells.


The role of the left end of the H-2b haplotype in the male-specific cytotoxic T cell response. The male-specific cytotoxic T cell response was tested in various mouse strains. We found that priming with 10(7) nonirradiated or 2 x 10(7) X-irradiated cells (2000 Rad) was similarly effective in B6 mice. We have avoided possible allogeneic effects due to priming F1 hybrids with parental cells and tested all mice after the same time interval for generation of male-specific cytotoxic T lymphocytes in vitro. Under these conditions, we found an absolute requirement for H-2b gene products, encoded left of B, in order to see male-specific responses.


Subsensitivity of the norepinephrine receptor-coupled adenylate cyclase system in brain: effects of nisoxetine versus fluoxetine. Chronic administration of the norepinephrine (NE) reuptake inhibitor nisoxetine reduced the sensitivity of the NE receptor-coupled adenylate cyclase system in rat cortex. This subsensitivity, unlike that caused by desipramine (DMI), was not related to a reduction in specific beta-adrenergic receptor binding. The specific serotonin reuptake inhibitor fluoxetine had no effect on either neurohormonal sensitivity or 3H-dihydroalprenolol binding.


Fibrin in fibroblast cultures--a metabolic study as a contribution to inflammation and tissue repair. Embryonic rat fibroblasts were cultured in the presence of fibrin under fibrinolytic and fibrinostatic conditions both in proliferating and confluent stages. The proliferation rate, glucose consumption, glycosaminoglycan contents and distribution pattern were determined. Additionally the influence on rat fibroblast cultures of fibrinogen and its splitting products were reinvestigated. Basing on the experimental results and a literature survey the role of fibrin in chronic inflammation was emphasized. Experimental results: 1. First step of tissue injury was simulated by formation of fibrin above a confluent fibroblast monolayer. The small degree of fibrinolysis with the cultures was sufficient to prevent all metabolic changes except a decrease of sulfate incorporation (immediately reversibly injury). Inhibition of fibrinolysis resulted in a decrease of proliferation and HA contents additionally, but in an increase of total GAG concentration and SO4-GAG. This behaviour continued during the beginning of cell proliferation. 2. The following step of fibrin contraction, improvement of nutrient supply, and cell proliferation was artificially achieved by growing non-confluent cells on the preformed fibrin network. Fibrin enhanced the cell proliferation, total GAG concentration, HA, and the turnover of SO4-GAG (sulfate incorporation). In rapidly proliferating cultures no influence of anti-fibrinolytic agents was observed. 3. On the preformed, partially contracted fibrin the cells grew to confluence: a) Without inhibition of the fibrinolysis, the parameters of the fibrin-free controls were obtained; repair seems to be completed. b) When fibrinolysis was inhibited the cells continued proliferating apparently with a tendency of enhanced HA and decreased SO4-GAG (a stage of "chronic inflammation"). 4. Purified fibrin fractions as well as the supernatant of fibrin containing fibrinopeptides were shown to advance cell proliferation.


Role of soluble cytotoxic factor in concanavalin A-induced cellular cytotoxicity to rabbit erythrocytes. A new sensitive and simplified method for detecting concanavalin A-induced cellular cytotoxicity was developed by using 51Cr-labeled rabbit erythrocytes as target cells, and a soluble cytotoxic factor (SCF) to rabbit erythrocytes was demonstrated with this system. From morphological studies, this factor appeared to play a major role in cellular cytotoxicity. The cytotoxic activity of SCF was removed by absorption with rabbit erythrocytes. Furthermore, the target cells pretreated with SCF and washed were subsequently destroyed. These results may indicate that SCF exerts its effect through binding to cellular receptors. Some monosaccharides showed inhibitory effects on the cytolysis of rabbit erythrocytes by SCF and on the adsorption of SCF activity to them. The significance of these findings in elucidation of the action of SCF was discussed.


Transcriptionally active and inactive regions of nucleolar chromatin in amplified nucleoli of fully grown oocytes of hibernating frogs, Rana pipiens (Amphibia, Anura). A quantitative electron microscopic study. Chromatin structures contained in nuclei of full-grown oocytes of hibernating northern leopard frogs, Rana pipiens, kept at 4 degrees C were examined by light and electron microscopy, with special emphasis on the morphology of spread nucleoli. Light microscopic inspection of the in situ arrangement revealed that at this stage of oogenesis the numerous amplified nucleoli, together with the chromosomes, were included in a centrally located aggregate. Characteristically, the nucleoli appeared spheroidal and showed large size differences; many of them revealed a caveolated interior and close association with large dense bodies of granular (GDB) or fibrillar (FDB) substructure. A spreading procedure involving limited dispersal of nucleolar chromatin allowed the analysis of a large number of individual nucleoli from a specific nucleus. Electron microscopy showed that different types of nucleoli which could be distinguished in terms of transcriptional activity occurred in the same nucleus: (i) Nucleoli in which nearly all pre-rRNA gene regions appeared as fully covered by lateral fibrils, indicative of active transcription ('active nucleoli'); (ii) nucleoli that contained exclusively or predominantly chromatin strands free of lateral fibrils and were characterized by a uniformly beaded appearance, interpreted as transcriptionally inactive, nucleosome-packed chromatin ('inactive nucleoli'); and (iii) nucleoli in which a number of typical arrays of lateral fibril gradients occurred besides other regions that were free of such fibrils and apparently non-transcribed ('partly inactive nucleoli'). Quantitative evaluations of the proportions of active and inactive nucleolar chromatin indicated that a minimum of 70% of nucleolar DNA is not transcribed at this stage of oogenesis. Details of the pattern and ultrastructural organization of active and inactive chromatin regions are presented. Lampbrush chromosome structures were observed in the same nuclei and also showed transcriptional structures, though often with reduced packing density of lateral fibrils. The observations show that a number of genes of both kinds, those coding for pre-rRNAs and those coding for proteins, are transcribed in full-grown oocytes of hibernating frogs at 4 degrees C. However, the data also indicate that the number of transcribed genes and the frequency of transcriptional events are greatly reduced at this stage of oogenesis, especially in the nucleolar chromatin.


Complete elimination of mitosis and DNA synthesis in the lens of the hypophysectomized frog: effects on cell migration and fiber growth. Three weeks after hypophysectomy mitosis and DNA synthesis are absent in the lens of the leopard frog (Rana iiens). By labeling germinative zone cells in their last DNA synthetic period we were able to follow them in the absence of further proliferation. By this means it has been demonstrated that migration of epithelial cells to the equator of the lens is stopped. Based on indirect measurements it seems that lens fiber formation also ceases. A correlation coefficient of 0.86 was computed between average labeling index and average distance migrated. In hypophysectomized animals the correlation coefficient between time and migration was 0.02 while in intact animals it is 0.87.


The lectin binding sites on the plasma membrane components of human lymphoblastoid cell lines. The plasma membrane components of five human B-cell lines and three human T-cell lines were separated by dodecyl sulfate polyacrylamide gel electrophoresis, incubated with the radioactive labeled lectins from lentil, castor bean, wheat germ, Phaseolus bean, peanut, gorse and the Roman snail and the molecular weights of the binding sites determined. The lentil, castor bean and wheat germ lectin bound to multiple components from molecular weights (Mr) 20 000 to 200 000 within the plasma membranes, whereas peanut lectin bound preferentially to glycoproteins of Mr 150 000 and 83 000 in B-cells, and 150 000 and 130 000 in T-cells. The gorse lectin bound to a 220 000 component in B-cells which was not labeled in T-cells.


Strain-dependent differences in murine susceptibility to coccidia. Differences in susceptibility of strains of mice to Eimeria ferrisi were observed by infecting eight strains of mice with six infectious dose levels and comparing the mortality rate among the strains for a period of 12 days. Mice of the C57BL/6 and HA/ICR strains were susceptible, and those of A/He, AKR, BALB/c, CBA, C3H/Anf, and DBA/2 strains were resistant to coccidial infection. Resistance was a dominant genetic expression, as indicated by the resistant response of F(1) hybrids of susceptible C57BL/6 and resistant CBA, C3H/Anf, or DBA/2 strains. An E. ferrisi infection in congenitally athymic nu/nu mice and phenotypically normal heterozygous nu/+ mice was used to determine how thymus-dependent immunoincompetence in cell-mediated immunity of the nu/nu mouse affected resistance to infection in a genetic background of the resistant BALB/c mouse. Results of primary and challenge infections in these two strains of mice suggested that resistance is thymus dependent. Furthermore, impairment of thymus-dependent cell-mediated immunity in resistant AKR mice by treatment with mouse antithymus serum led to partial susceptibility. However, susceptible C57BL/6 and HA/ICR strains are phenotypically normal mice, and previous evidence showed that C57BL/6 mice are not completely immunoincompetent in cell-mediated reactivity to coccidia. Collectively, our data show that cell-mediated immunity is necessary for resistance but may be subjected to modification by genetic expression of the host. The possible role of immune response genes in the control of coccidial immunity is discussed.


Growth requirements of human cervical epithelial cells in culture. Diploid cells derived from the portio surface of the cervix uteri of adult women can be grown in culture, from single cells. Ultrastructurally the colonies of growing cells show the features of stratified squamous epithelium and exhibit some of the differentiated characteristics of this epithelium in vivo. The successful serial cultivation of cervical epithelial cells, HCE, depends upon the presence of a non-dividing fibroblast feeder layer which provides both attachment and growth factors for epithelial cells. Lethally irradiated Wi-38, cervical fibroblasts or mouse fibroblast lines are all effective in promoting HCE colony formation and growth. Hydrocortisone and epidermal growth factor increase HCE colony size in the presence of a feeder cell layer. Culture lifetime was studied in five strains and ranged from 20-38 population doublings, with cells from older patients exhibiting a shorter culture life-time.


Effect of anti-mouse type-1 interferon globulin on the evolution of Moloney sarcoma virus induced disease in mice. The prolonged administration of potent sheep anti-mouse type-1 interferon globulin (anti-IF IgG) had a marked potentiating effect on Moloney sarcoma virus (MSV) infection in mice. The extent of resistance to the MSV-induced disease was age-related. In 4-week-old BALB/c mice, anti-IF IgG consistently induced 70-80% mortality due to the progression of early or late tumours and erythroleukaemia, whereas mortality of control mice was significantly lower. The same effect was obtained in 1-year-old BALB/c mice. However, in 4-week-old C57BL/6 or 6-week old BALB/c mice, anti-IF IgG enhanced only the growth of early tumours but had no effect on their regression. Antigenic stimulation with normal sheep globulin suppressed the growth of early tumours in suckling BALB/c or C57BL/6 mice and enhanced the evolution of late MSV-induced disease in older mice.


Clonal analysis of the action of GM-CSF on the proliferation and differentiation of myelomonocytic leukemic cells. With 214 subclones of the BALB/c myelomonocytic leukemia WEHI-3B, the granulocyte-macrophage colony-stimulating factor (GM-CSF) in impure or purified form, consistently increased the proportion of colonies exhibiting partial or complete differentiation in agar cultures. GM-CSF also increased colony size and content of daughter colony-forming cells. Serial recloning of WEHI-3B colonies in the presence of GM-CSF showed that when colonies differentiated completely, self-replication of the colony-forming cell was suppressed (clonal extinction). However, WEHI-3B cells exhibited clonal instability and even in the continuous presence of GM-CSF many colony-forming cells still generated cells able to form undifferentiated colonies. It appears unlikely that GM-CSF can completely suppress the progressive proliferation of a myeloid leukemic population of the WEHI-3B type.


Transfer of natural resistance to Marek's disease (JMV) with non-immune spleen cells. I. Studies of cell population transferring resistance. A "natural" resistance to Marek's disease, as well as to the malignancy caused by the laboratory JMV line of Marek's disease, develops with age. Resistance to this malignancy can be transferred from non-immunized, 8-week-old resistant chickens to newly hatched susceptible ones with spleen cells in a B-locus isogeneic combination. The cell transferring resistance does not seem to belong to the major T-cell, B-cell, or macrophage populations, and seems consequently to belong to the functionally heterogenous "third cell" population.


Health selection among members of a Danish Trade Union. The effect of selection on the mortality of members of the Danish carpenters and cabinet makers trade union is reported. Some 40 000 persons entering or leaving the Union between January 1971 to June 1976 were followed until September 1977, and deaths identified by record linkage with the central person-register. The male leaving cohort had a statistically significant higher age adjusted mortality rate than the male entry cohort with a relative death risk of 1.65. For females the difference was not significant but the relative death risk was estimated to be 1.42. Males leaving to or coming from well paid and socially esteemed jobs had significant lower mortality rates than the remainder. The influence of these results on the choice of study design is discussed.


Hearing impairment following therapy of Haemophilus influenzae meningitis. From 97 children with bacteriologically confirmed Haemophilus influenzae meningitis, 39 were treated with chloramphenicol (before 1970) and 58 with ampicillin (since 1970). In 1977 all patients were followed up with history, clinical examination, and audiometry. Sensorineural hearing defect was found in 5 chloramphenicol patients and in 10 ampicillin patients. Of the 82 patients for whom treatment was begun within 48 h of onset of symptoms, only two showed hearing deficit, while 13 of the 15 patients in whom treatment was begun later suffered from hearing impairment. It appears that it is not the antibiotic, but the delay between onset of symptoms and start of therapy, that is decisive for the occurrence of inner ear impairment.


Lymphocyte surface and cytoplasmic changes associated with translational motility and spontaneous capping of Ig. Murine B-lymphocytes during translatory motion undergo a series of changes with respect to their morphology and distribution of surface immunoglobulins (Ig). The sequence of events comprising these changes was followed by fluorescence microscopy and a correlated detection of surface features by scanning microscopy on exactly the same cell. A round, presumably non-motile lymphocyte exhibited a random distribution of Ig and its surface displayed evenly distributed microvilli. Formation of a ruffled edge at one pole, accompanied by a decreased fluorescence at this pole marked the initial events of lymphocyte motility. In the subsequent stages, the ruffled edge became progressively prominent and displayed a constriction at its base, while the microvilli were displaced to the opposite pole. Ig in such lymphocytes was localized at the trailing, microvilli-rich pole. Thin sections of motile lymphocytes revealed Ig, microtubules, microfilaments and coated vesicles as the characteristic features of the trailing end. These observations may have bearing on the mechanism of lymphocyte motility and spontaneous capping of Ig.


Ultraviolet-induced DNA excision repair in human B and T lymphocytes. III. Repair in lymphocytes from chronic lymphocytic leukaemia. There have been conflicting reports about the capacity of lymphocytes from individuals with chronic lymphocytic leukaemia (CLL) to undertake u.v.-induced DNA repair. We have examined repair in CLL cells and in control and age-matched purified B and T lymphocytes by a technique independent of incorporation of radioactive precursor, i.e. by the recovery of normal sedimentation behaviour of nucleoid bodies obtained from these cells by lysis in high salt and non-ionic detergent. Recovery of normal sedimentation is associated with restoration of DNA supercoiling. CLL cells were found to be as sensitive to u.v. and to repair at similar rates as age-matched B controls. They are considerably more sensitive than young B cells and repair less efficiently. Reasons for the reported discrepancies in CLL repair are discussed.


Acylovir in oral and ganglionic herpes simplex virus infections. The local and trigeminal ganglionic therapeutic efficacy of two topical and systemic antiviral drugs was studied in mouse lips inoculated with herpes simplex virus type 1 after thermal injury. Application of topical 3% acylovir (acycloguanosine) ointment three times daily for four days completely blocked the replication of virus in the lips, and the healing process was greatly accelerated compared with that in placebo-treated infected controls. However, neither the healing process nor the viral replication was influenced by similar therapy with 3% vidarabine ointment. When given systemically for four days, starting one day after inoculation, acyclovir (40-60 mg/kg per day) and vidarabine (50 mg/kg per day) significantly reduced the clinical manifestations on the lips and viral titers of cultures obtained from the lips. Establishment of viral latency in the trigeminal ganglion was significnatly inhibited by systemic acyclovir (60 mg/kg per day), whereas systemic vidarabine (50 mg/kg per day) was ineffective. These data suggest that acyclovir may be one of the most promising antiviral agents for the management of oral herpes viral infections and trigeminal ganglionic latency of virus as demonstrated in the mouse model.


The effects of calcium deprivation upon mechanical and electrophysiological parameters in skeletal muscle fibres of the frog. 1. The effects of Ca2+ deprivation upon mechanical and electrophysiological parameters of single muscle fibres from the m. semitendinosus and the m. iliofibularis of the frog were investigated. 2. When the external free Ca concentration was reduced in steps of one order of magnitude from 10(-3) to 10(-9) M, using up to 10 mM-EGTA and in the presence of 3 mM-Mg2+, the maximum force of K contractures declined by 5-15%, the plateau of maximum force shortened, and in most cases the phase of spontaneous relaxation lengthened. 3. In Ringer solution containing 10(-9) M-Ca2+ and 1 mM-Mg2+ 85% of maximum tetanic force could be maintained for at least 15 sec (5 Hz; 3 degrees C). 4. The reduction of external Ca2+ from 10(-3) to 10(-9) M and its replacement by Mg2+ induced a 20-30 mV shift towards more negative potentials of the 'steady state' inactivation curve (which relates maximum force upon full depolarization to the logarithm of the K concentration or the corresponding membrane potential during the conditioning period). 5. The same alteration in concentrations of divalent cations caused little or no change in the shape and potential dependence of the activation curve (which relates maximum force to the logarithm of the external K concentration of the corresponding membrane potential). 6. The threshold potential for the onset of delayed rectification (point voltage clamp) and that for the initiation of an action potential did not change when external Ca2+ was reduced to 10(-9) M and replaced by Mg2+. 7. When the concentration of EGTA2- was increased to 80 mM (in the presence of 5 mM-Mg2+) twitch height dropped to very small values within a few minutes. However, tetanic force (50 Hz) reaching 20-85% of the original value could still be induced after 1 hr in high EGTA2-. 8. The experiments show that external Ca2+ acts upon excitation-contraction coupling mainly by impeding 'inactivation'. A hypothesis is proposed in which the plateau of maximum force during a contracture is the consequence of a regenerative Cai2+-dependent shift of the inactivation curve towards more positive potentials.


The labelling of vesicles in frog endothelial cells with ferritin. 1. The labelling of endothelial cell vesicles with ferritin has been investigated by electron microscopy. Single capillaries in the frog mesentery have been perfused with solutions of known concentrations of ferritin for known periods before fixing the tissue in situ by superfusion with osmium tetroxide. 2. At 17 degrees C, the percentage of lumenal vesicles labelled with ferritin increased as the period of perfusion was increased up to 16 sec prior to fixation. When perfusions were longer than 16 sec, the percentage of vesicles labelled with ferritin remained fairly constant at 70%. 3. At 3 degrees C, no more than 25% of the lumenal vesicles were labelled during the first 30 sec. 4. After correcting the data for losses of ferritin due to sectioning, the distribution of ferritin molecules in the lumenal vesicles was consistent with a Poisson distribution. 5. After perfusions of 16 sec or longer, the number of ferritin molecules per labelled vesicle was roughly three to four times less than would be predicted from the lumenal concentration. 6. At all times there was a gradient of vesicles labelled with ferritin across the endothelial cells, i.e. the percentage of lumenal vesicles labelled was greater than that for cytoplasmic vesicles which in turn was greater than that for vesicles at the ablumenal surface. 7. Whereas the labelling of lumenal vesicles from zero time up to 16-20 sec, the main increase in labelling of cytoplasmic vesicles occurred between 10 and 20 sec. 8. It is concluded that there is a major diffusion barrier to ferritin molecules either close to the endothelial cell surface or across the necks of the lumenal vesicles. It also appears that ferritin molecules do not have access to vesicles during the latter part of their residence at the lumenal surface.


[Lymphopenia and variations in T and B lymphocytes appearing immediately after irradiation (author's transl)]. Immunity tests were conducted in 21 patients with cancer, before and two months after irradiation. T and B lymphocyte counts were normal before irradiation when compared to a control group. Lymphopenia was present after irradiation affecting mainly the T lymphocytes (P = 0.005), whereas changes in B lymphocytes were not significant. These results suggest that irradiation has an immunosuppressive effect which should be studied in greater detail to establish possible therapeutic applications.


Immunobiology of primary neoplasms of the C.N.S. Preliminary results. A preliminary report on the immunological monitoring of primary intracranial neoplasms is presented. The most important findings concerning B-cells and T-cells mediated immunity and delayed hypersensitivity reactions in this kind of patients, are discussed. Among the fairly significant immunobiological pictures, the Authors stress the "normal behaviour" of the B-cells dependent pool, the undebatable depression of the delayed hypersensitivity reactions, and the noticeable failure of the T-cell dependent pool, particularly marked in malignant gliomas, which are also characterized by the presence of cells with natural cytotoxic activity.


Activation of the frog sartorius acetylcholine receptor by a covalently attached group. The frog sartorius motor endplate was treated with the specific disulfide bond reducing agent dithiothreitol and subsequently exposed to a covalently reacting compound (the nitrophenyl ester of p-carboxyphenyltrimethylammonium iodide, NPTMB) known to activate the dithiothreitol-reduced acetylcholine receptor in Electrophorus electroplax. NPTMB causes a maximum depolarization of about 35 mV when applied to the dithiothreitol-treated sartorious motor endplate. It is ineffective on postjunctional membrane prior to disulfide bond reduction and on extrajunctional regions, reduced or unreduced. High concentrations of a competitive antagonist such as (+)-tubocurarine prevent reaction between NPTMB and the reduced receptor and cause a repolarization of the membrane when applied to the already-depolarized preparation. We conclude that in frog muscle, as in electroplax, the attached activator bridges the acetylcholine binding site of the reduced receptor between a sulfhydryl group, to which it is covalently bound, and a negative subsite, with which it forms a reversible ionic band.


Coupled transepithelial sodium and potassium transport across isolated frog skin: effect of ouabain, amiloride and the polyene antibiotic filipin. Addition of the polyene antibiotic filipin (50 microM) to the outside bathing solution (OBS) of the isolated frog skin resulted in a highly significant active outward transport of K+ because filipin per se increases the nonspecific Na+ and K+ permeability of the outward facing membrane. The K+ transport was calculated from the chemically determined changes in K+ concentrations in the solution bathing the two sides of the skin. The active transepithelial K+ transport required the presence of Na+ in the OBS, but not in the inside bathing solution (IBS), and it was inhibited by the Na+, K+-ATPase inhibitor ouabain. The addition of Ba++ to the IBS in the presence of filipin in the OBS resulted in an activation of the transepithelial K+ transport and in an inhibition of the active Na+ transport. This is in agreement with the notion that Ba++ decreases the passive K+ permeability of the inward facing membrane. In the presence of amiloride (which blocks the specific Na permeability of the outward facing membrane) and Ba++ there was a good correlation between the active Na+ and K+ transport. It is concluded that the active transepithelial K+ transport is carried out by a coupled electrogenic Na-K pump, and it is suggested that the pump ratio (Na/K) is 1.5.


The effect of thymopoietin32-36 and ubiquitin on spontaneous immunopathology of New Zealand mice. The effects of synthetic thymopoeitin32-36 and purified ubiquitin, in daily doses of 1 or 10 microgram, were studied in New Zealand mice. The most striking result was a 4-month delay in the appearance of Coombs' positive tests or Coombs' antibodies in New Zealand black (NZB) mice treated from 4 wk of age with ubiquitin. Ubiquitin also reduced the spleen weight in the animals and stimulated suppressor T cell activity in shorter term studies of older NZB and black and white (B/W) mice. Thymopoietin was also active in this assay and improved the mitogen responsiveness of lymph node cells in older treated NZB and B/W mice. Thymopoietin injections, from 4 wk of age, reduced the titer of Coombs' antibodies and thymocytotoxic antibodies in NZB mice and caused an increase in Thy 1+ spleen cells in these animals. In correspondingly treated B/W mice, thymopoietin reduced the anti-DNA antibody titer. While our present injection protocol did not result in clinical cure of the genetically determined autoimmune diseases of NZB and B/W mice, they do point to the feasibility of selective immunoregulation by these peptides in diseases associated with altered states of immune reactivity.


Voltage fluctuations at the frog sartorius motor endplate produced by a covalently attached activator. The depolarization that develops after covalent attachment of trimethylammonium benzoyl to the dithiothreitol-reduced frog sartorius acetylcholine receptor is accompanied by a small increase in voltage fluctuations. The amplitude of the elementary voltage event produced by the covalently attached activator is about 0.04 microV, almost an order of magnitude below the acetylcholine shot-effect amplitude in the control preparation, and about one-fourth the acetylcholine shot amplitude after disulfide-bond reduction. Spectral density plots of trimethylammonium-benzoyl noise can be analyzed in terms of two relaxation rates that bracket the single rate observed in response to acetylcholine.


Serum proteins--transferrin, ceruloplasmin, albumin, alpha 1-acid glycoprotein, alpha 1-antitrypsin--in rheumatic disorders. Serum levels of carrier proteins, transferrin, ceruloplasmin and albumin were determined in patients with rheumatic disorders, along with serum levels of acute phase proteins, ceruloplasmin, alpha 1-acid glycoprotein and alpha 1-antitrypsin. Depressed levels of transferrin occurred in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Albumin was reduced in SLE and RA men. Acute phase reactants which are protective in inflammation were elevated in RA, osteoarthritis (OA), gout, pseudogout (PsG), and SLE. All of these rheumatic disorders show biochemical changes compatible with systemic inflammatory disease including gout and PsG which are considered local disorders and OA which is considered noninflammatory arthritis.


Age-related changes in the immune system of mice of eight medium and long-lived strains and hybrids. I. Organ, cellular, and activity changes. Fifty-three organ, cellular and activity indices were assessed in aging mice of 8 strains and hybrids (5 inbred strains, 1 random bred strain and 2 hybrids of inbred strains) in an attempt to determine which aspects of immunologic aging are characteristic of the species. The results indicate that thymic weight, cellular, and activity indices exhibit a statistically significant negative correlation with age for mice of all 8 strains and hybrids; and B cell cellular indices show a statistically significant positive correlation with age for all mice, while the B cell activity index, lipopolysaccharide response, is dependent on the strain or hybrid. This correlation study supports the view that the T cell component of the immune system deteriorates with age while the B cell component remains relatively intact. Further, the results suggest that thymic aging is a characteristic of the mouse species and that the intrinsic "clock" for immunologic aging resides in the thymus, because most splenic and lymph node T cell activity and cellular indices are associated with thymic weight and cellular indices. Finally, the findings that indices which correlate best with age show the same trend for all strains and hybrids examined suggest that (a) if randomly occurring somatic mutation does play a role in immunologic aging, its influence is limited, and (b) genetic factors not easily influenced by environmental factors regulate immunologic aging.


[Studies for proteolysis in malignant tumours (author's transl)]. It's well known that increased proteolytic activity in plasma as well as in interstitial fluids is often associated with malignant tumours. There are numerous reports that cell cultures of malignant origin contain plasminogen activators responsible for an increased proteolysis. Our studies showed that patients with a carcinoma excrete in their urine a significant higher amount of an acid-stable inhibitor than healthy patients. This urine inhibitor is a split product (MW: 30,000) of the Inter-alpha-trypsin inhibitor (MW: 180,000). We conclude that the increased amount of acid-stable split products is the result of increased proteolysis in patients with malignant tumours. In contrast to other authors we do not think that the activation of plasmin by plasminogen is responsible for the proteolytic cleavage of ITI. Otherwise proteolysis by Cathepsin G and granulocytic Elastase would be reasonable. So enhanced proteolysis seems to be a sign of general enzymatic change associated with transformation.


Two cases of Kartagener's syndrome.

Two cases of Kartagener's syndrome. Two cases of the syndrome of bronchiectasis, chronic sinusitis and dextrocardia with situs inversus (Kartagener's syndrome) are described. This rare disorder may be important in further understanding of cilial function in humans.


Histopathological studies on experimental cryptococcosis in nude mice. Cryptococcosis in nude (nu/nu) mice was examined histopathologically. In addition, effects of carrageenan and lymph node cell transfer against Cryptococcus infection were investigated. As controls, heterozygous littermates (nu/+mice) and mice of strain ddy (ddy mice) were employed. Each mouse was inoculated intravenously with 10(5) yeast cells of Cryptococcus neoformans suspended in 0.2 ml phosphate-buffered saline. Two mice out of each group were sacrificed at appropriate intervals up to 25 days after inoculation and histopathological sections were prepared from them. They were stained with H & E and by PAS method. Histopathological characteristic in the brain was cyst formation with no cellular response. The brain was more severely in the nu/nu mice than in either the nu/+ ddy mice. In the liver, there was a major difference in histopathological findings between the nu/nu and either of the other groups of mouse. In the nu/nu mice, cyst formation with no cellular response was induced, and on the contrary granuloma formation in the nu/+ and ddy mice. However, the granuloma formation was inhibited in the livers of the nu/+ and ddy mice by administration of carrageenan, and induced in the nu/nu mice be cell transfer. In the spleen and lymph nodes, lesions were severer in nu/nu mice than in either the nu/+ or ddy mice. These results suggested that the fungus' invasiveness of mice was strongly influenced by T-cell dependent mechanism.


Host defense in Cryptococcosis. III. In vivo alteration of immunity. The present studies utilize an inbred mouse model to evaluate the adoptive transfer of spleen cells to augment immunity against Cryptococcus neoformans. Protection against cryptococcosis was transferred using spleen cells obtained from mice surviving cryptococcosis. These spleen cell donors had no detectable anticryptococcal antibody. Also, treatment with antimouse-thymocyte globulin ablated dermal hypersensitivity reactions of immunized mice, and shortened survival in both immunized and unimmunized mice. These in vivo studies further support a major role for cell-mediated immunity in host defense against experimental cryptococcosis.


Floating Myodil--a new sign of fat in the ventricles. A case in which a remarkable series of CT studies demonstrated a dermoid cyst is reported. There was leakage of fat into the ventricular system which caused hydrocephalus due to adhesions partly obstructing the fourth ventricular outlets. The latter was confirmed by a ventriculogram using Myodil which dissolved in, or combined with, the fat produced by the tumour. This resulted in a high attenuation substance of lower specific gravity than CSF, which appeared to cause acute ventriculitis.


Frontal horn coarctation: CT demonstration. A report of two cases. The CT aspects of frontal horn coarctation by ependymal fusion in two cases are described with post-mortem verification. These ependymal fusions in the lateral ventricles are seen frequently on air ventriculograms, especially in the occipital horns. Ependymal fusions in the frontal horns are rare and not very well known. These fusions are clearly seen on CT and post-mortem examinations. The frontal horns appear asymmetrical on CT and this asymmetry evokes frontal horn compression (by an isodense tumour for instance), or contralateral frontal horn dilatation. Some CT details of ventricular coaractation makes it easy to differentiate tumoural compression from controlateral subcortical atrophy.


Vitrectomy methods in anterior segment surgery. We have used vitrectomy instrumentation and techniques to treat a variety of conditions affecting the anterior segment, including: 1) an occluded or inadequate pupillary space, 2) complications of vitreous in the anterior chamber, 3) epithelial ingrowth, 4) complicated lens surgery, and 5) total hyphema. The vitrectomy methods provided controlled excision of intraocular tissues under optimum visualization using a closed-eye system with normal intraocular pressure and the ability to use techniques such as intraocular diathermy. Our experience has been favorable in this series of 117 cases. Of these, 104 cases (89%) were anatomically successful, 70 eyes (60%) had a significant postoperative improvement in vision. The detailed results of vitrectomy surgery for anterior segment disorders are presented for each indication.


Closed vitrectomy: the Grieshaber instrument. Description of Grieshaber nibbler for closed vitreous surgery: tip diameter is 1.6 mm, cutting is by four exquisitely cutting blades mounted on axis supported at both ends. Control console determines mode and speed of rotation. Oscillating cutting mode is recommended. Infusion is at the instrument's tip instead of its side. Unusually powerful but adjustable endo-illumination is available through fiberoptics. The fiberoptics tip is shaped to facilitate its introduction into the eye. A separate channel permits suction reversal. Five brief case descriptions illustrate versatility of the instrument. Its main advantages are its exquisite cutting properties, its powerful and adjustable endo-illumination, and its tip-end infusion hole.


Filtering surgery in children: barriers to success. The use of trabeculectomy in advanced pediatric glaucoma is reviewed. Intraocular pressure was controlled in only 50% of the patients, and the best visual results was 20/200. Complications of vitreous loss, scleral collapse, ectasia, retinal detachment, and endophthalmitis were encountered. No evidence was found to support the claim that in the seriously compromised buphthalmic eyes, trabeculectomy is safer than other filtering operations since it filters under a scleral flap.


Whole-body single-photon emission computed tomography using dual, large-field-of-view scintillation cameras. A whole-body single-photon emission computed tomography system (SPECT) consisting of two large-field-of-view scintillation cameras mounted on a rotatable gantry, a minicomputer and a display station has been designed, constructed and evaluated. In its usual mode of operation, eleven contiguous transverse sections, each 12.5 or 25 mm thick, are reconstructed from projection data acquired during a single, continuous 360 degree rotation lasting from 2 to 22 min. A generalised filtered and weighted backprojection algorithm is used to reconstruct data obtained with conventional parallel-hole collimators in the case of body scanning, or with specially designed fan beam collimators in the case of centrally positioned organs. A simple, yet effective, correction is used to compensate for the effects of gamma ray attenuation within the patient. In addition to providing transverse section images, the system is capable of simultaneous acquisition of opposed conventional scintigrams, the reconstruction of longitudinal section images, and the acquisition of gated cardiac transverse sections. Resolutions in the reconstructed images are typically 15 mm for body scans and 11 mm for brain scans, with only slight variations in sensitivity and resolution within the image. Phantoms and clinical data demonstrate that the SPECT system generates high quality section images while maintaining most of the flexibility of normal scintillation cameras, with the added advantage of dual heads.


Improved diagnostic accuracy of a modified oral pancreatic function test. The oral pancreatic function test (PFT) depends upon urinary recovery of p-aminobenzoic acid (PABA) released by chymotrypsin hydrolysis of orally administered N-benzoyl-L-tyrosyl-p-aminobenzoid acid. The diagnostic value of the test is limited because falsely abnormal results frequently occur in patients with bowel or liver disease in whom PABA recovery is impaired by abnormal absorption or hepatic conjugation, even though pancreatic function is normal. To overcome this problem, we have modified the oral PFT to correct for impaired PABA absorption and conjugation. Results of the oral PFT have been compared with urinary recovery of an equivalent dose of free PABA in order to derive a PABA excretion index (PEI). When the modified oral PFT is used, the PEI clearly distinguished patients with pancreatic disease from normal subjects. In patients with small-bowel or liver disease and normal exocrine pancreatic function, the PEI results were similar to those of normal subjects, although a previous oral PFT had been falsey abnormal. The modified test can therefore distinguish abnormal results due to pancreatic disease from the falsely abnormal results found in liver and small-bowel disease.


Cross-reactive cytotoxic T cells to alphavirus infection. Secondary Tc cells immune to alphaviruses (BEB, SIN and SFV) cross-react between serologically defined subgroups at the level of target lysis and at the level of induction of response. Despite this apparently complete Tc cell cross-reactivity between BEB, SIN and SFV, antisera raised against BEB and SIN showed virus specificity in their ability to block Tc cell-mediated lysis of alphavirus-infected targets. This result suggests that Tc cells recognize the same viral antigen molecule as antibodies, but with less specificity. Other possible interpretations are discussed.


Gastrointestinal hemorrhage: angiodiagnosis and angiotherapy. Angiographic methods cannot and should not be applied to every patient with GI bleeding. Three out of four patients stop bleeding with conservative measures (bed rest, volume replacement, sedation, etc.). Major indications for angiography: patients who continue to bleed, despite conservative measures; when endoscopy is not available, is contraindicated, or inconclusive; when other diagnostic tests and/or laparotomy have failed to demonstrate the site and cause of bleeding. Angiography must be available at all times, and must be performed with expediency and with competence.


The effect of specific antibody on the generation of cytotoxic T lymphocytes and the recovery of mice from influenza virus infection. A study has been made of the effect of humoral antibody on the generation of specific cytotoxic T cells (Tc) in the spleen or lungs after intravenous injection or intranasal inoculation of infectious influenza virus. Antibody injected before or at the same time as virus inhibited completely the generation of Tc in the spleen. If injected 1 h after virus, the inhibition was reduced by 50%, and little inhibition occurred if antibody was injected 6 h after virus. This suggested that antibody failed to influence Tc generation once infection of stimulating cells had occurred. Antibody  injected intravenously 24 h after intranasal inoculation of virus into normal mice did not affect the level of cytotoxic activity present in the lungs, and trace amounts only (less than 1 log10 EID50) could be recovered from the lungs at 6 days. As there is a high titre (greater than 6 log10 EID50) of infectious virus in the lungs of mice 24 h after infection, this represents a very efficient control mechanism. The same protocol carried out with athymic mice gave only a partial clearance (c. 3 log10 EID50) of virus in the lungs. It was suggested that a major role of humoral antibody was to limit infection by the virus, and in this respect it complemented the action of Tc.


Intraembryonic origin of lymphoid stem cells in the chicken: studies with sex chromosome and IgG allotype markers in histocompatible yolk sac-embryo chimaeras. Two-day-old chick embryonic bodies were transplanted onto the area vasculosa of age-matched histocompatible blastoderms, resulting in the development of yolk sac-embryo chimaeras. Eighteen of these succeeded in hatching and became adults. Differences in the sex chromosomes and in IgG allotype between the embryo and the yolk sac were used to study the contribution of these two components to the lymphoid cell development. At 5-7 weeks of age the chimaeras proved to be completely normal in the IgM and IgG antibody production against human gamma globulin and Brucella abortus and in the lymphocyte responses to phytohaemagglutinin and concanavalin A. For the sex chromosome analyses bursa cells and specifically stimulated B and T lymphocytes were used. The latter was achieved by stimulating thymus, spleen, and bone marrow cells in vitro with anti-Ig and Con A. Only four out of 1498 mitoses analysed belonged to the sex opposite to that of the bird. Among the chimaeras eleven were marked through IgG allotypes. At the age of 3-20 weeks all eleven chimaeras showed serum IgG of the embryo allotype and none of the yolk sac type. These results, based on the use of two different markers, indicate that lymphoid stem cells in the chicken are originally derived from an intraembryonic source and not from the yolk sac.


EMG-controlled functional electrical stimulation of the paretic hand. A new apparatus is described which delivers a functional electric stimulation, controlled by the peak EMG output signal as recorded from the forearm muscles. Twelve paretic hands were stimulated with this apparatus. The EMG output, the stimulus strength, the stimulus frequency, and the corresponding improvement of the wrist extension force were measured. Different arrangements of electrodes and various relay adjustments were tested. The investigations showed that even severely paretic muscles were capable of delivering an efficient EMG output, and the resulting improvement of wrist extension force was statistically significant. The necessary stimulus intensity showed no relationship to the degree of paresis, but a certain relationship to the recovery tendency of the hand was evident. Acceptance of the apparatus among the patients was satisfactory; only a few complained of pain during stimulation.


Evidence for a central monoaminergic influence on urinary bladder control mechanism. The aim of the present study was to investigate a possible central monoaminergic influence on the control mechanism of the urinary bladder in rats. A selective central nervous stimulation was accomplished by injection of monoaminergic precursor (L-dopa and 5-HTP) after enzymatic blockade of its peripheral metabolisation. The bladder response was recorded with a cytometric procedure. The central adrenergic stimulation with L-dopa resulted in a hyperactive bladder response, with higher intravesical pressure and more prominent detrusor contractions than in control rats. Injection of 5-HTP had no such effect. The hyperactive bladder response to L-dopa was abolished by prior administration of a central dopamine receptor blocking agent (spiroperiodol). This indicated that the central effect on the bladder was elicited by dopaminergic structures. Peripheral adrenergic stimulation with metabolites of L-dopa--dopamine and noradrenaline--gave no measurable bladder response. The study showed that activation of central adrenergic mechanisms influenced urinary bladder control, i.e. evoked a hyperactive bladder response.


Screening for Trichomonas vaginalis infection by use of acridine orange fluorescent microscopy. The acridine orange test for detection of Trichomonas vaginalis in smears has been adapted for delayed examination of specimens. Mailed-in slides stained by acridine orange were compared with on-site wet mounts; the acridine orange test detected 96% of all positives, whereas only 76% were detected by wet mounts. In a similar comparison with Papanicolaou smears, the acridine orange test detected 89% as compared with 67% detected by Papanicolaou smears.


Do oral contraceptives inhibit Trichomonas vaginalis? Usage of oral contraceptives was recorded for 114 women with trichomoniasis, 179 women with yeast infection, and 333 women with gonorrhea. Usage by each group was compared with that of 517 women with no genital infection. The proportion of oral contraceptive users was significantly smaller among those with trichomoniasis (P less than 0.002), significantly larger among those with yeast infection (P less than 0.001), but not significantly different among those with gonorrhea. Among 80 women with both trichomoniasis and gonorrhea, a significantly smaller proportion used oral contraceptives as compared with a group of 253 women who had gonorrhea alone (P less than 0.002). The results suggest that oral contraceptives may inhibit trichomoniasis and enhance infection of the vagina by yeasts.


IgM anti-IgM cold lymphocytotoxins to B cells. Cytotoxic antibodies to B lymphocytes have been shown to be IgM. They are not absorbed by red blood cells and therefore not absorbed by red blood cells and therefore not directed against the I antigen of red cells. They are also not inhibited by mannose, as are certain natural cytotoxins against lymphocytes. Methods for producing purified eluates of IgM anti-IgM antibodies are given. These antibodies are postulated to be immunoregulative by acting on B lymphocytes.


Natamycin treatment of ringworm in cattle in the United Kingdom. A total of 258 cattle clinically affected with Trichophyton verrucosum (ringworm) were treated twice by spraying with a suspension containing the fungicidal antibiotic natamycin. One-hundred-and-forty-seven in-contact, but unaffected cattle were also similarly treated. Forty-one of the affected animals were examined mycologically and clinically as they were taken to be representative of the whole group. At eight weeks after the last treatment 93 per cent of the affected animals had completely recovered and the remaining 7 per cent had improved markedly; 70 per cent of the mycologically examined animals proved negative at the same time. No reinfection of the recovered animals or spread of the disease to the treated in-contact animals was seen up to six months after treatment.


The variety of synaptic vesicles in the interpeduncular nucleus (ITP) of the frog. The electron microscope has revealed a large variety of synaptic vesicles in the interpeduncular nucleus (ITP) of the frog "Rana esculenta". They vary in shape, size and electron density. There are two types of synapses which show only translucent spherical vesicles: in one type the vesicles are 40 nm, in the other type they are 70 nm in diameter. In other types of synapses the translucent vesicles may be mixed with those with dense core. Large granules, 160 nm in diameter, already reported in the ITP (KEMALI 1977a), are also shown as well as tiny flat mixed with large flat dense core vesicles of dumb-bell shape. Two types of axo-axonic synapses are illustrated while no crest synapses have been demonstrated. The results suggest that the afferents to the ITP might be more numerous than those reported in the literature or that--as in the case of the habenular afferents which consist of cholinergic and peptergic fibres--each projecting nucleus to the ITP has different types of fibres with more than one type of transmitter. Furthermore, due to the vesicles sizes, we may consider the ITP as a site in the vertebrate central nervous system where conventional neurotransmitter structures coexist with probable neurohumoral elements.


[Detection of dyschromatopsias and professional orientation]. Certain professions necessitate correct recognition of colour in their practice. Early defection of coloured vision abnormalities and professional orientation are therefore very important, especially as it is known that 8 % of the population presents a congenital dyschromatopsy of which one fourth (about 2 %) are serious dyschromatopsies which will prevent the practice of a certain number of professions.


[The effect of vasopressive drugs in managing bleedings from oesophageal varices and the intestinal tract (author's transl)]. The therapeutic effect of TGLVP a new hormonogen of vasopression in demonstrated in a pilot study: 9 patients suffering from bleeding oesophageal varices (in total 16) could be sufficiently treated by TGLVP, as well as 9 patients (in total 13) with abdominal haemorrhage of unknown aetiology and localization. Good results can be expected by TGLVP to bring gastrointestinal bleedings to a standstill.


[Use of prostaglandin F 2-alpha in placental period (author's transl)]. Reported in this paper is the intravenous application of prostaglandin F 2-alpha in the placental period and in cases of severe postpartum haemorrhage. -- Intravenous infusion of per-minute amounts between 40 and 80 micrograms in cases of atonic haemorrhage or between 30 and 45 micrograms in the placental period, in general, produced uterine contraction and clearly reduced blood loss.


[Aetiopathology and forms of obstetric coagulopathies (author's transl)]. An account is given of the pathological mechanism of coagulopathies resulting from excessive loss of blood, exhaustive consumption of coagulation factors or hyperfibrinolysis. While there is no unambiguous differentiation between various forms of coagulopathies in obstetrics, major characteristics should be well understood for therapeutic decision-making. The early high-accuracy laboratory test, therefore, is imperative.


[Spontaneous evacuation of a traumatic retroperitoneal hematoma through the colon]. Retroperitneal hemorrhage following blunt trauma of the abdomen is an ever more frequent problem confronting the surgeon in everyday practice. This paper presents an interesting and exceptionally rare case concerning a patient with a blunt injury of the abdomen which resulted in the rupture of the retroperitoneal portion of the colon between the descendens and sigmoid. A resultant retroperitoneal hematoma was palpable as an elastic mass. Contamination with bacteria lead to infection of the hematoma with the subsequent formation of an abscess. Later this abscess spontaneously evacuated itself through the rupture in the colon which was verified with irigography. As a late consequence of this abscess drainage, the colon became constricted. This process as of yet has not caused any difficulties in passage but nonthe-less surgery was indicated which the patient refused. The authors believe that the retroperitoneal hematoma caused by blunt injury of the abdomen is one of the most difficult diagnostic problems because this anatomical region is inaccessible and lesions within its confines are difficult to detect.


Epiglottis acuta treated with nasotracheal intubation. Twenty children, ranging in age from 1--9 years, and one adult suffering from epiglottis acuta were treated with nasotracheal intubation performed under general anaesthesia and with ampicillin. Clinical cure was obtained in all cases with a mean intubation time of 34 hours. The diagnosis, epiglottis acuta, was suspected by the referring physician in 10 cases. The incidence of epiglottis acuta compared to laryngitis acuta was found to be 1:30. The mean hospital stay was 5.4 days. It is concluded that treatment of acute epiglottis by nasotracheal intubation in the hands of experienced anaesthesiologists and with close observation in an intesnive care unit, is a safe method of management with negligible morbidity and mortality.


Myocardial performance early after aorto-coronary bypass surgery and the influence of nitroprusside infusion. The central and peripheral circulation were studied in 12 patients after aortocoronary bypass surgery. During the initial 5 h after termination of cardiopulmonary bypass, the oesophageal temperature rose from 36.5 degrees C to 39.4 degrees C, concomitant with cutaneous vasoconstriction and an increase in systemic vascular resistance (SVR) and mean arterial blood pressure (MABP). The oxygen uptake index (Vo2I) increased by 57% during the rewarming period. The cardiac index (CI), which was constant at 2.8 l.min-1.m-2, was too low to satisfy this oxygen demand and the arterio-venous oxygen content difference (AVDo2) increased to 3.0 mmol . l-1 by the 3rd hour. After 5 h, SVR had decreased and cutaneous vasodilation began. Vo2I and AVDo2 decreased. The postoperative myocardial function was moderately impaired and deteriorated after the cutaneous vasodilation. Twelve patients were given an infusion of sodium nitroprusside during the postoperative period (0.25--2.5 micrograms . kg-1 . min-1). The rewarming pattern was not influenced by this infusion, but the initial increases in MABP and SVR were eliminated. The myocardial performance was better in the nitroprusside group. CI was significantly higher than in the control group (3.5 l.min-1.m-2) and AVDo2 remained normal.


Myocardial performance early after aorto-coronary bypass surgery. Cardioplegic arrest versus coronary perfusion. Haemodynamic adaptation was studied during the first 10 h after aorto-coronary bypass surgery. In a control group of 12 patients the heart was fibrillating and perfused during cardiopulmonary bypass (at 30 degrees C), and in 11 patients cold cardioplegic arrest was used. The first 4--5 h were characterized by rewarming, with increasing oesophageal temperature, cutaneous vasoconstriction and elevated systemic vascular resistance (SVR). A phase of vasodilation followed. In the control group the oxygen uptake index increased by 57% during rewarming, but the cardiac index (CI) was constant (about 2.9 l . min-1.m-2). The arterio-venous oxygen content difference (AVDo2) therefore increased (max. 3.0 mmol . l-1). The postoperative left ventricular performance was better and the serum levels of aspartate aminotransferase (ASAT) during the first 2 days postoperatively were lower in the cardioplegic patients than in the controls, indicating more efficient myocardial preservation. In the cardioplegic-hypothermic group, CI was constant at about 3.2 l . min-1.m-2 (significantly higher than in the control group) and AVDo2 remained normal during the rewarming period. The heart rate was lower initially in the cardioplegic patients than in the controls, implying a favourable influence on myocardial oxygen consumption. The better myocardial function in the cardioplegic-hypothermic group was associated with an only moderately increased SVR. This suggests that the elevated SVR in the control group could have been due to myocardial depression.


Enflurane in patients with coronary artery disease. In 12 patients with coronary artery disease, hypertensive periods during aortocoronary bypass surgery were treated with 1 MAC enflurane. The effect of enflurane on the major determinants of myocardial oxygen consumption was studied. Systolic arterial pressure was reduced to a level of about 120 mmHg (16 kPa). The heart rate diminished by 16.5%. The cardiac index during enflurane application was unchanged. Pulmonary artery wedge pressure was measured at short intervals and remained unchanged. The fall in arterial pressure and heart rate under unchanged preload produced a significant reduction in myocardial oxygen consumption as determined by calculation of the systolic wall tension and the tension time index. In five patients, the O2 content in coronary sinus blood was measured and the arterial-coronary sinus O2 difference was found to be diminished. In the concentration used, enflurane reduced the myocardial oxygen consumption of patients with coronary artery disease.


The immunodepressive effect of human glucoproteins and their possible role in the nonrejection process during pregnancy. Human chorionic gonadotrophin (HCG) and human chorionic somatomammotrophin (HCS) were shown to suppress the proliferative T and B cell response induced by different mitogens in human and mouse lymphocytes. Thyroid stimulating hormone (TSH), sharing the alpha-chain subunit with HCG was devoid of effect suggesting that the immunosuppressive entity is localized within the beta-chain subunit. Human growth hormone (HGH) which is partly biologically cross-reactive with HCS did not impair mitogen responsiveness. HCG was also able to inhibit the differentiation of cells since the induction of antibody-formation was depressed. Expression of plaque forming cells was also reduced by addition of HCG directly in the PFC assay possibly reflecting the anti-complementary effect of this hormone, since cell mediated lysis of target cells by Con A activated lymphocytes, which is not complement-dependent, was unaffected by adding HCG in the assay system.


The vascular supply of the endolymphatic sac. The vascular anatomy of the endolymphatic sac in guinea pigs was examined following intravascular injection of silicone rubber (Microfil). Methacrylate resin of low viscosity (Mercox) was used to obtain vascular corrosion casts for scanning electron microscopy, which allowed more accurate differentiation between arteries and veins. The extensive vascular system around the sac comprises both arteries and veins, as well as lymphatic vessels. The arterial supply is derived mainly from the posterior meningeal artery in the posterior cranial fossa. In some cases a small artery also leads to the sac from the posterior vestibular artery in the labyrinth (in 7 of the 35 animals investigated). It courses together with the vein of the vestibular aqueduct along the walls of the endolymphatic duct. The blood is drained over the intermediate portion of the endolymphatic sac, which becomes lodged in a rich meshwork of capillaries, venules, veins and a few small arteries. A few venous trunks from both sac walls fuse with the vein of the vestibular aqueduct, which drains blood from the vestibule to the sigmoid sinus. Scanning electron microscopy also revealed numerous anastomosing vessels within bone channels with adjacent bone marrow sinusoids, which also probably contribute to the vascular supply of the endolymphatic sac.


Synaptic structures in the type II hair cell in the vestibular system of the guinea pig. A freeze-fracture and TEM study. The synaptic contacts of the type II hair cell in the vestibular system of the guinea pig was described in thin-sectioned and freeze-fractured specimens. Synaptic bodies were present at the apposition with both large and small afferent terminals. About 20% of the synaptic bodies observed consisted of complexes of two or more adjacent synaptic discs. In freeze-fracture replicas, the cytoplasmic leaflet of the hair cell plamalemma beneath the synaptic body had a bar-shaped aggregate of large particles. The size and shape of the particle aggregate was the same as that of the synaptic body. Small plasmalemmal deformations, interpreted as sites of synaptic vesicle exocytosis, were found immediately adjacent to the particle aggregate. On the postsynaptic membrane, an aggregate of intramembrane particles was present at the synaptic junction. The type II hair cell had no gap junctions or close membrane appositions between it an the apposed afferent fiber. Efferent boutons ending on the type II hair cell had no intramembrane particle specialization on the postsynaptic membrane; however those efferent boutons ending on large and small afferent fibers had an aggregate of medium-sized particles on the external leaflet of the postsynaptic bouton beneath the presynaptic active zone.


Electronystagmography in the laboratory rat. A method is described for obtaining electronystagmograms from the awake laboratory rat. Threshold valves for rotation impulse and oscillatory acceleration were determined, as well as the time constant for the horizontal semicircular canal. The time constant appeared to be small. This might be attributed to the rapid natural head movements in this species. No visual suppression of vestibular nystagmus was found in the rat.


Cochleo-vestibular correlations in Meniere's disease. The cochlear and vestibular functions were investigated in a sample of 36 patients with unilateral Meniere's disease. Caloric reactions and hearing thresholds were compared separately at several frequencies. A topodiagnostic relationship between the cochlear and vestibular function was discovered. Using four qualitative categories, a significantly high correlation was obtained between the basal hearing loss (4000 Hz) and unilateral weakness, whereas no correlation was obtained when evaluating the more apical hearing loss (lower frequencies 250-1 000 Hz). A normal caloric reaction can be reasonably expected in cases of unilateral Meniere's disease if the hearing loss is less than approx. 40 dB HL at 4 000 Hz.


Vasopressin for bleeding from the head and neck. Excessive bleeding from the head and neck sometimes presents a therapeutic problem. Ten patients with this type of haemorrhage have been treated with continous vasopressin infusion for 1-3 days. Haemostasis was quickly established in eight cases. No serious side effects were noted. Infusion of vasopressin has a rapid, beneficial effect on haemorrhage from branches of the external carotid artery.


Histiocytosis X. V. Serum calcitonin concentrations and osteolytic activity. Serum calcitonin determinations were carried out in 11 patients with histiocytosis X, 5 having lytic bone lesions. All serum calcitonin concentrations were within normal range. This makes serum calcitonin determinations useless as a marker of osteolytic activity in patients with histiocytosis X.


Application of Solcograft in vascular surgery. Incorporation of Solcograft was studied experimentally and clinically. The graft was found to facilitate the formation of continuous endothelium which starts at the vessel graft boundary and from newly formed capillaries. Transmission and scanning microscopical investigations revealed neointima, neomedia and neoadventitia formation in 3--4 months. Complications such as obliteration were unfrequent. Aneurysm formation did not occur, the potency rate was satisfacory. Experience in 20 clinical cases are reported in detail. As to its usefulness in reconstructive vascular surgery, Solcograft is placed behind the saphenous graft. The graft is particularly suitable for patch plastics.


The kinetics of immunoglobulin synthesis by pokeweed mitogen stimulated peripheral blood lymphocytes in multiple myeloma. As a means of investigating the immunoglobulin (Ig) deficiency in multiple myeloma, the effects of pokeweed mitogen (PWM) on morphologic transformation and concomitant immunoglobulin synthesis and secretion kinetics were studied in peripheral blood lymphocytes (PBL) of normals and patients with myeloma. Lymphocyte Ig production kinetics, both in the unstimulated state and after five days of culture with PWM, were evaluated by 3H-leucine incorporation. B-lymphocytes were found to be decreased by EC3 rosetting in the myeloma patients studied. In addition their lymphocytes had a mean of 30% transformation compared to 53% for normals (P less than 0.005). After five days of mitogen stimulation in culture, myeloma PBL failed to show the rise in intracellular Ig production seen in normal PBL under similar conditions. Thus, myeloma patients were found to have decreased numbers of EC3 rosetting B-cells, decreased morphologic transformation rate in response to mitogenic stimulation, and failure to increase intracellular Ig after mitogenic stimulation. Possible etiologic mechanisms for the decreased Ig production are discussed.


Intensive leukapheresis in the management of cytopenias in patients with chronic lymphocytic leukaemia (CLL) and lymphocytic lymphoma. The role of leukapheresis was explored in the management of anaemia and thrombocytopenia complicating the accumulation of lymphoid cells in patients with chronic lymphocytic leukaemia and lymphoma. The aim of this study was to determine the efficiency of this procedure in correcting these complicating features and to assess the length of response and the clinical well being of the patients. Twenty such patients with either chronic lymphocytic leukaemia or lymphocytic lymphoma were studied using a Continuous Flow Cell Separator (Aminco Celltrifuge). All had persistent significant anaemia and/or thrombocytopenia prior to the institution of leukapheresis. The procedure was carried out on alternate days until significant reduction in total circulating lymphoid cells had been achieved, an average of 2.9 x 10(11) cells being removed on each occasion. Thirteen of the twenty patients showed a significant elevation of both haemoglobin and platelet level concomitant with reduction in lymphoid cells. A reduction in organomegaly was also observed. These patients were classified as "responders," but the other patients failed to show correction of the haematologic parameters. This procedure permitted a number of responder patients to receive more specific treatment but in some it obviated the necessity for any further management for up to 12 months. Surface marker studies were also carried out on the lymphocytes of these patients. The patients who showed the best response to leukapheresis had cells characteristic of those seen in chronic lymphocytic leukaemia. The reduction of cells (82%) was greater in those who responded to this treatment than in the non-responder group (72%). The procedure was well tolerated by all patients and overall provided a long-term control of disease which outweighed the initial cost incurred.


[Monitoring equipment and electric everyday medicine. Prevention of failures (author's transl)]. Certain electrical equipments such as monitoring device, defibrillator, heart stimulator need in everyday medicine often deceive their users by not always supplying the expected services. This state of affair is due both to the lack of coordination between doctors and equipment fabricators, to lack of maintenance and to insufficient information from doctors. However, checking procedures guarantee a certain label of performance.


beta-Blockade therapy for supraventricular tachyarrhythmias after coronary surgery: a propranolol withdrawal syndrome? A high incidence of cardiac arrhythmias and hypertension has been noted after coronary artery bypass surgery in patients previously treated with oral propranolol. Forty-two patients undergoing coronary bypass surgery had propranolol withdrawal 10 hours before surgery and were randomized into a group treated with propranolol immediately postoperatively, and a nontreatment group. Patients treated with prophylactic propranolol had a significantly lower incidence of postoperative supraventricular arrhythmias compared to patints who received no prophylaxis. All the arrhythmias responded rapidly to 1 mg of intravenous propranolol therapy, whether it was used as a primary treatment or as a supplement to prophylactic propranolol. The findings suggest that (1) there is a high incidence of supraventricular arrhythmias and sinus tachycardia after coronary artery bypass which might reflect an abrupt propranolol withdrawal, and (2) that perioperative prophylactic or supplementary propranolol therapy will successfully prevent or treat most of these arrhythmias.


[Corneal distrophy of Groenouw type I and chromosomic delection (22p-) in one family (author's transl)]. Authors report a family in which three members presented a type I Corneal Distrophy of Groenouw; two of them also presented a delection of short arms of a 22 chromosome, while the third presented the delection but not the corneal distrophy. The absence of relationship between the corneal distrophy and the 22 delection in this family proves that the latter is a familial marker, not being the cause of the disease.


Cellular and humoral requirements for T-cell development. T-cells develop as a consequence of intrathymic and postthymic events, in which hemopoietic progenitors are differentiated into precursors and effector cells. We are proposing that such process includes three integrated steps: (1) T-cell differentiation; (2) selection of the T-cell repertoire and (3) specialization into functional subsets of T-cells. Although there is evidence of specific and nonspecific humoral factors (i.e. thymic extracts, etc.) affecting T-cell differentiation, it is also proposed that the most critical component in this integrated process is the consequence of direct cell to cell interactions between precursor and inducer cells. Thus, the three processes are the consequence of the appropriate or condordant matching of precursor-inducer populations, both at intra- and extrathymic sites. It is also proposed that MHC determinants are critical in permitting the appropriate matching. The model can thus account for nonfunctional differentiation when the appropraite matching is not available and with intrathymic selection by excess cell production favoring the appropriate matching.


Two mechanisms of cell-mediated cytotoxicity: Ca++ transport modulation by lymphotoxin and transmembrane channel formation by antibody and nonadherent spleen cells. Lymphotoxin is a protein with a MW of 45,000 daltons derived from activated lymphocytes that kills target cells nonspecifically. Kinetic studies indicate that there is a lag period of about 4 hours before cytotoxicity becomes apparent, even at high concentrations of lymphotoxin. Therefore, the role of lymphotoxin in cell-mediated cytotoxicity would be restricted to situations in which more rapid mechanisms are not operative. It has found that lymphotoxin increases the rate of 45Ca++ uptake by the mouse L-cells used as targets. This effect and the cytotoxicity are abrogated by ouabain. A lymphotoxin-resistent L-cell mutant did not display the 45Ca++ uptake effect. It is not known whether the Ca++ effect is primary or secondary. Neutralization experiments with anti-lymphotoxin have indicated that there are at least two distinct pathways by which immune lymphocytes can destroy target cells in vitro--one that involves secretion of a nonspecific soluble factor, i.e., lymphotoxin, and another that probably requires intimate contact between the plasma membranes of the target and killer cells. This "membrane contact" mechanism may involve formation of channels in the target cell membranes. The transmembrane channel concept is a working hypothesis that is based on experiments by Henkart and Blumenthal in which it was found that antibody and lymphocytes jointly produce ion-conducting channels in planar bilayers of "oxidized cholesterol." In order to supplement and extend this approach we have made an exploratory study of 86Rb+ and 51Cr marker release from lecithin/cholesterol/dicetyl phosphate liposomes by antibody and nonadherent mouse spleen cells. Evidence is presented indicating that the antibody and cells cause direct synergistic marker release from liposomes into the fluid medium. This indicates that they have the capacity to damage phospholipid bilayers. Hence, it seems worthwhile to conduct further studies of the liposome model in order to uncover the mechanism of membrane damage and to assess its relevance to cell-mediated cytotoxicity.


In vivo generation and regulation of killer T-cells directed towards hapten-coupled syngeneic cells. We have extended our studies which show that hapten-specific killer T-cells can be generated in vivo towards hapten-conjugated, syngeneic spleen cells provided an auxiliary antigenic stimulus is incorporated. M1s antigen served in this auxiliary capacity by stimulating helper T-cells. Natural or experimental tolerance to these antigens abrogated cytotoxicity. Effecting tolerance in host animals towards target hapten also prevented development of the genetically restricted killer T-cells. Thus, cytolytic T-cells can be controlled equally at the levels of helper and pre-killer cells. While adoptive transfer of hapten-specific tolerance by means of spleen cells did not abrogate appearance of hapten-specific killer T-cells, it did prevent hapten-specific DTH. Thus, the mechanism for regulating the latter may differ significantly from that for CML.


In vitro antibacterial activity of cefoperazone (T-1551), a new semisynthetic cephalosporin. Cefoperazone, a new semisynthetic cephalosporin, has a broad spectrum of antibacterial activity. It is as active as cefazolin and cefamandole against gram-positive bacteria and is more active than cefazolin and cefamandole against such gram-negative bacilli as Escherichia coli, Klebsiella pneumoniae, Proteus species, Pseudomonas aeruginosa, Citrobacter freundii, Enterobacter cloacae, and Serratia marcescens. The superiority of cefoperazone over cefazolin and cefamandole with respect to activity against P. aeruginosa by more than 200-fold was especially remarkable. As with other beta-lactam antibiotics, there was only a small spread between the minimum inhibitory concentrations and the minimum bactericidal concentrations of cefoperazone and a significant decrease in activity with an increase in inoculum size. Activity was not altered significantly by the addition of human serum to the test medium. Cefoperazone is relatively stable to hydrolysis to beta-lactamases produced by gram-negative bacteria. Relative rates of hydrolysis of cefoperazone by cephalosporinases are 7.0 to 0.01, with reference to cephaloridine hydrolysis (base, 100). Cefoperazone is also more stable than penicillin G and cephaloridine to various types of penicillinases.


Comparison of activity and beta-lactamase stability of cefotaxime with those of six other cephalosporins. A study of the susceptibility to cefotaxime and six other cephalosporins in 213 nonselected strains of nine different bacterial species clearly showed that cefotaxime was the most active against aerobic gram-negative bacilli. The same pattern emerged with 84 cephalothin-resistant strains of five enterobacterial species, but the mean minimal inhibitory concentration values for all cephalosporins were about twofold higher in this group of strains. Cephalothin was the most active antibiotic against Staphylococcus aureus. The inoculus effect of 10 cephalothin-resistant strains was relatively small, but it was most marked for cefamandole, as compared with that of three other new cephalosporins, including cefotaxime. The susceptibility of these cephalosporins to beta-lactamases from 12 beta-lactamase-producing enterobacterial strains was determined. Half of these were slightly active against cefotaxime and had similar activity against cefuroxime. Cefoxitin was not degraded at all, and cefamandole was the most susceptible. No correlation between beta-lactamase susceptibility and minimal inhibitory concentration values of different cephalosporins was found. Cefotaxime combined high intrinsic antibiotic activity with marked resistance to beta-lactamase inactivation.


Clavulanic acid and penicillin treatment of Staphylococcus aureus renal infection in mice. Clavulanic acid, an inhibitor of beta-lactamase, was used together with penicillin to treat infection caused by a penicillinase-producing Staphylococcus aureus. Clavulanic acid + penicillin administered to mice, prophylactically or in treatment of established infection, reduced morbidity, bacterial counts in the kidneys, and/or mortality; these differences were statistically significant when compared with those obtained by using penicillin or clavulanic acid alone.


Lymphocyte changes in beta-thalassaemia major. Lymphocyte subpopulations were studied in 20 hypertransfused patients with beta-thalassaemia major, some of whom had been splenectomised. B-lymphocytes were normal but T-lymphocytes were decreased in all patients. The T-cell count was lower in the splenectomised patients than in the nonsplenectomised ones. In the former, the active rosette-forming lymphocytes were also diminished, but the difference was not significant. In all patients the percentage of null cells was greater and the activity of K-cells increased compared with controls.


[Teratoma of the 4th ventricle and precocious puberty. Case report]. A case of precocious puberty and diabetes insipidus in a 7 years old boy due to a malignant teratoma in the IVth ventricle is reported. The tumor had grown into the IIIrd and lateral ventricles as found on the necropsy. The original site of the tumor and the possible physiopathological mechanisms for the precocious puberty are discussed.


Multiple use of benzoin as an aid in neurosurgical practice: the watertight benzoin dressing. The author presents a survey of his experience with the use of benzoin as an aid to prevent and to treat wound complications as: CSF leakage ruptured meningoceles, prevention of leakage and wound infections, during the use of external cranial drainage, indwelling catheters or implanted cannulas and electrodes. A few other handy uses are also mentioned.


[Macular involvement in retinitis albescens (author's transl)]. Two cases of retinitis albescens with macular involvement are reported. Fundus changes and functional examination has been taken into account for the differential diagnosis of the condition from fundus albipunctatus cum hemeralopia.


[Investigations for simplification of the clinical rotation test of irritability of the human vestibular organ (author's transl)]. Fifty ear-sound adolescents were rotated by constant acceleration and deceleration. These investigations yielded three results. 1. The nystagmus of acceleration and deceleration period permits a more exact statement about rotation irritability of peripheral vestibular organ than the per-rotatoric fading nystagmus during constant rotation. 2. The stop out of constant rotation causes only a fading nystagmus, the postrotatorius I. Consequently, deceleration should substitute the stop with regard to its greater exactness. 3. Statistical comparison shows that electronystagmograms of acceleration and deceleration correspond to electronystagmograms of right and left rotation. Therefore, the clinical rotation test is practicable with only one direction of rotation. In this case, deceleration has to be of the same strength and duration as the acceleration.


Affinity chromatography in the separation of human alpha 1-antitrypsin (alpha 1-AT) and antithrombin-III (AT-III). The two antiproteases alpha 1-antitrypsin (alpha 1-AT) and antithrombin-III (AT-III) have been purified simultaneously from human plasma. Purification procedure consisted of gel filtration on Sephadex G-200 after initial processing of plasma, followed by ion exchange chromatography on DEAE-Sephadex A50 and DEAE-Cellulose, at a pH of 9.0 and pH 8.3 respectively. The two proteins could not be separated by any of these procedures including a lower pH (7.4) in ion exchange chromatography. Affinity chromatography on heparin-Sepharose separated the proteins since alpha 1-AT did not bind to the matrix. Alpha 1-AT unbound to the heparin-Sepharose was subsequently purified through con A-Sepharose affinity column. The final yield of both the proteins was about 20%. The molecular weight estimated on SDS electrophoresis for AT-III and alpha 1-AT was 63,000 and 50,000, respectively.


Thiamphenicol as an immunosuppressant in active systemic lupus erythematosus with nephritis. Thirteen patients with active systemic lupus erythematosus (SLE) and biopsy proven nephropathy were treated with thiamphenicol for two weeks. Laboratory indices of SLE disease activity (antinuclear factor, complement activity and ESR) were improved after the course of treatment in half of the patients and did not change significantly in the rest. Thiamphenicol may have value as an alternative to currently popular immunosuppressive drugs in the management of systemic lupus erythematosus.


Cell-mediated cytotoxicity of lymphocytes from chickens inoculated with herpesvirus of turkey against a Marek's disease lymphoma cell line (MSB-1). Using a new device which increases the sensitivity of detection of specific immune lysis of target cells by labeling them with [35S]-methionine, the in vitro cell-mediated cytotoxic response of spleen lymphocytes and peripheral blood lymphocytes from chickens vaccinated with herpesvirus of turkey (HVT), O1 strain, against MSB-1 line cells was clearly demonstrated. The cytotoxic activity was clearly inhibited by pretreatment of effector lymphocytes with anti-T lymphocyte serum and complement. The activity was greater using T cells purified from spleen lymphocytes and peripheral blood lymphocytes than with the unfractionated cells, indicating that T lymphocytes play the main role in effector activity. Using sera from HVG-vaccinated chickens, no significant cytotoxic effects were detected in the complement-dependent antibody cytotoxicity test against MSB-1 cells. These results suggest that cellular immunity against the surface antigen of Marek's disease (MD) lymphoma cells is mainly related to the preventive mechanism against MD incidence by HVT vaccination.


Stability of polyadenylic and polyadenylated ribonucleic acids in radish (Raphanus sativus) seedlings. The stability of polyadenylic acid and polyadenylated RNA was investigated in young radish (Raphanus sativus) seedlings. We first studied the decay of poly(A) content, using a [3H]poly(U) assay, following a complete block of transcription by cordycepin (200 microgram/ml). Two lifetime classes of polyadenylic acid have been determined in these seedlings: a short-lived component with a half-life of 30 min which represents 60% of poly(A) and a more stable component with varying half-lives of which the majority range from 4-10 h and a few are considerably longer. During this period rRNA was shown to decay linearly, taking about 41 h for half of this RNA to disappear. The life-time of the other moiety of polyadenylated-RNA was analysed by continuous labelling with [3H]uridine. We have been able to demonstrate that a significant part of the mRNA molecules turns over with a half-life similar to that of the more slowly turning-over poly(A). No evidence could be obtained for rapidly turning-over messenger RNA. Thus the rapidly turning over poly(A) could correspond to a poly(A) turn-over independent of the remainder of the sequence. When labelling was very long, an apparent steady-state was reached and we determined the polyadenylated RNA content of seedlings to be 2.2% of whole cell RNA. Finally, these results were compared with those previously obtained in studying early germination of radish embryo axes. In contrast with stored mRNA which is rapidly degraded following imbibition, part of the mRNA present in 22 h old seedlings is stable for several hours.


[The role of ochronotic arthropathies in rheumatology]. In alkaptonuric patients, cartilage, fibrocartilage and tendons are slowly impregnated by homogentisic acid. This leads to pigment deposition between and on the surface of collagen fibres (ochronosis) which hardens the tissues as in leather tanning, and can render them breakable. Ochronotic intervertebral discs show a tendency of calcification and ossification, which produces a characteristic radiological picture. Ochronotic cartilage is rather often split off in the weight bearing zones of the knee, shoulder and hip. This is followed by osteoarthrotic changes with a synovial reaction frequently leading to an osteochondromatosis. The labelling of the pigmented ochronotic cartilage thus can support a didactic demonstration of the nature of osteoarthrotic remodelling. It underlines that such remodelling consists mainly of non specific changes developing independently of the cause of the original cartilage lesion.


[Morphologic indication for the participation of neutrophil granulocytes in rheumatic cartilage destruction]. Cartilage destruction in rheumatoid arthritis may be mediated by enzymes of the synovial fluid and by cells of the proliferating pannus tissue. Neutrophilic granulocytes are usually said to affect the cartilage via the synovial fluid, and  their local occurrence in the pannus-cartilage border is denied. However, a morphological study on pannus tissue and cartilage by use of histochemistry and immunfluorescence (leucocytes antielastase) exhibited an accumulation of neutrophilic granulocytes in the immediate vicinity of the cartilage in destruction. This result is in contrast to the observation of most investigators reporting studies of the pannus cartilage junction. Experimental datas of the effect of elastase moreover indicate that this enzyme is capable to penetrate into  the cartilage and to degrade proteoglycans. Therefore the results show that the occurrence of neutrophilic granulocytes at the pannus-cartilage border is an important phenomenon for understanding the progressive cartilage destruction and that elastase may be at least one enzyme responsible for the degradation of the cartilage matrix.


Urinary incontinence: prevalence and needs. The prevalence of recognised urinary incontinence in a community was found to be 1%; the prevalence of unrecognised incontinence was 3.3% in men and 8% in women in a group practice of 7000 patients. The approach to investigation and management of urinary incontinence in a urodynamic unit and the staffing of this unit are described.


On the problem of counting and sizing mitochondria: a general reappraisal based on ultrastructural studies of mammalian lymphocytes. The authors ask the question whether the parameters "numbers" and "volume" are suitable for the morphometric analysis of mitochondria. In several types of cell, irregularity of mitochondrial shape makes it technically difficult, if not impossible, to obtain reliable stereological estimates of mean organelle volume or number per unit volume. Of more fundamental concern is whether number of mitochondria per cell is of any real value as a structural correlate of respiratory potential and hence as a measure of cell function. Alternative parameters might serve better for this purpose. Though the problem is illustrated by reference to quantitative studies of lymphocytes, it is also pertinent to the investigation of many other cell types.


The hypothalamo-hypophysial system of the lamprey, Lampetra fluviatilis L. III. High-resolution radioautography of monoaminergic structures in neurohemal regions. The distribution of monoaminergic structures was studied in the proximal neurosecretory contact region and neurohypophysis of the lamprey by light and electron microscopic radioautography. Only weak radioautographic reactions were found in the proximal neurosecretory contact region 1 h after injection of 3H-dopamine. High-resolution radioautography revealed some labeled neurosecretory terminals mainly in contact with the basement membrane of the connective tissue layer separating the proximal neurosecretory contact region from the hypophysial pars distalis. The number of silver grains as well as the number of neurosecretory terminals marked by the presence of labeled dopamine was much higher in the neurohypophysis of the same species. In the latter, labeled neurosecretory terminals were found in contact with the connective tissue layer containing blood vessels of the general circulation. Some neurosecretory terminals make synaptoid contacts with tanycyte perikarya and their basal processes. According to their ultrastructure and the size of their granules, the labeled neurosecretory terminals are identical with the B type terminals described in both neurohemal regions (transmission electron microscopy). No labeled neurosecretory terminals were observed in the proximal neurosecretory contact region and the neurohypophysis of lampreys treated with the serotonin precursor, 3H-5-hydroxytryptophan.


Role of radiotherapy and chemotherapy in the treatment of lymphomas. The recent developments and results of treatment in Hodgkin's disease suggest that staging laparotomy is indicated in certain selected groups of patients and should not be performed routinely in patients whose therapy is unlikely to be changed by the findings.Early stage nodal Hodgkin's disease is best treated by extended radiotherapy. The exact role of adjuvant chemotherapy is not settled, but there are certain groups of high-risk patients who should receive chemotherapy, such as those with extensive mediastinal disease or advanced IIIA patients. In the advanced stages, chemotherapy assumes the primary role and with the MOPP programme (chlormethine, vincristine, procarbazine, and prednisone), alone or alternating with ABVD (doxorubicin, bleomycin, vinblastine, and imidazole carboxamide), a substantial number of patients can be controlled or cured.The therapeutic approach to non-Hodgkin's lymphoma should be guided mainly by the histological findings, favourable or unfavourable, and to a lesser degree also by the stage of the disease. In these patients, chemotherapy rather than radiotherapy is the treatment of choice. In the favourable histology group, a conservative approach is usually justified in the majority of patients, while in the unfavourable histology group, aggressive combination chemotherapy containing adriamycin is the recommended therapy.In underprivileged populations, the abdominal and intestinal localization of lymphomas is more common than in Europe and North America. Two lymphomas of special interest are Burkitt's lymphoma and intestinal lymphoma in their varying aspects. In both diseases, the importance of environmental factors is highly suggestive. Referral of such patients to centres involved in the management of these diseases is essential.


Pattern analysis in the study of infantile diarrhoea and other epidemiological problems. The patterns imposed on records of epidemiological variables by spatial, temporal, and other factors demand a special approach for their identification, characterization, and interpretation. Over the last 10 years, a methodology based on pattern analysis has been developed and put to the test in elucidating selected epidemiological problems. The aim of this approach is to link the pattern or its detailed features to factors likely to be important in understanding the origins of the disease and the mechanisms underlying its occurrence; such knowledge may in turn suggest methods that can be used to control the disease. Pattern analysis provides a battery of techniques that can greatly enhance the cost-effectiveness of epidemiological investigations. To exemplify these techniques, the applications of pattern analysis in the study of the infantile diarrhoeal complex and in elucidating the epidemic spread of wildlife rabies are described. Some other examples are mentioned briefly and comments are made on the more important techniques available.


Recommended safety requirements for the preparation of lepromin: a WHO Memorandum. The need for standardizing the preparation of lepromin and establishing safety requirements for it was recognized by the Scientific Working Group on the Immunology of Leprosy (IMMLEP) and its Steering Committee in 1978. It has now recommended the preparation of standard integral (Mitsuda-type) lepromin and, in collaboration with the WHO Biologicals unit, has drafted requirements for its preparation and testing. These direct that the source material should be Mycobacterium leprae from biopsy specimens of skin obtained from human (lepromatous) tissues or from the tissues of armadillos infected with M. leprae. The procedures to be followed for processing and testing the source material and for the preparation of lepromin from it are described. Requirements are laid down for the safety testing and labelling of the final product. In future, IMMLEP will consider supporting only those projects involving the use of lepromin prepared in accordance with these regulations.


Single haemolysis for the assay of antibodies to some haemagglutinating arboviruses. The single radial haemolysis reaction has been shown to be suitable for the quantitative assay of specific antibody to West Nile and Sindbis viruses. Only 5 mul of undiluted serum are needed for the test, which can be performed on crude preparations of antigen and without removal of nonspecific inhibitors. It is therefore a very simple procedure. Moreover, it appears to be more specific than the classical haemagglutination-inhibition tests.


Immunization during a cerebrospinal meningitis epidemic in the Mongolian People's Republic, 1974-75. An epidemic of cerebrospinal meningitis (CSM) in the Mongolian People's Republic, starting in 1969, reached its peak in 1974. In that year and in early 1975, 65 000 children in the 0-8-years age group in the main towns and in the provinces were immunized with meningococcal vaccine of serogroup A. The morbidity rates due to CSM were 12 times higher in the non-immunized than in the immunized children. This result demonstrates the value of an immunization programme to control epidemics of CSM.