The analgesic effect of transcutaneous electrical nerve stimulation (TNS) in patients with rheumatoid arthritis. A comparative study of different pulse patterns. Transcutaneous electrical nerve stimulation (TNS) was used on 20 patients with severe wrist pain due to rheumatoid arthritis. Three different stimulation frequencies were used: high 70 Hz stimulation (70 TNS), low frequency 3 Hz stimulation (3 TNS) and brief trains of stimuli with an internal frequency of 70 Hz and with a repetition rate of 3 Hz (3-70 TNS). The analgesic effect was evaluated on the patient's own estimate of pain relief and by means of a loading test in which the length of time the patient could hold a weight before and after TNS was used. The loading test and the patients' own estimate of pain relief corresponded well. After 70 TNS, 18 patients could double their loading time. The corresponding figure for 3-70 TNS was 16 patients and for 3 TNS 5 patients. The average duration of pain relief after cessation of stimulation was 18 h for 70 TNS and 15 h for 3-70 TNS, while those who responded to 3 TNS experienced pain relief for only 4 h on average.


Long term results of peripheral conditioning stimulation as an analgesic measure in chronic pain. In the present study 123 patients with chronic pain, consecutively referred for symptomatic pain treatment, were given peripheral conditioning stimulation as an analgesic measure and were followed for 2 years or till they terminated the treatment. The stimulation was either conventional transcutaneous nerve stimulation (TNS) [35] of mainly cutaneous afferents with high frequency (10-100 Hz) or acupuncture-like TNS [11] where muscle nerves are activated at a low repetition rate (1-4 Hz) with small trains of stimuli. The follow-up showed that 55, 41 and 31% of the patients continued the treatment after 3, 12 and 24 months, respectively. About 30% of the patients had to use acupuncture-like TNS to get useful analgesia, defined as a desire of the patient to continue stimulation treatment. Three-quarters of the successfully relieved patients reported more than 50% pain relief as measured from visual analogue scales and half of these reported an increased social activity and a decrease of analgesic drug intake by more than 50%. Psychogenic and visceral pains were less suitable for TNS treatment. It is concluded that peripheral conditioning stimulation is a valuable therapy in cases of chronic pain and that both conventional and acupuncture-like TNS should be tried before considering implantable devices or destructive surgery.


[Serum and articular immune complexes detection by the antibody-dependent cytotoxicity inhibition reaction in inflammatory rheumatological conditions and connective tissue disorders (author's transl)]. Detection of circulating and intra-articular soluble immune complexes, has been done in 28 rheumatoid arthritis, 8 mixed connective tissue diseases and 8 other connective tissue diseases. The method used, is based on a competition reaction in the antibody dependent lymphocytotoxicity reaction (ADC). In rheumatoid arthritis serum immune complexes were detected in 75% of the seropositive cases and 66% of the seronegative ones. The mean level of complexes is higher in the former form of the disease. In a given patient, the concentration of immune complexes in joint fluid, is higher than in serum. Immune complexes were present in the serum of 75% of patients with mixed connective tissue disease, but, here, at a concentration lower than in rheumatoid arthritis and systemic lupus erythematosus. It is proposed that measurement of serum immune complexes, can also be an interesting parameter in the follow-up of the patients.


[Acute cerebellitis in infectious mononucleosis. One case (author's transl)]. A nineteen year old man present an original clinical case of acute cerebellitis in infectious mononucleosis. Eighteen months after the acute phase of the illness, there persisted a large deficit in the circulating B lymphocytes. A short review of pertinent litterature is presented and current physiopathological hypothesis are discussed. Briefly, delayed immunity and personal predisposition appear to play important etiological roles.


[Upper gastrointestinal haemorrhage in the patients aged over 65 years. The contribution of endoscopy (author's transl)]. One hundred and eighty four patients aged over 65 years and hospitalised for gastrointestinal haemorrhage of high origin underwent emergency oesophago-gastro-duodenoscopy. It was thereby possible to make an aetiological diagnosis in 94.5% of cases. The study demonstrated certain special features: the preponderance of acute gastro-duodenal lesions, possibly explained by the high consumption of gastrotoxic drugs in the elderly subject; the relative frequency of oesophagitis (11%), one out of two cases being responsible for the bleeding; the discovery of a hiatal hernia in 59 patients (1/3 of cases), 25% of them bleeding from a lesion directly related to the latter. Bleeding was in large quantity in 57% of cases. Mortality, which was quite high (17%) appeared to be more related to the underlying general condition than to the haemorrhage itself. Endoscopy gave rise to complications in 8 patients, including 3 who died.


Quantification of BCG-induced reactions of T and B areas in peripheral lymphoid organs of young adult BALB/c mice. A histomorphometrical and autoradiographical study. Significant structural alterations of the axillary lymph nodes and spleens were revealed by histomorphometry following intraperitoneal injection of BCG into young adult BALB/c mice. The relative proportions of the germinal center areas were increased in lymph nodes as well as in spleens. The overall proportion of the B cell areas, however, showed a significant increase only in the spleens, compared to a significant reduction in the lymph nodes. By contrast, T cell areas appeared significantly reduced in the spleens, while their size was almost doubled in the lymph nodes. The labeling index in the lymph node paracortical areas was also doubled autoradiographically. The structural changes in the lymph nodes and spleens differed not only in quality, but also in their time course. In lymph nodes, the altered proportions of the T and B cell areas persisted from the second through the sixth week after BCG treatment. By contrast, structural changes in the spleen began to subside 2 weeks after treatment, and after 6 weeks the proportions of the T and B cell areas in the spleen had returned to normal. These quantitative morphologic findings suggest a difference in the functional roles of lymph nodes and spleen in the systemic immune response to BCG.


[New aspects in the treatment of allergic asthma (author's transl)]. Preventive measures in atopic persons comprise genetic advice, identification of, and prevention of contact with, the more common antigens in infancy and, later on, avoidance of exposure to antigens during the flowering season. In view of the complexity of the asthmatic attack the diagnosis must include all relevant parameters as otherwise consistent treatment is impossible. The only causal therapy is avoidance of exposure to antigens and also to unspecific (physicochemical) noxae which are nearly always superimposed. The value of specific immunotherapy varies according to the antigen or combination of antigens. The final verdict has to await the results of controlled studies in carefully classified and analysed groups, including investigations of immune parameters and uninterrupted registration of exposure to antigens. Until the efficiency, indications and mode of application of immunotherapy have been clearly established desensitization is preferable, provided the allergen has been identified and proved to be active, and exposure to the antigen cannot be avoided. The relatively high success rate obtained with placebos is presumably attributable to concurrent symptomatic treatment and avoidance of contact with the antigen. The already broad spectrum of adjuvent therapy is being constantly and successfully enlarged. Attempts to stimulate the production of antigen-specific suppressor T-cells by denatured antigens, and thereby prevent IgE production, are promising. Until a causal anti-allergy therapy has been developed a carefully and individually planned somatic and psychic polytherapy must remain the rule.


[Liebow's desquamative pneumonia--a separate disease entity or a form of chronic interstitial pneumonia? (author's transl)]. When in 1965 Liebow first described desquamative interstitial pneumonia (DIP) and differentiated it from other types of interstitial pneumonia he believed it to be a separate disease entity. The fact that the observed cases were of a relatively benign nature seemed to confirm this view. However, during the past years there have been reports of cases which took a less benign course; it was also observed that disorders with features similar to DIP could be produced by various exogenous noxae. The question, therefore, arises, whether DIP is, in fact, a separate disease entity or a specific pulmonary reaction to a variety of similarly acting noxae.


Insulin-stimulated protein phosphorylation in 3T3-L1 preadipocytes. A protein of molecular weight 31,000 became labeled with 32P within 5 min after addition of insulin to differentiated 3T3-L1 preadipocytes previously incubated for 55 min with 32Pi. The effect was mimicked by antisera directed against the insulin receptor and was eliminated by anti-insulin antiserum. Incorporation of 32P into this protein was more than 20-fold greater in insulin-treated cells than in cells not exposed to the hormone. At concentrations greater than required with insulin, epidermal growth factor and serum (1-5%) also stimulated phosphorylation whereas 1-isoproterenol, a beta-adrenergic agonist that increases intracellular accumulation of cyclic AMP, was without effect. The 31,000-dalton protein has been tentatively identified as ribosomal protein S6 by two-dimensional polyacrylamide gel electrophoresis. Incorporation of 32P into S6 could be detected within the same time period (5 min) and at the same insulin concentrations (0.1-1.0 nM) as are required to stimulate hexose uptake in both 3T3-L1 cells and mature mammalian adipocytes. The mechanism by which this phosphorylation either mediates or reflects the intracellular actions of insulin remains to be elucidated.


AU cell-surface antigen of human malignant melanoma: solubilization and partial characterization. AU antigen is defined by reactions of sera from patient AU with cell-surface antigens of cultured autologous melanoma cells (SK-MEL-28). Past studies established that no available cell type other than AU melanoma expressed AU antigen. By use of antibody inhibition tests for antigen detection, limited papain digestion of AU melanoma cells was found to result in the solubilization of AU antigen along with beta2-microglobulin (beta 2m) and HLA allogeneic and xenogeneic specificities. Comparable papain treatment of other melanoma and non-melanoma cell lines solubilized beta 2m and HLA, but did not result in the release of antigen with AU reactivity. Maximum yield of AU antigen from AU melanoma cells was obtained after very short (5-15 min) digestion times in contrast to the more prolonged proteolysis required for maximum HLA and beta 2m release. AU antigen was not immunoprecipitated by rabbit antiserum against beta 2m or HLA under conditions leading to partial or complete removal of beta 2m and HLA. At least a proportion of the molecules with AU determinants appear to be glycoproteins, as indicated by specific affinity for Lens culinaris hemagglutinin (LcH). After affinity chromatography on LcH-agarose, the specific activity of AU antigen was increased 50-fold. As determined by gel filtration chromatography, AU antigen has a molecular weight in the range of 20,000-50,000.


Crawling movements of lymphocytes on and beneath fibroblasts in culture. Some lymphocytes become highly motile upon immunological stimulation in vivo or in vitro. When introduced into a culture of 3T3 or L cells and followed by live-cell microscopy, some of these lymphocytes were observed to crawl on top of, along the edges of, and preferentially beneath the attached fibroblasts. The crawling could be as rapid as 20 mum/min, easily detectable without a time-lapse device. The striking ability of crawling lymphocytes to penetrate beneath attached 3T3 cells provided a quantitative means to compare the crawling activity of different lymphocyte populations under various conditions. Crawling was diminished by inhibitors of energy metabolism, by agents that disrupt the cytoskeleton, and by absence of Mg(2+) and Ca(2+), but not of Ca(2+) alone. Crawling lymphocytes were virtually absent in normal thymus and spleen cells. They increased greatly in 5-day mixed lymphocyte cultures and in peritoneal exudate lymphocytes taken after mice had been immunized with allogeneic tumor cells. T cells accounted for most of the crawlers. Of two T-cell leukemias tested, R1(+) cells were crawlers whereas EL-4 cells were not. The H-2 haplotype of the 3T3 fibroblasts (i.e., whether syngeneic or allogeneic) had no apparent effect on lymphocyte crawling activity. The crawling may relate to the exploration of cell surface antigens by lymphocytes (immune surveillance), to the mode of action of cytotoxic T cells, to the migration of lymphocytes across blood vessel walls, or to the penetration of lymphocytes into "solid" masses of normal tissue or tumor cells.


Colony-stimulating factor (CSF) radioimmunoassay: detection of a CSF subclass stimulating macrophage production. Colony-stimulating factors (CSFs) stimulate the differentiation of immature precursor cells to mature granulocytes and macrophages. Purified 125I-labeled murine L cell CSF has been used to develop a radioimmunoassay (RIA) that detects a subclass of CSFs that stimulates macrophage production. Murine CSF preparations that contain this subclass of CSF complete for all of the CSF binding sites on anti-L cell CSF antibody. With the exception of mouse serum, which can contain inhibitors of the bioassay, there is complete correspondence between activities determined by RIA and those determined by bioassay. The RIA is slightly more sensitive than the bioassay, detecting approximately 0.3 fmol of purified L cell CSF. It also detect this subclass of CSF in chickens, rats, and humans. In the mouse, the subclass is distinguished from other CSFs by a murine cell bioassay dose-response curve in which 90% of the response occurs over a 10-fold (rather than a 100-fold) increase in concentration, by stimulating the formation of colonies containing a high proportion of mononuclear (rather than granulocytic) cells, and by certain physical characteristics.


Effects of increasing serotonergic receptor activity in brain on prostagladin E1-induced fever in rabbits. In rabbits, increasing serotonergic receptor activity or funtional serotonin in brain with either the inhibitors of serotonin reuptake (e.g. fluoxetine and chlorimipramine) or the serotonin precursor 5-hydroxytryptophan in combination with the peripheral decarboxylase inhibitor benserazide, greatly reduced the fever induced by intraventricular prostaglandin E1. The data indicate the brain serotonin plays a role in the elaboration or modulation of the prostaglandin E1-induced fever.


Angiodysplasia of the colon.

Angiodysplasia of the colon. Angiodysplasia of the colon was diagnosed by arteriography in 33 patients. Approximately one fourth of the lesions were located in the left side of the colon. Three patients with sigmoid lesions had a second lesion elsewhere in the gastrointestinal tract. The lesions on the left involved a more extensive segment of bowel than those on the right. Almost one third of the patients were younger than 60, and 2 were in their thirties. The angiodysplasia is the source of the bleeding in most patients, and its resection results in cure.


"Blind pouch" syndrome: a cause of gastrointestinal bleeding. A case of blind pouch formation presenting as gastrointestinal bleeding 23 years following side-to-side small bowel anastomosis to relieve obstruction is reported. Although rare, blind pouches may occasionally be encountered. Familiarity with the clinical and radiographic features can aid in a prompt and precise preoperative diagnosis.


Cerebrospinal fluid shunt function and hydrocephalus in the pediatric age group: a radiographic/clinical correlation. Eighty-four pediatric patients were evaluated clinically and radiographically on 112 separate admissions for suspected increased intracranial pressure and possible shunt malfunction. The shunt system was tested clinically in each patient and correlated with the ventricular size as determined by CT. Of the patients with enlarged ventricles, 87% had an improperly functioning shunt and 13% had a normally functioning shunt. Of the patients with normal or small ventricles, 93% had a normally functioning shunt. Thus the "false negative" rate was 4% (small ventricles with a nonfunctioning shunt) and the "false positive" rate was 13% (large ventricles with a functioning shunt).


[Transhepatic emergency obliteration of bleeding gastro-esophageal varices (author's transl)]. The hemorrage following gastro-esophageal varices cause a high degree of mortality. Personal experience is presented consisting in 15 patients suffering from cirrosis with inoperable hemorrages. These patients underwent transhepatic emergency obliteration of the varices. The hemorrage stopped in 10 patients, 6 of whom later on underwent surgical treatment with porto-systemical anastomosis. In 5 patients the hemorrage reappeared at various intervals from the procedure. Owing to the possible recanalization of the obliterated varices the procedure should be considered essentially as a preoperative management.


Para-aminobenzoate inhibition of precipitation of urine salts. Lehmann's observation that potassium para-aminobenzoate has a "salt precipitating preventive effect" in urine was confirmed in rats. This effect persisted during the 3-week period of drug administration. There was associated no significant change in urine volume, osmolality, or per cent solids. Since there is a large clinical experience in the chronic use of even larger doses, it would appear quite feasible to determine the clinical usefulness of this property of para-aminobenzoate in the prevention of recurrent renal calculi.


Binding of benzo(a)pyrene into lung and thymocyte nuclear fractions. Binding of (3H)benzo(a)pyrene into lung and thymocyte nuclear fractions is studied in short term cultures. DNA, RNA and protein in the subnuclear fractions is separated and tightly bound radioactivity is measured. Among the fractions, proteins of the matrix sediment fraction display the highest specific radioactivity. DNA has a low specific radioactivity as compared to that of RNA and protein in all fractions. In thymocyte matrix extract and chromatin fractions the specific radioactivity of RNA exceeds that of protein. Lung nonhistones display a 30 times higher specific radioactivity as compared to histones. The corresponding ratio of the thymocyte fractions is about 10.


[Clinical and radiological aspects of maxillo-nasal dysostosis: "naso-maxillo-vertebral syndrome". A study of 34 new cases (author's transl)]. Maxillo-nasal dysostosis is not uncommon as we have noted 34 new cases in eight years. The most characteristic anomalies, well described by Binder, are nasal hypoplasia both of bone and cartilage with agenesis of the nasal spine, as well as a characteristic rearrangement of the naso-labial muscles. On first seeing the patient the disease is generally recognized by the very typical aspect of the nose. There very often exists however other dental, mandibular and cervical spine anomolies. It is indispensable to look for these anomalies in the work up of patients with this malformation syndrome "the naso-maxillo-vertebral syndrome", in order to better understand the disease and better treat the patients.


[Partial resection of the tongue (author's transl)]. An improved simplified technique is described for reducing the volume of the tongue by operation. A plastic support has been designed on which the tongue can be spread out symmetrically and fixed in position. Gallbladder forceps are applied to the base of the tongue to avoid hemorrhage. An initial incision is made through the whole thickness of the tongue down to the support, and a partial resectomy performed, followed by apposition of the wound edges. The results obtained with this procedure are far superior to those previously reported using other techniques: the operation takes less time and there is almost no loss of blood.


Macrophage/T-lymphocyte interaction in the immune response to PPD in humans. The proliferative response of sensitized human T cells to low concentrations of purified protein derivative of tuberculin (PPD) in vitro has previously been shown to depend on the presence of autologous or HLA-D-compatible macrophages (M phi). In this paper we present evidence that the M phi/T cell interaction requires viable M phi and does not involve a soluble factor. T cells from neonates do not respond to PPD in our system, while M phi from neonates are able to present PPD to T cells from HLA-D matched sensitized adults. It is also demonstrated that the previously reported HLA-D restriction of T cell/M phi cooperation is not due to T cell mediated killing of allogeneic macrophages in vitro.


A chemical approach to the mechanism of B-lymphocyte activation. III. The B-cell-activating structure of T-independent antigens resides ultimately in the carrier. Non-immunogenic dinitrophenyl-polymethylmethacrylate and dinitrophenyl-cellulose were rendered immunogenic by introducing, or by exposing, hydroxyl groups; i.e. hydrogen bonds. Conversely, acetylation of Ficoll yielded a polymer no longer functioning as a good carrier, and a similar result was obtained when dipole and hydrogen bond-supplying groups of polyacrylamide were replaced by more hydrophobic chains. All these findings point towards the existence of a carrier-associated lymphocyte-triggering structure. Despite the latter conclusion, the carrier need not be a polyclonal antibody inductor. The possibility of a signal not resulting in polyclonal antibody induction was tested with the system Ficoll/dinitrophenyl-Ficoll: whereas a pulse of Ficoll specifically impaired the immunogenicity of dinitrophenyl-Ficoll, it did not elicit a significant antibody level increase over background. Nevertheless, repetitive Ficoll inoculations into mice gradually increased the basal anti-trinitrophenyl antibody level, and concomitantly the anti-dinitrophenyl response to dinitrophenyl-Ficoll was specifically impaired since the anti-trinitrophenyl response to trinitrophenyl-LPS was unaffected. The two main conclusions are that (1) the ultimate lymphocyte-triggering structure resides in the carrier, and (2) the mere presence of that carrier-associated structure does not mean polyclonal antibody induction, at least under conventional test conditions (i.e. one pulse, 2 days in culture).


Colonoscopy in lower gastro-intestinal haemorrhage. The value of colonoscopy in the diagnosis and management of lower gastro-intestinal haemorrhage was assessed in 107 patients who were examined during a 2-year period. The main indications were to define uncertain radiological findings, to further investigate the cause of bleeding in patients with normal barium studies and to carry out polypectomy. Radiological lesions were confirmed in 27, defined in 12, and refuted in 14 patients. Twenty-eight lesions were demonstrated on colonoscopy which were not diagnosed by barium enema or sigmoidoscopy. A diagnosis was made by colonoscopy in more than two-thirds of the patients with frank blood loss and normal radiographs. In cases of occult bleeding it was farless helpful. Colonoscopy significantly improved diagnosis and management of gastro-intestinal bleeding when the cause was in doubt after standard investigations. In addition, 37 polyps were removed through the colonoscope from 30 patients.


Tests and management affecting survival after portacaval and spenorenal shunts. New data were derived from records of 115 patients undergoing portacaval or spenorenal shunts from 1966 to 1973. The last serum bilirubin level determined before a shunt was the best predictor of operative mortality. The strongest predictor of long term survival was the first serum albumin level measured after admission. Operative mortality was strongly correlated with intraoperative clotting disorders; however, the prothrombin time and the partial thromboplastin time predicated long term survival. Clinical assessment added unique information to conclusion derived from laboratory tests. Results of operation were independent of the skill and experience of the surgeon, except that the best risk patients perhaps may have done better when operated upon by the most experienced surgeons. Once a patient has stabilized after a bleeding episode, he might as well be operated upon at the same admission rather than be discharged to be operated upon at a later arbitrary time.


Percutaneous transluminal dilatation of coronary artery stenosis. Percutaneous transluminal dilatation (PTD) of coronary stenosis is performed by means of a balloon-tipped catheter introduced from a peripheral artery. PTD was attempted in 56 patients; stenosis was successfully dilated in 38 patients (68%). The method failed in 18 patients: in 6 (11%) of them an abrupt closure of the stenosed artery or a beginning infarction necessitated an emergency revascularization. There were no serious complications or deaths; one patient developed a transmural infarction in spite of the immediate bypass grafting. PTD was also successful in 6 out of 9 patients with recurrent angina following previous coronary bypass grafting. Intraoperative dilatation by coronary arteriotomy was attempted in 6 patients, but the results were inconclusive. PTD is a new method of treatment of coronary artery disease; it represents an addition rather than an alternative to coronary bypass grafting. The decision for PTD should be made jointly by cardiologist and surgeon; the ideal patient has a short history of angina with narrow, proximal stenosis without any calcifications. Cardiosurgical standby is mandatory during PTD; the results are best and the risk lowest in patients with single vessel disease.


In vitro metabolism of testosterone by cultured Sertoli cells and the effect of FSH. Cultures of Sertoli cells isolated from testes of 18-and 36-day-old Long Evans rats were used to investigate their capacity to metabolize testosterone and the effect of FSH on such metabolism. Three different approaches were used: 1) investigation of the metabolism of radiolabeled testosterone under saturating substrate conditions; 2) study of the metabolism of radiolabeled testosterone utilizing trace amounts of high specific activity substrates; 3) the utilization of radioimmunoassay for measurement of estradiol-17 beta. The following steroids were isolated and identified by recrystallization to constant specific acitvity from the control and FSH-treated cultures; testosterone (unconverted substrate), androstenedione, dihydrotestosterone, 3 alpha-hydroxy-5 alpha-androstan-17-one and 5 alpha-androstane-3 alpha, 17 beta-diol. Radioimmunoassay data suggests that the Sertoli cells produce an estradiol-17 beta-like compound from unlabeled testosterone and that this production is stimulated by FSH. However, the radioactive metabolite from all our studies that behaved chromatographically like estradiol--17 beta failed to crystallize to constant specific activity, while in each experiment, authentic radiolabeled estradiol-17 beta added as recovery tracer did. The data demonstrate that : 1) cultures of Sertoli cells from immature rats have 5 alpha-reductase, 3 alpha- and 17 beta-hydroxysteroid oxidoreductase activities; 2) these enzymes may be affected by FSH; 3) based on radiolabeled metabolic techniques, Sertoli cells were unable to biotransform testosterone to estradiol-17 beta even in the presence of FSH.


Removal of myelotoxicity from antilymphocytic sera. Antilymphocyte sera (ALS) were prepared by different methods and examined for their myelotoxicity by bone marrow colony-forming assay, both before and after absorption with B cell antigens. The results show that myelotoxicity can readily be removed from some, but not all, ALS. The source of antigen and the immunisation protocol used determine the degree of myelotoxicity and hence the number of absorptions required. Non-myelotoxic ALS may be suitable for the prevention of graft-versus-host disease (GVHD) by in vitro treatment of bone marrow before transplantation.


A mixed antiglobulin test for the detection of immunoglobulin G antibody to lymphocytes. A mixed antiglobulin test with lymphocytes as test antigens has been developed for the detection of IgG antibodies. Free lymphocytes were counted before and after the addition of anti-D-coated indicator erythrocytes to quantitate the test. The optimal ratio of lymphocytes to indicator erythrocytes was 1: 30. Both anti-T and anti-B lymphocyte antibodies were detected by the test. Nonspecific agglutination of B lymphocytes and detector erythrocytes was avoided by the use of an appropriate dilution of the goat anti-human gamma chain reagent. Unlike cytotoxicity tests it could be used with dead lymphocytes that were frozen and stored intact as well as with live lymphocytes. Lymphocytes were better test antigens than were kidney cells from the same donors in the test. The mixed antiglobulin test with lymphocytes was also more sensitive in the detection of antibodies in hemodialysis patients than was the microlymphocytotoxicity test.


Pathology of proliferative haemorrhagic enteropathy in pigs. Examination of the small intestine of pigs with proliferative haemorrhagic enteropathy showed changes consistent with defects in vascular permeability. Early in the disease there were many eosinophils and distension of lacteals and intercellular spaces with proteinaceous material. Later the predominant features were red blood cells and exudate in tissue spaces. This was most severe and extensive at the tips of villi which were covered by a cast of cells and fibrinous exudate. Adenomatous intestinal mucosal cells contained organisms that were free within the apical cytoplasm and were morphologically identical with those seen in the related disease, porcine intestinal adenomatosis. Also these bacteria were seen free in the subepithelial mucosal area, in blood vessels and within membrane-bound vesicles in phagocytic cells in the mucosa and its blood vessels. Mast cells were prominent in some areas as were thrombosed vessels.


[Nature of the blocking action of the sera of oncological patients on T-lymphocytes]. Some sera of tumor patients render a blocking effect on the activity of autologous and allogenic T lymphocytes in blasttransformation test to PHA and spontaneous rosette-formation. The activity that block spontaneous rosette-forming reaction is directed against the population of postthymic peripheral lymphocytes but not that of thymocytes. No correlation was found between the serum activity, which block RSP and RBT, and antibodies to PHA, lymphocytotoxins, C-reactive protein and the rheumatoid factor.


[Possibility of using fish and amphibians for detecting the carcinogenic action of nitrosomorpholine and its chemical precursors]. When dissolved in water nitrosomorpholine induced in frogs Rana temporaria and aquarium fish adenomas and cancer, hemocytoblastosis, adenomatous polyps and adenocarcinomas of the intestine, mesenchymomas. A combined action of sodium nitrite and morpholine would induce the tumors concerned, but taken separately NN and M produced only a toxic effect. The morpholine nitration appears to proceed both endogenously and directly in water. It seems rational to use animals of the aqueous medium as an indicator of nitrosoamines and their precursors contamination of hydrosphere.


Enhanced yield of antihemophilic factor and von Willebrand factor by cryoprecipitation with polyethylene glycol. A procedure involving cryoprecipitation of human plasma in the presence of polyethylene glycol results in consistently higher yields of antihemophilic factor and von Willebrand factor than were heretofore achieved by cryoprecipitation alone. The resulting AHF and vWF are at least as pure as ordinary cryoprecipitate and can easily be further purified by additional processing. The method is expected to be especially useful in the preparation of AHF and vWF concentrates for the treatment of patients with hemophilia or von Willebrand's disease.


[Demonstration of cytoplasmatic immunoglobulins in pleural fluids (author's transl)]. Immunopathological investigations for demonstration of intracytoplasmatic immunoglobulins (zIg) were carried out in 100 pleural fluids of different aetiology. In 1/3 of all fluids gamma-globulin and IgG were found in plasma cells and lymphoblasts (immunocytes). Most often zIg were seen in postpneumonic and tumorous effusions, very sparse in tuberculosis. Among different organ tumors bronchial carcinomas exhibit a high percentage of positive findings.


[The specificity of peptide-PABA-test (author's transl)]. Exocrine pancreatic function was determined by oral administration of N-benzoyl-L-tyrosyl-p-aminobenzoic acid (peptic-PABA-test) in 120 controls, 74 patients with chronic pancreatitis, 35 patients with acute pancreatitis 2--6 weeks after recovery, 201 patients with a variety of gastro-intestinal diseases and in 10 patients with anorexia nervosa. In the control group, 70% +/- 18% of the oral administered dose of PABA was found within 6 hours in the urine. In contrast the group of chronic pancreatic patients excreted only 40% +/- 13% over the same period. "False negative" PABA excretion was found in 11 (9%) of the 120 persons with no pancreas disease. "False positive" PABA excretion was found in 13 (17,5%) of the 74 patients with chronic pancreatitis. The test was not influenced by age or sex. After stomach resection or cholecystectomy and in patients with ulcus duodeni, chronic hepatitis, functional diarrhea, Crohn's disease, colitis ulcerosa and acute pancreatitis 2--6 weeks after recovery the peptide-PABA-test was not distored. Diminished PABA excretion was encountered in some patients with toxic liver disease, inflammatory disease of the small intensine like M. Whipple, celiac disease and unspecific enteritis and in a few patients with cholelithiasis. Low PABA excretion was found in early all patients with partial small intestinal resection, terminal liver cirrhosis or liver metastasis with ascites and in all patients with anorexia nervosa.


Assay of immunoglobulins in supernatants of lymphoid cell lines by conventional laser nephelometry. An adaptation of the nephelometric assay for serum immunoglobulins has been developed for detection and quantitation of extracellular immunoglobulins in cultures of lymphoblastoid cell lines. This assay employs the standard equipment for laser nephelometry and commercial reagents for immunoglobulin quantitation. By adjusting dilutions of controls and sample volumes of culture supernatants, amounts of IgG and IgM below 1 microgram/ml can be detected in culture supernatants. At concentrations between 1 and 4 microgram/ml, day-to-day and within-run variations for IgM assays were 16 and 11% respectively. The possibility of measuring immunoglobulins secreted by cell lines by conventional laser nephelometry opens several areas of application in the study of the functional activity of B cells and of cell-cell interactions.


T and B lymphocytes in the liver and peripheral blood of subjects with acute and chronic hepatitis. E and EAC rosette-forming cells in the peripheral blood and in the liver of subjects with acute and chronic hepatitis were studied. We found a highly significant reduction (P less than 0.01) of E rosette percentage in the lymphocytes isolated from the liver patients with chronic persistent, and chronic active, hepatitis. EAC rosette-forming cells were significantly increased in the liver of patients with chronic active hepatis (P less than 0.01). In this condition lymphocytes with Fc receptor were also found.


[Diameter of coronary arteries before and after bypass grafting (author's transl)]. Patients with patent coronary bypass grafts showed the followings: 1. a decrease in prestenotic coronary diameter due to a reduction in flow. 2. An increase of the poststenotic segment of the bypassed vessel due to an increase in flow via the venous graft. 3. An increase of the bypassed stenosis, mainly due to a general decrease of vessel diameter proximal to the stenosis. 4. No change in diameter in non bypassed arteries. The postoperative changes in diameter were not dependent on the time elapsed since surgery and were independent from the severity of coronary sclerosis and the number of risk factors. A correlation was found between the amount of the diameter changes and the amount of reduction in exercise induced ST-segment depression. The decrease in coronary diameter proximal to the stenosis is not due to progression of coronary sclerosis but to a functional change. A narrow poststenotic vessel does not constitute a contraindication for bypass grafting because its true diameter is flow dependent and cannot be judged with certainty from the preoperative angiogram.


[Disturbed growth in height in multiple cartilaginous exostoses (author's transl)]. Basing on the hypothesis that reduced body height in patients with multiple cartilaginous exostoses would be mainly accounted for by shorter extremities, not by a shorter trunk, the authors clinically examined 19 exostosis patients in respect of thigh, lower leg, upper and lower arm, as well as height of the seated patient. The dimensions were compared by the method of matched pairs, with 19 volunteers without diseased skeleton, who corresponded with one of the exostosis patients in respect of age, sex and height of seated patient. Results were evaluated according to Wilcoxon's test. This showed a statistically significant reduction in length of the extremities in adults with multiple cartilaginous exostoses.


Studies on the prevalence of renal disease and hypertension in relation to schistosomiasis. IV. Systemic blood pressure hypertension and related features. Two comparable rural communities but with varying endemicity of urinary schistosomiasis in environs of Ibadan, Nigeria, have been studied by a total cross-sectional population survey. It has been found that:- (i) schistosomiasis does not predispose to raised blood pressure (ii) both diastolic and systolic blood pressure increase with age. (iii) prevalence of systemic hypertension is higher in females than males (iv) body weight and height are related to hypertension in both males and females (v) parity would seem to be related to hypertension in the females (vi) except in the younger female group (1--19 years) where polyuria, frontal headache, palpitations appear related to systolic hypertension, raised blood pressure would appear to have no symptoms. In particular headache in any part of the head bears no clear relationship. (vii) The majority of hypertensives would appear to belong to the primary variety but proteinuria among females has been found to be significantly related to hypertension.


Alpha-1-antitrypsin levels and phenotypes in some healthy Nigerians--. A preliminary report. Levels of serum Alpha-1-Antitrypsin were determined in 59 healthy adults and in-cord samples of 42 newborn Nigerians using the immunochemical method of Mancini. The protease inhibitor phenotypes were also determined in these samples by Iso-electric focusing in an LKB multiphor electrophoresis system. The mean adult serum level was 106% of internationally accepted levels. The mean cord level was 75% of the adult mean. The finding of a rare genetic variant 'S' in two of the 96 sera is higher than figures hitherto quoted in the literature. We thus believe that it will be very interesting to study a larger sample of Nigerians in the future.


The economic potential and the role of aspirin and alcohol ingestion in relation to haematemesis and meleana. The economic potential and the role of aspirin and alcohol ingestion have been explored in relation to acute upper gastrointestinal haemorrhage complicating duodenal ulcer disease or portal hypertension. Of special interest in the study was the clear indication of the relevance of socioeconomic impact in the haemorrhage patients, the majority of whom were found to belong to the class of unskilled wage earners. Though a history of regular ingestion of salicylate compounds and alcohol was commonly obtained on specific questioning, only in six of the thirty-one patients could the onset of the overt haemorrhage be attributed to adverse synergism between these two groups of drugs.


[T- and B-lymphocyte count in the spleen and lymph nodes of guinea pigs administered oxytetracycline intramuscularly]. The E and EAC rosette formation tests, carried out in order to determine the count of T and B lymphocytes in the spleen and lymph nodes of guinea pigs after several intramuscular of oxytetracycline, showed a decrease in the ability of B lymphocytes in the reaction of EAC rosette formation with the simultaneous rise of the level of "zero" cells without surface receptors characteristic of T and B lymphocytes. The data obtained in this study indicated the possibility for tetracyclines to effect the differntiation and ripening of the medullary precursors of B lymphocytes.


Arterio-appendiceal fistula after arterial reconstruction with synthetic graft. A patient who 5 years previously had an aortoiliac reconstruction with a dacron graft developed intestinal bleeding. At laparotomy this was found to be due to a fistula between a pseudoaneurysm at the right iliac artery anastomosis and the appendix. Resection of the aneurysm and adjacent parts of artery and graft with additional appendectomy prevented further intestinal bleeding. A search of the literature produced only one previously reported case similar to this.


Hemobilia in haemochromatosis--localized by 99mTechnetium-albumin scintiphotography. Hemobilia in a patient with haemochromatosis is reported. Preoperatively the bleeding was localized with abdominal scintiphotography after I.V. injection of 99mTechnetium-labelled albumin. The bleeding was ascribed to rupture of a varicose vein into the gallbladder.


The effect of single and double trauma on the mitotic activity of bone marrow and thymus. Different types of trauma and antigenic challenge bring about significant increases in the mitotic rates of bone marrow and thymus. This cell response probably occurs in order to produce leucocytes and macrophages, which are needed for the defence of the organism on injury. The present investigation shows that when two traumatic injuries take place only two days after each other, the cell response to the second trauma becomes completely abolished. With an interval of 10 days, however, the cellular proliferation has returned although delayed.


Atherosclerosis of the left main coronary artery: 5 years results of surgical treatment. Three hundred consecutive patients received coronary arterial bypass grafts as treatment for stenosis of the left main coronary artery. Ostial stenosis was more prevalent among women (P less than 0.001). Operative (hospital) mortality was 4 percent (12 of 300). Among 148 survivors who underwent recatheterization after a mean interval of 16.5 months, the graft patency rate was 88 percent. After a minimal follow-up period of 49 months and a mean interval of 69 months, 75 percent of the survivors were asymptomatic and 94 percent were employed or fully active. The actuarial 5 year survival rate was 88.2 percent. The presence of right coronary artery disease, abnormal preoperative ventricular function and incomplete revascularization adversely affected survival, but the differences did not reach statistical significance. Comparison of this long-term follow-up study with controlled and noncontrolled studies of nonsurgical treatment of obstructions of the left main coronary artery indicates that myocardial revascularization alleviates cardiac symptoms and increases life expectancy in patients with severe atherosclerosis of this artery.


Mechanism of relief of angina after coronary bypass surgery: an angiographic study. Coronary angiography was performed before and after coronary revascularization in 67 patients. The interval between studies ranged from 1 to 38 months (average 9.9). The patients were separated into four clinical groups on the basis of their symptoms at the time of restudy; Group I, 13 asymptomatic patients; Group II, 19 patients with nonanginal chest pain (18 cases) or dyspnea (1 case); Group III, 12 patients whose angina was relieved but not eliminated; and Group IV, 23 patients whose angina was not alleviated. The graft patency rate was 72 percent in Group I, 78 percent in Group II, 61 percent in Group IIII and 34 percent in Group IV. The sum of diseased, but not bypassed and unsuccessfully bypassed arteries per patient was 1.6 in Groups I and II. 2.9 in Group III and 4.0 in Group IV. The incidence of perioperative myocardial infarction, defined using enzymatic and electrocardiographic criteria, was 8 percent for Group I, 26 percent for Group II, 25 percent for Group III and 52 percent for Group IV. Anginal relief after coronary bypass surgery is achieved by successful and complete revascularization rather than by perioperative myocardial infarction.


[Mural thromboses of the right heart. Clinico-pathological study]. 39 instances of mural thrombosis of the right side of the heart were observed among 2000 cases of post-mortem examinations. The right atrium was the most frequent site of thrombosis; the right ventricle was involved in 8 cases. The relationships between right sided thrombosis and rhythm disturbances, myocardial or valvular disease, myocardial infarction, pulmonary disease, neoplasm, sepsis and disturbance of coagulation are discussed. The high incidence of pulmonary embolism and their relationship with thrombosis of the right side of the heart are emphasized.


[Combined treatment of carotid and coronary artery insufficiency (author's transl)]. The association of a coronary insufficiency and a significant stenosis of the carotid trunks brings up a difficult problem of operative strategy. In a series of 142 patients operated by an aortocoronary vein graft 5 presented a bilateral carotid stenosis, of which two had a history of transient ischemic accidents. These were operated either in sequence: carotid then coronary, or by a simultaneous procedure. In conclusion it appears the planning of surgical procedures in cases of such combined vascular insufficiencies depends on the relative severity of both lesions, and in a case of unstable angina a simultaneous carotid-coronary operation is warranted.


Ionic composition of the endolymph and sensory transduction in labyrinthine organs. The role of various ions in stimuli conversion has been investigated in isolated frog semicircular canals, by replacing the endolymph with solutions deprived in turn of Na+, K+, Cl- and Ca++. Mechanical and electrical stimuli were employed and slow ampullar and nerve potentials were recorded, together with the afferent discharge of impulses in the eighth nerve. The results support evidence that K+ is the carrier of the receptor current, as postulated in Davis' hypothesis, while Ca++ is essential in the processes which allow the current to be modulated during cupula deflections and therefore endon hair cells with mechanical sensitivity.


Efferent controlled integrating fuctions of primary vestibular afferents. The vestibular type II receptor cells of mammalians are multiply innervated. Their afferents are integrating neurons consisting of many inputs but only one output. They transform the irregular spontaneous input activity into a regular output. Under the influence of efferent activity following the stimulation of the contralateral labyrinth, this regular output activity becomes irregular. This efferent influence upon afferent spontaneous activity is analysed by means of an existing computer model of an integrating cell. The analysis confirms a high functional interdependence of both labyrinths.


The vestibulo-ocular reflex in newborn rats. To study the development of vestibular functioning, the vestibulo-ocular reflex was tested in rats of increasing age. High frequency electrical stimulation of the vestibular nerve elicited characteristic conjugate eye movements in newborn rats well before the eyes were open (about day 15 after birth) and before the semi-circular canals had reached full adult size (about day 22 after birth). The threshold currents decreased during growth.


Effects of diethyl-stilboestrol on single fibres of frog skeletal muscle. The effects of diethyl-stilboestrol (DES), one of the most potent estrogens, were studied on single muscle fibres of the frog. In relatively low concentrations (5 muM), DES greatly potentiates the twitch response of the fibre without significantly affecting the amplitude of the tetanus response. The twitch potentiation is accompanied by an increase in time to peak tension and marked prolongation of the relaxation phase. In tetanic response the half decay time after the last stimulus is also prolonged by DES. DES causes no changes in the resting or action potential of the muscle fibre. The S-shaped curve relating peak contracture tension and caffeine concentration is shifted towards lower caffeine concentrations by DES. Dantrolene greatly suppresses the DES potentiated twitch. It is concluded that DES potentiates the twitch response and prolongs the relaxation time by inhibition of the calcium re-uptake by the sarcoplasmic reticulum.


Binocular counterrolling in humans during dynamic rotation. Seven subjects 18 to 66 years old underwent 360 degrees rotation at a constant velocity of 3 degrees/sec, in 27 trials beginning randomly right ear down or left ear down. A camera on the rotating chair photographed both eyes every 10 degrees. Dual projectors measured counterrolling, the image from one projector being aligned and rotated until it was superimposed on the image from the other. Right and left eyes were measured independently. The group reached maximum counterrolling at about 70 degrees and 270 degrees in rotations to the right, with values of about -6 degrees and 4 degrees respectively. Rotations to the left reached maximum at 50 degrees and 270 degrees with about 4.5 degrees and -5.25 degrees respectively. Individual subjects showed ranges of counterrolling varying from 4.03 degrees to 17.44 degrees, mean 11.30 degrees. More counterrolling was observed when subjects were tilted to right than to left. The downward eye counterrolled more than the upward. Amount of counterrolling was inversely correlated with age.


Multiple Ig classes on rabbit B lymphocytes. Rabbit PBL were studied regarding the presence of different classes of s-Ig, under experimental conditions, ensuring the endogeneous origin of these proteins. About 40% of the lymphocytes are B cells (Fab positive and a1 positive in a1 homozygous rabbits). IgG positive lymphocytes could be found, but only using and anti dll conjugate (allotype located on the Fd gamma region of IgG). Anti Fc gamma conjugates were negative. Most of the B cells are IgM positive, most of these IgM cells however were also positive for either IgG or IgA. Np lymphocytes were found bearing both IgG and IgA. Careful analysis of the percentages of various isotypes found on B cells suggests that some "IgD" positive lymphocytes could be present. Results are discussed in relation to B cell differentiation.


Vestibular effects of antibiotics introduced in the inner ear. Behavioral and electrophysiological studies in the frog. The aim of this study was to find a rapid and suitable method for testing the toxicity of drugs upon the vestibular end organs. The experiments were performed in the frog and the action of two antibiotics, streptomycin sulphate and penicillin G, was studied by carefully observing the equilibrium behaviour of the animals and recording the spontaneous activity of the nerve of the horizontal semicircular canal. The results obtained show that: 1) injection of streptomycin sulphate (20 microgram) directly into the labyrinthic cavity elicited disorders of the equilibrium and reduced the spontaneous activity of the horizontal canal nerve; 2) these disorders were reversible or not depending on the animal; 3) there is a good correlation between behavioral observations and electrophysiological data (i.e. the activity of the ampullary nerve was low in frogs whose behaviour was impaired at the time of sacrifice; the activity did not differ from controls when the normal behaviour was completely restored); 4) injection of penicillin G or 0.7% NaCl into the labyrinthic cavity had no effect on the equilibrium of the frogs or on the activity of the ampullary nerve; 5) intramuscular or intralymphatic injections of streptomycin sulphate produced a neuromuscular block but did not alter the activity of the ampullary nerve. In conclusion, the question of ototoxicity is discussed.


Relationship between stimulation of sodium transport across frog skin and Ledakrin concentration. Relationship between stimulation of sodium transport across frog skin and Ledakrin concentration. Acta Physiol. Pol., 1979, 30 (2): 261--265. Using the method of measurements of the short circuit current, introduced by Ussing, the relationship was investigated between stimulation of sodium ion transport across frog skin and the concentration of Ledakrin. It was found that the optimum concentration of the drug for investigating changes in ion transport is 10(-5) g per 1 ml of medium.


Studies of allospecific suppressor cells in culture. Allospecific suppressor T cells can be generated by allostimulating thymus, spleen and lymph node cells in culture. Bone marrow cells do not yield suppressor lymphocytes. While the efficiency of thymocytes for suppressor cell generation decreases with the age of thymus donors, the efficiency of spleen increases with age. Generation of suppressor lymphocytes depends on cell replication and protein synthesis. The suppressor function as such does not require cell replication. Induction of suppressor T cells in culture requires cell to cell interaction of cortical type and medullar type T cells.


Suppressor cells in Trypanosoma congolense-infected mice. Spleen cells from mice infected with T. congolense strongly suppressed lymphocyte stimulation induced in normal spleen cells by incubation with mitogens or allogeneic cells. Cell dilution studies showed that suppressor activity was extremely strong. Suppressor cell activity was markedly reduced by treatment of spleen cell populations with mitomycin-C and was unaffected by treatment with anti-Thy.1 sera and complement. Removal of cells which bound carbonyl iron or which bound to nylon columns, decreased but did not abolish suppressor activity.


Basic mechanisms of lymphocyte recirculation in Lewis rats. Lymphocyte locomotion in vivo depends upon an intact network of subplasmalemmal contractile microfilaments which are linked through the membrane to surface receptors, and the distribution and stabilization of recognition receptors may be controlled by microtubules and/or 10-nm filaments in the cytoplasm. The differential effects of cytochalasin-A and colchicine on lymphocyte homing and locomotion have proven useful in dissecting the subcellular events underlying the process of lymphocyte recirculation.


Comparative pharmacology of a 1:10 combination of indomethacin-sodium salicylate. It has been found that gastrointestinal side-effects of indomethacin could be abolished when administered in combination indomethacin:sodium salicylate (ratio 1:10). In this paper comparative pharmacological data of this combination and its basal compounds are presented. Acute toxicity of the combined preparation was 72 times less in rats than that of indomethacin alone. All therapeutic indexes were markedly increased in the combination of indomethacin-sodium salicylate compared with the separate drug treatments.


Effects of the vestibular system on human development, Part I. Overview of functions and effects of stimulation. Studies concerned with the effects of vestibular stimulation on human development and function are reviewed and some implications for therapy are suggested in this paper. Studies are included that relate to changes in the vestibulo-ocular reflex with age, effects of vestibular stimulation on smiling, crying, general activity, and visual attentiveness of infants; and studies that show that typical sequelae to vestibular stimulation are reduced following long-term stimulation. The importance of reviews of the literature and transference of research results to therapeutic use are stressed, with the implication that vestibular-based therapy will improve as occupational therapists become more aware of related research.


Cell-mediated cytotoxicity and humoral immune response in ascorbic acid-deficient guinea pigs. Guinea pigs were divided into three dietary groups: ascorbic-acid deficient, pair-fed, and ad libitum control. Two weeks later guinea pigs were immunized intradermally with 5 x 10(8) chicken erythrocytes in Freund's complete adjuvant. Hemagglutinating antibody titers to chicken erythrocytes 2 weeks after immunization were comparable in all three dietary groups. In vitro 51Cr release from labeled chicken erythrocyte target cells incubated with lymphoid cells from spleens of ascorbic acid-deficient guinea pigs was significantly less than with spleen cells from pair-fed and ad libitum control guinea pigs. The percentage of splenic lymphoid cells that formed rosettes with rabbit erythrocytes, a T cell marker, was the same in all three dietary groups. The defect of ascorbic acid deficiency may reflect an impairment of T lymphocytes function in cell-mediated cytotoxicity or a change in number or function of another cell type.


[Hereditary angioedema by defict of C1 esterase. Our experience in 8 cases]. Eight cases of hereditary angioedema, all of them with low values of C1-sterase inhibitor are analyzed. In 7 cases the C3 and C4 components of the complement were assessed; the results showed marked descent of C4. The 8 patients came from 4 different families; only 2 of them were males. Six patients presented digestive disorders, reporting colic pain, nausea and vomiting. In 1 of them the abdominal picture was the only evidence of the disease. In 5 patients the angioedema episodes occurred following traumatisms and in 3 because of emotional states. The duration of the attacks varied from several hours to six days. There was a familial history in all cases. Three of the patients had repeated episodes of pharyngolaryngeal angioedema, two of them requiring emergency tracheotomy because of suffocating crisis. Six patients were treated with Epsilon aminocaproic acid (16 to 20 gr daily) or with tranexamic acid (1 to 3 gr. daily). In 4 cases the results were excellent with either of these antifibrinolytic drugs. No side effects were observed in the tranexamic acid therapy whilst they were frequent in the treatment with Epsilon aminocaproic acid.


Antibody against hepatitis A in seven European countries. II. Statistical analysis of cross-sectional surveys. The age-specific prevalence of hepatitis A antibodies has been analyzed using a catalytic epidemic model for populations in seven European countries: West Germany, Norway, Greece, Switzerland, Holland, France and Sweden. The results indicate a significant decline in the force of infection in recent decades. However, there are substantial differences between the countries, especially between the Scandinavian countries and Greece. The incidence of hepatitis A in Norway and Sweden has declined since 1930, while a downward trend in incidence in Greece may have started only recently.


Cell mediated immune regulation in autoimmunity. Autoimmunity is the term for the immune conditions characterized by a specific humoral or cell mediated response to the body's own tissues. The termination of the natural state of self tolerance may lead to immunopathological manifestations with clinical consequences, i.e. autoimmune diseases. In a very general sense, one may classify autoimmune diseases into two groups with respect to the underlying mechanism: 1. There are autoimmune diseases which develop in the presence of a normal intact regulation mechanism. 2. Another group whose development must be understood on the basis of a cellular dysfunction. In the first case, dequestered or semi-sequestered autoantigens are liberated as a consequence of exogenic influences inducing the sensitization of immunocompetent cells. The immune system then reacts with these autoantigens in the same way as with foreign substances. This kind of autoimmune disease will, however, not be dealt with here. In the second case, autoantigens are normally, i.e. in healthy individuals, accessible to the immunocompetent cells. To understand the reason for the development of an autoimmune reaction one must first clarify the mechanism of self tolerance. Then one must examine the way in which a break of this physiological state takes place. One of the major unanswered questions is the relative importance of antibody-mediated and cell-mediated immune mechanisms in the onset and further development of autoimmune diseases. Recently it has been suggested that a dysfunction at the cellular level might represent the basic cause which induces the termination of selftolerance. Most of the conceptions about the mechanism by which autoimmune diseases are triggered were gained through experiments with animals. It is, however, difficult to use these experimental results to explain human diseases; in humans many questions are still open. Undoubtedly, the mechanisms of induction and maintenance of self tolerance and also the ways in which autoimmune diseases may be induced, are not uniform. In all these cases, cells and cellular interactions as well as the corresponding cellular products are decisive. The majority of autoimmune diseases are mediated by antibodies as can be demonstrated in transfer experiments, for instance. Experimental Autoimmune Thyroiditis (EAT), rather than by sensitized cells. An example of the latter would be Experimental Autoimmune Encephalitis (EAE). In principle the following can be said of all these kinds of autoimmune diseases as well as of selftolerance: 1. Induction of autoantibodies is in principle possible. 2. Self antigens important in autoimmune diseases are T-dependent. 3. Self-reacting lymphocytes (T- and/or B-cells) are present in "normal" individuals.


Diet and serum cholesterol: do zero correlations negate the relationship? The confounding that results from the uncontrolled conditions under which most epidemiologic observations are made is sufficient to undermine their validity with respect to investigation of the relationship between diet and serum cholesterol. In this paper, the authors show, using both a mathematical model and referring to empirical data, that if certain variances are sufficiently great, even when there is cause and effect, correlation coefficients close to zero would be expected from the actual data of a cross-sectional study. Cross-sectional designs are therefore not suitable for studying this relationship.


An acquired cell-directed inhibitor of neutrophil chemotaxis and hypogammaglobulinemia. An unusual combination of host defense abnormalities was demonstrated in an adult male with recurrent pulmonary infections due to a variety of microorganisms. Polymorphonuclear neutrophil chemotaxis was defective. Other neutrophil and T-lymphocyte function tests were normal. The patient's serum also showed a severe deficiency of IgG, no detectable IgA, IgM, or IgD, and increased IgE. The chemotactic defect was shown to be due to a cell-directed inhibitor in the patient's serum. The effect of the inhibitor on chemotaxis could be antagonized by factors in normal serum. The chemotaxis defect persisted for several months, but eventually returned to normal.


Fibroblast interferon treatment of a patient with chronic active hepatitis. Increased number of circulating T lymphocytes and elimination of rosette-inhibitory factor. A 23 year old woman with chronic active hepatitis documented by liver biopsy demonstrated persistent hepatitis B surface antigen, hepatitis B virus specific DNA polymerase hepatitis B core antigen (HBcAg), for approximately one year. The number of circulating T lymphocytes that rosetted with sheep erythrocytes was decreased, and a rosette-inhibitory factor was present in her peripheral blood. Interferon treatment (1 X 10(6) U/day intramuscularly for 82 days) resulted in a decrease of HBsAg and disappearance of HBcAg, (HBeAg) and specific DNA polymerase. In addition, the number of T lymphocytes increased to normal, and the rosette-inhibitory factor disappeared from the circulation. These findings suggest that the effect of interferon in chronic active hepatitis is mediated in part through its action on the immune system.


Variables associated with changes in spirometry in patients with obstructive lung diseases. One hundred fifty subjects were enrolled in a long-term study of obstructive lung diseases; 84 of these were subjected to five or more spirometric studies over a period of two or more years. Stepdown regression analysis was performed to determine the association between many different variables and the annual rates of change in the forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). The following associations were noted to be significant (p less than 0.03); more favorable rates of change of the FVC and FEV1 were associated with a higher alpha1-antitrypsin level and older age. Less favorable changes were associated with more years of cigarette smoking, more airway reactivity and more frequent lower respiratory tract illnesses.


Avascular necrosis in systemic lupus erythematosus. Silent symmetric osteonecroses. The symptomatic joint disease secondary to avascular necrosis of bone (ANB) in 31 of 375 (8 per cent) patients with systemic lupus erythematosus (SLE) was characterized by polyarticular (90 per cent) and symmetric (83 per cent) involvement. Progressive deterioration requiring orthopedic intervention occurred in 11 (35 per cent) patients. No distinguishing clinical or treatment differences were found comparing patients with symptomatic ANB and selected cortico-steroid-treated, asymptomatic, control subjects with SLE. Complete roentgenographic surveys revealed symmetric, polyarticular abnormalities of subchondral and cortical bone consistent with ANB in eight of 31 (26 per cent) of the control subjects. A positive correlation was found between roentgenographic ANB and disease treatment with high doses of corticosteroids. The study suggests that ANB may be present in excess of 30 per cent of the patients with SLE and is most often subclinical, asymptomatic and nonprogressive.


Asbestos-associated neoplasms of B cell lineage. Three different neoplasms of B cell lineage, chronic lymphocytic leukemia, immunoglobulin A (IgA) myeloma and immunoglobulin G (IgG) myeloma were detected in three patients who had heavy occupational exposure to asbestos dust. Two of the patients had coexistent pulmonary asbestosis, whereas the third patient had a pleural mesothelioma subsequent to his initial presentation with myeloma. Defective cell-mediated immunity and hyperactivity of B cell function have previously been noted in patients with asbestosis. We suggest the possibility that these asbestos-related immunologic derangements may predispose to the development of immunoproliferative and lymphoproliferative neoplasms, since such tumors have been observed in a variety of other settings, characterized by protracted hyperactivity of the immune system.


Proliferative diabetic retinopathy in patients with defects of platelet function. A 71-year-old woman had von Willebrand's disease, an inheritable abnormality of platelet activity, and developed diabetic retinal neovascularization. A 59-year-old man had a myeoloproliferative disorder with thrombocythemia but may have had retinal changes before the development of his platelet dysfunction. The occurrence of diabetic proliferative retinopathy in patients with reduced platelet activity suggests that platelet induced microcirculatory abnormalities may not be required for neovascularization.


Cone-rod dystrophy: a case report.

Cone-rod dystrophy: a case report. Cone-rod dystrophy is considered one of the rarer hereditary retinal degenerations. This disease can be easily mistaken for a number of other conditions because of its unusual characteristics. This paper discusses these characteristics and presents a case report to illustrate how the optometrist can effectively manage patients with this disease.


Acid alpha-naphthyl acetate esterase activity in human neoplastic lymphoid cells. Usefulness as a T-cell marker. Previous studies have shown that a distinctive pattern of acid alpha-naphthyl acetate esterase (ANAE) activity (focal reaction product) characterizes normal human peripheral blood and tissue T lymphocytes but is absent from thymocytes and certain mitogen-stimulated T-cell blasts. In the present study mononuclear cell suspensions prepared from the peripheral blood and tissue specimens of 35 patients with lymphoid malignancies were simultaneously analyzed for surface immunoglobulin, sheep erythrocyte rosette formation, Ia antigens, and ANAE activity. The neoplastic cells from 16 patients with Ia+ SIg+ E- (B cell) malignancies, 4 patients with Ia+ SIg- E- (non-B, non-T) acute lymphoblastic leukemia, and 3 patients with Ia- SIg- E- (null cell) malignancies failed to exhibit ANAE activity. The neoplastic cells from 5 patients with Ia- SIg- E+ (T cell-derived) malignancies, including three cutaneous lymphomas, displayed characteristic T-pattern positivity, and in each case the percentage of E+ and ANAE+ cells was comparable. The neoplastic cells from 4 patients with Ia- SIg- E+ (T cell-derived) acute lymphoblastic leukemia were ANAE-. The expression of ANAE activity in T cell-derived malignancies may parallel its expression in the stages of normal T-cell differentiation and may prove to be a useful marker with which to sort out T-cell phenotypes.


Intracellular localization of markers within injected or cut frog muscle fibers. Many experimental procedures require drastic alterations of muscle fibers, such as cutting the fiber or injecting molecular probes through microelectrodes. We report the ultrastructure of similarly altered muscle fibers and the intracellular distribution of injected horseradish peroxidase (HRP). Cut fibers appear structurally normal at distances greater than 500 microM from the cut end, however, the structure deteriorates nearer to the cut. HRP diffuses longitudinally about 2,000 micrometer from the cut end and the concentration is uniform over the fiber's cross section. If HRP is introduced intracellularly either by pressure injection or through a nick in the sarcolemma, it distributes in a C-shaped annulus extending approximately 2,000 micrometer longitudinally and 1-20 micrometer radially. The ultrastructure of injected or nicked fibers appears normal. The HRP freely entered the junctional gap between T-system and sarcoplasmic reticulum (SR) but was excluded from either structure. Occasionally, a light pillar could be seen between T-system and SR; the space of these pillars suggest they are the central area of the "feet" appearing light against the dark marker.


Electrical and transport characteristics of skin of larval Rana catesbeiana. Carefully dissected, mounted, and bathed with Ringer solution, the larval bullfrog skin has a resistance of about 9,000 omega.cm2 and a stable transepithelial electrical potential of about 20 mV (inside +). A short-circuit current of about 2 microA.cm-2 is generated that is comparable in magnitude to the net inward flux of Na+. At open circuit the flux ratio equation for Na+ is not satisfied. Larval skin is less sensitive to ouabain, amiloride, and ADH than adult skin. The current-voltage (C-V) relationship across the preparation is not linear; there are distinct breaks in both the hyperpolarizing and hypopolarizing regions. The former break, at about +130 mV, corresponds with a break observed in adult skin that corresponds with ENa. The shunt resistance (RS) and active pathway resistance (RA) were estimated by C-V curve analysis and by ion substitution. The two methods yielded comparable values with RS about 11 k omega.cm2 and RA about 62 k omega.cm2. It is suggested that transport is limited by the number of entry sites for sodium at the apical border of transport cells.


Action of adenosine on chloride active transport of isolated frog cornea. Addition of adenosine (10-7 to 10-4 M) to the tear side of isolated corneas (Rana catesbeiana) produced a rapid, sustained increase in short-circuit current, potential difference, and radioisotopic chloride net flux. The increased net chloride flux accounted for the increased short-circuit current. Adenosine, a known activator of adenyl cyclase in other tissues, exerted its effects on chloride transport through a receptor different from the one described for epinephrine and prostaglandins in the corneal epithelium. Propranolol inhibited the epinephrine response but not the adenosine effect. Dipolyphloretin phosphate inhibited prostaglandin responses but did not affect the adenosine stimulation of chloride transport. Adenine and/or ribose, parts of the adenosine molecule, had no stimulatory effect, but 5'-AMP had a partial effect. The activation of the chloride pump with DBcAMP blocked the response to adenosine. Adenosine interacted with the effects of theophylline. Adenosine, a naturally occurring molecule, stimulated chloride transport by activation of adenyl cyclase through a separate membrane receptor in the corneal eqithelium.


Matched control study of distal splenorenal and portacaval shunts in the treatment of bleeding esophageal varices. A matched control study was conducted to compare the effects of portacaval shunting with those of distal splenorenal shunting in patients with advanced hepatic cirrhosis and bleeding gastroesophageal varices. Patients in whom distal splenorenal shunts were performed had significantly less postoperative encephalopathy and hepatic failure and a significantly longer survival than did patients who underwent portacaval shunts.


[Changes in the outer plexiform layer of the rabbit retina after long-term application of vincristine]. Rabbits which had been intravenously injected with Vincristine for six weeks showed changes in the outer plexiform layer of the retina after one year, which suggests the destruction of receptor cells, bipolar ganglion cells, and horizontal cells. Compensated cell damage accompanied by loss of microtubuli in the cytoplasma, autolytic vacuoles, granular material deposits, and membrane changes of the ribbon complex were frequently observed. A comparison between axons and dendrites showed a predominance of damaged dendritis over axons. Because short-term studies have not produced the same results, different regeneration capacities, which might have their origin in the endoplasmatic reticulum, are discussed.


Measurement of vessel width on fundus photographs. Many factors play a role in determining the width of retinal vessels, based on fundus photographs. We have tried to estimate their influence by comparing experimentally six different measuring methods, taking into account film and developer, intra- and interindividual reproducibility of results under short- and long-term conditions, and training in measuring technique. Our method of choice was tenfold projection of the negatives on a fine-grained wax layer screen and use of a very narrow marker line to be aligned with the vessel borders. Width determinations on pictures of good definition, yet low contrast, repeated by a trained observer on consecutive days, lay with a 95% probability within an interval of about 9 micron on the retina. The width so determined is, of course, relative and only a rough approximation to the absolute width, because of photographic bias, interobserver difference, and uncertainly of the refractive power of the eye. The method appears to be especially suitable for the study of intraindividual variations; however, because of photographic bias, conclusions should be drawn only when based on several pictures.


Comparison of isometric muscle training and electrical stimulation supplementing isometric muscle training in the recovery after major knee ligament surgery. A preliminary report. Eight patients undergoing reconstruction of the anterior cruciate ligament were randomly allocated into two groups. The control group received a standard plaster cast and isometric muscle training. The stimulated group received a standard plaster cast, isometric training, and percutaneous electrical stimulation during the recovery period. The patients were examined clinically and with repeated muscle biopsies before surgery, 1 week after surgery, and 5 weeks after surgery at the time of removal of the cast. The electrically stimulated group had better muscle function from a clinical point of view and their succinate dehydrogenase activities were significantly higher than those in the control group. Electrical stimulation thus could prevent the fall in oxidative enzyme activity which was noted in the control group. The results suggest that percutaneous electrical stimulation may be a way of preventing muscle atrophy after major knee ligament surgery in athletes.


Measurement of vessel tortuosity on fundus photographs. Quantitative measurement of vessel tortuosity and its variation on fundus photographs is a sensitive means of obtaining information about the course of an asphyctic event in newborns, virtually independent of bias produced by the photographic process. We subdivide a tortuous vessel into single arcs and measure the chord length and the arrow height (Pfeilhöhe) of every arc on a projected image of the film. From these figures, a fairly accurate value for the relative length increase of the arc, as compared with the chord, can be derived by a simple approximation formula [Eq. (5)]. It is shown that neglect of the third dimension, not visible on an ordinary photograph, entails only a small error. Trained observers achieve results reproducible to about 1% in relative length variation.


[Proof of glycosaminoglycans in the corneal endothelium]. The corneal endothelium of three species (man, dog, and guinea pig) was examined for glycosaminoglycans by using TEM, REM, and EDAX (energy-dispersive analysis of X-rays). Since no clear results can be determined by using ruthenium red (RR) alone, a testicular hyaluronidase was used to digest the glycocalyx. After incubation with hyaluronidase, the dark RR borderline of the outer leaflet of the cell membrane became more fluffy when examined by using TEM and REM. When EDAX was applied, the Ru peak became smaller compared with the S peak. These impressive results had not been found when the material was fixed in glutaraldehyde for 24 h before incubation. Considering the individual results, it can be concluded that RR, even wouthout OsO4, marks the acid groups of glycosaminoglycans that might be in the cell membrane, as well as other acid groups. There was no difference in the results among the three species used in this experiment. Some pictures showed that RR/OsO4 penetrates through the intercellular space into the Descemet's membrane.


Leukocyte migration inhibitory factor in primary and recurrent ocular infections by herpes simplex-virus. Using a direct assay of leukocyte migration inhibitory factor (LMIF), cell-mediated immunity to herpes simplex virus (HSV) antigen was measured in patients who had primary and recurrent ocular HSV infections. Those with primary and recurrent epithelial disease had a significantly lower production of LMIF than a control population than had had no herpetic infection for at least a year or longer (P less than 0.001). On the contrary, patients with deep stromal involvement and anterior uveitis showed significant migration inhibition with HSV antigen, similar to the one found in the healthy control group. The clinical and possible therapeutic implications of thes findings are discussed.


Immunologic studies of patients with histoplasmosis. Immunologic responses of patients with active histoplasmosis (Group I) were compared to the responses of healthy persons with positive histoplasmin skin-test reactions (Group II), and to those of healthy persons with negative histoplasmin skin-test reactions (Group III). Cellular immune responses were significantly depressed in patients. Seven (54 per cent) of 13 patients failed to respond to histoplasmin skin testing, and two (15 per cent) failed to respond to skin-test antigens unrelated to Histoplasma capsulatum. Lymphocyte transformation (LT) responses of patients were severely depressed in vitro (p less than 0.001) to Histoplasma antigens when compared to the responses of healthy, histoplasmin-reactive donors. Transformation responses to Candida antigen were not impaired in the patient population. Culturing lymphocytes of patients in serum obtained from healthy donors as opposed to autologous serum resulted in a significant (p less than 0.05) increase in LT responses to H. capsulatum. Responses to Candida antigen and to mitogens were not affected by the serum source. Serum-mediated suppression of LT responses correlated (p less than 0.01) with complement-fixing antibody titers to Histoplasma yeast-phase antigen and suggests that antibody, either alone or complexed with antigen, may suppress T-cell response in vitro in this disease.


Interrelationships between neutrophil elastase, serum alpha, -antitrypsin, lung function and chest radiography in patients with chronic airflow obstruction. We assayed protease and elastase activity of lysosomal granules of purified neutrophil suspensions in 58 patients with chronic irreversible airflow obstruction and compared them to 26 healthy control subjects. Denatured hemoglobin and tritiated elastin were used as substrates for protease and elastase assays. Forty-two patients had M antitrypsin phemotype, five had MS, and 11 had Z variant (five were homozygotes and six were heterozygotes). We did not find significant differences in mean lysosomal elastase or protease activity between patients with normal antitrypsin and control subjects; however, a few patients had concentrations of neutrophil elastase that exceeded the range among control subjects. There was no significant correlation between neutrophil protease or elastase activity and age, smoking, degree of airway obstruction, diffusing capacity, lung elastic recoil, or radiologic presence of emphysema in patients with M and MS antitrypsin. In patients with Z variant antitrypsin, protease and elastase concentrations per unit of lysosomal protein were not significantly different from those in control subjects or M patients; however, both elastase and protease content per 108 neurtophils was significantly higher in homozygous and heterozygous Z patients as compared to normalsubjects and M patients, which suggest an increase in the neutrophil content of protease and elastase in patients with Z antitrypsin deficiency. These results suggest that hte concentrations of protease and elastase in neutrophils do not appear to interact as additive risk factors in the pulmonary impairment of most patients with chronic airflow obstruction, but may be of importance as risk factors in patients with Z or MZ phenotype and in a few patients with M phenotype.


Localization of the immune response in sarcoidosis. Pulmonary sarcoidosis is an interstitial disease characterized by granulomas within the lung parenchyma, anergy to a variety of skin tests, and decreased numbers of circulating T-lymphocytes. To evaluate the effector cell populations present at sites of disease in patients with active pulmonary sarcoidosis, inflammatory and immune effector cells were isolated from lung via bronchoalveolar lavage and compared to comparable cell populations from the peripheral blood of the same patients and similar cell populations of normal subjects and patients with idiopathic pulmonary fibrosis. Patients with sarcoidosis had a marked increase in the percentage of T-lymphocytes in the lung despite a significant peripheral blood T-lymphocytopenia. In addition, many of these T-lymphocytes demonstrated surface marker characteristics associated with lymphocyte activation, and they spontaneously secreted leukocyte inhibitory factor. In contrast to patients with sarcoidosis, normal subjects and patients with idiopathic pulmonary fibrosis had similar percentages of T-lymphocytes in lung and blood, and there was no evidence for T-lymphocyte activation. Analysis of lymphocytes in uninvolved marrow from 7 of 8 patients with sarcoidosis revealed proportions of T-lymphocytes similar to those in the marrows of normal subjects and patients with idiopathic pulmonary fibrosis. In comparison, one patient with sarcoidosis had large numbers of T-lymphocytes in bone marrow, but only in areas where there were granulomas in the marrow. These studies suggest that: (1) the alveolitis of pulmonary sarcoidosis is characterized by large numbers of activated T-lymphocytes, and (2) there is an anatomic localization of the immune response in sarcoidosis in that analysis of uninvolved tissues such as peripheral blood may not reflect local immune responses at sites of granuloma formation.


[Kartagener's syndrome (author's transl)]. A case of a nine year and eight months old child with Kartagener's syndrome (triad) is described: chronic maxillary sinusitis, bronchiectasis and "situs inversus totalis". Literature is reviewed. It is important to understand genetical and etiology aspects of bronchiectasis. Diagnosis was considered on the basis of physical and radiographic examination.


Immunologic and coagulation disorders in chlorpromazine-treated patients. The prevalence of immunologic and coagulation disorders in 75 schizophrenic patients treated with chlorpromazine or other antipsychotic drugs was evaluated. Four groups were studied: Group A, chlorpromazine treatment for more than 2 1/2 years; Group B, chlorpromazine and other antipsychotic drug treatment for more than 2 1/2 years; Group C, chlorpromazine treatment for less than 2 1/2 years; Group D, no chlorpromazine, but other antipsychotic drug treatment. Significant elevation of serum IgM and prolongation of partial thromboplastin time were noted in patients who had long-term chlorpromazine treatment. The latter was caused by a circulating inhibitor resembling that seen with systemic lupus erythematosus. There was a significant correlation between the IgM level versus chlorpromazine dose or duration of treatment and the partial thromboplastin time versus chlorpromazine dose or duration of treatment. In Groups A and B, 63% had a positive antinuclear antibody test (greater than or equal to 1:80), 40% had antibodies to native DNA, and 58% had antibodies to nucleoprotein. These antibodies were negative in the other groups. The percentages of T lymphocytes were below normal in 13 of 41 patients treated with chlopromazine. Twenty of 42 patients in Groups A and B, and none of 28 in Groups C and D had splenomegaly. This study indicates that most patients on long-term chlorpromazine treatment develop one or more immunologic abnormalities.


Hereditary C2 deficiency associated with common variable immunodeficiency. Homozygous C2 deficiency in a 19-year-old boy was associated with variable immunodeficiency manifested by marked hypoimmunoglobulinemia and impaired antibody responses, normal circulating B lymphocytes, and subnormal T-cell functions. Neither antilymphocytic autoantibodies nor chromosomal abnormalities were found. Serum immunoglobulin levels were within normal limits in his parents and brother who were heterozygous for C2 deficiency. The patient's lymphocytes were homozygous at the HLA-D locus but expressed an antigen different from DW2.


[Digestive manifestations of Rendu-Osler's disease (author's transl)]. Rendu-Osler disease, hereditary hemorrhagic telangiectasia is a genetic disorder, autosomal dominent. Telangiectasia of the skin, face, trunk, upper and lower extremities are associated with angiomas of the oral and nasopharyngal membranes, lips, tongue and internal organs (intestine tract, liver, spleen, blood, lung, brain). They are source of melena, hematemesis, hematuria, hemoptysis with severe anemia. dilated blood vessels forming cavernous spaces, flattened endothelial cells, no perivascular infiltration, degeneration of the perivascular connective tissue, elastic and muscular fibers missing around the vessels. Therefore hemorrhages are not able to stop spontaneously. Ultrastructural changes : formation of gaps along the thinned-out endothelial lining of dilated vessels, gaps plugged with thrombi. Anormal perivascular collagenous tissue, perivascular smooth muscles elongated and irregular in shape, did not surround the vessels. Liver cirrhosis and blood loss (gastrointestinal hemorrhages sometimes massive) are the only digestive manifestation of the severity. Systematic replacement of iron and blood transfusions are the most helpful forms of treatment.


Acute vestibular paralysis in herpes zoster oticus. A case of herpes zoster oticus is presented in which the lateral and superior semicircular canals of the labyrinth were affected unilaterally. The results of several electronystagmographic examinations are described and correlated with the patient's description of symptoms. This case study indicates that disease affecting the lateral semicircular canal is reliably detected by the conventional caloric test. However, the fact that the posterior semicircular canal remained intact could not be inferred from the results of the caloric test in this case. Also the appearance of nystagmus upon eye closure appears to have been a more sensitive index of the state of the disease process than was the caloric test.


Structure and development of vestibular hair cells in the larval bullfrog. Structure and development of hair cells in vestibular sensory organs of the larval bullfrog were examined with scanning electron microscopy. The larval vestibular sensory epithelia resembled those of the adult frog. Based on morphology of the ciliary tufts, seven hair cell types were identified. One of them, the type A hair cell, appears to be the morphogenetic precursor of other hair cell types. The size of the stereocilia of type A hair cells is comparable to the surrounding microvilli. The distribution of immature type A hair cells suggests that the periphery of the sensory epithelia is the principal growth zone and the site of formation of new hair cells. However, a far greater number of type A hair cells were found in high frequency sensitive sensory organs (sacculus, amphibian and basilar papillae) than low frequency sensitive vestibular sensory structures (canal cristae, utriculus and lagena). This phenomenon may suggest that the time period required for the maturation of type A hair cells to their ultimate hair cell types in the low frequency sensitive vestibular organs is shorter than in the high frequency sensory structures. It is also possible that the low frequency sensitive vestibular organs may have completed their morphogenetic development in the early larval stages, while morphogenesis of hair cells in the high frequency sensory structures continues throughout the lifetime of a bullfrog.


Latent allotypes: a window to a genetic enigma. Recent data concerning the expression of latent allotypes (allotypes present in low concentration and not anticipated from breeding data) are presented. Using various sensitive assays, latent allotypes of groups a, b and d have been observed in sera, IgG samples, isolated antibody fractions and on lymphoid cell surfaces. Recently, molecules bearing latent group a allotypes have been isolated from IgG samples and from specific antibody fractions by immunoadsorbent chromatography and subsequently typed for VH and CH allotypes. In several preparations latent group d allotypes were observed. IgG clearance rates were measured by intravenous injection of rabbits with differentially radiolabelled (125I and 131I) allotype matched and non-matched IgG samples. In no instance was allotype matched IgG cleared faster than non-matched, although the converse was true in several rabbits, suggesting in vivo recognition of allotypes as a possible regulatory mechanism. Genetic models that can account for latent allotypes require the presence of information in the genome that is not expressed under normal conditions, and, furthermore, these models must include inherited regulation mechanisms to govern synthesis from this information. Available data do not require that all Ig genes are present in all members of a species, but may suggest the presence of genes for limited groups of allotypes.


A and b allotypy in Oryctolagus and Lepus species. It had been previously shown by the description in wild rabbits Oryctolagus cuniculus of unknown allotypic specificities belonging to the a series and the b series, that the genetic polymorphism found in domestic rabbits was only a part of the genetic polymorphism of the species O. cuniculus. To the known a1, a2 and a3 allotypic specificities have been added in the last years a100 and a101 which are under the control of allelic genes at the a locus. Studies of cross-reactivities in the a system is a way to detect variants of a given allotypic specificity. The phylogenetic studies in the hare Lepus capensis demonstrate that a2 and a3 determinants are allotypic, apparently without polymorphism in this species; indeed, all the tested hares have either a2 or a3 determinants or both. Four presumably "new" allotypic specificities of the b series, A93, A94, A95 and A96 have been found in a population of wild rabbits O. cuniculus from an Island in Tunisia. A95 allotypic specificities against which specific antisera have been prepared, shows cross-reactivities with b4, b5 and b6 allotypes of domestic rabbit. Genetic data demonstrate that A95 is indeed under the control of an allele at the b locus. If schematic mechanisms involving duplication and mutations of genes are suitable to understand the presence of variants and their cross-reactivities, one has to understand how so many genes are involved in allotypy and how it remains stable during evolution.


In nature of idiotypes associated with anti-p-azophenylarsonate antibodies in A/J mice. Antiphenylarsonate (anti-Ar) hybridomas were prepared according to Milstein and Köhler with the cell line 45.6TG1.7 and A/J spleen. About 20% of initial wells with anti-Ar activity expressed the major A/J cross-reactive idiotype. Many wells contained anti-Ar antibodies whose binding to Ar-coated plates was strongly inhibited by antiidiotypic (anti-id) antibody but which did not compete effectively with labelled serum antibody for anti-id. Three such hybridoma products (HP) were cloned twice in agar; a 4th was cloned once. All were IgG1K. Each of the four HP, when specifically purified from a BGG-Ar-Sepharose and then radiolabelled, was strongly bound by anti-id. Pooled purified anti-Ar antibodies and anti-Ar antiserum from 9 of 10 mice competed with each HP for anti-id. The serum of the mouse which was non-inhibitory contained normal amounts of the major cross-reactive idiotype. These results demonstrate the presence of cross-reactive anti-Ar idiotypes other than the major idiotype in the A/J strain. Such idiotypes represent a small proportion of the anti-Ar population. Serological analysis of the four HP, which may reflect the serum antibody population, suggest that these "minor" idiotypes may be quite heterogeneous. An HP which did compete with the major cross-reactive idiotype for anti-id failed to compete with three of the four HP described above. This provides support for the concept that the "minor" idiotypes are serologically distinct from the major cross-reactive idiotype.


Some studies on idiotypes and anti-idiotypic reactions and receptors in anti-allo-MHC T-cell immunity. The fine specificity of immunocompetent T lymphocytes is reflected on their outer surface by their display of idiotype-positive receptor molecules. Interference with these structures using antiidiotypic reagents may trigger or eliminate the cell depending on the external conditions. When analyzing the distribution pattern of idiotypes on murine allo-MHC activated T blasts it was found that proliferating "helper" T and killer T cells display non-overlapping sets of idiotypes. Furthermore, it was found that antiidiotypic antibodies in vitro may mimic the allo-MHC antigens in the T-cell triggering capacity and may indeed in some systems be superior to allogeneic stimulator cells in this regard. This capacity of antiidiotypic antibodies to functionally mimic and replace allo-MHC structures in T-cell triggering ability is discussed in relation to self-MHC reactivity and biochemical and functional similarities between Ig molecules and MHC structures.


Growth curves, microscopic morphology, and subcultures of beta-lactamase-positive and -negative Haemophilus influenzae under the influence of ampicillin and cefamandole. In contrast to the results obtained with ampicillin, the minimum inhibitory concentrations of cefamandole against Haemophilus influenzae were within the same range (0.5 to 1.5 mug/ml) whether or not the strains were beta-lactamase producers. The minimum bactericidal concentrations were somewhat higher for beta-lactamase-positive strains (6.4 mug/ml) than for negative strains (1.2 mug/ml). In a culture with high initial microbial density, monitored by recording optical densities, the addition of 10 mug of cefamandole per ml brought about rapid lysis of a beta-lactamase-negative strain. Observation of a beta-lactamase-positive strain revealed, in the early part of the growth curve, absence of lysis and an increase of biomass similar to that observed in a drug-free control curve. In contrast to the results obtained with ampicillin, the culture consisted uniformly of spherical forms, probably in the process of division, which were capable of generating colonies. When the microbial density exposed to cefamandole was increased still further, persistent bacillary forms were observed, and after 24 h hydrolysis had eliminated every trace of microbiologically active cefamandole.