[Course of the rheumatic process in mitral heart defects after primary and repeated courses of treatment with titrated gamma-globulin]. Titrated gamma-globulin, which the authors used in the preoperative management of patients with acquired valvular disease and minimum rheumatism activity, contained high titers of antibodies against the antigens of streptococcus (streptokinase, streptohyaluronidase, streptolysin 0) and Coxsackie A13, A18, and B3 viruses. Its use in combination with antirheumatic agents did not cause any complications and made it possible to reduce the activity of the process in most cases with grade I and after repeated courses also in grade II activity of rheumatism. Treatment with titrated gamma-globulin stimulates the organism's defence forces (factors of nonspecific immunity: complement, lysozyme, interferon) and leads to diminution of the isolation of cardiotropic viruses from blood and bioptic material of the atria of patients.


Distribution of five antigens in hepatocellular carcinoma. A variety of antigens may be detected in the serum of patients with hepatocellular carcinoma (HCC). The incidence and distribution of five antigens in 37 HCC and their relation to each other in a given tumor was examined by the peroxidase-antiperoxidase technique using formalin-fixed paraffin-embedded tissues. alpha 1-Antitrypsin was frequently expressed in HCC (73 per cent of cases), whereas alpha-fetoprotein and carcinoembryonic antigen were less common. HBsAg, but not HBcAg, was observed in tumor cells in seven of nine HCC from HBsAg-positive patients. In 20 HCC (54 per cent), two or more antigens, most frequently alpha 1-antitrypsin and alpha-fetoprotein, were detected. Double staining for simultaneous localization of two antigens in the same tissue section revealed that different antigens were usually present in different tumor cells, although some cells displayed two antigens simultaneously. These findings suggest that hepatocellular carcinoma cells are functionally heterogeneous, even if they appear histologically monomorphic.


The effect of developmental disabilities on mental health. Behavioral abnormalities in the developmentally disabled child are usually ascribed to parental mismanagement of a child perceived as abnormal. (Review of the available data points to the existence of primary behavioral abnormalities due directly to the cerebral dysfunction.) This has important implications for parental counseling and management.


Structure, function, and antigenicity of cholera toxin. Chemical modification of intact cholera toxin or its B subunit by either partial nitration or reduction and alkylation did not result in significant loss of biological activity as determined by measurement of cyclic AMP in Chinese hamster ovary cells. Complete nitration or succinylation in the presence of guanidine hydrochloride resulted in complete loss of biological activity and significantly affected the immunoreactivity of the toxin and B subunit. Compositional analyses of both the isolated alpha and gamma chains of the toxin were typical of globular proteins and did not reveal significant hydrophobicity. Analysis of antigenic relationships by radioimmunoassay indicated a partial crossreactivity between the alpha chain and the B subunit of cholera toxin. Since previous structural studies of the beta chain of cholera toxin indicated chemical similarity with the glycoprotein hormones [Kurosky et al. Science 195:299 (1977)], radioimmunoassay procedures were employed to investigate for possible crossreactivity. No evidence of crossreactivity between cholera toxin subunits and subunits of ovine luteinizing hormone was found.


Electrocoagulation: palliative surgery to control metastatic cutaneous malignancy. The adaptation of the principles of electrocoagulation to controlling symptomatic cutaneous metastatic disease is discussed. The technique permits minimal anesthesia, excellent hemostasis, local control, satisfactory cosmesis with reduced hospitalization. Two illustrative cases are reported of metastatic malignant melanoma and metastatic leiomyosarcoma.


Cancer of the breast. Radiation therapy. There are many questions that have to be answered concerning the role of radiotherapy in the management of primary breast cancer. Hopefully, prospective clinical trials will provide some answers, but more basic research into the biology of breast cancer and the host-tumor relationship will be needed. There are indications that radiotherapy alone, or following minimal extirpative surgery in selected cases, may be as effective for control of breast cancer as conventional mastectomies. The role of radiotherapy following segmental mastectomy, with or without axillary dissection, needs to be clarified. The possibility exists that high LET (linear energy transfer) radiation such as neutron or pi meson beams may provide better local control than conventional radiation. Thus, it may be possible to treat effectively all primary breast cancers with such radiations and obviate the need for any type of mastectomy. It remains to be demonstrated whether adjuvant chemotherapy is as effective as radiotherapy in preventing chest wall and regional node recurrences. If it is not, there may be a place for both adjuvant chemotherapy and radiotherapy in the treatment of operable cancer of the breast. Likewise, effective chemotherapy combined with radiotherapy may increase the local and regional control achieved with radiotherapy alone and make more primary lesions suitable for treatment without mastectomy. Meyer (1970) recently called attention to the leukopenia and cellualr immune deficiency produced by irradiation to the thorax and mediastinum. Further study is necessary to define exactly how much immunosuppression results from radiotherapy, its clinical significance and what can be done to avoid or counter it. If Stjervsward's thesis (1974) concerning the deleterious effects of radiotherapy on survival is correct, then it is of great importance to identify those patients most likely to be adversely affected by radiotherapy. Conversely, it may be possible in the future to identify a subgroup of patients who would not be adversely affected by radiation and who would be most likely to benefit from it.


Heterogeneity of HLA-BW35 based on the diallelic BW4-BW6 system. Utilizing the diallelic BW4-BW6 system of antigens and antibodies, we divided subjects possessing HLA-BW35 into two groups, depending on the association of their BW35 antigens with BW4 or BW6, and demonstrated in family studies that the associated antigens appeared to be inherited together. Absorption experiments were performed to establish the validity of the typings. Anti-human beta2-microglobulin was used in an effort to "map" the location of the BW4 and BW6 antigenic determinants on the HLA molecule.


Effect of age on axoplasmic transport of cholinesterase in rat sciatic nerves. Senile muscle atrophy has been attributed to an impaired ability of old nerves to transport trophic factors. To evaluate the effect of age on axoplasmic transport, we measured the accumulation of cholinesterase activity above a ligature around sciatic nerves of young (7--8 months), middle-aged (19--20 months), and old (31--32 months) male rats. Protein content and cholinesterase activity per mm of nerve were higher in middle-aged and old than in young nerves. However, accumulation of cholinesterase activity was significantly lower by middle age and was strikingly reduced by old age. This large reduction in axoplasmic transport appeared to result from factors other than axonal loss. A model in which old nerves have an increased number of temporary focal blockages of particle movement in axoplasmic channels is proposed to explain the decreased transport.


Altered plasma lipid and lipoprotein levels associated with oral contraceptive and oestrogen use. Report from the Medications Working Group of the Lipid Research Clinics Program. In a study of women attending ten North American Lipid Research Clinics plasma total cholesterol, triglyceride, low density (L.D.L.), very low density (V.L.D.L.), and high density (H.D.L.) lipoprotein levels in those taking oral contraceptives (O.C.) and in those taking oestrogens for menopausal symptoms were compared with those in women not taking gonadal hormones, after adjustment for age, educational attainment, and body-mass index, O.C. and oestrogen users were leaner than non-users. Compared with controls, O.C. users showed increased cholesterol, triglyceride, and L.D.L.-cholesterol and V.L.D.L.-cholesterol levels, but H.D.L.-cholesterol levels were similar. Cholesterol, triglyceride, and H.D.L.-cholesterol and V.L.D.L.-cholesterol levels were positively associated with the quantity of the oestrogen component of the O.C. preparations. Compared with non-users, menopausal oestrogen users had slightly lower cholesterol and triglyceride levels, significant decreases in L.D.L.-cholesterol and V.L.D.L.-cholesterol, and a significant increase in H.D.L.-cholesterol.


Multiple biotin-dependent carboxylase deficiencies associated with defects in T-cell and B-cell immunity. Three siblings presented in early childhood with central-nervous-system (CNS) dysfunction, candida dermatitis, keratoconjunctivitis, and alopecia. Two were studied immunologically and had absent delayed-hypersensitivity skin-test responses and absent in-vitro lymphocyte responses to candida antigen. One of them had selective IgA deficiency and no antibody response to pneumococcal polysaccharide immunisation, and the other had a subnormal percentage of T lymphocytes in peripheral blood. The first two siblings died with progressive CNS deterioration and overwhelming infection. The third child, who presented with a periorificial candida dermatitis, alopecia, keratoconjunctivitis, and intermittent ataxia at eighteen months of age, had intermittent lactic acidosis and raised excretion of beta-hydroxyproprionate, methylcitrate, beta-methylcrotonylglycine, and beta-hydroxyisovalerate in urine. After four days of oral biotin, 10 mg/per day, the metabolites in her urine were significantly reduced, suggesting a biotin-responsive multiple carboxylase deficiency. These findings, taken with previous reports of immune defects in patients with disorders of branched-chain aminoacid catabolism, suggest a new biochemical basis for primary immunodeficiency disease.


Biotin-responsive alopecia and developmental regression. A 10-month-old boy presented with dermatitis and alopecia and became severely hypotonic. Screening for urinary organic acids revealed a large quantity of 3-hydroxyisovaleric acid and raised levels of beta-methylcrotonylglycine and 3-hydroxypropionate. Activities of propionyl CoA carboxylase, beta-methylcrotonyl CoA carboxylase, and pyruvate carboxylase in cultured fibroblasts were normal. Treatment with oral biotin resulted in a dramatic clinical improvement, which might therefore suggest a defect in biotin absorption or transport.


Salt intake and diuretic treatment of hypertension. 24 h urinary sodium excretion was used to monitor salt intake in 36 patients with essential hypertension to determine whether limitation of the antihypertensive action of thiazide diuretics could be explained by increased salt appetitie stimulated by salt depletion. Sodium excretion in these patients was similar before treatment to that observed in normotensive controls, and no change was observed during 2 years' treatment with bendrofluazide. However, plasma-renin rose progressively over the 2 years even in 5 of 8 patients whose renin was not stimulated initially by diuretics. Thus, there is no evidence that a voluntary increase in salt intake limits the efficacy of diuretic treatment; on the other hand, progressive stimulation of the renin-angiotensin system may be an important limiting factor to the antihypertensive action of diuretics. If so, the antihypertensive effect of dietary salt restriction may be similarly limited.


Induction of specific tolerance in rabbits by kidney allografting and short periods of cyclosporin-A treatment. A short period of daily treatment with cyclosporin A (25 mg/kg orally or 18 mg/kg by intramuscular injection) induced specific tolerance lasting more than 12 months in 60% of nephrectomised rabbits allografted with one kidney. Tolerant rabbits accepted second kidney and skin allografts from the original donor even though all immunosuppressive therapy had been withdrawn at least 70 days earlier, while third party allografts were rejected normally. These results strongly support the hypothesis that cyclosporin A induces operational tolerance to antigens in a donor-specific, not tissue-specific fashion.


Lactase degradation by human enteric bacteria. Twelve non-pathogenic bacteria and two yeast strains isolated from the duodenal aspirate or mucosa of five children with diarrhoea were tested for their ability to degrade non-human lactase in vitro. Both yeast strains and eleven of the bacterial strains significantly reduced lactase activity. A similar action on human lactase could be a cause of lactose intolerance.


Risk factors for death in treated hypertensive patients. Report from the D.H.S.S. Hypertension Care Computing Project. A prospective study was performed to determine factors at presentation influencing survival in 2587 treated hypertensive patients who were followed for an average of 4 years. 86% had been referred to hospital clinics with hypertension and 14% were seen solely by their general practitioners. Of the 156 deaths, 81% were from cardiovascular causes. Independent risk factors for cardiovascular death were age, impairment of renal function, smoking habits, and systolic blood-pressure before treatment. Other independent factors of importance were proteinuria, history of myocardial infarction, and retinal changes of accelerated hypertension. Increased weight, serum cholesterol, and serum uric acid were not independent risk factors. Although these results agree substantially with data for normal populations, notable exceptions were impairment of renal function, which was very important in hypertensives, and raised serum cholesterol, which was not an independent risk factor in this hypertensive population.


Eight years' experience with a weekday gynaecological ward. Between 1971 and 1978, 9651 patients were admitted to a gynaecological ward in use five days a week. 39.5% of patients were admitted as "day cases", the rest as "overnight stay" patients. Patients can choose between local or general anaesthesia and between day care or overnight stay. The procedures carried out were termination of pregnancy (41.3%), laparoscopy (14.1%), minor gynaecological procedures (41.2%), and urological procedures (3.4%). Despite an 80% increase in work load during these 8 years the waiting list, which fell by 62% in the first year, has been maintained at that level. The advantages of having such a unit in a modern gynaecological service are discussed.


Combined management of malignant teratoma of the testis. Intensive chemotherapy with bleomycin and vinblastine was used as initial treatment in patients with advanced testicular teratoma and after relapse following lymph-node irradiation in patients with early-stage disease. Between January, 1976, and March, 1978, 84 patients, 28 with early disease and 56 with advanced disease, were treated. All 28 men with early-stage disease are alive and disease-free. Patients with advanced disease were divided into two groups. Patients with bulky multiple lung metastases and those with liver involvement did poorly, only 4 of 23 (17.4%) being disease-free. Conversely, patients with bulky abdominal nodes and those with limited lung disease did well, 17 of 21 previously untreated patients (80.9%) being alive and disease-free. Within the latter group, 16 patients were managed with chemotherapy and radiotherapy and/or surgery. Of these, 15 (93.4%) are disease-free.


Chronic cryptic Q-fever infection of the heart. Evidence of chronic Coxiella burneti infection of the heart, a disease previously considered peculiar to patients with valvular heart-disease, was found in a patient during routine serological tests before resection of a ventricular aneurysm and also by isolation of the rickettsia from the resected tissue. The patient had no symptoms or signs of Q-fever endocarditis and none of the laboratory evidence usually associated with it.


Negro alpha-thalassaemia is caused by deletion of a single alpha-globin gene. Studies in two Jamaican Negro families, including haematological and haemoglobin analysis, haemoglobin synthesis, and globin messenger-RNA assay, have defined two alpha-thalassaemia phenotypes which resemble the severe (alpha-thalassaemia 1) and mild (alpha-thalassaemia 2) forms of the disorder described in Orientals. Genetic analysis suggests that subjects with the alpha-thalassaemia-1 phenotype are homozygous for the alpha-thalassaemia-2 determinant. Restriction-endonuclease mapping shows that alpha-thalassaemia-2 results from the deletion of one of the linked pair of alpha-chain genes. Hence the genotypes of the alpha-thalassaemia heterozygotes and homozygotes in these families are -alpha/alpha alpha and -alpha/-alpha respectively. If these are the usual alpha-thalassaemia genotypes in Negroes, these findings explain the difference in clinical expression of the disorder between Orientals and Negroes--in particular, the absence of haemoglobin Bart's hydrops and the rarity of haemoglobin-H disease in Negroes.


Male infertility due to sulphasalazine.

Male infertility due to sulphasalazine. Four young immigrants whose ulcerative colitis was controlled by sulphasalazine had oligospermia and infertility. No other cause for infertility was found in any of them nor in their wives. Findings on semen analyses rapidly improved in all patients on withdrawal of sulphasalazine, which resulted in four pregnancies in three of the wives. Reintroduction of sulphasalazine was followed by rapid deterioration in the semen of two patients. The frequency and importance of the effect of sulphasalazine on fertility requires further evaluation.


Oral clonidine as a growth hormone stimulation test. A single oral dose of 0.15 mg/m2 of clonidine was given to eighteen healthy children and adolescents and to seven patients with hypopituitarism. In healthy subjects there was a pronounced increase in plasma growth hormone from 4.9 +/- 1.3 ng/ml (+/- SEM) to 34.4 +/- 4.5 ng/ml. In the patients with hypopituitarism there was no change in growth-hormone concentrations. Clonidine induced a slight increase in blood glucose in healthy subjects and a slight decrease in patients with hypopituitarism. During the test systolic blood-pressure decreased by a mean of 20 mm Hg in the healthy subjects and by 25 mm Hg in the patients with hypopituitarism. The only side-effect observed was drowsiness. Oral administration of clonidine, a well-tolerated drug, seems to be a simple test for of GH reserves in children and adolescents.


Hairy-cell leukaemia with polyarteritis nodosa. In four patients a systemic vasculitis similar to polyarteritis nodosa developed within 2 years of the onset of hairy-cell leukaemia. Arteriographic studies in two patients revealed microaneurysms, and biopsy specimens in three patients revealed a vasculitis affecting medium-sized vessels. Blood neutrophilia and neutrophilic vascular infiltrate were absent. One patient had circulating immune complexes. Two patients responded to corticosteroids alone, one required cyclophosphamide as well as steroids, and one improved without chemotherapy. The association of vasculitis with hairy-cell leukaemia may provide insight into the pathogenesis of arteritis.


Relationship of oestrogen-receptor status to survival in breast cancer. The oestrogen-receptor (E.R.) content of the primary tumour was measured in 133 postmenopausal women with operable breast cancer. 79 (59%) were positive for E.R. and 54 (41%) negative. Curves of life survival show that women with E.R.-positive tumours live longer than those with E.R.-negative tumours.


Autoimmune disease and the theory of clonal abortion. Is it still relevant? Explanations for self-tolerance and its failure in autoimmune disease remain conjectural. Earlier deletional theories and the later clonal abortion theory as a basis for central B-cell (and possibly T-cell) tolerance seemed to conflict with various experimental and clinical observations, including those relating to the ability to induce autoimmune reactivity in normal adult animals. Accordingly, immunoregulatory controls have dominated discussions. However, there is recent compelling experimental evidence in favour of clonal abortion of B lymphocytes in the absence of T-cell help. It is proposed that two sets of regulatory systems operate at different stages in life to establish and maintain self-recognition: a central tolerance operates through clonal abortion during embryonic and early postnatal life and during childhood and beyond, ancillary regulatory systems deal with the self-reactive cells which emerge in a milieu in which helper influences interfere with clonal abortion.


Aspiration cytology and outpatient excision of breast lumps. Fine-needle aspiration biopsy was performed in 30 consecutive women with clinically non-malignant breast lumps. All aspirates were shown to be benign on cytology and the lumps were excised under local anaesthetic at the outpatient department. Frozen section and paraffin section histology of the excised lump confirmed the diagnosis. Follow-up at the outpatient department and a postal questionnaire revealed the following wound complications: redness (70%), bruising (55%), and discharge (35%). Outpatient excision of solid breast lumps is a safe, rapid, and economical method of treating non-malignant breast lumps, if it is preceded by an accurate cytological interpretation of a technically satisfactory aspirate.


Epidemic of breast enlargement in an Italian school. An outbreak of breast enlargement in girls and boys attending a school in Milan, first noted in November, 1977, was followed up until the end of 1978. 213 boys aged 3-14 years and 110 girls aged 3-7 years were studied; control children attending five other schools were also examined. In total 1647 boys and 476 girls were examined. Breast enlargement was significantly more common in boys (29.0%) and girls (21.6%) aged 3-5 years, boys (58.0%) aged 6-10, and girls (67.1%) aged 6-7 from the school in Milan, than in age and sex matched children at control schools. Breast enlargement was not pronounced and disappeared within 8 months. Hormonal determinations were within normal limits except for 17 beta-oestradiol which was slightly raised. Although oestrogen contamination was not detected when samples of school meals were tested, an uncontrolled supply of poultry and beef was suspected as being the cause of this outbreak.


Training of doctors and delivery of health care in developing countries. In the past two decades, the training of doctors in developing countries has become confused with the delivery of health care. There should be a balance in the financial aid directed to rural and to urban areas; at present rural areas receive too much. The urban hospital, and especially the national teaching hospital, where most of the teaching, care of the seriously sick, and research are done, is in decline. In the training of doctors, the vital clinical approach, oriented towards the individual patient, is losing ground.


[Radiotherapy of colorectal carcinomas (author's transl)]. The authors are of the opinion that radiotherapy is always indicated for colorectal carcinoma patients: (1) Operable carcinomas should be given radiation treatment before operation; postoperative saturation of high-risk cases at the full tumor dose is recommended. (2) Inoperable or partially operated carcinomas should be treated with tumoricidal radiation dose. (3) Radiotherapy is also indicated for cases of local recurrence, especially in the floor of the pelvis, in view of the frequent lack of possible operative access. The necessary dose rate must take into account any prior radiation load. (4) The excellent palliative results are themselves a recommendation for radiotherapy.


[Clinical observations and therapy of the papillomas of the mucous membrane in the otorhinolaryngology (author's transl)]. It's possible papillomas of oral, pharyngeal and laryngeal regions concerning clinical and prognostical aspects to divide under a unit principle. In addition to the criterion of juvenile/adult you must consider solitary or multiple appearance, as well as the macroscopical keratinization. An adequate classification under the aspect of the different malignancy on the basis of morphological and clinical examination of 30 papillomas is proposed. The group of adult, multiple and unkeratinized papillomas of the larynx shows in opposite of opinions of today a tendency of malignancy. Infusion therapy with Bleomycin leads to a volume reduction and to a prolongation of the interval on the papillomas of the larynx, who tend to a malignant degeneration and to a short interval.


Hormonal effects on the regulation of hepatic heme biosynthesis. Drug-induced porphyrin accumulation occurs in chick embryo liver cells maintained in serum-free Waymouth MD 705/1 medium. Addition of insulin and thyroxine to the medium results in a marked enhancement of porphyrin accumulation. The addition of hydrocortisone results in a further enhancement of porphyrine accumulation. Several agents which are reported to increase intracellular adenosine 3':5'-monophosphate (cAMP) levels, viz. glucagon, sodium fluoride, cAMP or its dibutyryl derivative, 3-isobutyl-1-methylxanthine and papaverine enhanced drug-induced porphyrin biosynthesis. On the other have, agents which are reported to decrease intra-cellular cAMP levels, viz. alloxan and imidazole, diminished drug-induced porphyrin accumulation. cAMP appears to enhance, but not to function as a "second messenger" in drug-induced porphyrin biosynthesis. Drug-induced porphyrin accumulation in chick embryo liver cells depend upon the insulin to glucagon ratio. A low level of porphyrin accumulation occurs at insulin to glucagon ratios similar to those found following glucose administration in vivo, suggesting a possible explanation for the therapeutic effect of glucose in hepatic porphyria. The 5 alpha A(A:B trans) and 5 beta H(A:Bcis) steroids are equipotent in inducing delta-aminolevulinic acid synthetase and porphyrin accumulation in chick embryo liver cells maintained in serum-free culture medium. Thus, there is no specific steric requirement for porphyrin-inducing activity in steroids.


[Treatment with immunoglobulins (author's transl)]. Passive immunisation by injecting gamma-globulin prepared from a large donor pool or specific antibodies from selected single donors is of great importance in daily practice for prophylaxis. An example is given for each of the 3 most important indications: a) gamma-Globulin for viral disease (e.g. measles prophylaxis); b) Antitoxic immunoglobulins (e.g. tetanus prophylaxis); c) Rhesus-anti-D-gamma-globulin for prophylaxis of rhesus sensitization. In contrast, substitution with great amounts of gammg-globulin is of little importance for the practizing paediatrician, since such cases are rare. This is the domain of the specialist who should be consulted for planning the therapeutic procedure. Data are given on immunoglobulin preparations commercially available and their application. Side effects are listed. They are particularly severe and dangerous in patients with profound hypo-gamma-globulinemia.


[Immunosuppression (author's transl)].

[Immunosuppression (author's transl)]. Among different procedures of immunosuppression in man medical treatment with cytotoxic drugs has become the most important. Biological methods are still under development but promise to gain in importance since they are more specific and have fewer side effects. The clinical effect of immunosuppressive therapy in organ transplantation is undisputed. Its effects has been proven in some but not all immuno-inflammatory diseases. Before immunosuppressive therapy is started it must be known whether it is effective in the particular disease involved. The severity of the disease has to be critically balanced against the possible side effects of cytotoxic drugs.


[Cellular bases of immunological recognition. Antigen-binding receptors of T-lymphocytes]. The chemical nature, structural peculiarities, immunological specificity of antigen-binding receptors of various T cell subpopulations and the differences of these receptors from the whole Ig molecule were characterized by using a number of techniques, in particular, the selective absorption of T lymphocytes on corresponding target cell monolayers with the following elution of adherent lymphocytes. Participation of H-antigens, Ia-proteins, Ir-gene and Ig V-gene products in processes related to the specific contact of different T subpopulations with an antigen is discussed and a concept on T cell receptors is outlined. According to this concept, receptor active centres of two antigen-recognizing T subpopulations, antigen-reactive cells and effector cell precursors, differ in their nature, being represented by Ir-gene products and V-gene products, respectively. Each of these products is bound to the cell surface with a H-antigen molecule which functions as a constant portion of the receptor in both cell types. These receptors or their subunits freely moving in the cell membrane probably become stabilized during antigen-driven differentiation. This may be accomplished either by combination of several subunits into one multivalent molecule or by replacing the constant part of the receptor molecule by other plasma cell membrane proteins (Ia-proteins in helpers,  differentiation antigens in killers). Three steps of the lethal T killer-target interaction are described, as well as the conditions promoting or inhibiting each of these steps. Possible mechanism of disturbance of cell membrane permeability resulting in lysis of target cells are discussed.


[mRNA of mouse plasmacytoma. Reverse transcription and translation in cell-free systems]. Total poly(A)-mRNA from polyribosomes of MOPC 21 mouse myeloma were investigated. Poly(A)-mRNA was released by two successive chromatography on oligo (dT)-cellulose. A 14S fraction of total poly(A)-mRNA was obtained and partially purified by sucrose gradient centrifigation followed by acrylamide gel electrophoresis. As estimated from the electrophoretic analysis, the 14S mRNA has three components, one of which appears to be 18S rRNA and two others--mRNAs with molecular weight of 5.2.10(5) and 3.8.10(5), respectively. Total poly(A)-mRNA and partially purified 14S mRNA were active when employed as a template in a reverse transcription and cell-free system from wheat germ. DNA complementary to the 14S mRNA was prepared with avian myeloblastosis virus RNA-dependent DNA polymerase. This cDNA was heterogeneous in size with the average size of about 800 nucleotides when analyzed by gel electrophoresis in 98% formamide. The maximal length was about 1100 nucleotides that consistent with full template length. About half of the translation product directed by the 14S mRNA migrated as mature L-chain Ig (upon polyacrylamide gel electrophoresis in sodium dodecylsulfate). The presented data suggested that 14S mRNA species contain mRNA L-chain Ig.


Suppression and reversal of allergic encephalomyelitis in rhesus monkeys with basic protein and peptides. We have extended earlier studies on the suppression of clinically evident experimental allergic encephalomyelitis (EAE) in monkeys, repeated injections of human basis protein. The results confirm that after suppressive treatment, recovered animals remain clinically normal and do not show spontaneous recurrence of symptoms. However, recovered animals are susceptible to EAE upon renewed challenge, and they develop the disease more rapidly and more severely than after the initial challenge; resuppression is also accomplished in these cases by the same methods used previously. The results indicate further that the basic protein or peptide T administered without mycobacteria is effective in suppressing the development of basic protein-induced EAE regardless of the species from which it was derived.


Electron microscopic identification of mammillary body terminals in the rat's AV thalamic nucleus by means of anterograde transport of HRP. A quantitative comparison with the EM degeneration and EM autoradiographic techniques. A comparison has been made between the number of horseradish peroxidase (HRP)-labeled mammillary body terminals in the antero-ventral (AV) nucleus and the number of such terminals labeled with the electron microscopic (EM) autoradiographic [6] and EM degeneration technique [6]. With the antero-grade HRP technique less terminals were labeled than with the autoradiographic technique, but more than with the degeneration technique. Furthermore it may be concluded that the anterograde HRP technique is suitable for determining the type of terminal and does not require the long exposure time of the autoradiographic technique.


Retrograde transport of bisbenzimide and propidium iodide through axons to their parent cell bodies. Two fluorescent substances bisbenzimide (Bb), which fluoresces yellow-green and propidium iodide (PI), which fluoresces orange were found to be transported retrogradely through axons to their parent cell bodies in rat and cat. Bb gives a very strong and long lasting fluorescent retrograde neuronal labeling and is very effectively transported over long distances both in rat and cat. Bb and PI also label glial nuclei around retrogradely labeled neurons. Bb in addition labels glial nuclei along axons through which it is transported. Bb and PI can be transported retrogradely through two divergent collaterals to one and the same cell.


Immunochemical studies of myelin basic protein in shiverer mouse devoid of major dense line of myelin. The myelin-deficient mutant Shiverer (Shi/Shi) lacks basic protein (MBP) in the myelin of its central nervous system (CNS). Less than 3% of the normal content in MBP is present in a brain extract of Shi/Shi as determined by radioimmunoassay. Indirect immunofluorescence is negative when using specific anti-MBP serum. The importance of Shi/Shi (as compared to other hypomelinating mutants) stems from the specificity of this genetic lesion, i.e. the lack of basic protein.


Transganglionic transport of horseradish peroxidase in primary sensory neurons. The cut end of the sciatic nerve of adult rats was exposed to horseradish peroxidase (HRP). The rats were allowed to survive for 12 h--5 days. 12--18 h postoperatively small dorsal root ganglion cells more heavily labeled than large ones. After 48--72 h more large cells were intensely labeled. From 18 h onwards large amounts of HRP labeling was observed ipsilaterally in the superficial laminae of the dorsal horn, from 48 h also in deeper laminae and in the gracile nucleus. The heavy labeling clearly indicates the potential of the present approach for mapping purposes. The findings also indicate that short postoperative survivals can be used for rather selective marking of small cells and fibers.


Fuorescent retrograde neuronal labeling in rat by means of substances binding specifically to adenine-thymine rich DNA. Six fluorescent substances, binding specifically to adenine-thymine rich DNA, were injected in rat caudate-putamen. This resulted in retrograde axonal transport and fluorescent retrograde labeling of neurons in center-medium parafascicular nucleus, substantia nigra and dorsal raphe. Two of these substances, i.e. "True Blue' and 'Granular Blue', give a very striking blue fluorescent retrograde neuronal labeling. Mid-thoracic spinal injections of these two substances in rat also resulted in a pronounced retrograde fluorescent labeling of neurons of the descending brainstem pathways and of neurons in the sensori-motor cortex.


Hypothalamic projection to the pulvinar-LP complex in the cat: a study by the silver impregnation method. This study was designated to determine the exact terminal portion of the hypothalamo-thalamic projection found in our previous study by the HRP method [7]. Electrolytic lesions were made in the brains of 13 adult cats, and the ensuing degenerating fibers were impregnated with Nauta-Gygax and Fink-Heimer methods. Following the lesions of the hypothalamic small nucleus which had been reported to receive abundant HRP transport from the pulvinar-LP complex, terminal degeneration concentrated in the dorsolateral marginal area of LP, forming a well-defined and dorsomedially stretched slim column along the medial border of the pulvinar. The level of its appearance approximately corresponds with the stereotaxic coronal plane, Fr. 7.0. In the contralateral same thalamic  area the degenerating fibers were also traced though they were much fewer.


Forebrain projections of the ventral tegmentum as studied by axonal transport of [3H]dopamine in the rat. Twenty-four hours after [3H]dopamine ([3H]DA) injections into different parts of the ventral tegmentum the radioactivity recovered in the forebrain showed a highly regional distribution which corresponded to well-known DA projections. Selective degeneration of DA-neurons with 6-hydroxydopamine (6-OHDA) markedly reduced the axoplasmic transport after [3H]DA injections. The ventral tegmental area (VTA) was found to project primarily to the nucleus accumbens, olfactory tubercle and amygdala. The DA-innervation of the entorhinal cortex and the amygdala derive from cells widely distributed in the VTA and SN.


Fast axonal transport in rat sciatic nerve. Inhibition by pineal indoles. The effect of pineal indoles on fast axoplasmic transport of proteins in the sciatic nerve was examined in rats injected with [3H]leucine in the sixth lumbar dorsal root ganglion. Melatonin (350-1100 nmol) applied locally in the sciatic nerve impaired significantly axonal transport. At a 350-nmol dose all other indoles tested (i.e., 5-hydroxyindoleacetic acid, 5-methoxyindoleacetic acid, serotonin, N-acetylserotonin, tryptamine, 5-methoxytryptamine) were less potent than melatonin to impair fast axonal flow. Vinblastine injected either into the ganglion or in the sciatic nerve markedly inhibited axonal transport.


Observations on the morphology of intracellularly stained gamma-motoneurons in relation to their axon conduction velocity. Hindlimb gamma-motoneurons of adult cats were stained intracellularly with horseradish peroxidase. The gamma-motor-axons had intramedullary diameters between 2.0 micron and 2.4 micron and lacked recurrent collaterals. The conduction velocity of the gamma-motor-axons (20-29 m/sec) was close to what could be predicted from the relationship between conduction velocity and intramedullary diameter of much thicker adult alpha-motor-axons. However, the gamma-motor-axons were conducting much faster than alpha-motor-axons of 1-week-old kittens in spite of the fact that these two types of axons had about the same dimensions intramedullarly.


Visualization of the HRP reaction product using the polarization microscope. The reaction product of horseradish peroxidase (HRP) staining can be visualized with considerable contrast using the polarization microscope. This is illustrated on whole mount preparations of the cat retina which were stained after injection of HRP into the superior colliculus. When the specimen is placed between two crossed polarizing filters, the stained cells appear rather bright, in contrast to the other components of the tissue which remain dark. The visualization with the polarization microscope was compared with bright-field and dark-field illumination and was found to be superior to them.


[Immunochemical study of the water-soluble lens proteins in the embryo of Xenopus laevis with the mutation of periodic albinism]. The crystallins of ap mutants of Xenopus laevis have been studied in comparison with those of normal embryos and adults using the complex of immunochemical methods (immunoelectrophoresis, immunodiffusion, immunoadsorption, immunofluorescence, isoelectrofocusing with immunoidentification). The analysis was carried out with antisera to electrophoretic fractions of the mutant lens. 11 organ-specific antigens were found in the lens of both the normal and mutant animals. These proteins are heterogenous by electrophoretic mobility, isoelectrical point, antigenic and species specificity. Each class of crystallins contains antigens which are specific: a) for amphibians only, b) for lower vertebrates, c) for vertebrates in general. No qualitative differences were found between crystallins of the normal and mutant animals. Immunofluorescence analysis has shown that crystalins appear in the normal and mutant embryos practically at the same time. No significant differences in the appearance of specific immunofluorescence between the normal and mutant embryos were found (with various antisera). gamma-crystallins and, perhaps, a part of the primary lens fibers. Alpha-crystallins appear later. gamma-crystallins are first identified the synthesis of which manifests itself at the advanced developmental stages. The quantitative predominance of some beta--gamma-crystallins in the mutant lens detected by us (electrophoresis, isoelectrofocusing) is not related to their earlier synthesis in the embryogenesis.


Histochemical identification of T cells in oral lichen planus. Lysosomal activity was demonstrated in the majority of the lymphocytes forming the mononuclear cell infiltrate in oral lichen planus. Staining for acid phosphatase, N-acetyl-beta-D-glucosaminidase, nonspecific esterase, and beta-glucuronidase was present in these cells in tissue sections, indicating their T cell origin. Small numbers of enzyme-negative lymphocytes were also present. Macrophages showing stronger staining were found scattered through the infiltrates in large numbers. These observations indicate roles for T cells and macrophages in the pathogenesis of lichen planus.


[Infectious toxic hypotension--effect and dosage of midodrine (author's transl)]. A new alpha-sympathicomimetic drug with peroral effect is midodrine. The effective oral dosage in infancy and childhood is 0.06 mg/kg/dosi. The therapeutic effect, comparing the drug with etilefrin is shown in 120 children with pneumonia, enteritis, meningitis in a random study. The results give an increase in blood pressure and a decrease in heart frequency, statistically proved, on the first day of treatment. Therefore it seems that midodrine is qualified for the treatment of hypotension in infectious diseases.


Cryohypophysectomy for bone pain of metastatic breast cancer. In a series of 22 patients, cryohypophysectomy gave relief of bone pain from metastatic breast cancer for 3 months in 55% of patients and for 6 months in 32% of patients. On average they were pain free for 55% of their remaining life. Advantages of this technique are the avoidance of a major operation, the mild disturbance to the patient, a short hospital stay and the paucity of significant complications apart from a need for hormone replacement.


Drugs or drums: what relieves postoperative pain? The cybernetic model of analgesia is a simple servo-loop: altered sensory input--complaints--medication--temporary restoration of acceptable processing of the sensory input--return of altered sensations. Under ordinary clinical circumstances the functioning of this mechanism is masked by "noise" generated by the interaction of several persons who provide the medication and time factors prolonging the interval between the onset of complaints and the action of the medication. Demand analgesia (DA) has been designed to provide prompt pain relief under the patient's direct control. The technique turned out to be useful also for the investigation of acute pain's course. The present protocol was designed to study the precision with which patients respond to minute changes in the level of a narcotic (hydromorphone) at the target site: this was achieved by varying in a double-blind fashion the amount of narcotic delivered in response to triggering the apparatus and noting how the patient adapts the dosing interval in response to the imposed changes. Thirty-four patients were studied following extensive surgery. Observation times ranged from 16 to 75 h (median 45 h) during which 89 dose changes were initiated. While the majority of subjects adapted successfully to up to 4-fold variations in drug delivery, a sizeable minority (7/34) triggered the apparatus in response to some clue other than the amount of drug received. These non-drug responders seem to correspond to the "placebo reactors" of other therapeutic settings. Our calculations allowed the estimation of how large was the contribution of drug action and non-drug action to the overall therapeutic effect. In the drug-responsive group, the mean contribution of drug action was 78%, while among the non-drug responders this amounted to only 40%. The difference between these two figures is statistically significant (P less than 0.02), at the same time it also reveals important contributions of non-drug factors in drug responders and vice versa. Whether a subject behaves as a placebo reactor or not might depend on the circumstances rather than on innate mechanisms.


Cloning of an almost full-length chicken conalbumin double-stranded cDNA. Chicken conalbumin double-stranded cDNA (con-dscDNA) was synthesized from a laying hen oviduct mRNA preparation enriched for conalbumin mRNA (con-mRNA). The dscDNA was inserted by blunt-end ligation into the Sal I site of plasmid pBR322 which had been repaired with DNA polymerase I to create Taq I sites on each side of the inserted fragment. After bacterial transformation, one hybrid recombinant, pBR322-con1, which contains the largest inserted dscDNA (about 2350 bp) was shown to hybridize specifically to the RNA which is translated into conalbumin. Electron microscopic examination of hybrid molecules between con-mRNA and pBR322-con1 DNA indicate that the inserted con-dscDNA is an almost full-length double-stranded transcript of conalbumin mRNA.


Detection of AKR MuLV-specific RNA in AKR mouse cells by in situ hybridization. Conditions for the detection of complex RNA sequences by in situ hybridization have been investigated by using a single-stranded 3H-cDNA probe complementary to the AKR MuLV genome and in vitro cultured AKR mouse cells which spontaneously produce AKR MuLV. It is shown that fixation with glutaraldehyde at low concentration allows cellular RNA to be sufficiently well retained during the annealing process and that stringent conditions in situ can be maintained by means of formamide. Some conditions which promote atypical and non-specific binding of the probe have been identified.


Effects of ethidium bromide on the production of ribosomal RNA in cultured mouse cells. A treatment of primary mouse kidney cell cultures with 5 microM Ethidium Bromide (Eth Br) reduces the transcription of nuclear-coded genes and especially of ribosomal RNA genes. This effect was consistently observed when comparing drug-treated and control cells for (i), the incorporation of 3H uridine into total nuclear and B RNA polymerases as determined in isolated nuclei. It became more pronounced with exposure time; however, after removal of the drug, there was a progressive recovery of RNA synthesis culminating in the complete reversal of the drug effect. That this effect is probably not due only to the suppression of mitochondrial protein synthesis by the drug, is shown by a comparative study of the effects of chloramphenicol treatment. In addition, in the cytoplasm Eth Br depresses the labeling of 28 S rRNA more than that of 18 S whereas no abnormal accumulation of 28 S rRNA is observed in the nucleus. It is suggested that Eth Br may affect either the stability of the 28 S rRNA or its rate of formation from the 32 S precursor.


The influenza virus: Antigenic composition and immune response. The architecture and chemical composition of the influenza virus particle is described with particular reference to the protein constituents and their genetic control. The dominant role in infection of the surface proteins - haemagglutinins and neuraminidases - acting as antigens and undergoing variation in time known as antigenic drift and shift is explained. The immuno-diffusion technique has illuminated the interrelationships of the haemagglutinins of influenza A viruses recovered over long periods of time. The H0 and H1 haemagglutinins are now regarded as a single sub-type with H2 and H3 representing the haemagglutinins of the 1957 and 1968 sub-types. Animal influenza viruses of pigs, horses and birds are described. A relation to human influenza strains has been shown to exist in certain instances as is the capacity of some human strains to pass to the animal kingdom.


[Tumour immunology (author's transl)].

[Tumour immunology (author's transl)]. The anti-tumour immune mechanism as it operates in vivo and in vitro is reviewed. Tumour-specific antigens on the surface of the tumour cell induce cellular (lymphocytes, macrophages) and humoral (antibodies, mediators) reactions which are capable of destroying the tumour cell. The combined operation of these mechanisms is described in detail, e.g. opsonization of tumour cells, enhancement, escape mechanism, specific versus unspecific reactions, potentiation. Analyses of tumour-specific cell-mediated reactions gain more and more importance as attempts to influence the function and differentiation of individual cells become more and more successful.


[Immunotherapy of malignant growths (author's transl)]. Our knowledge of antigens which are associated with different types of malignant tumours is steadily increasing. These antigens exist in considerable numbers, but, so far with few exceptions, only their presence can be demonstrated by certain methods; to isolate and identify them has not yet been possible. These antigens are, therefore, suitable not so much for the primary diagnosis, but rather, like the carcinoembryonic antigen, the tissue-polypeptide antigen or the alpha-feto-protein, for assessing the success of treatment. Active immunization has recently received a fresh impulse by the use of the enzyme neuraminidase, derived from Vibrio cholerae, in the treatment of tumour cells. There is no passive specific immunotherapy in human cancer. As to specific active immunotherapy BCG, Corynebacterium parvum and preparations of these and other micro-organisms together with polynucleotides, levamisol, statolon, tilorone have been employed. Although the results are not uniform they are promising. Attempts at cellular transfer of immunity are not very encouraging. It should be emphasized that the findings apply to human cancer. Experimental studies have produced very interesting results.


[Visualization of the thoracic duct during surgical operations (author's transl)]. Anaesthetists generally object, because of the risk of aspiration, to the pre-operative administration of coloured cream for visualizing the thoracic duct during surgical operations on the oesophagus, lung hilus and major vessels of the mediastinum. The possibility was, therefore, studied to mark the thoracic duct without involving the digestive tract. The following method was developed: a dye was injected into the wall of the distant portion of the oesophagus; the dye passes into the lymphatics and is transported first into the abdominal vessels and subsequently into the thoracic duct. Six dyes were tested in animal experiments. Evans blue and patent blue proved suitable.


[Tracheal stenosis (author's transl)].

[Tracheal stenosis (author's transl)]. 13 cases of stenosis of the trachea are reported and its causes are reviewed. The main causal factors are malignant and benign growths, but chronic granulating tracheitis consequent on prolonged artificial ventilation also plays a role. The extent of the stenosis necessitated partial resection of the trachea in 9 patients. Problems attendant on the operation are reviewed with special reference to after-treatment. In cases of inoperable cancer with tracheal narrowing endoscopic removal of tumour tissue may be life-prolonging measure.


[Prevention and clinical aspects of pneumoconiosis induced by organic dusts (author's transl)]. Only those pneumoconioses induced by organic dusts are discussed which are met with in Germany. They comprise: byssinosis which is caused by toxic agents in cotton and flax, farmer's lung, sprayer's fever, exogenous allergic alveolitis due to thermophil actinomyces in the dust of mouldy agricultural meterials or the air of air-conditioning systems, bird fancier's lung which is caused by antigens in animal waste products. Byssinosis and farmer's lung have now been acknowledged as occupational diseases.


[Polychemotherapy of inoperable bronchogenic carcinoma: preliminary results (author's transl)]. Preliminary results indicate that BACO and SAKK are capable of inducing remission in 80-90% of cases of small-cell bronchogenic carcinoma; these remissions last for about 6 months and not only prolong, but improve the quality of, life. In view of the small number of cases so far observed no assessment can as yet be made of the superiority of one or the other method concerning the incidence and duration of remissions and survival time. In cases of squamous cell cancer the two therapeutic methods succeeded in only 30-40% of the patients in inducing partical remissions and they did not appear to improve the quality of life. The question whether the treatment actually prolongs life as compared with the natural course of the disease remains open.


Cycloheximide inhibition of hormonal induction of alpha 2u-globulin mRNA. The induction of hepatic alpha 2u-globulin synthesis by glucocorticoids in isolated hepatocytes occurs via an increase in the level of its mRNA as measured by cell-free translation and by hydbridization to an alpha 2u-globulin cDNA probe. To explore whether induction of this mRNA is a direct or an indirect consequence of the interaction of the dexamethasone-receptor complex with the alpha 2u-globulin genome, the requirement for ongoing protein synthesis was examined. Concentrations of cycloheximide too low to prevent precursor incorporation into total poly(A)-containing RNA do prevent the hormonal induction of alpha 2u-globulin mRNA. Furthermore, incorporation of 3H-labeled amino acids into total protein was decreased by only 40-50%, and the appearance of the dexamethasone-induced glycosylated forms of alpha 2u-globulin was completely prevented in these cycloheximide-treated hepatocytes. The results suggest that the synthesis of a protein mediator(s) may be required for the induction of alpha 2u-globulin mRNA by glucocorticoids and that the steroid-receptor complex may not interact directly with the alpha 2u-globulin genome.


Noncovalent intermolecular crosslinks are produced by bleomycin reaction with duplex DNA. Reaction of covalently closed circular PM2 bacteriophage DNA with the anticancer drug bleomycin produces nicked circular (form II) and linear duplex (form III) DNA [Lloyd, R.S., Haidle, C.W. & Robberson, D.L. (1978) Biochemistry 17, 1890-1896]. As the reaction proceeds, the frequencies of both form II and form III DNA increase and, concomitantly, an increasing fraction of the DNA mass is found to be in crosslinked structures. Approximately 16% of the PM2 DNA mass is found to be crosslinked after 30 min of reaction with bleomycin at 0.5 microgram/ml. The proportion of each form found in any given crosslinked structure is directly related to the concentration of uncrosslinked (monomeric) forms. Multiple sites of crosslinking occur, and these frequently extend over a region of approximately 500 nucleotide pairs. The intermolecular crosslinked bonds are dissociated by extensive dialysis or by the addition of salt at high concentration (0.8 M NaCl), as would be expected if the bonds were noncovalent. Because intramolecular covalent crosslinks between complementary strands are not detected, it is suggested that intermolecular crosslinks are formed by noncovalent association of bleomycin molecules bound to each of the forms of DNA.


beta 0 thalassemia, a nonsense mutation in man. We determined the complete nucleotide sequence of the 5' noncoding region and the first 74 amino acids of the nonfunctional beta-globin mRNA in a patient with homozygous beta 0 thalassemia. We identified the molecular defect as a single nucleotide substitution in the coding region of the mRNA. At the position corresponding to amino acid 17, replacement of an adenine by a uracil changes the triplet AAG, which codes for lysine in the normal beta chain, to an amber termination codon, UAG. This type of beta 0 thalassemia represents an example of a nonsense mutation in man.


Virolysis of mouse mammary tumor virus by sera from breast cancer patients. All type C retroviruses are lysed by human serum in apparently antibody-independent, complement-mediated reactions. In contrast, we have now determined that the mouse mammary tumor virus (MMTV), a type B retrovirus, is not disrupted by normal human serum. MMTV was lysed, however, when rabbit antibody to whole MMTV was added to the serum. By taking advantage of this dependence of MMTV lysis on specific antibody, a virolytic assay was developed, based on the measurement of reverse transcriptase released from disrupted virions, to search for evidence of antibodies to MMTV in human sera. Significantly greater virolytic activity was detected in the sera of patients with breast cancer than in sera of patients with benign disease (P less than 0.001) or colorectal cancer (P less than 0.001) or in sera from apparently healthy individuals (P less than 0.002). This assay thus appears to be able to detect a unique attribute, possibly the presence of an antibody crossreacting with MMTV, in serum in patient with breast cancer.


[Radiology of joint trauma (author's transl)]. Demonstration of the value of diagnostic radiology in the field of surgical trauma, especially in trauma of the skeletal system. Recommendation to place special emphasis on optimal X-ray technique - in the radiography of acute trauma as well as in follow-up studies.


Transrenal ureteral embolization.

Transrenal ureteral embolization. Transrenal closure of the ureter with butyl-2-cyanoacrylate using adjuvant balloon catheter occlusion was successfully performed for the palliative management of inoperable vesicovaginal and vesicosacral fistulas in 3 patients. Unilateral percutaneous nephrostomy provided supravesical urinary diversion as well as access for permanent embolization of the ureter. The contralateral kidney was nonfunctional in 2 patients. In the third, in addition to unilateral ureteral occlusion, the contralateral kidney was defunctionalized by embolization of the renal artery ("radiological nephrectomy") to avoid the need for bilateral nephrostomy drainage.


Adjuvant chemotherapy in large-bowel cancer: demonstration of effectiveness of single agent chemotherapy in a prospectively controlled,, randomized trial. In a prospectively randomized study, the effect of adjuvant chemotherapy with 5-FU on survival and recurrence rates was analyzed in 299 evaluable patients with colorectal carcinoma who either underwent a curative or a palliative resection. In the treatment group, chemotherapy consisted of the intravenous administration of 12 mg/kg daily of 5-FU for 4 consecutive days, then 6 mg/kg on alternate days, to the point of toxicity, or to a maximum of five doses, followed by 12mg/kg weekly for 1 year. Some degree of drug toxicity was seen in the majority of patients, was rarely severe, and there have been no drug-related deaths. Analysis of the survival curves and disease-free interval curves reveal definite evidence of drug benefit in two unfavorable subgroups, namely patients with Dukes C tumors and in patients whose tumor was located in the rectum. In the chemotherapy groups, patients who were treated to toxicity (WBC less than 4000 mm3), the disease-free interval was significantly longer than the nonleukopenic patients. We conclude that the addition of 5-FU to the surgical treatment of colorectal carcinoma provides a small, but significant benefit in patients with colorectal cancer in certain unfavorable subgroups, namely patients with Dukes C lesions and patients with rectal carcinoma.


Adjvant treatment of tongue and floor of the mouth cancers. Since January 1974, 95 patients with anterior tongue and floor of the mouth cancers were included in a randomized trial. After stratification according to staging and initial treatment, one-third of the patients received chemotherapy for 2 years (methotrexate 400 mg followed by citrovorum factor 100 mg + bleomycin 60 mg/week, during the first 15 weeks), one-third of the patients received immunotherapy with weekly C. parvum injections during 2 years, while the remaining third did not receive any treatment. If adjuvant treatment seems to delay recurrence it did not significantly decrease the recurrence rate. Survival is also not signigicantly modified by adjuvant treatment and was better for patients with small tumors. Patients who previously received radiotherapy did not benefit from adjuvant therapy.


Secondary MLC responses of primed lymphocytes after selective sensitization to non-HLA-D determinants. Two HLA-B,D-identical siblings, who differed only for the HLA-A region because of a maternal recombinational event, were studied in primary (1 degrees) and secondary (2 degrees) mixed lymphocyte culture (MLC). The HLA-A:B recombinant child did not respond to its HLA-B,D-identical sibling in either 1 degrees or 2 degrees MLC. In the reciprocal combination the non-recombinant child responded only weakly in 1 degrees MLC but responded significantly in 2 degrees MLC to the HLA-A:B recombinant child. Thus, it was possible to selectively prime to a non-HLA-D determinant, which is controlled by a gene located distal to HLA-B. Because this determinant was not present on T-cells, it could be distinguished from the serologically defined antigen controlled by the HLA-A locus. Such primed lymphocytes, as well as lymphocytes primed between HLA-identical siblings, revealed high autologous control responses which were not observed when using lymphocytes primed in conventional one-haplotype combinations. The significant 2 degrees MLC response to autologous cells after sensitization to allogeneic cells may reflect recognition of self antigens and raises the question to what extent genetic similarity between responding and stimulating cells is required in the priming phase to elicit a 2 degrees response to autologous cells.


Alloantigens derived from stimulator cells and bound onto MLC-activated rat T lymphoblasts. Rat T lymphocytes were activated in MLC (mixed leucocyte culture) against allogeneic stimulator cells. A few percent of such T blasts could be shown to carry IgM on their surface when a mixture of T and B lymphocytes was used as responder cells. The immunoglobulin was absent when purified T lymphocytes served as responders. A large proportion of MLC T lymphoblasts could be shown to carry stimulator alloantigens on their surface. These antigens were demonstrated (a) by indirect immunofluorescence using anti-stimulator alloantibody and FITC (fluorescein isothiocyanate Isomer I)-labelled F(ab)2 fragments of rabbit anti-rat Ig; (b) by autoradiography after internal labelling of stimulator cells, which showed the transfer of label from stimulator to responder cells. For biochemical analysis T blasts were restimulated with internally labelled allogeneic or syngeneic stimulator cells, and bound radiolabelled stimulator alloantigens were analysed on SDS-PAGE (sodium lauryl sulphate polyacrylamide gel electrophoresis). The results suggest that intact SD antigens with a molecular weight of 45,000 daltons and LD determinants with a molecular weight of 34,000 daltons derived from stimulator cells are found on MLC T blasts. No evidence of binding of the 27,000-dalton Ia chain to T blasts was found. Possible arrangements of these molecules on the responder blasts is discussed.


Quantification of the pregnancy-specific beta1-glycoprotein (SP1) by immunoprecipitation techniques: the influence of a cross-reacting high molecular weight alpha2-protein. Two serum proteins with SP1 determinants were separated by means of size chromatography and preparative zone electrophoresis. One of the proteins had beta1 electrophoretic mobility and an estimated molecular weight of 90,000, and the other had alpha2-mobility and a molecular weight around 400,000. When available antibody preparations to SP1 were used, the high molecular weight protein formed immunoprecipitates only when polyethyleneglycol (PEG) was added to the agarose. It is shown that the high molecular weight protein has a pronounced effect on quantification of SP1 by rocket immunoelectrophoresis, whereas the effect was less pronounced but still considerable when quantification was performed by radial immunodiffusion.


Con-A-activated T cells secrete factors with polyclonal B-cell-activating properties. Concanavalin A induced polyclonal antibody synthesis in normal spleen cells in vitro. Optimal responses were obtained by Con A concentrations lower than those optimal for induction of DNA synthesis. T cells, but not macrophages, were necessary for the effect. Spleen cells from nude mice were not activated, whereas cells from the LPS non-responder stain C3H/HeJ were activated to polyclonal antibody synthesis by Con A. Supernatants from Con A activated spleen cells could by themselves induce polyclonal antibody synthesis in untreated spleen cell cultures, even when Con A had been removed by absorption with Sephadex G-50 and when alpha-methyl-mannoside was present in the secondary cultures. T cells produced the active supernatants, which were competent to induce polyclonal antibody synthesis, but not DNA synthesis, in both H-2-incompatible and compatible strains. When the supernants were absorbed with erythrocyte antigens, they specifically induced an enhanced response, in secondary cultures, to the antigen used for absorption. Possible mechanisms of this specific effect are discussed.


Endotoxins of anaerobic gram-negative rods. Endotoxic lipopolysaccharides (LPS) isolated from Fusobacterium are similar to those of Salmonella with respect to chemical composition, O-antigenic specificity and endotoxic activity. Bacteroides LPS are highly atypical with respect to the chemical composition, and their endotoxic activity is low. O-Antigenic specificity is present. B. fragilis LPS is chemotactic for polymorphonuclear leukocytes in vitro and in vivo. The chemotactic activity is brought about by activation of the alternative complement pathway.


On the occurrence of serum antibodies to Bacteroides fragilis and serogroups of E. coli in patients with Crohn's disease. Eight strains of Bacteroides fragilis, five isolated from patients with Crohn's disease and three from healthy individuals, and according to biochemical tests belonging to four subspecies, were subjected to a serologic examination with tube agglutination and passive hemagglutination (HA) tests using hyperimmune rabbit antisera. A close antigenic relationship was demonstrated between two of the strains and minor relationships between three other strains. Cross absorption experiments showed that the antigenically related strains had common antigen(s) besides strain specific antigens. Crude antigens of each of the eight B. fragilis strains, and eight known serotypes of nonenteropathic E. coli, were used in passive HA tests to study the occurrence of circulating hemagglutinins in patients with Crohn's disease, and in control patients and healthy individuals with no obvious intestinal disease. It was found that patients with Crohn's disease had higher titres against B. fragilis than control patients and healthy individuals (the p-value was less than 0.01 if titres greater than or equal to 1:40 were chosen as comparison, equal for males and females). Higher titres were also recorded for Crohn's patients against the various serotypes of E. coli than for control patients and healthy individuals (if titres less than or equal to 1:160 were chosen as comparison the p-value was less than 0.01 for men and less than 0.001 for women.


[Considerations on the radiological treatment of inoperable bronchogenic carcinomas or recurrences after surgical intervention]. From 1964 to 1977, 315 carcinomas of the bronchus either inoperable or recurring following surgery were treated by radiotherapy using high energy machines (telecobalt therapy and/or Betatron: X-rays or electrons). 116 patients (36.8%) had well-differentiated squamous cell carcinomas, 70 (22.2%) had undifferentiated or poorly differentiated carcinomas, 97 (30.8%) had small-cell anaplasic carcinomas, and 32 patients (10.2%) had adenocarcinomas or other types of bronchial carcinoma. 199 patients (63.2%) were treated exclusively by radiotherapy and 116 (36.8%) by surgery followed by radiotherapy: 28 had exploratory thoracotomies, 73 curative resections and 15 palliative resections. At the end of irradiation treatment 140 patients (44.5%) showed a subjective and objective (clinical and radiological) improvement, whereas 111 patients, (35.2%) although chest X-rays showed no radiological improvement, had a subjective response; 64 patients (20.3%) showed deterioration. 33.5% of the patients (88/263) lived at least 1 year after completion of radiotherapy: in 25.9% (42/162) the treatment was exclusively radiotherapy and 45.5% (46/101) underwent irradiation after surgery. 12.4% (31/249) of the patients were alive 2 years after completion of irradiation and 5.4% (11/203) after 5 years.


[Prenatal diagnosis. Review, personal and prospective studies]. 1. In a review of methods developed for the identification of fetal malformations, the technique, risks and results of amniocentesis are presented. 2. Large series already published have demonstrated the relative simplicity and feasibility of the procedure as well as current indications for its utilization. These include the detection of chromosomal anomalies, the determination of sex (in certain sex-linked disorders), documentation of enzymatic and metabolic deficiencies, and the demonstration of open lesions of the neural tube by appropriate techniques. 3. Experience with over 500 cases personally tested by the authors entirely confirms the major indications for and benefits of this modern method for the detection and prevention of severe congenital anomalies during early pregnancy. 4. The identification of chromosomal alterations is currently the major objective of the method. Increased risks are associated with pregnancies involving a maternal age of 35 years or older (which account for 1-3% of aneuploidies), the birth of a previous infant with free trisomy 21 (1% recurrence risk) or secondary to a parental chromosome translocation (as much as 10% risk of aneuploidy). Fetal karyotyping for determination of sex, in cases where the mother is a carrier of an X-linked recessive gene (on average, 50% of male offspring will be affected), is an inadequate method of diagnosis to be utilized only until alternative techniques render possible specific diagnosis of the anomalies under consideration (hemophilias A and B, muscular dystrophy, etc). 5. Several of these techniques are now nearing development through the advent of fetoscopy and advanced ultrasound methodology, and have already been applied to the detection of certain sex-linked disorders and also for diagnosis of hemoglobinopathies (thalassemias, sickel cell anemia) and other conditions requiring the obtaining of fetal blood for diagnosis. Technology allowing direct examination of fetal parts by means of optical instruments is particularly useful in cases where a severe fetal morphologic malformation cannot currently be identified by indirect visualization (ultrasound) or by analysis of cytogenetic or molecular markers. 6. Pathological accumulations of alpha-fetoprotein which are associated with diverse feto-placental abnormalities (particularly open malformations of the neural tube) can be detected in the amniotic fluid and/or maternal blood. In extension of this approach, it is foreseeable that conditions existing prenatally will be diagnosed in a growing number of cases from the study of fetal cells and molecules which can be isolated from the venous blood of pregnant women. This will become feasible as a result of some well-developed techniques which allow separation of fetal from maternal cells and metabolites, and also to some extremely fine analytic techniques, notably examination of the DNA itself by means of restriction enzymes.


The diagnosis and management of hairy-cell leukaemia. Over a 4-year period 203 patients with various types of leukaemia were treated by the Haematology Unit at the Johannesburg Hospital. Ten of them were suffering from the condition known as hairy-cell leukaemia or leukaemic reticulo-endotheliosis. They were all men, and ranged in age from 29 to 67 years (mean 56 years). The majority presented with pancytopenia, and there was invariably splenomegaly, while lymphadenopathy was rare. Hairy cells were identified microscopically in the peripheral blood of 7 patients and in 5 the specific cytochemical marker, tartrate-resistant acid phosphatase, was present. In addition, in a further 2 patients this feature, which was not identified in the peripheral blood, was found in the splenic cells. The bone marrow trephine biopsy specimens characteristically showed extensive lymphoid infiltration associated with a dense disordered deposition of reticulin fibres. Electron microscopical and immunological studies proved to be of doubtful diagnostic value. Splenectomy was carried out on 9 patients, and there was tumour involvement in all the spleens removed. Two patients died from septicaemia, the one before splenectomy and the other 9 months after the operation. The 8 remaining patients have had their subjective symptoms alleviated and their peripheral blood indices have been improved by splenectomy, and none has required further treatment for periods now ranging from 7 to 41 months.


Cardiovascular hemodynamics after opsonic alpha-2-surface binding glycoprotein therapy in injured patients. Depression of reticuloendothelial (RE) phagocytic function has been clearly documented following trauma and operation. This phagocytic failure is mediated in part by depletion of an opsonic glycoprotein. Depletion of this opsonic protein may result in prolonged blood retention of potentially harmful particulates that may interfere with the microcirculation and may possibly result in altered organ function. Isolation and identification of this opsonic protein has led to the finding of the identity between opsonic glycoprotein and cold insoluble globulin (CIg) or so-called plasma fibronectin. Since CIg is concentrated in cryoprecipitate, this blood component was used as a readily available source of opsonic protein for replacement studies. Nine patients were studied following a 1-hour infusion of cryoprecipitate obtained from 10 units of plasma and suspended in a volume of 250 ml. Both the pulmonary shunt fraction and the fraction of dead space ventilation decreased significantly (P = 0.02) after cryoprecipitate administration. Limb blood flow (P = 0.001), limb oxygen consumption (P = 0.001), and reactive hyperemia of the limb (P = 0.05) increased significantly following cryoprecipitate infusion. Cardiac output, total oxygen consumption did not change consistently. The data demonstrate that the infusion of cryoprecipitate resulted in improved pulmonary and microcirculatory function--possibly due to opsonic glycoprotein replacement.


The major histocompatibility complex of Rhesus monkeys. XII: Cellular typing for D locus antigens in families. Typing cells (TC) were used for the identification of D locus antigens in rhesus monkey families. The antigens defined by this cellular method always segregated with the other RhLA-controlled markers except in one offspring with a proven recombination within the RhLA region; in that case, the D antigen was inherited in coupling with an antigen of the Ia1 locus (the analog of the human DR locus). With two exceptions, each TC or group of TC's was associated with one of the serologically defined Ia1 antigens. The two exceptions were associated with "blanks" of that series. Interestingly, two independent (mutually MLC responsive) TC groups appeared to be associated with the same Ia1 antigen 75. Equally noteworthy was the observed "inclusion phenomenon" among cells of several TC groups, each associated with a single Ia1 antigen or blank of that series. In these cases, some of the TC's of the group were unidirectionally MLC-responsive against other cells of the same group. Certain pitfalls of cellular typing are discussed; unexpected "false positive" results were attributed to prior immunization with products of non-D loci which have described recently (van Es & Balner 1978b).


Lack of linkage between acute intermittent porphyria and the A and B loci of the HLA system. Forty-six members of a family known to have Porphyria were studied. As the disease is often latent clinically, erythrocyte uroporphyrinogen I synthetase activity was determined to classify the subjects as being healthy or carriers. HLA--A, B, C, Bf, GLO antigens were determined. No linkage between acute intermittent Porphyria and the HLA system was noted in this family.


B cell antigens of Black Americans.

B cell antigens of Black Americans. Fourty-four unrelated North American Blacks and one Black family were tested for B-cell specific antigens with 7th International Workshop antisera. DR specificities were clearly defined in this group, but were generally less frequent than reported for Black Americans in the 7th Workshop report and were most similar in frequency to those reported for African Blacks. Five new B-cell specificities (DuB40-43, 45) were identified. In contradistinction to Caucasians, Black Americans type for HLA-D with homozygous typing cells failed to exhibit strong linkage disequilibrium between D and DR types.


Cross-reactions of HLA antibodies: VII. Rate of sensitization and serological specificity. Varying the sensitization time of the complement-dependent antibody mediated cytotoxicity test, while carefully controlling other test conditions, has enabled us to characterize the subtle reactivities of several broadly reactive sera. In particular, we can discriminate between classes of cells, e.g., HLA-B7 from B27; subclasses cells, e.g., Bw51 from Bw52; and cells carrying new antigens, e.g., Ao79. This manipulation of the cytotoxicity test is discussed in view of its usefulness in separating primary from cross-reactive specificities and in detecting new specificities.


HLA-A, -B, and -D antigens in paralytic poliomyelitis. Sixty-two unrelated Caucasian patients from the Munich area who had had paralytic poliomyelitis in the 1950s and the early 1960s were analyzed. HLA-A and -B typing was performed for 26 antigens. HLA-D tying was done using six different established homozygous typing cells defining the specificities Dw1-Dw5 and Dw11, plus one locally defined typing cell. None of the HLA-A, -B or -D determinants showed a significant deviation in frequency from control populations. Of interest may be a decrease of B8 and an increase of Bw16 (Bw38/39) and B27, but these deviations are not significant in their P values are corrected for the number of comparisons made.


Analysis of progesterone in unextracted serum: a method using danazol [17 alpha-pregn-4-en-20-yno(2, 3-d) isoxazol-17-ol] a blocker of steroid binding to proteins. A technique has been developed in which progesterone may be measured by radioimmunoassay in unextracted serum. The method depends on the displacement of progesterone from serum binding proteins by danazol, [17 alpha-pregn-4-en-20-yno (2,3-d) isoxazol-17-ol], a compound which also blocks recombination of free progesterone with proteins and does not cross react with the progesterone antiserum. This new method saves time and labour, and fulfills the criteria of sensitivity and precision for clinical use. The results correlate well with those of conventional assays for progesterone.


Antisera reactive directly to estrone sulfate. Derivatives of estrone were prepared and linked to bovine serum albumin or its methyl-esterified form to produce immunogens which were effective in raising antisera to estrone sulfate. The most effective was estrone-3-methylphosphonothioate, electrostatically complexed with methylated bovine serum albumin. The ionically combined hapten functioned as an antigenic determinant as do covalently bound haptens when administered to sheep in emulsions with Freund's complete adjuvant. Estrone-3-phosphate covalently or electrostatically linked to bovine serum albumin also produced antisera reactive to estrone sulfate. Estrone sulfate itself, after electrostatically complexing to methylated bovine serum albumin and administration with Freund's complete adjuvant to sheep, was ineffective in producing antisera. The sera which had workable titres to estrone sulfate showed considerable cross-reaction with free estrone but was otherwise highly specific with little or no reaction with other steroid sulfates, glucosiduronates or other free steroids. Radioimmunoassay curves using [6,7-3H]-estrone sulfate were highly sensitive and were effective in the range of 5-250 pg estrone sulfate.


Cytoplasmic differentiation antigens of human epidermal cells. Three immunologically distinct types of cytoplasmic antigens have been found to be expressed concurrently in normal human skin. These antigens are tissue but not species specific and differ by their location in different subpopulations of cells. One type is present only in the superficial layers of the epidermis, another only in basal cells, and the third is present in all keratinocytes. All subjects studied to date have all three types of antigens in their skin. There seems to be two subgroups of antigens of each type. One subgroup consists of antigens expressed universally in all subjects. The other consists of a family of variably expressed antigens which are common to some but not all persons. They may represent genetically determined alloantigens different from HLA. The superficial basal cell antigens are absent or greatly decreased in expression in malignant, but not in benign, tumors of the epidermis. This finding, along with the stratification of the antigens in different layers of the skin, suggests that epidermal cytoplasmic antigens are differentiation antigens.


Analysis of guinea pig membrane proteins recognized by heterologous antilymphocyte sera. Specific recognition of Ia alloantigens. Heterologous antilymphocytes sera (ALS) produced in several species against a variety of guinea pig lymphocytes populations were studied by immunoprecipitation experiments and polyacrylamide gel electrophoretic analyses to characterize the membrane proteins recognized by these antisera. Although a number of different proteins were recognized by these sera, high-titered antibodies against guinea pig Ia antigens could be demonstrated in all ALS, including those produced against thymocytes. Furthermore, selective absorptions and sequential precipitation experiments revealed significant levels of xenoantibodies that recognized specific Ia alloantigenic determinants. The potential significance of antibodies against Ia antigens in heterologous antilymphocyte and antithymocyte sera is discussed.


Combination chemotherapy with vinblastine, bleomycin and methotrexate in DTIC-resistant metastatic melanoma. Fifteen patients with metastatic DTIC-resistant malignant melanoma were treated with vinblastine, bleomycin and methotrexate combination chemotherapy. Three patients showed an objective response (one complete response). The therapy was well tolerated and easy to administer. This combination appears to produce in DTIC-resistance patients a response rate similar to that obtained with DTIC.


Fetal specific serum proteins of the Indian buffalo. Fetal specific serum proteins of the Indian buffalo were investigated using rabbit antibuffalo fetal serum, absorbed with lyophilised adult buffalo serum, and subjected to gel diffusion and immunoelectrophoretic analysis. AFP was found to be the major fetal specific serum protein of the Indian buffalo. A close antigenic relationship between the fetal specific serum proteins of the buffalo, sheep and goat and a distant relationship between these proteins of ruminants and man was found by immunological cross reaction studies.


[Fractionation of the Trichinella spiralis antigen and allergy diagnosis trails]. Experiments were carried out to fractionate an antigen of Trichinella spiralis with Sephadex G-50 and G-100. The specificty of the fractions has been followed up by means of the intradermal allergic reaction in six pigs, experimentally infected with Trichenalla spiralis, one with Trichocephalus suis and three, born by trichinellosis-affected sows. The second fraction has been tested also on four pigs, experimentally inoculated with Ascaris suum, nine--with Ascarsis suum and Oesophagostomum and 19 healthy pigs. The intradermal allergic tests were effected with thrichinellous fractions, diluted 1:1000. The results obtained from the investigations indicate that the best separation of the complete trichinellous antigen, obtained from lyophilized trichinellae, is achieved with Sephadex G-100. In the case of an intradermal allergic test, a well-expressed reaction is attained with the 2nd fraction and the 1st fraction, the reaction being maintained for a longer times with the 2nd fraction.


[Effect of axoplasmic flow elimination and denervation on the contents of protein, nucleic acids and glycogen in rat muscle]. Disturbance of the axoplasmic flow was evoked by ligation of the sciatic nerve with a silk thread moistened with 0.05 solution of colchicine (exposition for 30 s). No intoxication was observed in the animals, the motor function of the operated extremety was preserved. Two weeks after elimination of the axoplasmic flow practically the same changes in the content of contractile and sarcoplasmic proteins, glycogen, DNA and RNA were observed in musculi gastrocnemius as with surgical denervation. The data obtained evidence for an important role of the axoplasmic flow to maintain the normal metabolism in muscles.


[Aspects related to the antigenic structure and serological specificity of brucellae phylogenetically related to S- and R-forms and dissociated into R-variants]. The antigenic structures and serological properties of Brucellae S- and R-forms, phylogenetically differentiated, and dissociated R-variants are studied by means of gel-precipitation, immunoelectrophoresis and fixation of the complement. The Brucella suis 1330S, Brucella suis 1330R, Brucella ovis 02 and Brucella abortus 99 are involved in the experiments. Both specific and general antigenic structures are established in all strains studied, but only homologous antibodies from the antigen-antibody complex in the complement-fixation test, induced by the phylogenetically differentiated S- and R-forms (Brucella ovis) or brucellae, diverged into R-variants. Cross complement-fixation tests between the antisera, prepared against S-forms and antigens from natural R-forms (Brucella ovis) or dissociative R-forms (R-variants) have not been observed. Also cross reactions between antisera, induced by R-forms (natural R-forms--Brucella ovis, or dissociative R-variants) and antigens, obtained from S-forms of brucellae are found.


[Residual action of Neguvon, Neocidol, Nuvanol and Dursban on the imaginal and larval stages of the housefly]. It is shown that Dursban, Neocydol and Neguvon preparations, mixed with swine manure at amounts of 500 mg/kg, kill 100 per cent the larvae of the domestic fly up to the 30th, 20th and 10th day, respectively, while the Neguvon and Neocydol preparations in cattle manure, up to the 10th day. Lower concentrations possess a residual effect of a shorter duration. It is also shown that the type of the surfaces and the pH of the mater on which the preparations are placed markedly affect the inctesicide activity and the residual effect of the preparations. The highest activity and the longest residual effect manifest preparations that have been placed on surfaces with a low absorption capacity. The highest effect has been achieved when the preparations are smeared on glass, a lower one, when placed on wood, and the poorest, when laid on mortar.


Epidemiological investigations on viral hepatitis in preschool and school communities. Note II. Evaluation of the prophylactic efficiency of standard gammaglobulin administration. At the beginning of the 1977--1978 schoolyear 10% standard gammaglobulin (0.03 ml/kg body weight) was administered to 974 preschool children and 530 schoolchildren. Representative groups of children were tested serologically and virologically before gammaglobulin administration and 3 months afterwards. No statistically significant reductions of viral hepatitis morbidity were recorded in the protected groups as against controls.


[Joint use of thyroid and antithyroid preparations]. On the model of the mammary gland cancer, induced by a carcinogen in rats, it is shown that thyroxine (in a dose approximately equal to the physiological one, which per se would stimulate neoplasia or renders no effect) increases the antineoplastic action of the thyroid function inhibitors when administered simultaneously. Thus, they may be considered a positive compensation factor. Simultaneous application of the thyroid hormone with a hypolipidemic preparation--cetamiphene seems to be mostly advantageous.


[Search for viral genetic information in human tumor DNA by means of transfection]. In embryonal human cell culture there was found the biological activity of DNA preparations, obtained from peripheral blood cells of acute leukemia patients, which was manifested in the production of virus-like RNA-containing particles, as evidenced by the radioisotope analysis findings and by the reverse transcriptase content in these particles. Also, a rapid growth of the cultures was noted. The DNA preparations from rhabdomyosarcoma, neurinoma and synovial sarcoma in man would cause only an enhancement of human embryonal cell cultures growth. No production of virus-like particles in the latter was noted.


[Cytological diagnosis of prostatic cancer]. The authors has made 836 cytological assays in 184 patients with adenoma and cancer of the prostate. Eighty patients were examined using the complex technic (the puncture material and secretion of the prostate, and urine for the presence of atypical cells). Cytographs characteristic of such prestatic lesions are described.


Immunofluorescent staining of platelet suspensions and detection of antiplatelet antibody in patients with idiopathic thrombocytopenic purpura. Direct immunofluorescent staining of 31 specimens of platelets obtained from 13 cases of idiopathic thrombocytopenic purpura (ITP) revealed positive staining on the surface of platelets for both immunoglobulins (Igs) and human B1C globulin in 9 specimens, for only Igs in 1 specimen and for human B1C alone in 5 specimens. The pattern of the positive immunofluorescent staining was granular. Indirect immunofluorescent staining of normal platelets in serum obtained from patients with ITP was positive for antiplatelet antibody in 9 out of 31 specimens. This suggests that platelets in patients with ITP may be damaged by an antiplatelet autoantibody acting directly on the platelet surface and/or by antigen antibody complexes binding via Fc IgG receptors on the surface of the platelets.


Freedom from transmission of hepatitis-B of gamma-globulin and heat-inactivated plasma protein fraction prepared from contaminated human plasma by fractionation with solid-phase polyelectrolytes. Plasma contaminated with hepatitis B surface antigen (HBsAg) and shown by others to be infectious when injected in a dilution of 1:1,000,000 in chimpanzees, was fractionated by a solid-phase polyelectrolyte (PE) procedure for its content of plasma protein fraction (PPF) and gamma-globulin (immune serum globulin; ISG). Quantitative Ausria II radioimmunoassays showed that nearly half the HBsAg was bound by the PE and could be eluted at low pH, while the rest was found in the heat-inactivated PPF. When the ISG was concentrated to 16%, the 13 mg/kg (comparable to a human dose) was injected intramuscularly in 6 chimpanzees, or when the PPF was heated at 60 degrees C for h and injected intravenously in 2 chimpanzees, there was no clinical or laboratory evidence of hepatitis B infection after 12 months, although 1 chimp of 2 who received the same material showed a borderline positive anti-HBsAg antibody result on one of 52 weekly serum samples. Since the new PE fractionation method is essentially nondenaturing, and simpler than the classical ethanol procedures, it was important to establish the noninfectivity of the final products.


Recognition of a non-HLA-ABC antigen present on B and T lymphocytes and monocytes only detectable with the indirect immunofluorescence test. The serum of a 39-year-old male under long-term platelet transfusion therapy for hypoplastic anemia with thrombocytopenia was investigated for the presence of leukocyte and platelet antibodies after the patients had received platelet concentrates from more than 700 random donors. The serological studies of his serum revealed: (1) the absence of platelet-reactive antibodies; (2) the absence of agglutinating or cytotoxic antibodies against leukocytes; (3) the presence of at least two granulocyte-specific antibodies, one with the specificity anti-NA2 and the other with an undefined specificity, both only detectable by indirect immunofluorescence, and (4) the presence of cytotoxic-negative fluorescence-positive peripheral-blood-mononuclear-cell-reactive antibodies, not directed against HLA-A, B or C antigens. The significance and implications of these findings are briefly discussed.


A new case of gamma-3 heavy chain disease. Biochemical and immunological investigations. A new gamma 3 heavy chain disease (gamma 3-HCD) protein (Emm) is described. A molecular weight of 70,000-80,000 daltons was estimated. Antigenic analysis showed that protein Emm lacks light chains and the CH1 domain of heavy chains, whereas the antigenic determinants of the gamma 3 Fc fragment (CH2 and CH3 domains) as well as those of the gamma 3 hinge region were present. Since the anomalous protein was temporarily present in serum Emm, a transient triggering of a cell clone which produces the gamma 3-HCD protein is suggested.


Subtypic linearity in the bovine B blood group system. The technique of proteolytic digestion employing the enzymes trypsin, chymotrypsin, and protease was used to investigate the physical order of subtypic determinants occurring on bovine erythrocytes. In the B system subgroup Y1, Y2, the determinants behaved as if linearly arranged in the same order as predicted from their serological behavior; furthermore, the differences between the two subtypes appeared to be quantitative rather than qualitative. In the E'1, E'2, E'3 subgroup, however, the subtypic determinants did not appear  to be physically linear, although they are serologically linear.


Macrophage heterogeneity.

Macrophage heterogeneity. Macrophages are a mobile, functionally diverse group of cells which may be recruited and stimulated to a high degree of metabolic activity. Heterogeneity may be detected from one site to another and result from local influences, e.g. lung v. peritoneal cells, or occur within a population and arise dur to different stages of differentiation, maturation or activation or possibly from distinct cell lines. Recruitment and turnover are important determinants of the diversity of cells at any one site. In addition, anti-tumour, anti-microbial and secretory capacities of macrophages are greatly influenced by the degree and nature of stimulation possibly affecting only a subpopulation of the cells. Accessory cell activity is also a function of a minor population of macrophages which have distinct surface antigens. The sources of the heterogeneity and the interrelationship between the macrophages subpopulations remain to be determined.


[Persistent infection in murine L cells infected with the parainfluenza virus SV5]. Persistent infection of mouse L cells was achieved by serial passages of undiluted parainfluenza SV5 virus. At the level of the 10--12th passage a stationary noncytocidal type of persistent infection was established. A low level of the infectious virus produced by the persistently infected cells was observed; the number of cells synthesizing the virus-specific antigen detectable by immunofluorescence was high. Persistently infected cells were resistant to the infection with the homologous virus and sensitive to superinfection with heterologous viruses. The persisting virus had marked interfering activity. The possibility of participation of defective interfering particles and endogenous oncornavirus in the maintenance of the persistent infection is discussed.


[Hemagglutinin antigens of influenza viruses isolated from man and birds]. Immunological analysis has shown hemagglutinins of avian viruses like hemagglutinins of human viruses to have a complex antigenic composition. Three antigenic determinants were discovered in hemagglutinin of A/Chicken/12/71 virus previously designated H3 and in hemagglutinin of A/Tern/18/73 virus previously designated Hav7. The H3 determinant and the second determinant are identical in avian and A/Hong Kong/1/68 human viruses. In addition, hemagglutinins of avian viruses have a determinant specific for each virus which is lacking in human influenza virus hemagglutinin.


[Search for a new antigen associated with oncornavirus D in human breast cancer tumors]. An antigen similar in its specificity to a nonvirion antigen emerging in stationary tissue culture cells spontaneously or experimentally infected with oncornavirus D was found in mammary gland cancer tumour tissues of 9 out of 54 examined patients. This virus-associated antigen was absent in 17 examined specimens of benign tumours of the same localization (fibroadenomas, mastopathies) or in the organs of a normal adult man or human embryo.