Isolation of Neisseria meningitidis in urogenital/rectal infections. In 9 cases (6 men, 3 women) during 1975 we have isolated N. meningitidis from routine samples from urogenital/rectal locations to be examined for gonococci by culture. One of the men harboured meningococci in the rectum, the other 5 in the urethra. Two of the women had meningococci in the cervix and one in the urethra. Of the meningococci isolated, one belonged to serogroup A, 6 to group B and 2 to group C. Six of the patients, 4 men and 2 women, who attended the Department of Venereal Diseases, are described in greater detail. Of these, only one had symptoms. The meningococci disappeared spontaneously in 5 cases, whilst a man with unsymptomatic infection still harboured meningococci in the rectum after one month. Two of the 4 men were homosexual.


Survival of Neisseria gonorrhoeae on surfaces. The survival of Neisseria gonorrhoeae was investigated. It was found that gonococci could survive 24 hours in urethral secretion on a glass slide and on a towel at 22 degrees C, and 120 hours at 4 degrees C. A method was developed by which the survival of gonococci could be followed in vitro. With this method, gonococci grown in vitro were found to be protected by human serum, in contrast to gonococci resuspended in NaCl. The factors affecting the survival are discussed.


Crohn's disease--non-caseating granulomas on the legs. A 27-year-old black man with Crohn's disease and nodules on the legs is described. Such nodules constitute one of three types of cutaneous manifestations which have a histological picture of a non-caseating granuloma. The two other varieties of skin lesions described are: that resulting from a direct spread from the gastrointestinal tract, and that resulting from spread over contiguous skin.


Ultrastructural changes in disseminated connective tissue nevi. Skin biopsy specimens from a patient with disseminated connective tissue nevi and from her son and daughter who had no such clinical alterations were studied with the electron microscope. The nevi showed increased amounts of thick elastic fibres, which were composed of irregularly arranged, often finger-like, subunits surrounded by a thready material. Both structures probably represent malformed components of elastic fibres, the thready material representing malformed elastic fibrils. Many of the collagen fibrils showed increased diameters and twistings, which alterations are believed to represent malformation of collagen. The fibroblasts showed changes which might be related to a pathological protein synthesis. Examination of biopsy specimens from normal skin of the patient and from the skin of her son and daughter failed to demonstrate similar alterations. The present case is regarded as an entity, distinct from dermatofibrosis lenticularis disseminata and from shagreen patch.


Early changes in human epidermis following thermal burn: an electron microscopic study. Early alterations in the epidermis of human volunteers following 60 degrees and 95 degrees C burns were studied by means of electron microscopy. The blister was induced at 30 seconds following a 60 degrees C burn for 1 and 3 minutes by disintegration of the basal cells just above the basement membrane, and, in addition, for 3 minutes by disruption of the intercellular bridges adjacent to the desmosomes in the suprabasal cells. The keratinocytes of the separated epidermis revealed intracytoplasmic vacuoles, widening of the intercellular spaces and, in some cells, vacuolization of the mitochondria. At 30 seconds following a 95 degrees C burn for 3 seconds, the blister was induced by complete breakage of the basal and suprabasal cells which demonstrated karyorrhexis, aggregated tonofibrils and breaks in the plasma membrane. The keratinocytes of the blister roof showed aggregation of the tonofibrils at the periphery, and vacuolization of mitochondria and endoplasmic reticulum. The desmosomes and basement membrane revealed no alterations with 60 degrees and 95 degrees C burns.


Ulstrastructural study of leukodermic skin in Waardenburg-Klein syndrome. The skin of a patient with Waardenburg syndrome has been studied by electron microscope. In leukodermic skin, there were neither melanocytes nor indeterminate cells; Langerhans cells were normal in number and distribution. On the edge of the lesion, melanocytes were few and appeared degenerated, with abnormal melanosomes; indeterminate cells were observed in suprabasal areas. Healthy skin also showed melanosome abnormalities. These findings are discussed and compared with the characteristics of piebaldism.


Cellular aspects of phototoxic reactions induced by kynurenic acid. I. Establishment of an experimental model utilizing in vitro cultivated cells. Kynurenic acid is an endogenously occurring tryptophan metabolite, which, under certain conditions, may accumulate in human tissues. In earlier work kynurenic acid showed a pronounced photohemolytic capacity, and conclusive evidence has been presented that the reaction is mediated by singlet oxygen. The aim of the present study was to gain further information about the cellular mechanisms involved in the photo-oxidative damage induced by kynurenic acid. This paper is mainly concerned with the establishment of a proper experimental model utilizing in vitro cultivated cells, but basal cytotoxic effects revealed by the use of cell growth curves, and light- and scanning electron microscopic examinations are also described.


Virus-like structures in lupus erythematosus discoides. Biopsy specimens from typical skin lesions of DLE patients were studied by means of electron microscopy. Virus-like structures were discovered in the cytoplasm of fibrocytes, endothelial cells and keratinocytes. After prolonged chloroquine treatment a decrease in the frequency and size of these structures was observed.


In vitro growth of mouse hair root.

In vitro growth of mouse hair root. Hair roots from mouse dorsal skin continued to grow in culture medium for 10 h or more after isolation. Under observation by time-lapse cinematography, the cultured hair roots appeared to grow downward. We observed both the downward growth of the cultured hair roots as well as the transfer of melanosomes from melanocytes to cortical cells. The hair roots were also capable of incorporating the labelled amino acid and thymidine.


Glutathionedopa in malignant melanoma.

Glutathionedopa in malignant melanoma. A human melanoma metastasis was found to contain a substance identical with synthetic glutathionedopa when examined by means of an automatic amino acid analyser, chromatography on a Dowex-50 column, thin-layer electrophoresis, and by fluorimetry. The presence of glutathionedopa in melanoma tissue and of enzymes capable of hydrolysing the glutathione moiety of the molecule, together with the absence of glutathionedopa in the urine, suggest that glutathionedopa is an intermediate substance in the formation of 5-S-cysteinyldopa.


Increased succinate dehydrogenase activity of lymphocytes in eczema. Succinate dehydrogenase activity has been studied in the peripheral blood lymphocytes from controls and patients with a variety of skin and other diseases. Increased activity has been found in eczematous dermatitis and dermographism, and also in one patient with chronic lymphatic leukemia. Normal levels were found in psoriasis. The enzyme activity is broadly correlated with the extent and activity of the disease process.


Studies on cold insoluble globulin in dermatological patients. II. Its immunochemical quantitation in citrated plasma in a group of unselected dermatological inpatients. Cold insoluble globulin (CIG) is the main non-clottable protein of heparin precipitable fraction from dermatological patients. CIG is a glycoprotein with a molecular weight of about 440 000. It is found on cell membranes on fibroblasts and is a normal protein of human plasma and serum. Levels of CIG in citrated plasma are sex- and age-dependent, but the origin and its physiological significance is unknown. In plasma of 294 dermatological patients, levels of CIG were elevated in eczema contactum allergicum (males and females 30-49 years), psoriatic arthritis (females 50 years and above) and were depressed in dermatitis herpetiformis (males 30-49 years).


Complement as an essential factor for indirect immunofluorescence in cases of pemphigoid. Hitherto in the literature no proof has been published of a complement activation on the basement membrane in cases of pemphigoid. In this paper, for the first time, it is demonstrated, even if only in vitro, that complement, whose presence in the region of the basement membrane has long been known, plays an active role in a reaction. Through the action of the haemolytic system (amboceptor and sheep erythrocytes) and of anti C3 on reaction specimens for indirect immunofluorescence in pemphigoid, it is shown that the indicator reaction of the fluorescein-labelled anti-IgG with the immune complex attached to the basement membrane is markedly dependent on complement. Free, dissolved IgG is precipitated by appropriate anti-serum, even without complement.


An in vitro study of depressed cell-mediated immunity and of T and B lymphocytes in atopic dermatitis. Lymphocyte transformation tests, E binding(T) rosette assay and immunofluorescent preparations of B cells were studied in patients with atopic dermatitis, and also in healthy controls. Most of the patients were found to have high levels of IgE in serum. The patients were studied both during severe bouts of dermatitis and also when the dermatitis was almost healed. Lymphocyte transformation tests showed that patients were hyporeactive to PPD and herpes simplex antigen in vitro, both during periods of severe dermatitis and also when the dermatitis was in remission. The response to PHA in the patients was normal in vitro. No factors which could reduce cell-mediated immunity in vitro were found in patients' sera. A decreased number of T lymphocytes and a slight increase in the number of immunoglobulin-bearing lymphocytes (B cells) were demonstrated in the patients, both during remission and during recurrence of severe dermatitis. In 3 of 8 patients, increased numbers of IgE-bearing lymphocytes were found to be present when the patients had severe dermatitis. A possible correlation between high serum levels of IgE and depressed cell-mediated immunity in patients with atopic dermatitis is discussed.


The histocompatibility antigens in patients with Behçet's disease. Twenty-one patients with Behçet's disease were typed for HLA antigens. The controls were 50 subjects randomly chosen from a local population and 24 apparently healthy subjects of the same ethnic groupings as those of the patients. The study revealed significant differences in the frequencies of various antigens in the above three groups, the most obvious of them related to HLA-B5 and HLA-Bw35, HLA-B5 was demonstrated in 71% of the patients as compared with 18% in the local population group and 12.5% in the ethnically related healthy subjects. The incidences of HLA-Bw35 were 66.7%, 32% and 37.5% respectively. In 86% of the patients, at least one of these two antigens was present. It is suggested that besides contributing to the understanding of the disease process, the determining of associated specific antigens may constitute a further diagnostic acid in doubtful cases of Behçet's disease.


Genetic markers in psoriasis. Correlations to age at onset, continuity of symptoms and the risk of developing the disease. In a study on genetic markers (22 HLA antigens, 6 blood group types, 3 serum groups and 3 red cell enzymes) in psoriatic patients the following statistically significant differences were found between patients and controls: 1) The HLA factors B13 and Bw17, the Lewis blood group Le(a-b-) and the blood group factor A were overrepresented among the patients. A decrease in the frequencies of the HLA factors B7 and B8 was noted, confirming several similar findings by other investigators. 2) In the Ss (MNSs), C3 and haptoglobin (Hp) systems the psoriatic patients showed a decreased frequency of heterozygotes. 3) Among patients with continuous symptoms the blood group factor A and the blood group Fy (a+b-) were overrepresented. 4) Patients with late onset of psoriasis showed an increase in the blood group (Fy(a+bb-) and a decrease in the haptoglobin type 2-2. Relative risk figures have been calculated for different phenotypes. Certain genetic combinations were found to be grossly overrepresented among the patients. The mechanisms behind the associations appear to differ. In three systems (Ss, C3 and Hp) the deviations in psoriatic patients suggest the presence of heterozygote advantage.


Allergenicity of epoxy resins in the guinea pig. The sensitizing capacity of epoxy resins of diglycidylether-Bisphenol A type was investigated using the "guinea pig maximization test". One isolated resin had a molecular weight (MW) of 340, which is the lowest among this type of epoxy resin. The other resins were mixtures with different MWs. Their distribution is not known, but only their average MW. The low molecular weight resin sensitized all of the animals and can be classified as an extreme allergen. The sensitizing capacity decreased in inverse proportion to the increase in the average MW of the resin mixtures. The cross-testing also indicated that the resin mixtures with higher average MW contained enough of the low MW resin (MW 340) to render this resin a sensitizer. Bisphenol A did not sensitize the animals at all but epichlorhydrin sensitized 60%. It is evident that in order to formulate hypoallergenic epoxy resins it will be necessary to achieve sensitization of animals with isolated resins of varying molecular weight.


Patch testing with mineral wool (Rockwool). 25% of 315 tested subjects exhibited skin reactions when patch tested with mineral wool. Coating of the mineral fibres with phenol-formaldehyde did not influence the skin reactions. The reactions seem to be induced mechanically, as the mineral without the fibres did not give any reactions. No allergic reactions to the chemical additives were demonstrated. Macroscopically, the reactions may simulate an allergic response; microscopically, they seem to be toxic, sometimes with prominent spongiosis.


Hypomelanosis of Ito.

Hypomelanosis of Ito. Hypomelanosis of Ito appears to be a disorder of hypopigmentation. Findings from histochemical and electronmicroscopic studies indicate that pigment cells from the hypopigmented areas have short dendrites and synthesize less than normal amounts of melanin. The syndrome may have two forms; a cutaneous and neurocutaneous variety. In the more severe neurocutaneous variety, the phenotypic pigmentary abnormalities probably reflect a biochemical defect in all tissues derived from the neuro-ectodermal anlage.


Familial multiple lipomatosis.

Familial multiple lipomatosis. A clinical study was made of 14 cases of multiple symmetrical lipomata in two families. There were 7 female and 7 male patients. In one family the members affected were observed in four generations. The disease set in during the third or fourth decade of life. The lipomata ranged in size from that of a pea to that of a hen's egg. They were limited to the forearms and trunk were asymptomatic.


Hydrocortisone (cortisol) concentration and penetration gradient. Hydrocortisone (Cortisol) was incorporated into four different ointments at four concentrations (0.1% 0.3%, 1%, and 3%) and the amounts of the drug penetrating from these preparations into the different layers of excised skin were investigated. The effect of removing the horny layer on the penetration was also determined. Below a level of 1% ointments with intact horny layer and 0.3% with removed layer, a change in the ointment concentration alters the tissue concentration in the ratio 1:1. Above this level doubling of the concentration in the ointments causes an increase of tissue concentrations of only 20-50%. The removal of the horny layer increases the dermal concentrations 100 fold at each ointment concentration. Furthermore, a vasoconstriction test was performed with the different ointments. An increase in the concentrations above the 1% level failed to increase the effect on the vascular system of the skin. The in vitro and in vivo results are discussed with respect to the consequences on affected skin and the therapeutic efficacy of steroid preparations of different concentrations.


The treatment of balanitis xerotica obliterans with testosterone propionate ointment. Balanitis xerotica obliterans (BXO) and kraurosis penis are thought to be synonymous. Clinically and histopathologically they probably represent the same disease process as lichen sclerosus et atrophicus (LSA) but also involve the urethral mucosa. The treatment of choice is considered to be 2 1/2% testosterone propionate ointment which gives better results than strong corticosteroid applications, yet without their side effects.


Primary amenorrhea with a new mosaic 46,XXqi/47,XXqi Xp-. Consideration on the X isochromosome formation and X chromosome inactivation. A case of Turner's syndrome was found to be 46,XXqi/47XX,qi Xp-, a new mosaic. The origin of such a mosaic, the formation of the Xq isochromosome using the C-banding technique, and the X chromosome inactivation are discussed. The Xq isochromosome was apparently monocentric, but probably with two strictly close centromeres. The inactivated X seemed to be the Xqi or the normal X alternatively.


Use of banding techniques for zygosity diagnosis in twins. Detailed comparison of human variant chromosomes found by Q- and C-banding technique is performed in a pair of twins to show that these variants can be used for zygosity diagnosis.


Catabolism of alpha-fetoprotein in carbon tetrachloride-injured rats. The rate of alpha-fetoprotein (AFP) catabolism in carbon tetrachloride (CCl4)-treated rats was estimated to be essentially the same as that found in control adult and young rats. The blockade of the reticuloendothelial system by carbon particle resulted in slightly shorter t1/2 values of AFP. The amount of AFP synthesized pet day in CCl4-treated rats was theoretically calculated to be nearly 10-fold increase over that in control rats. Thus, the elevation of serum AFP concentrations in CCl4-treated rats is derived from the increased synthesis of AFP by injured liver.


Serum glycoproteins in autoimmune diseases. The concentration of IgA, IgG, IgM, coeruloplasmin, alpha-2-macroglobulin, beta-1-C-globulin, transferrin as well as of alpha-2-haptoglobin, orosomucoid and haemopexin has been studied in the serum of patients with disseminated lupus erythematosus, chronic progressive polyarthritis and immunopathological syndromes. The concentration of the carbohydrate components bound to serum proteins was also determined. In disseminated lupus erythematosus, the concentration of IgA, IgG, IgM, coeruloplasmin, and hexose, hexosamine and sialic acid bound to proteins, as well as of seromucoid was increased. In chronic progressive polyarthritis the IgA, IgG, IgM, coeruloplasmin, alpha-2-macroglobulin and beta-1-C-globulin concentration and the carbohydrate components bound to serum proteins rose. In immunopathological syndromes, too, the serum IgA, IgG, IgM, coeruloplasmin, and protein-bound hexosamine and sialic acid levels were increased. Under the effect of treatment, the elevated glycoprotein concentrations usually decrease, but the level of carbohydrate components bound to serum proteins hardly changes. The pathogenic and diagnostic significance of serum glycoproteins is discussed.


Movement of horseradish peroxidase in the cornea, sclera and the anterior uvea. The anterior chambers of rabbit, monkey and human eyes were perfused with horseradish peroxidase. The perfusion was started immediately after enucleation of the monkey and human eyes, while the rabbit eyes were perfused in situ after the animals had been killed. Comparative results were obtained after 1 h or perfusion and were mainly based on frozen sections. Intensive staining was found in the Descemet's membrane, the sclera and the iridial stroma, considerably more than in the corneal stroma and in the ciliary body base. In the vervet monkey and human eyes only traces of peroxidase reaction products were seen in the stroma of the ciliary body base. The movement of the protein tracer from the anterior chamber into the corneal stroma is probably dependent upon vesicular transport across the corneal endothelium. The Discemet's membrane was interpreted to be more porous than the corneal stroma. A transcorneal and a corneo-scleral movement appeared to be more efficient than the uveo-scleral one, at least in the vervet monkey and the human eyes.


The permeability of the human ciliary and iridial epithelium to horseradish peroxidase. An in vitro study. The permeability of the human ciliary epithelium to horseradish peroxidase (PO) has been studied in vitro with the electron microscope. Ciliary body and iris specimens were obtained from freshly enucleated eyes. PO was applied at the stromal side of the epithelium, and was left for 120 min. The movement of PO through the intercellular spaces of the human ciliary epithelium was blocked apically in the lateral intercellular spaces of the non-pigmented epithelial cells, indicating that these cells are girdled by zonulae occludentes. In the iridial epithelium, the same distribution pattern of peroxidase reaction products (PORP) was found, i.e. the progression of PO was blocked apically in the lateral intercellular spaces of the posterior epithelial cells. The study indicates that the human ciliary and iridial epithelium contains a system of zonulae occludentes, which represents a diffusion barrier to high molecular, water soluble substances. This is consistent with previous studies in several species of animals.


The appearance of the outflow apparatus of the eye after staining with ruthenium red. The outflow apparatus from adult baboon and rabbit eyes was stained with the inorganic dye ruthenium red. The ruthenium reaction product coated the surface of the trabecular meshwork cells and the canalicular endothelial cells. Deposits also impregnated the various connective tissue elements within the trabeculae and the extracellular spaces of the endothelial meshwork. A fine fibrillar network could also be identified with ruthenium red and this was present in the trabecular cores and the extracellular spaces of the endothelial meshwork. It was considered that the fibrillar network may represent a matrix of glycosaminoglycans and glycoproteins. The significance of these materials in relation to aqueous outflow was discussed.


[Psychological schoolability investigation as a part of screening psychological disorders--experiences by screeningtest (author's transl)]. A psychological method is described, which operates by demands on graphic reproductions. The method is able to screen mental retarded Preschool children. The screening of this children is necessary too, to find out psychopathological defects. In the age between 5;8 and 6;10 years 345 children were tested and 199 disorders were demonstrable.


Enhancement and stabilization effect of EDTA on Sendai virus neuraminidase activity. EDTA was found to enhance, and exert a stabilizing effect on, Sendai virus neuraminidase activity. The effect was dependent on the molecular form of the enzyme and on the nature of the substrate. The "native form" (enzyme bound to the virions) was less influenced than the "mixed form" (enzyme separated from the surface of virions together with other glycoproteins), which in turn was less influenced than the purified enzyme. On the other hand, the stimulation by EDTA of neuraminidase-induced hydrolysis of fetuin was higher than that of ovomucoid. The kinetic data obtained indicate that EDTA modifies the enzyme in such a manner that the affinity of the substrate for the enzyme is increased.


Pseudo bundle branch block produced by premature impulses arising in the bundle branches. Pseudo bundle branch block, a previously unreported arrhythmia produced by concealed premature impulses arising in the bundle branches, was seen in two patients with sick sinus node syndrome. Although concealed conduction was not apparent in either the surface or intracardiac leads, the latter were essential in localizing the site of manifest impulse formation. Patient 1, with left bundle branch extrasystoles, had pseudo bundle branch block and pseudo atrioventricular block that depended on the timing and extent of concealment of premature depolarization. Because of the coexisting sinus bradycardia in this patient, electrical stimulation and the recording of the right ventricular apical electrograms gave additional information that helped corroborate the postulated mechanisms. Patient 2 had right bundle branch extrasystoles with sinus beats that showed a right bundle branch block pattern possibly caused by pseudo bundle branch block. In this case the possibility that both the automaticity and the conduction disturbance had a mechanical origin could not be excluded.


Diagnosis of acute leukemia. Variability of morphologic criteria. The diagnosis of acute leukemia depends on the morphologic appearance of Romanowsky-stained blast cells. Three commonly used and accepted criteria for distinguishing among blast cells of different acute leukemias are (1) nuclear chromatin pattern, (2) appearance of nucleoli, and (3) nuclear-cytoplasmic ratio. It is sometimes assumed that Romanowsky stains do not differ in their abilities to demonstrate characteristic features of blast cells. In the present study six different Romanowsky stains were applied to smears from a single bone marrow aspirate from each of 22 patients with acute leukemia. Marked, stain-dependent variation in the appearances of the same blast cell population was repeatedly observed for all modalities except nuclear-cytoplasmic ratio. The authors caution against generalizations regarding morphology and suggest that the exact stain employed is a significant variable in morphologic studies.


Gonorrhea: diagnosis by gram stain in the female adolescent. The Gram-stained smear of secretions in female children and adolescents was evaluated as a diagnostic aid in acute gonorrhea. A positive smear was defined as the presence of at least eight or more pairs of Gram-negative, kidney-bean-shaped diplococci in each of at least two polymorphonuclear leukocytes. When the Gram-stained smear was compared with culture results in female patients it detected two thirds of infections and had a very high specificity. When the smear was positive, the culture was positive in 96% of the cases. The Gram-stained smear of cervical secretions is recommended as a guide to the early diagnosis of gonorrhea and its prompt therapy in the pediatric age group.


Effect of systemic infection and raised serum Ig-G concentration on the D-xylose test. Urinary d-xylose excretion during five hours after a 25 gm. oral load was determined in 47 Zambian African patients; some had systemic infections. Serum albumin, total globulin and gamma-globulin concentrations were determined in all and immunoglobulins Ig-G, Ig-A, Ig-M and Ig-D in 36 of them. An inverse association between weight of xylose excreted and serum gamma-globulin (P less than 0.02) and Ig-G (P less than 0.002) concentrations was significant. Taken together with previous observations, those results indicate reduced xylose absorption in the presence of systemic infection. The mechanism of the association is unknown but seems likely to have a nutritional importance; systemic infections must be eradicated if the nutritional status of rural Africans is to be improved.


Prevention of mental retardation: the role of medicine. In the past 100 years striking progress has been made in the prevention of mental retardation. Since mental retardation is a symptom rather than a distinct disease entity, its prevention requires attention to many different areas. Heterozygote detection, specific factors of pregnancy, the current status of newborn screening, and major postnatal factors associated with mental retardation are some of the issues discussed in this centennial paper. Although considerable progress has been made, the causes and, hence, the modes of prevention of mental retardation for the majority of retarded individuals are unknown. Continued progress will require the combined efforts of both medical and social scientists if the goal, the prevention of mental retardation, is to be realized.


Transfer of hydrophilic molecules by placenta and yolk sac of the guinea pig. Prenatal transfer of hydrophilic materials was studied in chronic guinea pig preparations of ca. 30-65 days gestation. In most preparations the vitelline (yolk sac placenta) circulation of one of the fetuses was ligated between 1 and 20 days before the experiment. Fetal and maternal serum protein concentrations were recorded as a function of the number of days after ligation. Prenatal transfer of hydrophilic materials of 60-5,500 daltons molecular wt was consistent with diffusion, with some evidence of steric restriction of the larger molecules. There was no difference between operated and sham-operated or control fetuses. However, the transfer of radiolabeled homologous gamma globulin ceased after ligation of the yolk sac vessels. The transfer in control fetuses accounted for most of the prenatal requirements of this protein, as calculated from the increases in fetal weight and serum gamma globulin concentrations as a function of gestational age. There was evidence of a nonspecific suppression of yolk sac function by surgery but no evidence of fetal catabolism of gamma globulin.


The binding of chloroquine to normal and Kwashiorkor serum. The binding of chloroquine to kwashiorkor and normal serum was investigated. The results show that more drug is bound in kwashiorkor serum, and that this occurs predominantly at the gamma globulin fraction. Therapeutically, in malnutrition there is no significant abnormality of protein binding with respect to chloroquine.


Treatment of systemic lupus erythematosus with the T-cell immunopotentiator levamisole: a follow-up report of 16 patients under treatment for a minimum period of four months. Treatment of 16 SLE patients with levamisole resulted in significant reduction of a variety of clinical parameters of the disease. Clinical improvement was both subjective and objective. Thus, levamisole may represent a possible alternative or adjunctive approach to SLE therapy. Although proper assessment of its actual quantitative importance in the treatment of Lupus must await large scale studies under double-blind conditions, nevertheless, these preliminary results are very encouraging.


A ten-year study of carcinoma of the pancreas. During the 10 years from 1965 through 1974, 86 patients with adenocarcinoma of the pancreas were diagnosed or referred for treatment at the University of Oregon Health Sciences Center. The average age and survival in these patients is not significantly different from other published series. Only four patients had resectable tumors, and of these two survived over twelve months. Eight other patients also survived over twelve months, and no two of these had the same treatment regimens (although nine of the ten long-term survivors received some form of chemotherapy). Fourteen patients received a combination of chemotherapy and radiation therapy. While their average survival was only two months longer than that of the entire series, three were long-term survivors. Over 75% had significant palliation; this suggests that this treatment should be considered in selected cases.


The macrophage electrophoretic mobility (MEM) test for the diagnosis of hydatidiform mole and choriocarcinoma. Preliminary report. In 1970, Field and Caspary reported that lymphocytes from patients with malignant disease can be stimulated by a basic protein from human brain (human encephalitogenic protein--HEP). The stimulated lymphocytes are capable of releasing the macrophage-slowing factor, which reduces the electrophoretic mobility of guinea-pig macrophages. In general, this effect was not found with lymphocytes from patients without malignant disease. This paper deals with the application of the MEM test using HEP and HCG as antigen in the diagnosis of trophoblastic disease. We have found cellular sensitization against HCG in all patients with gestational trophoblastic tumours and against HEP in patients with hydatidiform moles of the group II or III as well as choriocarcinoma. Patients with malignant tumours of different localization showed a cellular sensitization against HEP, but only some against HCG. In pregnant women no cellular sensitization against HEP as well as HCG was detected. The results of the MEM test using HEP as antigen in patients with gestational trophoblastic tumours are compared with the clinical findings and the histological diagnosis. By means of this combination a more exact evaluation of the biological activity of the trophoblastic disease was obtained.


[Rhabdomyosarcoma in childhood. Report of 27 cases (author's transl)]. Twenty-seven cases of rhabdomyosarcoma in children between one month and 14 years of age are reported. The most frequent histologic type was the embryonal sarcoma and almost half of the cases were diagnosed in advanced clinical stages. Treatment consisted on the combination of surgery, radiotherapy and chemotherapy (vincristine, cyclophosphamide and actinomicin-D in non metastatic cases, plus adriamycin when metastases were present). The survival rate is 57.7% and the survival with no evidence of disease 53.8%, with observation periods from eight months to four years.


[Side effects of antibiotics in patients with thermal burns]. The possibilities of antibacterial therapy in the clinics of burn diseases has at present decreased because of increasing microflora resistance to antibiotics. This phenomenon is one of the most often causes of antibacterial drug side effects in burn patients. For control of infections complications in burn patients which are most often lethal it is necessary to use biologically active subtance, such as prodigiozan and lysozime in addition to the directed antibiotic therapy. The use of specific antitoxic antistaphylococcal drugs, such as antistaphylococcal plasma and antistaphylococcal gamma-globulin in combination with the antibiotics of the direct action provided effective control of infectious complications and sepsis of staphylococcal genesis in burn patients. Decamine proved to be effective along with the usual use of nystatin in cases with dysbacteriosis as a result of the antibiotic side effects. In the patients treated with decamine the sings of candidosis disappeared by the 5th--7th day. Therefore, for decreasing the side effects of antibiotics in the clinics of burn patients it is expedient to use antibiotics in combination with the biologically active and immune preparations which increases the efficacy of antibiotic therapy, impfoves the treatment results and decreases the antibiotic side effects.


Current concepts of tumor immunology. I. Basic immunologic concepts. Interest in tumor immunology grew out of the study of host response to microbial infections during the second half of the 19th century. However, the growth of interest in transplantation during the 1950s and 1960s is largely responsible for the great surge of scientific investigation into tumor immunobiology which we are experiencing today. Tumor cells possess certain abnormal antigens in addition to their normal complement of transplantation antigens. These abnormal antigens evoke an immune response in the host, which involves both the humoral and the cell-mediated systems. Though the cell-mediated (thymus derived) system is generally conceded the most important role in tumor cell destruction, the humoral (bursal-equivalent derived) system also plays a role in host response which is presently less clearly understood. Certain aspects of the humoral response (blocking factors) actually appear to inhibit the host response against a tumor. This complex system of host immune response to tumor has been termed the immunosurveillance system.


Degradation of lindane by cell-free preparations of Clostridium sphenoides. Cell-free preparation of Clostridium sphenoides degraded the insecticide lindane, the gamma-isomer of 1,2,3,4,5,6-hexachlorocyclohexane, to the gamma-isomer of 3,4,5,6-tetrachloro-1-cyclohexene. The activity appeared to be associated with the membrane fraction and required reduced glutathione. The tetrachlorocy-clohexene intermediate was further metabolized by the membrane fraction to unknown substances.


Comparative immunological study of catalases in the genus Micrococcus. Double immunodiffusion tests were performed with crude extracts from various Micrococcus species and antisera against catalase of Micrococcus luteus CCM 169. Cell-free extracts of M. lylae ATCC 27566 exhibited good cross-reaction. Cell-free extracts or catalase enriched preparations of M. varians reacted very weakly and no reaction has been found with preparation of M. kristinae, M. nishinomiyaensis, M. roseus and M. sedentarius. The quantitative microcomplement fixation assay also revealed a closer relationship between M. luteus and M. lylae than between M. luteus and M. varians. Strains of other Micrococcus species reacted in the microcomplement assay with M. luteus antiserum just a weakly as non-related strains, e.g. Staphylococcus aureus or Cellulomonas cartalyticum.


[Investigations about the incorporation of nucleotide precursors in single cell suspensions of ovarian- and cervix-carcinomas under the influence of cytostatic therapy (author's transl)]. The behaviour of 34 carcinomas of the cervix and 30 ovarian carcinomas under the influence of cytostatic agents was investigated in vitro by the method of Volm et al. The ovarian carcinomas showed a significantly higher incorporation rate of nucleotide precursors in the single cell suspensions. The incorporation rate in "chemosensitive" carcinomas was higher than in "chemoresistent" carcinomas independent of the type of the carcinomas. Carcinomas with a high decrease in incorporation rates of nucleotide precursors under the influence of cytostatic drugs were called chemosensitive. A cyclophosphamide-sensitivity in vitro was found in 9% of the carcinomas of the cervix and in 34% of the ovarian carcinomas. An adriamycin-sensitivity in vitro could be shown in 17% of the carcinomas of the cervix and in 46% of the ovarian carcinomas. These findings agree well with the experiences of cytostatic therapy of these carcinomas.


Morphometric study on the nucleoli of mesothelial and tumour cells being in pleural cavity effusions. An Opton cytophotometer was used for a comparative morphometric study on mesothelial and tumour cells obtained from pleural effusions. Tumour cells coming from malignant neoplasms with epithelial or mesenchymal origin were measured. Slides stained after Ambs X Grönemeyer and Smetana methods revealing RNP structures have been used. Both methods were valuable for nucleolar morphometry but the technical simplicity of the second one made it preferable. Nuclear and nucleolar surfaces as well as diameters and perimeters of nucleoli have been studied. Nucleolar/nuclear index, i.e. average number of the nucleoli per nuclear profile as well as nuclear/nucleolar surfaces ratio have been counted too. A clear difference of the average nucleolar size in tumour cells compared to that of mesothelial ones was established. The count of nuclear/nucleolar surfaces ratio-reveals that nucleolar enlargement in tumour cells is higher than nuclear one. In constant changes in the nucleolar/nuclear index was revealed in tumour cells.


Pleural fluid macrophages in lung infarct. Evidence and origin. In this study, which was undertaken after a personal error of diagnosis, we have tried to demonstrated why the cells found in the pleural fluid look alike cancerous cells and this aim has obviously lead us to discuss the origin of the abnormal cells. The cytologic and cytochemical study of pleural fluid cells in 9 cases of lung infarction and the comparizon with pathological patterns has lead the authors to believe that the abnormal cells present in the fluid are not mesothelial cells. The cytochemical stain on the smears and on the lung sections, evidencing iron pigment in the cytoplasma of some cells has lead us to consider them as alveolar macrophages. The simple technic may help in the diagnosis of lung infarction when the clinical features are not enough convincing.


The correlation of routine cytology with the contents of carcinoembryonic antigen and alpha-fetoprotein in pleural and peritoneal effusions. The levels of carcinoembryonic antigen (CEA) and of alpha-fetoprotein (AFP) were determined with radioimmunoassay in 63 samples of either pleural or peritoneal effusions. All samples were collected from 53 patients suspected for malignancy and were also studied with the routine cytological techniques. Elevated levels of CEA (above 20 ng/ml) were found in 14 out of 29 cytologically positive samples, in none of 6 cytologically suspected and of 14 cytologically negative samples. The highest levels of CEA (above 1,000 ng/ml) were found in samples from patients with gastrointestinal carcinomas, while negative results were most often found in lymphoreticular and ovarian malignancies. Elevated levels of AFP (above 5 ng/ml) were found in 9 samples (5 cytologically positive and 4 negative). Five of these exudates were negative for CEA. Positive results of AFP were most frequently found in samples derived from patients with secondary or primary liver tumours. The highest levels of AFP (6 and 30 ng/ml), were determined in samples of two hepatoma patients. The combined cytological and radioimmunological studies suggested malignancy in 52 out of 63 samples while cytology alone detected either neoplastic or suspected cells in  35 samples only.


Localization of alpha-fetoprotein synthesis in malignancies other than hepatoma. Immunofluorescence staining was applied to tissue with primary nonhepatic malignancies and/or their metastatic nodules in the liver. Tumor cells from the primary sites of two patients with carcinoma of the pancreas and one patient with Hodgkin's disease were found to be positive for alpha-fetoprotein (AFP). In five patients with gastrointestinal tract cancer, and two with nongastrointestinal tract carcinoma, the liver cells immediately adjacent to the metastiatic foci were positive for AFP. Negative results for AFP was found in seven patients with liver metastasis; of these seven patients, five had nongastrointestinal tract cancer, and two had cancer that arose in the gastrointestinal tract. It is unclear what influences the production of AFP in cases of liver metastasis, since some neoplasms from the same organ system do provoke this phenomenon, and others do not.


[New method of differential histological diagnosis of different forms of amyloidosis]. A new method for morphological diagnosis of various forms of amyloidosis based on the use of a hot buffered hexamine-silver solution is suggested. Its potentials are illustrated on 37 cases of primary, hereditary, and secondary human amyloidosis as well as experimental amyloidosis. The proposed method permits morphological differential diagnosis of amyloidosis in those cases where other methods failed to do it.


[Feulgen reaction conducted on unfixed smears]. After hydrolysis with 5N HCl at room temperature Feulgen's reaction either with Schiff's reagent or with some basic dyes instead of it can be carried out on the air-dried smears without any chemical fixation. Both reactions give quantitative results.


[Nonspecific esterase activity in malignant non-lymphogranulomatous lymphomas]. It is recommended to determine the activity of nonspecific esterase in malignant non-lymphogranulomatous lymphomas (MNL) and to use for this purpose 5-bromindoxylacetate with poststaining of sections with aluminous carmine. In lymph nodes, affected with MNL, this procedure facilitates the detection of the arrangement of reticular cells and the degree of MNL penetration with hystiocytes. Also such structural features of MNL as their follicular structure and infiltration of sinuses of lymph nodes with the tumor tissue are determined.


[Morphology of multiple cylindroma of the skin (histochemical and electron-microscopic study)]. The electron-microscopic study of skin cylindroma indicates that these tumors derive from the sweat glands, apparently the apocrine glands, and cells of the tumor and fibroblasts of the stroma take part in the formation of hyaline substance.


Methyl alcohol poisoning. IV. Alterations of the morphological findings of the retina and optic nerve. The ocular morphological findings of three methyl alcohol-intoxicated rhesus monkeys with optic disc swelling was investigated with light and electron microscopy in conjunction with intravascular horse radish peroxidase. Alterations observed in the optic nerve head were confined to the axons and consisted of swelling and clustering of the mitochondria, disruption of the neurotubules, the formation of vesicles, and enlargement of the axon segments in the prelaminar region. Swelling of the oligodendroglial cytoplasm in contact with the axons and of the astrocytes was seen in the retrolaminar optic nerve and the intraorbital optic nerve. Alterations were not observed in the retina. It is hypothesized that the alterations in the axons are the result of disrupted axoplasmic flow. Possible mechanisms relating methyl alcohol intoxication to disruption of axoplasmic flow are discussed.


Surface immunoglobulins, a possible mechanism for the persistence of Trypanosoma lewisi in the circulation of rats. The results presented below show that the dividing and adult forms of T. lewisi share common antigens and indicate that the persistence of adult forms in the circulation of rats immune to reinfection is not due to a change in surface antigens as has been postulated. Using a rabbit anti-rat immunoglobulin serum, the presence of rat immunoglobulins on the surface of adult trypanosomes could be demonstrated. These immunoglobulins were not complement-fixing or opsonic. It is suggested that these immunoglobulins are responsible for the persistence of the adult forms in the circulation of the rat.


Characteristics of the immune response in a patient with Whipple's disease. A patient with Whipple's disease has been studied to examine the effect of antibiotic therapy on the immune status of the patient, and the specific immune response to a cell wall deficient form of an alpha-haemolytic streptococcus (alpha HS) isolated from this patient. T lymphocyte numbers were reduced, and cutaneous anergy was present. Autoantibodies directed against smooth muscle and mitochondria were detected. These abnormal parameters became normal following antibiotic therapy. The specific immune response to the alphaHS was characterised by IgA antibody and lymphocyte sensitisation. The latter was detected as antigen-inducedd lymphocyte stimulation and antigen-induced leucocyte inhibition factor (LIF) production. Antibiotic therapy was associated with a fall in antibody titre and reduced LIF production. No defect in neutrophil function was found. These results are most consistent with the postulates that (i) immunological abnormalities in Whipple's disease are secondary to infection and (ii) the primary abnormality is an unusual pathogenic bacterium.


Effects of acronycine, bleomycin and cytosine arabinoside on the cell cycle. Some aspects of their interaction with radiation determined by pulse cytophotometry. The influence of three chemotherapeutic agents, acronycine, bleomycin and cytosine arabinoside, alone and combined with radiation, on cell cycle progression and viability of L-cells was examined. The percentages of cells in G1, S and (G2 + M)-phases as derived from pulse cytophotometric DNA distribution patterns were recorded as a function of exposure time. After 24-h treatment with 10 microgram/ml acronycine, 46.4% of cells were accumulated in (G2 + M)-phase compared to 12.1% in the controls. This accumulation was significantly enhanced by an irradiation with 150 rads of X-rays resulting in arresting 63.1% of cells in this phase. Similar findings were obtained after a 24-h treatment with 100 microgram/ml bleomycin. 54.4% of cells were arrested in (G2 + M)-phase by the chemical treatment alone, while the combined treatment, bleomycin and radiation, yielded an accumulation of 66.3% of cells in G2 + M. A 24-h exposure to 0.2 microgram/ml cytosine arabinoside (Ara-C) produced a reversible block of 72.8% of cells in S phase compared to 27.4% in the control cultures. This S block was less pronounced after the combined treatment (51.1%). Some implications of the results for combined therapy are discussed.


Antigenic characterization of Echinococcus granulosus cysts. Limited numbers of antigens were detected in the structural components of Echinococcus granulosus cysts by double diffusion and immunoelectrophoresis tests using homologous and heterologous antisera without antibody activity to host serum contaminants. Although antigens common to the germinal membranes, laminated layers and protoscoleces were demonstrated, no evidence was found of antigen sharing between the laminated layer and hydatid fluid from fertile and sterile cysts. These fluids, however, had antigenic determinants in common with protoscoleces. Antigens responsible for the formation of a characteristic cathodic are were detected but only in the three structural cyst components. In contrast, E. granulosus arc 5 antigens were found solely in hydatid fluid. These observations suggest that these two antigen groups are of somatic and metabolic origin, respectively. The results are discussed in terms of current knowledge of the immunobiology of hydatid cysts.


[Histochemical detection of HBsAg in liver biopsies using the orcein staining method]. Liver biopsies from 30 HBsAg seronegative and 33 HBsAg positive subjects affected by liver diseases were stained by orcein method for the histochemical detection of HBsAg. All biopsies from HBsAg negative cases were orcein negative. Staining was positive in 55% of seropositive patients. The frequency of the different patterns of the staining is analyzed and its value as a diagnostic and prognostic tool in chronic liver disease is discussed.


Hydroxyethyl starch. An agent for hypovolaemic schock treatment II. Urinary excretion in normal volunteers following three consecutive daily infusions. 1 Urinary hydroxyethyl starch (HES) concentrations were determined by the anthrone method, in four healthy normal male volunteers following three consecutive daily 500 ml infusions (total 1500 ml), in order to ascertain excretion rates under normal controlled conditions. 2 The HES was excreted at a rate of 2.57, 2.46, and 2.44 g/h during the first hour postinjection, on days 1, 2, and 3, respectively. 3 The rate during the interval 12-24 h postinjection, averaged 0.14, 0.21, and 0.10 g/h, on days 1,2, and 3, respectively. 4 In the intervals 24-72, 72-120, and 120-168 h after the third and final injection, the excretion rate was 0.07, 0.04, and 0.02 g/h, respectively. 5 Renal function, as assessed by serum creatinine and uric acid concentrations and 24 h void volumes, was normal during the entire period of observation. 6 The results indicate that HES is excreted at a similar rate following three consecutive daily infusions without evidence of renal injury.


Heavy metal pollution among autoworkers. II. Cadmium, chromium, copper, manganese, and nickel. Garages and auto-repair workshops may be polluted with other heavy metals besides lead. Blood of autoworkers with high lead content was analysed for cadmium, chromium, copper manganese, nickel, ALAD activity and carboxyhaemoglobin level. Cadmium and copper levels in blood of autoworkers were comparable with those of the control subjects while chroimium and nickel levels were significantly higher (P less than 0-01 for both metals), and scattered raised values of manganese were found. There was no significant mutual correlation between levels of various heavy metals determined in whole blood. High copper levels were slightly related to decreasing ALAD activity (P less than 0-1). Nineteen per cent of autoworkers were found to have an abnormally blood level of carboxyhaemoglobin. The amount of particulate heavy metal in autoworkshop air was not related to biochemical abnormalities found in the autoworkers. Various sources of pollution of these heavy metals in autoworkshops are discussed.


Fetal arrhythmia during pregnancy and labour. The significance of fetal arrhythmia presenting during pregnancy and labour has been examined in 68 patients. The different types of rhythm disorders diagnosed included 61 extrasystoles, 6 atrioventricular blocks and 1 auricular fibrillation. Extrasystoles were not associated with acidosis or organic cardiac disease. Atrioventricular block, though not associated with fetal hypoxia, was occasionally associated with congenital cardiac failure.


A comparative study of three low dose progestogens, chlormadinone acetate, megestrol acetate and norethisterone, as oral contraceptives. Three low dose progestogens, chlormadinone acetate (0-5 mg), megestrol acetate (0-5 mg) in oil, and norethisterone (0-35 mg), taken daily, were employed as oral contraceptives in postnatal women who desired to postpone their next pregnancy for up to a year. In a lower and middle social class population net pregnancy rates (life table) were five to six per 100 woman-years, of which about half were due to failure to take the tablets. Side effects other than menstrual disturbance were few. Norethisterone was the least likely of the three preparations to lead to discontinuation because of disturbance of menstruation. There were three ectopic gestations amongst 35 pregnancies in 4500 women-months of use. Ninety-five patients with varicose veins, 15 with a history of thrombophlebitis and 23 with a history of liver disease took progestogens without relevant untoward effects.


Two antigenic sites of tissue transglutaminase. The immunization of rabbits with purified guinea pig liver transglutaminase resulted in the appearance of two antibody populations against the enzyme: one which reacted only with the Ca2+-enzyme complex and another which reacted with the intact as well as the Ca2+-enzyme. The Ca2+-induced confomrational change of the enzyme molecule exposes a new antigenic determinant which initiates the production of a specific antibody population. When the glutamine substrate of the enzyme was a dipeptide, the result of the interaction of the Ca2+-enzyme and its isolated specific antibody was an apparent activation of the catalytic activity. However, when protein substrates were used, an inhibition was observed. The characterization of the mechanism of the activation and the inhibition has led to the conclusion that the consequence of the interaction of Ca 2+-enzyme and its specific antibody is not only a limited steric hindrance of the active center but, besides that, a stabilization of the otherwise labile Ca2+-enzyme. The other antibody population reacts with both forms of the enzyme and its inhibitory effect, which has been observed in each assay, could be due to a prevention of the Ca2+-induced formation of the active enzyme.


alpha-galactosidase A from human placenta. Stability and subunit size. alpha-Galactosidase A (alpha-D-galactoside galactohydrolase, EC 3.2.1.22) was purified from human placenta. The purified enzyme showed one major band on polyacrylamide gel electrophoresis and a single precipitin line on double immunodiffusion. Electrophoresis of the purified, S-carboxymethylated enzyme on sodium dodecyl sulfate polyacrylamide gel showed one component with a molecular weight of about 65 000, but electrophoresis of the non-S-carboxymethylated enzyme showed two components, a major band with a molecular weight of 67 500 and a diffuse band with a molecular weight of 47 000. We suggest that the smaller diffuse component is a degradation product and that the enzyme is a dimer with a molecular weight of approximately 150 000 and a subunit of molecular weight of about 67 500. Antibody raised against the purified enzyme quantitatively precipitated alpha-galactosidase A, but not alpha-galactosidase in Fabry's disease fibroblasts. The alpha-galactosidase A is very heat labile and pH sensitive. It is most stable in concentrated solution at low temperature and at a pH of 5.0 to 6.0. When added to plasma at 37 degrees C, it has a half-life of only 17 min. This imposes a serious obstacle to its use in the treatment of Fabry's disease.


Preparation of homogeneous human prostatic acid phosphatase using concanavalin A-sepharose 4-B. A simple, rapid and efficient procedure is presented for the purification of human prostatic acid phosphatase (orthophosphoric-monoester phosphohydrolase (acid optimum), EC 3.1.3.2) to homogeneity. The method employs two steps suitable for use with large quantities of material, followed by chromatography on concanavalin A-Sepharose as its sole column step. The procedure also permits the recovery of purified enzyme in higher yields than earlier methods.


[Inhibition of DNAse I activity in vivo]. Immune gamma-globulins containing antibodies to bovine DNAse I inhibit activities of bovine and mouse DNAse I both in vitro and in vivo. Bovine DNAse I was used as exogenous DNAse I in the in vivo studies and was injected to mice intraperitoneally in combination with gamma-globulins. The serous fluid of mice was used as a source of endogenous DNAse I. Both in in vitro and in vivo studies immune gamma-globulins caused a practically complete inhibition of bovine DNAse I activity, whereas the activity of mouse DNAse I (endogenous) was inhibited by 60-80%. Nonimmune gamma-globulins had no inhibitory effects whatsoever.


Monocytic differentiation of cluster cells in agar culture of normal human bone marrow. A cytochemical investigation. A cytochemical investigation was carried out on the cells that make up the clusters forming in agar cultures of normal human bone marrow after 3, 4, and 5 days of incubation. All the clusters were found to comprise young monocytes that were PAS, peroxidase, Sudan Black, and alpha-naphthyl and naphthol-ASD-acetate esterase positive. Lysozyme activity, investigated by the cytobacterial test, was absent in all cases. After 3 days of incubation a large number of pairs of lymphomonocytes or monocytes with the same cytochemical characteristics were observed. When a method of double esterase incubation (alpha-naphthyl or naphthol-ASD-acetate and naphthol-ASD-chloroacetate) was performed on the same slide, no cells of the granulocytic line or intermediate cells between these and the monocytes were observed in any of the clusters. These results indicate that there is direct monocytic differentiation of the colony-forming cells cultured. The origins and stages observed in the maturation of the monocytes are discussed.


Contribution of quantitative immunocytology to the study of lymphoid hemopathies. Forty-three patients with a lymphoid hemopathy, three with agammaglobulinemia and six normal controls were investigated with regard to their blood lymphocyte membrane-associated light chains. Detection and quantitation of antigenic determinants were performed by means of peroxidase-labeled antibodies. Compared to normal controls, values found in chronic lymphocytic leukemia (CLL) were very low (tenfold decrease). The number of antigenic determinants on lymphoid cells from patients with blast crises supervening in CLL, prolymphocytic leukemia, Waldenström's macroglobulinemia and Burkitt-cell acute leukemia were significantly higher than those seen in patients with CLL. The data obtained in this investigation through quantitative immunocytology constitutes a new parameter for the classification of lymphoid hemopathies and for an approach to their pathogenesis, in particular if the quantity of membrane immunoglobulin correlates with the stage of cell maturation.


[Immunologic study of tumors of the human thyroid gland]. The presence of specific antigens was shown in 6 of 17 cases of human thyroid carcinoma by the complement fixation test. These antigens were absent in the tissues obtained from healthy man and embryo. Immunological variants of these antigens were found in some patients. The specificity of the antigen determinants of the thyroid tumours is apparently determined by the substances of the protein origin.


[Induction of transplantable leukemia-like syndromes in mice by administration of antigens and immunostimulants]. Splenomegaly characterised by myeloid metaplasia was induced in BALB/c mice by the injection of antigens and immunostimulants. In difference from leukemoid reaction, this syndrome was transmissible both by the plasma and by the splenic cells. Small virus-like particles (30--50 nm) were revealed in the plasma, and RNA-containing viruses of type C--in the splenic cells.


[Isolation and characterization of 7S-beta1-globuline from human erythrocytes (author's transl)]. A new protein was isolated from lysates of washed human erythrocytes in a two step procedure using ionexchange chromatography and gel filtration. The protein has the electrophoretic mobility of a beta1-globulin. On ultracentrifugation the purified protein when dissolved in a 0.05 M phosphate buffer (pH 6.8), containing 0.2 M NaCl sediments with 6.88 S and shows a molecular weight of 150,000-180,000 daltons. In salt solutions with higher ionic strength the molecules dissociate reversibly into subunits which have a molecular weight of 40,000-45,000 daltons. The 7S-beta1-erythrocyte protein according to its behavior at ultracentrifugation, gel filtration and SDS poly-acrylamide gel electrophreses apparently is composed of 4 identical or similar subunits which are loosely held together by noncovalent bonds. Chemically the 7S-beta1-erythrocyte protein consists of 99% amino acids and 1% carbohydrates. The concentration of this protein in erythrocytes amounts to 250 mg per 100 ml packed red blood cells. The protein is not found in the membrane. In its physical, chemical and immunochemical properties the 7S-beta1-erythrocyte protein differs from all other well defined proteins and enzymes from human red cells thus far known.


Physical information in the external urinary stream of the normal and obstructed adult male. The qualitative status of physical information contained in the stream of the male lower urinary tract is traced from the bladder to the broken-up external stream. The progression of modifications of this information is discussed and it is argued that information remains in the drops. Electro-optical measurements of the drops leads to pulses which can be analysed for various types of information content. These confirms that there is potential clinical value in some aspects of the information.


Prostatectomy with a no-catheter technique. A method of no-catheter prostatectomy is described and the results of 350 operations are presented. It has been demonstrated that this method of prostatectomy can be done aseptically.


A Golgi analysis of caudate neurons in rats exposed to carbon monoxide. Interneurons of the caudate nucleus have been reported in the literature to respond to deafferentation by reduction in dendritic spines. In the studies reported here, caudate interneurons have been examined using the Golgi technique and increased numbers of spines were found in adult rats exposed to carbon monoxide as neonates. The development of spines on the caudate neurons was delayed for several days after an acute anoxic episode in 5-day-old rats exposed to carbon monoxide to the point of respiratory arrest. By the time the rats were 6 weeks old the caudate neurons had recovered to the point where they had essentially normal numbers of spines. At later ages (2- and 7-months old) the number of spines was greater in rats exposed perinatally to carbon monoxide than in control rats of the same age. The development of abnormal numbers of spines coincided with the time of recovery of rats from behavioral hyperactivity induced by carbon monoxide. The increased spines on the caudate neurons of the adult rats (7-months old) can be explained as a compensatory response to increased afferent flow to the caudate during the period of juvenile hyperactivity which reaches a peak at 6 weeks of age. It is proposed that the return to normal activity in the adult may be a consequence of increased activity of the caudate nucleus.


Arborization of initial axon collaterals of spinocervical tract cells stained intracellularly with horseradish peroxidase. The initial axon collateral arborizations of two feline spinocervical tract cells have been analysed after intracellular staining with horseradish peroxidase. The images of the cells were reconstructed in the light microscope from transverse serial sections. The cell bodies were situated in laminae IV or III of the lumbar dorsal horn. Each cell exhibited one initial collateral. These emerged from the parent axons at distances of about 310 and 580 micron, respectively, from the cell body. The collaterals branched, mainly symmetrically, in laminae III-VI and IV-VI, respectively. The total collateral lengths were about 12,000 and 10,900 micron; altogether 329 and 274 stained terminals were found per collateral in laminae III-VI and IV-VI, respectively. The great majority of boutons were found in laminae IV and V. The terminals were distributed mainly in spherically arranged groups of 3-12 boutons, usually connected to each other by thin terminal axons. The light microscopically investigated sections were 're-embedded' and processed for electron microscopy. The ultrastructural investigation showed boutons with axo-dendritic, axo-somatic or axo-axonal synapses.


The effects of ergosterol on the response of female chicks to oral oestrogens and progestogens. The chick-oviduct assay was used to investigate the effects of dietary ergosterol on the response to oral progestogens and oestrogens. 2. Progestogens alone had no effect on the oviduct but the hypertrophy due to oestrogen was greatly enhanced by simultaneous treatment with progestogen at all dose levels tested. 3. Ergosterol had no effect on any of the responses of the oviduct studied.


[Modified Giemsa technique for the study of characteristic chromosomes of leukemic C57Bl mice]. G-banded karyotypes have been studied in C57Bl control mice and in animals developing leukemia after i.p. injection of acellular extract of spleen or lymph nodes from isologous animals showing radiation induced leukemia. No visible differences could be detected with respect to the number, size and position of the G-bands between the two groups of animals. From the present observations and from previous work with conventional staining methods, it can be concluded that the development of such leukemia does not involve the presence of chromosome abnormalities.


The value of mediastinoscopy in the assessment of the operability of bronchial carcinoma respective five years survival after resection. Of 740 mediastinoscopies carried out from january 1966 to january 1976, 581 were performed to assess the operability of a pulmonary carcinoma. Of these, 42% were positive and 58% were negative. The remaining 159 mediastinoscopies were performed as aids in the diagnosis of affections of the lungs and mediastinum. Of these, 63% were positive and 37% were negative. Patients with bronchial carcinoma and a negative mediastinoscopy were regarded as operable; patients with a positive mediastinoscopy were regarded as inoperable because of mediastinal metastases (Nohl, 1956; Reynders, 1964; Carlens, 1965). Nevertheless a small number of patients with a positive mediastinoscopy were operated during an initial period.


[Alpha fetoprotein in maternal blood during normal and pathological pregnancies]. AFP was assayed in serum of normal pregnant women and in patients with pathological pregnancy. Pathological levels of AFP, defined as increased or decreased concentrations compared with the normal distribution, was detected in 83.5 % of pregnant women who delivered a dysmature child and in 88 % of those whose placenta was macroscopically sclerous. A longitudinal determination of AFP appears to be useful in the follow-up of risk of abortion.


Acute lindane poisoning with development of muscle necrosis. A 35-year-old man ingested food contaminated with lindane, an insecticide containing almost pure gamma hexachlorocyclohexane. Grand mal seizures and severe acidemia developed rapidly. The seizures recurred for nearly 2 hours, then ceased. In addition, the patient had muscle weakness and pain, headaches, episodic hypertension, myoglobinuria, acute renal failure and anemia. Pancreatitis developed 13 days after the ingestion of lindane. A muscle biopsy on the 15th day of illness demonstrated widespread necrosis and regeneration of muscle fibres. The patient's condition improved and he was discharged 24 days after the onset of his illness. During the year following the poisoning the patient noted difficulty with recent memory, loss of libido and easy fatigability. One year after lindane ingestion the results of physical examination, including those for muscle power and bulk, were normal.


Therapy of advanced squamous carcinoma of the lung: cyclophosphamide vesus "COMB". The four-drug combination of cyclophosphamide, vincristine, methyl CCNU and bleomycin was compared to CTX alone in a prospective randomized trial. Only one of 20 patients treated with COMB and one of 27 patients treated with CTX achieved a partial response. CTX was associated with a significantly better survival than COMB among patients who were ambulatory at onset of therapy. Survival among non-ambulatory patients was similar with both regimens.


Carcinoembryonic antigen, alpha-fetoprotein and carcinoplacental alkaline phosphatase in gastric carcinoma metastatic to the liver. Carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and carcinoplacental alkaline phosphatase (CPALP) were detected simultaneously in the sera and body fluids of two male patients with gastric carcinoma matestatic to the liver. At autopsy, widely disseminated gastric cancer of Borrmann III type with liver metastases was revealed in both bases. Histologically, they were moderately differentiated tubular and papillary adenocarcinomas with marked cellular atypia and necrosis. In Case 1, the properties of CPALP were identical to Nagao type CPALP, and in Case 2 the Variant type CPALP. Using immunofluorescence, CEA and CPALP were demonstrated in both primary and metastatic cells. However, only in Case 2 was AFP observed in some of the primary tumor cells.


[7-alpha-Hydroxylation of 5 alpha-androstane-3 beta, 17 beta-diol in human normal and hyperplastic prostates]. Incubation of 4-14C-5 alpha-androstane-3 beta, 17 beta-diol with human normal and hyperplastic prostate minces led to the NADPH-dependent production of a major polar radiometabolite which was identified as 5 alpha-androstane-3 beta, 7 alpha, 17 beta-triol and proved the presence of a 3 beta-hydroxysteroid-7 alpha-hydroxylase in prostate. Such evidences may bring new leads for the study of the mechanisms of androgenic steroid action in the prostate gland.


[Close genetic relation between determinants coding for the HLA-D region, detected by the technique of mixed primary and secondary lymphocyte culture and by serology of B lymphocytes]. In this study we report that: 1. Li determinants serologically detectable or closely linked structures are more associated to secondary responses than HLA-D specificities defined by HTC testing; 2. Other determinants from loci, MHC linked, or cross reactivity between Li determinants must be postulated to explain discrepancies between secondary responses and B serology; 3. Li determinants have an effect on the intensity of the reaction in primary allogenic proliferation.


[Purification of solubilized fucosyltransferase from lamb brain using ethylagarose gel]. The glycoprotein: fucosyl-transferase of the cerebral hemispheres, assayed with desialylated fetuin as exogenous acceptor, was the most active of the protein: glycosyltransferases tested in the brain. The addition of Titron X-100 to the membrane suspension, followed by high speed centrifugation, led to a solubilization of the enzyme. The use of hydrophobic chromatography on ethylagarose gave a good purification of this solubilized fucosyl-transferase, whose homogeneity has been shown by Ultrogel AcA 22, DEAE-cellulose chromatography and disc electrophoresis.


[7 alpha-Hydroxylation of 5 alpha-androstane-3 beta, 17 beta-diol in normal and hyperplastic human prostate]. Incubation of 4-14C-5 alpha-androstane-3 beta, 17 beta-diol with human normal and hyperplastic prostate minces led to the NADPH-dependent production of a major polar radiometabolite which was identified as 5 alpha-androstane-3 beta, 7 alpha, 17 beta-triol and proved the presence of a 3 beta-hydroxysteroid-7 alpha-hydroxylase in prostate. Such evidences may bring new leads for the study of the mechanisms of androgenic steroid action in the prostate gland.


[Placental origin of the progesterone binding protein in the pregnant guinea pig; immunohistoligical study]. The origin of the high affinity progesterone binding protein (PBP) occurring during pregnancy in the guinea pig serum has been investigated. An indirect immunofluorescence technique has been developed using a specific antiserum raised in rabbits. An accumulation of PBP-like immunofluorescent material was detected in the trophoblastic syncytium of the placenta tissue, whereas all other examined pregnant guinea pig organs gave negative reactions. It is concluded that this placental accumulation of immunoreactive PBP-like material may express a placental biosynthesis of this glycoprotein.


Contractile state of the left ventricle in man as evaluated from end-systolic pressure-volume relations. End-systolic pressure (PES), volume (VES), wall tension (TES) and circumference (CES) of the human left ventricle were studied at cardiac catheterization in 24 subjects with varying degrees of left ventricular dysfunction. Acute alterations in systolic load consistently resulted in changes in VES and CES, with a smaller volume and circumference characterizing the lower systolic load in each subject. End systolic pressure-volume lines were constructed by plotting PES against VES at the higher and lower systolic load in each subject. The slope of the resultant lines was considerably steeper for normal than for poorly contractile left ventricles. Vo, the volume axis intercept of the line (i.e., the theoretical VES at PES = O) was significantly smaller for normal than for poorly contractile ventricles. Similar findings were noted for Co, the theoretic end-systolic circumference at zero end-systolic ventricular wall tension. Post-extrasystolic potentiation resulted in decreased VES and CES with no change in PES and only a slight fall in TES. In conclusion, end-systolic pressure-volume and tension-circumference relations reflect the contractile state of left ventricular myocardium. Quantitation of these relationships may provide a useful new approach to the assessment of myocardial function in man.


beta2 microglobulinuria in a patient with nephrotoxicity secondary to mercuric chloride ingestion. A case of mercuric chloride intoxication is reported in which protein excretion was measured. Urinary albumin and low molecular weight proteins, including beta2 microglobulin, were greatly elevated following ingestion, reaching maximal values on the second day. The increased excretion of both albumin and beta2 microglobulin indicated the presence of both tubular and glomerular lesions. Data obtained on this patient suggest that the determination of beta2 microglobulin may be useful guide for the evaluation of renal tubular function.


Effectiveness of methods of teaching dental health to 9- to 10-year-old schoolchildren in the United Kingdom. Dental health education employing five different teaching methods was given to classes of 9- to 10-year-old schoolchildren. A control class received no teaching. The dental health knowledge of the classes was assessed before teaching, and immediately, 1 week and 3 months after teaching by the use of a questionnaire. All methods resulted in a variable increase in marks immediately after teaching. This was followed by a fall in marks for each class over the 3-month period. The poster and pack methods of presenting information, overall, had little or no effect on the recall of information. The talk, visual aids and project methods all significantly increased dental health knowledge for the 3-month period.


A long-term assessment of flurbiprofen.

A long-term assessment of flurbiprofen. A multi-centre open study of flurbiprofen was started in 1971 to provide regular clinical and laboratory data on patients with a variety of arthritic conditions. To date, 1220 patients have received the drug in a dosage varying from 75 mg to 400 mg daily. Flurbiprofen has been shown to be effective in relieving symptoms in the degenerative and inflammatory arthritides and side-effects have not proved a problem. Patients aged 65 years and over appear to tolerate the drug as well as their younger counterparts, an important finding in a group of patients notoriously intolerant of many drugs.


Treatment of ankylosing spondylitis with flurbiprofen and indomethacin. In a parallel, double-blind and randomized trial of 6-weeks' duration, flurbiprofen (150 mg to 200 mg daily) was compared with indomethacin (75 mg to 100 mg daily) in the management of 26 patients with active ankylosing spondylitis. None of the patients in either group withdrew from the study because of lack of efficacy of the drugs. Both drugs were equally effective in the relief of pain and tenderness of the affected joints. Overall subjective improvement, assessed by the patient and the investigator at the end of the trial, was present in 90% of the patients in the flurbiprofen group and in 75% of those in the indomethacin group. The mean values of all the spinal motion tests improved in the flurbiprofen group but not in the indomethacin group. Statistically significant improvement in the Schober test was achieved in the flurbiprofen group and in chest expansion in the indomethacin group. Characteristic untoward effects related to the central nervous system and gastro-intestinal tract were present in a few patients in both groups.


Efficacy and tolerance of flurbiprofen in the elderly using liquid and tablet formulations. An open study was carried out in 40 elderly patients suffering from osteoarthrosis of the hip to assess the effectiveness of 200 mg flurbiprofen daily, fiven either in tablet or liquid suspension form, over a period of 4 weeks. Statistical evaluation of the results in the 19 patients admitted to analysis showed that flurbiprofen produced significant improvement in daytime and overnight pain, and did not impair their mental status, as assessed on a modified Goldfarb scale. No significant differences were found between the response of the two groups, except for severity of night pain. Fourteen of the 19 patients included in the analysis reported side-effects, as did 18 of the 21 patients who were excluded. Only 7 patients (4 on tablets, 3 on liquid), however, were withdrawn from the trial for this reason.


Comparative study of the effectiveness of flurbiprofen given twice or 3-times daily. A double-blind trial was carried out in 15 patients with ankylosing spondylitis and 15 with coxarthrosis to assess the effectiveness of 300 mg flurbiprofen daily, administered in divided doses either twice or 3-times a day. Patients were allocated at random to receive treatment for 7 days either with a morning and evening dose of 150 mg flurbiprofen plus a mid-day dose of placebo, or with 3 doses of 100 mg flurbiprofen. They were then crossed over to the alternative regimen for a further 7 days. The results, evaluated by a 5-point rating scale of pain severity and of functional activity and by overall patient and doctor assessments, showed that flurbiprofen was effective in 66% of the 26 patients completing the trial. Tolerance was also assessed as being satisfactory in 83% of all patients. Comparison of the two treatment periods showed that 2 daily doses of flurbiprofen produced as good results as the 3-times daily regimen.


Flurbiprofen-aspirin interaction: a double-blind crossover study. Fifteen patients with seropositive rheumatoid arthritis were treated for 2-weeks periods with 150 mg flurbiprofen daily and with flubriprofen in the same dosage plus 3 g aspirin daily, the treatments being administered in random allocation. The results showed that there were no significant differences clinically between the two treatments. Serum levels of flurbiprofen were measured during both treatment periods in 4 patients. During the flurbiprofen and aspirin period there was a full in the serum levels of flurbiprofen was unchanged. No obvious reduction in clinical efficacy was apparent.


A comparative study of flurbiprofen and indomethacin in rheumatoid arthritis. A double-blind crossover trial of 200 mg flurbiprofen daily and 100 mg indomethacin daily, each given for 2 weeks separated by a 1-week placebo washout period, was carried out in 30 patients with rheumatoid arthritis. The results were analyzed for the 26 patients with complete records. No statistically significant differences were found between the two treatments with regard to subjective impression of pain severity, duration of morning stiffness, grip strength, joint size, haemoglobin and erythrocyte sedimentation rate. When the results for each treatment period were compared to baseline and both drugs considered individually, there was a statistically significant improvement from baseline. During the flurbiprofen treatment period the erythrocyte sedimentation rate showed a statistically significant fall, but not with indomethacin. During the placebo washout period between the active therapies, there was a statistically significant worsening in all parameters apart from the level of haemoglobin and erythrocyte sedimentation rate. These assessments showed little change. Five patients reported side-effects with indomethacin, and 1 with flurbiprofen. No side-effects were reported during the placebo period and although 4 patients were withdrawn, none was withdrawn because of side-effects. Patient preference was for flurbiprofen.


Flurbiprofen at night.

Flurbiprofen at night. Three double-blind crossover trials were used to study the effects of single doses of flurbiprofen at night on pain at night, duration of morning stiffness and sleep disturbance in patients with active rheumatoid arthritis. Flurbiprofen (150 mg) was shown to be superior to placebo and 150 mg was no more effective than 100 mg. Serum levels of the drug were significantly higher with 150 mg but did not correlate with clinical effects.


Lupus erythematosus cells in pleural effusion: the initial manifestation of procainamide-induced lupus erythematosus. A 63-year-old man developed an asymptomatic pleural effusion following the administration of 500 gm of procainamide hydrochloride over a six-month period. The diagnosis was initially suggested by the finding of lupus erythematosus cells in the pleural fluid. Lupus erythematosus cells and antinuclear antibodies appeared in the blood two months later and remained for a period of six months. The diagnosis was corroborated by the presence of antibodies to denatured DNA, but not to native DNA.


Isolabelling is a radiation-induced phenomenon. Human lymphocytes were incubated during two mitotic cycles in the presence of 5-bromodeoxyuridine and differentiation between chromatids was obtained with combined "Hoechst 33258" and azur-eosine staining. Analysis of non-irradiated cells revealed numerous sister chromatid exchanges (SCE) and no abnormalities of "harlequine" appearance of chromosomes. When, however, the cells were irradiated, an identical staining (IS, isostaining) of some chromosomes or chromosome segments were observed. Production of IS was accompanied by decrease of the frequency of SCE, the total frequency of SCE+IS remained, however, the same as in control. An antagonism between SCE and IS was established: the frequency of SCE decreased in the cells with multiple IS, and chromosomes with both SCE and IS were only rarely observed. Thus, IS is neither an artifact nor a physiologic event but a phenomenon induced by radiation. The reliable existence of IS is considered as an evidence for binemic structure of chromatid. It is suggested that some mechanism of lateral spread of genetic information is involved in the production of SCE. If delayed by radiation, the spread could be restricted only to a fraction of chromosome cross-section resulting in IS.


The interaction of Hoechst 33258 and BrdU substituted DNA in the formation of sister chromatid exchanges. Sister chromatid exchanges (SCEs) are induced in cultured Chinese hamster cells by treatment with 5-bromodeoxyuridine (BrdU) or with Hoechst 33258 (H33258) plus BrdU. The SCE frequencies depend upon the number of H33258 molecules available per cell (or per base pair) and the number of brdU molecules available per cell, and not solely upon molarity. In addition, H33258 and BrdU act synergistically to induce SCEs. At low BrdU concentrations H 33258 induces very few SCEs. At high BrdU concentrations and similar concentrations of H33258, however, SCE frequencies are significantly increased. SCE frequencies decrease with time in successively harvested cells because of the depletion of H33258 from the medium due to DNA binding.


[CSF cytology using prestained slides (author's transl)]. A new and rapid vital-stain method for the diagnosis of CSF cells demonstrates not only red blood cells but also white blood cell types, predominantly by differentiating nuclear patterns. 20 microliter untreated CSF are put on the prestained slides and a cover slip put over it. Differentiation can be made after 15 minutes. The lower limit is at 3-4 WBC/ml of CSF. At room temperature the preparation keeps for about an hour. The method is reproducible and has the advantage also over other routine methods that the CSF volume is very small and there is neither loss of cells nor cell denaturation.


[Refsum's syndrome (author's transl)].

[Refsum's syndrome (author's transl)]. Heredopathia atactica polyneuritiformis (Refsum's syndrome) is an autosomal recessively inherited lipidosis characterized by the following signs: peripheral hypertrophic polyneuropathy, cerebellar ataxia, atypical retinitis pigmentosa with night blindness and concentric limitation of the visual fields, anosmia, inner ear hearing disturbances, skeletal anomalies, ichthyotic skin changes, raised protein in the CSF without a cellular increase, and non-specific ECG changes. Biochemically it is a lipidosis with atypical increase of phytanic acid in blood, CSF, and tissues. The metabolic defect results from a degradation disturbance of exogenous phytanic acid. The report of a patient whose clinical picture plus chemical, neurophysiological and histological results led to the diagnosis of Refsum's syndrome is presented. Using a low phytol- and phytanic-acid diet a marked decrease of phytanic acid in the serum and an improvement of the clinico-neurological signs were observed.


[Staining of the surface layer in jaw tumors]. In the histological preparation for surface layer staining, saw cuts 100-300 micrometer thick of undecalcified bone or tooth are made with or without alloplastic implantation material. Only one side of the cut is stained for 4 hours. During this time the stain penetrates about 15 micrometer into the preparation. Deeper-lying cells and structures remain unstained and appear merely as shadows that are not troublesome. The time-consuming process of making thin sections is dispensed with and variously stained serial sections are possible.


Inflammatory cell count and identification in specific duodenitis. (Celiac disease, Whipple's disease and Crohn's disease). Comparison with jejunal findings. The authors studied the count and identification of inflammatory cells in duodenal biopsies of specific duodenitis. In celiac disease there is an increase of lymphocytes in the epithelial layer, and rich population of plasmacells in the lamina propria of duodenal mucosa. In Whipple's disease the reticulum cell component of lamina propria is increased, while total inflammatory cells are within normal limits, and both lymphocytes and plasmacells are decreased. The comparison between duodenal and jejunal findings shows similar data in celiac and Whipple's disease. In Crohn's disease the inflammatory cell count differs from controls only in presence of radiological or endoscopical features of duodenal involvement.


Demonstration of two alpha-globin genes per human haploid genome for normals and Hb J Mexico. Complementary DNA (cDNA) was prepared with viral RNA-dependent DNA polymerase using human globin messenger RNA (mRNA) as template. By selective hydridization to globin mRNA from beta-thalassaemics a probe which was greater than 85% complementary to alpha-globin mRNA was purified. This was hybridized in cDNA excess to human genomic DNA, and the rate and extent of hybridization confirmed that there are two genes for alpha-globin per haploid genome. Cellular DNA was also prepared from peripheral blood from cases expressing the alpha-globin chain mutant Hb J Mexico to varying extents. This DNA was identical in hybridization behaviour to normal DNA demonstrating that the imbalanced mutant chain synthesis seen physiologically is not due to a gene deletion.


Reverse transcription of thyroglobulin 33-S mRNA. Bovine thyroglobulin 33-S mRNA has been used as a template for the synthesis of a complementary DNA, using RNA-directed DNA polymerase from the avian myeloblastosis virus. The yield of the reaction was relatively poor and the size of the cDNA did not exceed 10 S. Nevertheless, a copy of high specific radioactivity (approximately 10(7) counts. min-1 microgram-1) could be obtained which hybridized specifically back to its template with an rot1/2 value about 5 times higher than that observed in hybridizations between hemoglobin mRNA (alpha + beta chain) and hemoglobin cDNA. This suggests that thyroglobulin mRNA does not contain extensive internal repetitive sequences. Quantification of thyroglobulin mRNA sequences among various RNA preparations from the beef thyroid was performed using cDNA/RNA hybridizations in RNA excess. The results confirmed that thyroglobulin mRNA represents the large majority of mRNA in membrane-bound polysomes and indicated the virtual absence of thyroglobulin sequences on free polyosomes. The cDNA transcribed from mRNA of bovine origin hybridized efficiently with thyroid RNA from goats, dogs and humans. Although the heterologuous hybrids exhibited the expected decrease in thermal stability, the bovine cDNA provides an appropriate probe for studies dealing with the expression of the thyroglobulin gene in various mammals including man.


False positive bone scan in bone tumors of the lower limb. When examined using bone scanning agents, eight out of nine patients with lower limb malignancy, and neither of two affected in the upper limb showed a pathologic focus of isotope uptake in an area distal to the tumor. On pathologic examination the positive findings proved false. Such misleading results were found to be avoidable if a tumor-seeking agent instead of a bone scanning one is used.


Electrophoretic mobility (EM)-test for childhood cancer diagnosis. Lymphocyte sensitization to myelin basic protein (encephalitogenic factor, EF) was determined in 193 children by measuring the electrophoretic mobility of indicator particles which had been incubated with the supernatant of the lymphocyte-antigen (EF) mixture. A significant decrease in electrophoretic migration time was found in 77 of 85 children with malignant tumours localized in brain, abdomen and extremities, in 36 of 38 children with acute lymphoblastic leukaemia (all except one in hematological remission), and in all 17 patients with lymphoma, in contrast to only 1 of 10 healthy children and 14 of 48 patients with non-malignant disorders. 10 of these 14 "false positive" patients, however, had auto-immune diseases. Thus, with false negative and false positive rates of less than 10%, this test could be of diagnostic help in patients with suspected malignant or auto-immune disease. Two examples of preoperative application of the EM-test are demonstrated.


The course of multiple sclerosis cases with extremely high gamma-globulin values in the cerebrospinal fluid. 40 selected cases of multiple sclerosis (MS) with extremely high gamma-globulin values in the cerebrospinal fluid (CSF) (over 25 rel%, upper normal limit 7.5 rel%) were matched with the same number of MS patients with normal CSF findings. Surprisingly, no definite relationship could be shown between the amount of CSF gamma-globulins and the various clinical criteria in MS, such as age, type of progression, duration of illness, remission, extent of plaques and gravity of the disease.


A clinical and urodynamic study of tadenan in the treatment of benign prostatic hypertrophy. 20 patients with benign prostatic hypertrophy were admitted to a double-blind noncrossover study for evaluation of the effect of Tadenan. Using either standard clinical criteria or urodynamic data obtained by the urinary drop spectrometer, no significant effect was found for the dosage and period of administration used.


Early demonstration of experimental aludrin-induced myocardial damage by the stain according to Lie et al. (HBFP). Catecholamine-induced alterations of the myocardium were studied in 48 rats following a single subcutaneous injection of 40 mg Aludrin/kg body weight after different intervals following the injection by means of the HBFP stain described by LIE et al. (1971). As early as 5 minutes following application of Aludrin extensive areas with ischemic fuchsinorrhagic cells could be demonstrated. Six hours post injection a decrease in the extent of the alterations could be observed. Five weeks following the injection only small feathery strands of scar tissue could be found in the experimental animals as sequela of the effect of Aludrin. The stain according to LIE et al. (1971) employed by us allows earliest demonstration of (catecholamine-induced) ischemic alterations in the myocardium.


An improved HRP method for the study of central nervous connections. The HRP tract-tracing method has been modified by the introduction of cryoprotective agents, thereby allowing the enzymatic reaction to take place at sub-zero temperatures. By using cold temperatures the enzymatic reaction can be better controlled, which in turn makes it possible to "push" the method to its maximum without obtaining excessive crystallization. The addition of antifreeze agents, however, changes the acid-base phenomena, which in turn have to be adjusted by the use of appropriate buffers. The overall result is a considerable increase in efficiency as compared with the commonly used HRP procedure.


The influence of immunization on some functions of polymorphonuclear leucocytes in vitro. Polymorphonuclear leucocytes (PMNL) obtained from immunized guinea pigs possess an affinity to antigen. The guinea pigs were immunized with human serum albumin (HSA) in complete Freund's adjuvant. The ability of PMNL to bind antigen was tested by means of the functional disorders induced by antigen after incubation with PMNL. The "immune" PMNL appeared to be more responsive to antigen when compared to PMNL obtained from non-immunized animals. The antigen decreases oxygen consumption, the phagocytosis coefficient and 14C-glycine incorporation in the "immune" PMNLs in vitro and also induces leakage of some lysosomal hydrolases from PMNL in the course of an 18 hrs incubation period.


[Immune mechanism of regulating the balance of chemical compounds of endogenous origin]. Specific autoantibodies of neutralizing character to histamine, serotonin, kallikrein, bradykuinine, acetylcholine, adrenalin, noradrenalin, insulin, and to the serotonin metabolite--5-hydroxyindolacetic acid, were found in donor serum (47.2%) and in intact rabbits, guinea pigs, rats, and mice (24.4%). Anti0odies to histamine, serotonin, kallikrein were found in a number of samples of commercial gamma-globulin. They were relatively often observed during the morning and day-time hours, in summer and in winter, in luteal phase of menstrual cycle, early in pregnancy (6-8 weeks), after surgical treatment, burns, inflammation, administration of foreign albumin, in the course of immunization by different antigens. The results of fractional analysis of serum showed that antibodies belonged to immunoglobulins with the constant of sedimantation 7S and 19S. The data obtained suggest the existence of an immune mechanism for the content regulation of different substances of endogenous origination in any organism.


[Adrenergic receptors in coronary arteries (author's transl)]. The relations between adrenergic nerve fibers and related receptors in the wall of the coronary arteries have been studied in man. On sections of these vessels morphological observations (H.E.) were carried out: histochemical staining of adrenergic mediators (Eranko reaction for norepinephrine, and Hillarp reaction for cathecolamines), and of beta-receptors by means of a beta-blocking fluorescent drug (pindolol-Visken LB 46). Our observations provide evidence of the presence of beta-receptors in the wall of the coronary arteries, but they are particularly concentrated in the periadventitial connective tissue, in the adventitia and in the intima-media transitional zone. Beta-adrenergic receptors are above all present in the most richly innervated part of the vascular wall, and are therefore in close rapport with adrenergic nerve fibers.


Production of alpha-fetoprotein by cultured rat ascites hepatoma cells determined in vivo as alpha-fetoprotein-negative. Three ascites hepatoma cells of the rat, AH-41B, AH-34, and AH-64B, which had been determined in vivo as alpha-fetoprotein-negative, were cultivated in vitro in a medium containing adenosine 3',5'-cyclic monophosphate (cyclic AMP), cyclic dibutyryl-AMP, or theophylline. The concentration of alpha-fetoprotein in culture media was measured by the 125 I-radioimmunoassay. Results demonstrated that the AH-41B cells produced alpha-fetoprotein in vitor, the concentration of which being elevated in the media with three substances, while the remaining AH-34 and AH-64B cells did not. A comment was made on the producibility of alpha-fetoprotein in the so-called alpha-fetoprotein-negative hepatoma cells.