[Technic of transvesical suprapubic adenomectomy for the control of hemorrhage and urinary infection]. The advantages of our method: 1. By omission of the urethral catheter the infection is nearly completely avoided. 2. It guarantees a good haemostasis. 3. It reduces the intraoperative and later complications of adenectomy (infection and anaemia). 4. It facilitates the postoperative treatment. 5. One avoids urethritis and strictures caused by the urethral catheter. 6. It shortens the postoperative period of rest. 7. One economises medicaments (antibiotically, antianaemically). 8. The possible break of the catgut thread at its removal is of no danger, as it is resorbed.


[Complications and risks of abdominal diseases in old surgical patients (author's transl)]. 732 patients older than 70 years suffering from abdominal diseases were studied regarding postoperative complications and mortality. The rate of complications in connection with surgical procedures corresponds to that of younger patients. But complication depending on organs and organ systems impaired by age and pre-existing diseases were found in higher percentage.


[Legal abortion during the first trimester of pregnancy at the University Hospital for Women in Novi Sad (1960-1975)]. The authors present the results of their own observations and investigations of legal abortions until the 12th week in the University Department of Gynaecologigy and Obstetrics of Novi Sad for the period 1960 to 1975. The analysis discusses success, failures and complications in 83,121 legal and 23,321 cases of other abortions registered in the Department in the mentioned period. In particular, injuries of the uterus at these interventions, haemorrhage after and during abortion and distinctly low mortality at legal abortions--1 case or 0.0012% are discussed.


[Mucoepidermoid carcinoma of the cervix uteri]. Among 147 re-examined carcinomas of the uterine cervix from the years 1970 till 1975 eight mucoepidermoid carcinomas were found and described. Furthermore we report on one case of a mucoepidermoid carcinoma in situ. The mucous substances are dyed with PAS and the Alcianblue-PAS reaction. A detailed definition of "minimal mucous appearance" is worked out in order to classify a carcinoma as a mucoepidermoid carcinoma. An increase in the mucous producing tendency of squamous cell carcinomas as well as in the number of mucoepidermoid carcinomas during the last two years is stressed.


The arrangement of lipopolysaccharides on the outer membrane of Yersinia enterocolitica: an electron microscopic study. One the cell surface of smooth of Yersinia enterocolitica 75 (Ye 75 S), and electron-lucent layer was identified in thin sections after incubation with Ye 75 S-antiserum. It is adjacent to the "double track" of the outer membrane. This layer does not appear on the analogously treated rough mutant (Ye 75 R), whose lipopolysaccharide (LPS) does not contain O-specific polysaccharides. It could be shown that this layer is formed by the O-specific side chains of LPS, which are unstained by routine methods. As the side chains of LPS obviosly make it difficult to visualize the LPS-strands in the outer membrane of rough strands was investigated. On Ye 75 R, the LPS-strands could be demonstrated only after treatment of cells with polymyxin B. After short time of exposure, the LPS appeared as contigous strand-like structures (diameter roughly 60 A) on the cell surface of cells which were negatively stained or dried by the critical-point-method. After prolonging polymyxin B treatment, "blebs" or "protrusions" appeared on the surface of Ye 75 cells, which were in negatively stained preparations and in thin sections identified as partly loosened LPS. The demonstration of LPS-strands in untreated cells was possible only on a "deep rough" mutant (Ye 161-45 a R), whose LPS contains only glucosamine and KDO besides lipid A. It is suggested that the LPS form a layer of contiguous strands (mid-to-distance 62 +/- 3 A) on the surface of negatively stained cells. According to this view, on the Ye 75 S, the O-specific side chains extend from this layer into the medium.


[Study of genetic control of synthesis of type III and 6th group-specific antigens of Flexner shigellae]. As revealed in experiments of interspecific and intraspecific crosses, the determinant responsible for the group-specific 6, as well as controling the synthesis of type III antigens of Sh. flexneri were localized near the lac-pro markers on the chromosome. In intraspecies crosses of bacteria of y variant with the donor Sh. flexneri 3c strain the percentage of linking of lac+a6+ was 32, and of lac+aIII+ --24. Genetic confirmation of the dependence of the function of the a6 (defined as att6) determinant on the presence of an antigenic complex 3,4 and of the association of the serological detection of the antigen III on the gene a6 was presented. On the basis of the data of Gemski et al it can be supposed that the determinant of the a6 served as the site of attachment of a specific converting phage.


[Natriuretic component of the osmoregulating reflex during postnatal dog ontogenesis]. In experiments on puppies ageing from 3 days up to 8 months, as well as on adult dogs, studies have been made of mechanisms of excretion of water and sodium during the increase of osmotic concentration in the blood circulation of the liver and spleen. It was found that in contrast to adult dogs, in which the osmotic shift decreases diuresis and increases sodium excretion, the decrease of diuresis in 1-month puppies is accompanied by a decrease of sodium excretion. Two-component osmoregulatory reaction is developed only to the 2nd month of life. Pituitrin P, injected intravenously, evoked the same reactions which were observed in osmoregulatory reflexes at various stages of ontogenesis. Studies on papillary-cortical osmotic and sodium gradients implies that kidney reactions to osmotic shifts are realized via neurohypophysial hormones; maturation of mechanisms realizing the osmotic papillary-cortical gradient takes place previously to those which realize sodium concentration gradient.


Sporadic non-toxic goitre. A long-term follow-up of 36 patients. Thirty-six patients with non-toxic goitre were reviewed after a mean period of 13 years. Initially 19 patients were iodine deficient (Group I) and 17 had normal plasma inorganic iodine (Group II). In general the iodine deficient patients had larger goitres, developed more complications (26% became hyperthyroid, hypothyroid or required partial thyroidectomy), and required more treatment. There were marked changes in thyroid function tests. In both groups thyroid uptake fell and PII rose though the final PII remained significantly lower in Group I patients. Thyroid and renal iodide clearance fell significantly in Group I patients only. In both groups the final mean total serum T3 levels were abnormally elevated whereas the mean PBI levels did not change significantly during the period of study and the final mean total T4 concentrations were noraml. All goitres became smaller and there were no complications in patients whose goitre became impalpable. No cases of malignancy and no postoperative recurrences of goitre were observed. It is suggested that the incidence of complications in those patients who persist with palpable goitres is sufficent to merit follow-up of this group.


Modified method of C banding using barium hydroxide. A modified centromeric heterochromatin banding technique using barium hydroxide octahydrate is described. The relationship between slide maturity and time of denaturation by barium-hydroxide is discussed.


Ultrastructural, optical and volume changes in brain mitochondria during gramicidin-induced ion uptake. Gramicidin-induced swelling of rat brain mitochondria was followed spectrophotometrically with a parallel analysis of changes in the ultrastructure, volume and eccentricity ratio of the mitochondria. Under the effect of gramicidin the expansion of the inner compartment occurs with an overall increase in volume. Mitochondria tend to be rounded although not entirely spherical in shape. The reversal of swelling with respiratory inhibitor (KCN, rotenone) results in a shrinkage of the inner compartment and is not accompanied by a proportional reduction of the outer compartment. Mitochondria fail to regain their original shape. It can be concluded that in the course of energy-dependent swelling the ability to contract might be retained, whereas other factors controlling the shape of the mitochondrion are irreversibly affected.


General health screening of four-year-olds in a Swedish country. V. A strategy for improving the effectiveness and the cost efficiency of the psychological screening program. Data presented in a previous paper pointed to the necessity for improving the overall sensitivity of the psychological screening program. The present report indicates possibilities for such an improvement without changing the screening methods. A comparison of the primary data of the true positives, the false positives and all the negatives (non-referred) revealed the necessity of more stringent referral criteria. It is predicted that the systematic application these criteria would result in an increase in the rate of true positives form 2.8 to 4.8% of the screened population. In addition a strategy aiming at a reduction of the costs without deteriorating the effectiveness and based on a differential application of the various elements of the screening program is presented.


Recent observations on the structure and composition of elastin. The ultrastructural organization of elastin has been studied by scanning and transmission electron microscopy of negatively stained specimens coupled with optical diffraction analyses. Purified elastin results from a composite assembly of interwoven branched and twisted thread-like entities of decreasing diameter. The ultimate filamentous component is a rope-like structure each with an overall diameter of 3.5-4.0 nm consisting of paired filaments of indefinite length each 1.5 nm in width and periodically linked longitudinally at a varying distance of 3.5 to 4.5 nm depending on the degree of stretch.


Elastase-like enzymes in aortas and human breast carcinomas: quantitative variations with age and pathology. Two neutral proteases have been isolated from aortas and human breast tumors. The aortic elastase-like enzyme has been further purified. The details of this purification procedure will be given and some of the properties of the purified enzyme (susceptibility to various kinds of substrates, degree of inhibition of serum inhibitors, alpha 1-antitrypsin and alpha 2-macroglobulin). This elastinolytic activity of the aorta increased with age and with the degree of atherosclerosis. Both parameters seem to act independently and in a cumulative fashion. Elastinolytic activity has been demonstrated in extracts of human breast carcinomas and is exponentially related to the age of the patient. There exists a parallel neosynthesis of elastin which increased also with the age of the patient. Some characteristics of the polymeric elastin isolated from the tumor tissue will be given. The possible role of this neutral protease present in human aortas and human breast carcinomas will be discussed.


The elastic system fibers.

The elastic system fibers. Using the tannic acid-glutaraldehyde fixation it was possible to clearly visualize, with reproducible results, the elastic fiber amorphous material because of its density. The microfibrillar component was also evidenced with a good performance. With this technique the ultrastructural patterns of the oxytalan and elaunin fibers were also demonstrated. The oxytalan fibers appeared as a bundle of microfibrils similar to elastic microfibrils without amorphous material. The elaunin fibers presented a dispersed amorphous material intermingled among the microfibrils. It was suggested by ultrastructural evidences that oxytalan and elaunin fibers may represent interruption in successive phases in the development of the elastic fibers.


The existence of inhibited lysyl oxidase and the presence of multiple forms. Considerable difficulty in puriying tissue lysyl oxidase has been previously encountered and the cause of this difficulty has now been ascertained. For these studies, we have used blood plasma lysyl oxidase as a model system. Blood plasma has been shown to contain considerable lysyl oxidase activity. The enzyme exists in a partially or completely inhibited state. Homogeneous preparations of the enzyme from the blood have been obtained by two different methods. Method A yields one form of lysyl oxidase while Method B yields three forms of the enzyme. The methods for the purification of the enzyme and some properties of the enzyme and preliminary data on the lysyl oxidase inhibitor will be discussed.


[Diagnosis and habilitation of hard of hearing-children in the region of Magdeburg/GDR (author's transl)]. Need of an early diagnosis and an early habilitation of hard of hearing-children is stressed. The authors are working with pupils from the school for deaf children of Halberstadt and from the school for hard of hearing-children of Magdeburg. Genetic counseling has to be integrated in the complex program of habilitation.


Selection of La Crosse virus variants by sentinel squirrels (Sciuris carolinensis) and chipmunks (Tamius striatus). Comparisons of La Crosse (LAC) virus strains, obtained from sentinel squirrels and chipmunks, were made using three viral markers: plaque size on Vero cells, virulence in 8 days old laboratory mice, and antigenic characteristics as measured by the plaque reduction neutralization test. All strains were in their first suckling mouse brain passage. The mean plaque size of viruses isolated from squirrels was slightly larger than the mean plaque size of viruses isolated from chipmunks. There were no differences in virulence and antigenic characteristics of LAC strains isolated from chipmunks compared to those from squirrels. However, significant differences in these characteristics between individual virus strains did occur, irrespective of the vertebrate species from which the strain was isolated. First suckling mouse brain passage of viremic blood apparently selected for a smaller mean plaque size than was present in the blood. These results indicate that the squirrel and chipmunk were not rapidly selecting for greatly divergent subpopulations of the three measured markers in nature. There were some indications, however, that even one suckling mouse brain passage of field LAC virus apparently decreased mean plaque size.


Ascending aorta-pulmonary artery anastomosis for cyanotic congenital heart disease. The course and prognosis of 208 patients with an ascending aorta to pulmonary artery anastomosis is reviewed. Mortality rate during, or within one month, of surgery was 24 per cent (50/208) and late mortality rate, prior to repair, was 10 per cent (21/208). An additional 5 per cent (10/208) died during subsequent intracardiac repair. Congestive heart failure developed in 25 per cent (53/208), pulmonary artery hypertension in 17 per cent (12/72), and pulmonary vascular obstruction in 6 per cent (4/72). An increase in orifice size of the stoma with time was documented in eight patients. Additional subsequent palliative surgery was required in 22 per cent (45/208). Mortality rate was directly related to age at operation and was highest in neonates less than one week of age. In infants with tetralogy of Fallot, a preliminary comparison of mortality rate between palliative surgery and primary repair clearly suggests that the latter is the preferred method of treatment.


Health effects of exposure to automobile exhaust--V. exposure of toll booth operators to automobile exhaust. The exposures of automobile toll booth collectors in the Boston area to selected air contaminants were monitored during the four seasons from 1972 to 1974. The highest carbon monoxide concentrations were found at the in-city toll booths and the highest lead levels at the surburban booths. Biological monitoring for carbon monoxide and lead exposure were closely related to airborne contaminant levels. The study supports the need for environmental control for toll booths located at busy highway and tunnels.


The effect of heterologous antisera on embryonic development. XIII. Lack of effect of antisera to alpha fetoprotein. This investigation was carried out to determine whether heterologous antisera to alpha fetoprotein (AFP) are embryotoxic to developing rat embryos. Homogeneous rat AFP was isolated and antisera directed against this glycoprotein were produced in rabbits, horse and goat. The effect of the antisera on embryonic development was examined by injecting the antisera intraperitoneally into pregnant rats on the ninth, eleventh and thirteenth days of gestation. The results demonstrated that there was no evidence of increased incidence of fetal abnormalities in 472 surviving fetuses of 42 injected rats. There was no evidence of increase embryonic death or retardation of intrauterine growth following administration of the antisera on the ninth, eleventh and thirteenth days of gestation. The localization of the injected antisera was examined by the indirect immunofluorescent method. The results showed that the heterologous AFP antibodies localized specifically in the visceral yolk sac placenta. No antibody localization was observed in the embryo proper or the chorioallantoic placenta. It is speculated that the localization of AFP antibodies in the visceral yolk sac does not interfere with the embryotrophic function of the visceral yolk sac placenta.


The surface characteristics of the plasma membrane of the exocrine pancreas. Regional differentiation of the plasma membrane and related structures of the exocrine pancreas has been studied ultrastructurally and cytochemically. Fixation with an osmium tetroxide-silver acetate solution produced abundant fine precipitates on the luminal and basal surface of the centroacinar but not the acinar cells. Staining with dialyzed iron (DI) revealed the heaviest concentration of anionic sites on the luminal plasma membrane of the acinar cells, including the surface of both the intercellular canaliculi and the main lumen. The reactive sites on the apical acinar plasmalemma appeared to consist of discrete globules. DI-reactivity of the lateral basal membranes was most prominent in the centroacinar cells and essentially absent in the acinar cells but was weak relative to that of the acinar-cell apical plasmalemma. The lamina lucida of the basement membrane of the duct stained with DI, but that of basement membrane under acinar cells did not. Sialidase digestion prior to DI staining abolished the staining of plasma membranes. These results indicate that duct epithelial cells, including most prominently the centroacinar cells, are chiefly responsible for electrolyte and fluid transport.


Chemical and immunological properties of a protein hydrolysate formula. Clinical observation suggested that a protein hydrolysate formula designed to serve as an oral elemental diet was capable of producing untoward reactions in some children with malabsorption syndromes caused by cow milk protein allergy. An immunological study of the antigenicity of this hydrolysate was undertaken. Although it is claimed that the hydrolysate is produced from casein, it was shown that it produced, after injection into animals, precipitating antibodies against at least three of the whey proteins. Analysis of the molecular weight of this hydrolysate showed it to contain a polypeptide fraction with molecular weight above 3,850.


Chloramphenicol binding to normal and kwashiorkor sera. The binding of chloramphenicol to normal and kwashiorkor sera was investigated in vitro. Chloramphenicol is predominantly albumin bound, although a significant degree of binding to the other major protein fractions occurs. From the clinical view point, a decreased degree of binding of kwashiorkor serum (+/-5%) is not of significance.


The changing incidence of association of hepatitis B with hepatocellular carcinoma in California. Two hundred seventy-nine patients who died of hepatocellular carcinoma were autopsied at Los Angeles County--USC Medical Center and the John Wesley--USC Liver Unit from 1949 through 1974, and tissues from 168 of these cases were available for staining for hepatitis B surface antigen (HBSAg). Twenty-one per cent of the livers had stainable HBSAg. There were prominent increases both in total numbers of hepatic cancers and in the percentages that were HBSAg-positive beginning about 1970, but the numbers of hepatocellular carcinomas arising in noncirrhotic livers also increased. From 1969 to 1974, 73% of those who had hepatocellular carcinomas arising to nonalcoholic but cirrhotic livers were HBSAg-positive. Racial differences in the incidences of cirrhosis, the incidences of hepatocellular carcinomas associated with HBSAg were found. The incidences of cirrhosis were: Caucasian 11%; Mexican 12.2%; Negro 5.7:; Oriental 10%. Hepatocellular carcinomas arose in 3.2% of Caucasians who had cirrhosis; 3.6% of Mexicans; 8.3% of Negroes; 47% or Orientals. Ten per cent of Caucasians who had hepatocellular carcinomas in cirrhotic livers were HBSAg-positive; 25% of Negroes; 12% of Mexicans; 47% of Orientals.


Stem cell (immunoblastic) lymphoma. A variant of B lymphocytic lymphoma. From a histologic review of cases coded as Hodgkin's disease and reticulum cell sarcoma, 12 cases were selected as examples of stem cell lymphoma in which the preponderant cell has characteristics of the B immunoblast. Clinically, these lesions affect the elderly (average age 57.3 years), disseminate early, and, with a few exceptions, progress rapidly to a fatal termination. Morphologically, the neoplastic stem cells, which have pyroninophilic cytoplasm, form diffuse infiltrates with an admixture of acidophilic cells. As a regional variation, the pattern in these lesions overlaps histologically with that seen in angioimmunoblastic lymphadenopathy. The overlap in patterns is presumptive evidence that the angioimmunoblastic pattern at times may be a precursory expression of the stem cell lymphoma. On the basis of morphologic features, these tumors are interpreted as a variant of B cell lymphomas.


Stainable iron in aspirated and needle-biopsy specimens of marrow: a source of error. Marrow iron was assessed in needle biopsy sections and in simultaneously obtained aspirated smears and aspirated clot sections from 251 patients. Significantly different amounts of stainable iron were observed in needle biopsy sections and aspirated smears in 15% of the specimens. The usual difference consisted of significantly less stainable iron in needle biopsy sections as compared to the aspirated smears (13%). Of clinical importance was the finding of absent stainable iron in 8% of the needle biopsy sections, in contrast to the definite deposits observed in the corresponding aspirated smear. Of similar interest was the observation that 6% of the needle biopsy sections had significantly less stainable iron than corresponding hemosiderotic smears. The amounts of stainable iron in needle biopsy sections were similar to the amounts observed in the corresponding aspirated clot sections. Evaluation of marrow iron using needle biopsy sections as well as aspirated clot sections differs from results observed in aspirated smears and could be a source of significant error in the assessment of iron stores.


Origin of ciliated alveolar epithelial cells in bleomycin-induced lung injury. Bleomycin is known to induce diffuse pulmonary fibrosis and epithelial metaplasia. The reaction of the alveolar epithelium following a single intravenous or multiple intraperitoneal injections of bleomycin to mice is now examined in a combined morphologic and cytodynamic study. Necrosis of Type 1 cells was observed, followed by proliferation of Type 2 cells, a common reparative process. The proliferated cells transformed to a variety of epithelial forms, including ciliated cells and cells with morphologic features intermediate between alveolar and bronchiolar epithelium. No evidence of cell injury or increased cell division was found in the bronchial epithelium. It is concluded that the metaplastic ciliated epithelial cells are produced by an abnormal reparative process in the alveolar epithelium. The results suggest that, whereas the "resting" Type 2 cell is not vulnerable to bleomycin, in the postmitotic phase the drug may modify the synthetic mechanisms of cellular differentiation and thereby induce metaplasia.


Histomorphological and histochemical study of mucosa of fallopian tube of ageing goat. The mucosa of infundibulum, ampulla and isthmus of fallopian tubes from 24 female goats aged from 2 months 24 days to 5 years 2 months and 18 days have been studied. The transition of mucosal folds, the lining epithelium and its cell types from Infundibulum towards uterine end, and changes in relation to the age and phases of estrous cycle have been reported. The most striking findings were: a) in goat the fallopian tube like that of sheep was lined chiefly by nonciliated type of cells in infundibulum, whereas the ciliated cells increased caudally, almost all being nonsecretory type in the isthmus; b) the presence of smooth muscle cells as identified with Gomori's one step trichrome stain was observed in the goat fallopian tube in case of mucosal folds specifically at the sites of branchings which anastomose with the adjacent ones; c) the PAS positive secretory material was found to be associated with glycogen acid mucopolysaccharides and mucoproteins as demonstrated by Best's carmine, Alcian blue-PAS and Bismark brown reactions, respectively.


Sulfide silver architectonics of rat, cat, and guinea pig spinal cord. A light microscopic study with Timm's method for demonstration of heavy metals. The distribution of heavy metals in the spinal cord of the cat, rat, and guinea pig has been studied histochemically with Timm's sulfide silver method. There was considerable variation in the degree of staining of the neuropil. The dorsal horn showed a laminar staining pattern corresponding to the cytoarchitectonic lamination. Lamina I in the cat and guinea pig was light. Lamina II in all three species was heavily stained. In the rat and guinea pig it could be subdivided in a ventral and a dorsal layer, and moreover in the rat a darkly staining borderzone abutting on lamina III was present. Lamina III, characterized by heterogeneous staining, also appeared dark, although less obvious in the guinea pig. In the ventral horn the coarser stained particles in lamina IX contrasted with the surrounding lamina. Cell staining varied between different cell groups, and within single cell populations. In the cat thoracic cord the cells in nucleus intermedio-lateralis (IL) and nucleus intercalatus (IC) stained very weakly. In Clarke's column and in the motoneuron area cells, uniform in Nissl preparations, could be seen different after Timm staining. The results are discussed in relation to other histochemical patterns, cytoarchitectonics, and terminal fields of afferents. Considerable correlation of the Timm pattern to these data was found.


The natural history of allergic disease in children. Optimal care of allergic children requires certain knowledge on the part of parents, primary physicians and allergists. One needs to be familiar with not only the mechanisms of allergic disease, the factors which may potentiate or "turn on" allergic symptoms in children of allergic families, but also the natural history of the commonest allergic syndromes in infancy and children. If a physician is thus prepared he can be of significant help in the prevention, amelioration and prognostication of the future course of allergic disease in children.


Renal tubular dysfunction in Minamata disease. Detection of renal tubular antigen and beta-2-microglobin in the urine. "Minamata disease" was found among the residents along Minamata bay contaminated with the effluent from an industrial plant using mercury. The patients were suffering from various neurologic disorders primarily due to organic mercury poisoning. Evidence is described of renal tubular dysfunction associated with this disease by the immunochemical demonstration or renal tubular epithelial antigen and beta-2-microglobulin in the urine. Nineteen patients with Minamata disease and 35 diseased and healthy control subjects were examined. The contents of urinary renal tubular epithelial antigen and beta-2-microglobulin, and the ratios of these proteins to albumin in individuals with Minamata disease were significantly different from the levels in healthy control subjects (P less than 0.05) were identical to those found in patients with tubular and the values, proteinuria. These results indicate that Minamata disease is associated with renal tubular dysfunction, and also suggest that these procedures would be useful for screening the nephrotoxicity in the environmental exposure of heavy metals.


Cell-mediated immunity to mouse tumors: some recent findings. Lymphocyte mediated immune reactions play a major role in the immunological defense against antigenic tumor cells. Serum factors (antigens, antigen-antibody complexes) can thwart these reactions, perhaps by interfering with a lymphocyte "activation" process. Blocking factors can be eluted from lymphoid cells harvested from tumor-bearing animals. One way of increasing cell-mediated reactivity to tumor antigens appears to be to sensitize (or "activate") lymphocytes against tumor antigens in vitro. Another way may be to inoculate animals with sera containing lymphocyte-dependent and unblocking antibodies. Preliminary evidence is presented that inoculation of such sera from rabbits immunized with mouse embryonie cells and extensively absorbed may delay the appearance of primary, methyleholanthrene-induced sarcomas in BALB/c mice; the mechanisms responsible for this delay remain unknown.


Experimental cancer immunotherapy: modification of tumor cells to increase immunogenicity. Firmly established transplantable C3H/HeJ mammary carcinomas can be inhibited by host challenge with Vibrio cholerae neuraminidase (VCN)-treated tumor cells. The effect is totally immunospecific, even VCN-treated tumors bearing shared mammary tumor virus (MTV) antigen cannot induce the regression. Thus, VCN is capable of increasing the immunogenicity of the private, unique-unshared tumor antigens on mammary carcinomas; VCN is incapable of increasing the immunogenicity of the shared MTV-associated tumor antigen even in syngeneic C3HeB/FeJ MTV-free mice. The immunoregressive effect of VCN-treated tumor cells can be augmented by subtotal or total surgical excision of large transplantable tumors. Spontaneous mammary tumors in retired breeder C3H/HeJ female mice can be made to regress by two immunological maneuvers: (1) repeated intratumor injections of VCN and/or BCG; and (2) total excision and immunotherapy with VCN-treated autochthonous mammary tumor cells. The use of VCN-treated transplantable mammary tumor cells sharing the MTV-associated antigen was not better than excision alone. The evidence supports the idea that active specific immunotherapy of spontaneous tumors with VCN-altered tumor cells may require the use of autochthonous cells.


Discussion paper: effect of supernatants from long-term lymphoid cell lines on metastatic cutaneous tumors following local injection. A fraction with lymphokine properties was isolated from supernatant medium of the continuous cultured human lymphoblast cell line, 1788. Culture medium containing 2% human serum was used for cell growth in order to minimize antigenicity of supernatant fractions isolated from the medium. The culture medium was passed through an Amicon XM-100 membrane, concentrated over a PM-10 membrane, lyophilized, and reconstituted to a final concentration of approximately 40:1. Studies in vivo and in vitro showed that the active fraction contained skin reactive factor (when injected intradermally into guinea pigs and humans), lymphotoxin, migration inhibition factor, chemotactic factor, and macrophage activation factor. This same preparation, when injected intralesionally into cutaneous tumors, induced an inflammatory reaction followed by tumor regression. The fraction confined between membranes of pore size 10,000-100,000 daltons was active in promoting tumor regression, while the fraction less than 10,000 daltons was inactive. Patients with skin lesions from metastatic carcinoma of the breast and other malignancies were studied, and 16 out of 30 treated lesions were judged to have undergone either complete or greater than 50% regression. Of these, 8 were biopsied before and after lymphokine injection, and 6 out of 9 were negative for tumor cells. Additional studies in vitro with material fractionated on Sephadex G-200 indicated that the macrophage-activating component binds to alpha-2 macroglobulin in the culture medium.


A system of rhinomanometry in the clinical evaluation of nasal decongestants. The utility of an anterior rhinomanometric method for the assessment of decongestant drug activity is illustrated with representative clinical data. Controlled studies employing topical nasal spray, nasal inhaler, and oral syrup formulations were conducted under single- or double-blind conditions in patients with allergic or coryzal rhinitis. The method provided an objective means to distinguish active from placebo (vehicle) treatments and to discriminate differences in decongestant activity between two active formulations. Furthermore, objectively determined increases in nasal patency paralleled the patients' subject-ve perception of improved airflow. In conclusion, this rhinomanometric methodology provided objective confirmation of drug activity with orally-administered, inhaled, and topically-applied decongestant drug formulations.


Experiments for producing specific immunological tolerance by intrauterinely administered immunocompetent human cells. As a consequence of living human leukocytes administered intrauterinely on the 16th day of pregnancy, it was not possible to study the litter since it fell victim to cannibalism immediately after delivery. After the administration of sonically disintegrate leukocyte antigen healthy newborns were dropped. Living human leukocytes administered before the age of 2 day to mice treated in this way, produced no GVH reaction ascertainable with loss of weight but a considerable number of deaths occurred in comparison to the control. Further possibilities of studying the anti-human anti-thymocyte serum by means of cell chimeras are discussed.


The steering function of T cells in expression of the antibody repertoire directed against multideterminant protein antigen. Limitation in the T-cell repertoire has the consequence of reducing the heterogeneity of antibody production. This has been demonstrated in three different systems, in which the T-cell restriction was imposed (1) by tolerance, (2) by peptide priming (3) by natural scarcity. Therefore, expressed repertoires may represent only a portion of the genetically prescribed V regions.


Structural and physiological characteristics of some sheathed bacteria. The fine structure and growth of two gram-negative and two gram-positive strains of sheathed bacteria, isolated from activated sludge, have been studied. Their anatomy is quite different from Sphaerotilus natans. The cells are rectangular, tightly joined together, non-motile and enclosed by a sheath which is thin in the gram-negative strains and rather electron-dense in the two larger gram positive strains. The four strains grow slowly and form pink filamentous flocs in liquid media.


A critical examination of the numerology of antigen-binding cells: evidence for multiple receptor specificities on single cells. The data available from other laboratories as well as our own on the frequency of cells recognizing major histocompatibility antigens or conventional protein and hapten antigens is critically evaluated. The frequency of specific binding for a large number of antigens is sufficiently high to support the idea that at least part of the antigen-binding cell population must have multiple specificities. Our results suggest that these multiple specific cells result from single cells synthesizing and displaying as many as 50-100 species of receptor, each at a frequency of 10(4) per cell. A model involving gene expansion of constant-region genes is suggested and some auxilliary evidence consistent with such C-gene expansion is presented.


Antigenicity of bdellovibrios.

Antigenicity of bdellovibrios. Antigenic relationships between 12 locally isolated bdellovibrios and 3 established reference strains (109D, 6-5-S, and UKi2) were investigated. Antigenicity of the strains was examined by use of the micro-complement fixation test, the serum and complement bactericidal test, and the immunodiffusion test. Antisera were prepared against one of the local strains (MS7) and against one of the established reference strains (UKi2). The complement fixation titers suggest a close relationship among all strains. Immunodiffusion tests produced lines of identity between the homologous strain MS7 and all other strains. It is suggested on the basis of these results that bdellovibrio may possess a common antigen.


A non-adrenergic inhibitory innervation in the rat stomach. The inhibitory response to nerve stimulation was studied in three isolated preparations of the rat stomach. Bethanidine and guanethidine in doses sufficient to block adrenergic neurotransmission reduced but never abolished the inhibitory response to field stimulation of the rat stomach strip. In similar concentration of these drugs, the response to vagus nerve stimulation was diminished; higher doses of blocking agent abolished this response. Relaxation to both field and vagus nerve stimulation could be evoked in stoamchs removed from rats which had received sufficient reserpine to deplte tissue stores of noradrenaline. The response to vagus nerve stimulation was abolished by each of three known ganglion blocking agents. These results show that the rat stomach contains a non-adrenergic inhibitory innervation which is probably the final stage in a vagal pathway.


Effect in vitro of 3-hydroxy-3-methylglutaric acid on the synthesis of mevalonate and its precursors. Addition of 3-hydroxy-3-methylglutaric acid (free HMG) to supernatant-microsomal preparation decreased the synthesis of acetoacetate, HMG-CoA and mevalonolactone by 12%, 33% and 75%, respectively, from [2-14C] acetate. Free HMG also inhibited the activity of HMG-CoA reductase in the microsomes. It is concluded that HMG,  apart from inhibiting the activity of HMG-CoA reductase (the rate limiting enzyme in cholesterogenesis) also interferes with the enzymatic steps involved in the conversion of acetate to HMG-CoA.


Hepatic origin of hyperammonemia induced by shock in normal rats. This study was undertaken in order to see whether instability in blood ammonia levels frequently observed in the anaesthesized rat could be explained by variations in blood pressure. In normal Wistar rats, anaesthesized with sodium pentobarbital, a bleeding of 1 ml/100 g body weigth produced in a few minutes a significant decrease in blood pressure and a significant increase in arterial blood ammonia level. With the blood pressure normalization following the blood reinfusion this hyperammonemia decreased but reappeared at high levels after a second and a third bleeding. The shock produced by an occlusion of the inferior vena cava above the renal veins gave similar results. The arterial hyperammonemia induced by shock did not result from muscle or renal ammonia production but is related to impaired hepatic uptake of portal ammonia. These results indicate that in the rat the blood pressure stability is a necessary precondition in any experiment on ammonia metabolism.


A correlation between the effects of calcium on intercellular adhesion and electrostatic repulsion between cells. Calcium ions enchance the mutual adhesiveness of HeLa cells harvested from suspension cultures in which growth is density inhibited. No significant effect of calcium is observed on the mutual adhesiveness of HeLa cells from fast growing suspension cultures. Agglutinative titration of the cells using poly-L-lysine, mol. wt 15000, shows that calcium ions reduce the strength of the repulsive forces on density inhibited HeLa cells. The agglutination curve of the nonrepulsive fast growing HeLa cells is not significantly modified by the addition of calcium. The results support the conclusion that the effect of calcium on the mutual adhesiveness of density inhibited cells is due to a weakening of the repulsive forces on these cells.


[Oniscoidea hemocyanins. Effect of pH on dissociation and structural data]. The pH has an influence on the molecular dissociation of the Oniscoidea hemocyanins. The dissociation electrophoretic patterns are characteristic for the species investigated. This method allows to confirm the systematic evolution and the adaptative possibilities of terrestrial Isopods. The hemocyanins of Oniscoidea are similar to those of Decapoda having a structure of comparable molecular weight protomers.


Effect of O-(beta-hydroxyethyl)-rutoside on the glucose metabolism of cultured human varicose saphenous veins. The flavonoid O-(beta-hydroxyethyl)-rutoside appears to have a slight inhibitory action upon the oxidative metabolism and lactate production of culured human varicose saphenous veins. The possibility that exogenous glucose would be utilized in other metabolic pathways is discussed.


Temperature regulation in a hypometabolic primate, the slow loris (Nycticebus coucang). Six slow loris were exposed to air temperatures between 10 degrees C and 40 degrees C. Rectal temperature was stable (mean, 34.8 degrees C) at air temperatures between 17 degrees C and 31 degrees C; at higher air temperatures, the animals became hyperthermic. Oxygen consumption was minimal at air temperatures of 31.4-36.6 degrees C; the mean value (0.250 ml O2 g-1 h-1) was only 36% of the expected level for a eutherian Mammal. The slow loris increased its heat production at lower air temperatures. Thermal polypnea occurred in response to heat, and some of the animals were able to dissipate their entire metabolic heat production at lower air temperatures. Thermal polypnea occurred in response to heat, and some of the animals were able the combined thermal conductance of the tissues and haircoat was 73% of the predicted values. It was concluded that, in spite of its low metabolic rate, the slow loris had effective responses to moderate cold, and that, in addition, it was well adapted to a hot climate.


Interaction between vagal and chemoreceptors afferents in ventilatory response to transient hypercapnia (anaesthetized rabbit). In rabbits anaesthetized with ethyl-carbamate, stimulation of chemoreceptors afferents was allowed by transient hypercapnia, before and after vagal blockade by DC current. In these relatively fast breathing animals, the transient hypercapnia produced light changes of inspiratory tidal volume (VI), inspiratory (TI) and expiratory durations (TE). Despite the identity of transient hypercapnia, it ensued that: (1) the higher the spontaneous VI and the lower the respiratory frequency (fR), the greater their respective changes (deltaVI and deltafR) during the ventilatory response; (2) after vagal blockade, greater changes in VI, TI, TE and mean inspiratory flow rate (VI/TI) occurred than in control state, while the relation between deltafR and fR was more significant than in control state. Respective roles played by vagal and chemoreceptors afferents in the ventilatory response to transient hypercapnia are discussed.


[Estimation of regional circulation in rats: results obtained by using 15 and 50 micron diameter microspheres and rubidium]. Radioactive microspheres, 15 or 50 micron in diameter, were used to estimate the distrubtion of cardiac output and the degree of shunting of microspheres through the systemic and pulmonary circulations in anaesthetized rats. Extraction of 15 micron spheres by the pulmonary capillaries was nearly 100% and the amounts of microspheres per gram of lung tissue were not significantly different in the various lobes of lung. After injection into the left ventricle, the proportion of microspheres shunted to the lungs was almost identical using 15 or 50 micron spheres. Similar results were observed after injection into the internal of external carotid artery. The distribution of cardiac output showed a significant difference between 15 and 50 micron spheres, the proportion of 50 micron spheres found in the stomach being higher, which suggests the existence in this organ of arteriovenous shunts larger than 15 micron. The rubidium method yielded higher fractions of cardiac output in the liver (hepatic artery), lung and skin whereas the microspheres distribution to the heart, spleen and digestive tract exceeded that of rubidium. The origins of these differences are discussed.


[Morpholigic and physiologic repercussions of partial removal of brown adipose tissue in rats acclimated to different temperatures]. Rats were chronically acclimated to 28 degrees C or 5 degrees C or submitted to daily variations of ambiant temperature. Ten or thirty days after removal of about 40% of the total brown adipose tissue (whole interscapular and 25% of abdominal tissues), the weight of the different pads of brown adipose tissue, thyroid and adrenals were determined. In all the groups, there was a large decrease of brown adipose tissue weight for the first ten days due to the shock following the operation. Then, the brown adipose tissue weight was restaured and, only in constant cold accliclimated rats, compensative hypertrophies of axillary and thoracic brown adipose tissue were found. Adrenals weight was significantly increased after the operation; in the two groups of cold acclimated rats, that increase was still significant one month later. However, the corticosterone production rate was not increased. These results are discussed in relation to the physiolocical role of brown adipose tissue in cold acclimated animals.


[Incorporation of plasma radiophosphate into the inorganic, organic acid-soluble and phospholipid phosphate fractions of the normal rabbit sciatic nerve and during Wallerian degeneration]. Inorganic phosphate exchanges between plasma and sciatic nerve have been measured in the rabbit using a 32PO4 tracer technique. Inorganic phosphate is taken up at the rate of 0.13 microng per hour and per 100 mg fresh weight. Incorporation of plasma radiophosphate is markedly increased into the inorganic and organic acid soluble phosphate fractions of the distal part of the sectioned sciatic nerve. This increase is already signficant within one hour after surgical division, spreading at least 3 cm distally within 6 hours. This high level of incorporation persists until the 29th day of degeneration. These results favour the hypothesis that the axonal continuity maintains the metabolic activity of the Schwann cells at an inframaximal level. We confirm the rapid decrease in total phospholipid concentration in the nerve undergoing Wallerian degeneration as well as the marked increase in their specific activity. We show however that this increase in specific activity is due partly to the increased specific activities of the precursors (organic acid soluble phosphates), partly to the disappearance of a metabolically insert pool (myelin phospholipids). The Schwann cells of the nerve undergoing Wallerian degeneration do not have a more active phospholipid metabolism than their normal counterparts.


Role of rat-liver alcohol dehydrogenase in the glycerol pathway to L-lactate in homogenates. 14C-Distribution in the C3-chain of L-lactate after incubation of various 14-C-labelled prescursors ([1-14C] and [3-14C] glycerol; [3-14C] glyceraldehyde and glycerid acid; D- and L-[3-14C] serine; [1-14C] fructose and [6-14C] glucose) with homogenate showed that (1) most of the glycerol is metabolized to L-lactate via D-glyceraldehyde; the remainder may possibly form L-lactate via dihydroxyacetone; (2) a part of D-glyceraldehyde and D-glyceric acid may produce glycerol before L-lactate is formed; (3) D and L-serine do not form measurable amounts of L-lactate via D-glyceric acid; (4) rat-liver alcohol dehydrogenase (E.N.1.1.1.1) does not contribute to conversion to L-lactate of dihydroxyacetone phosphate from fructose nor of D-glyceraldehyde phosphate from glucose.


[Volumetric and cytologic investigations of cytolysis of ascites tumor cells provoked by triton X-100 (author's transl)]. Concentration-effectivity curves of Triton X-100 activity on ascitic cells of mouse leukemia 1210 and Zajdela-Hepatoma in rats have been plotted by electronic determination of cell numbers, indicating only one part of cytolysis which follows a sudden decrease of cell volumes. A better characterization of the whole cytolysis can be realised by volumetricall particle counter analysis. It first displays an increase in cell volumes for several concentrations in connection with microscopically observed increase in cells staining relatively weak by eosin. Staining and swelling nearly simultaneosly reach their maximum. Furthermore a sudden diminution of the cells follows with a shift of cell volumes distribution curves to the left, determined by particle counter depending on temperature, e. g. a strong delay at 0 degrees C.


Viruses isolated from bats in Japan.

Viruses isolated from bats in Japan. Virus isolation has been attempted from the blood, spleen, liver and kidneys of bats. Nine viruses (1.1 per cent) have been isolated so far from 838 bats collected in different places in Japan. Two of the isolates (TOK-1350 and TOK-1362) were isolated from Vespertilio supernas collected in Fukushima Prefecture. They killed suckling mice within 3-5 days after intracerebral inoculation. The remaining seven isolates were all filtrable through Millipore filters (0.22 micron) and were pathogenic for suckling mice but not adults. One of seven strains (KY-5) was ether resistant and another (TOK-292) was partially ether resistant and both were resistant to sodium deoxycholate (SDC); another (KY-663) was partially resistant to SDC. The sucrose acetone (SA) antigen of each new isolate did not show haemagglutination (HA) with goose red cells, even after protamine or ultrasonic treatment. Complement fixing (CF) activity was found in four of the seven strains. Both TOK-949 and VS-820 were collected at the same place and probably have the same CF activity. The remaining five strains are apparently different. Both YF-17D and Rio Bravo gave high HI titre with antisera against KY-5, TOK-949, TOK-1280, VS-820 and VeJ-822. They thus seemed to be flaviviruses although they were distinct from Japanese encephalitis virus (JEV) strains. From 1 to 10 per cent of bat sera contained antibody against JEV.


Serological relationships between rotaviruses from different species as studied by complement fixation and neutralization. Human, piglet, mouse, foal, lamb, calf and rabbit rotaviruses all infected, but could not readily be subcultured in LLC MK2 cells. Cells infected with mouse and calf rotaviruses reacted by indirect immunofluorescence (FA) with convalescent serum from children, piglets, mice, foals, lambs, calves or rabbits, taken after rotavirus infection. Human, calf, piglet, mouse and foal rotaviruses reacted with human, calf, mouse, foal and lamb convalescent serum by complement fixation (CF). It was not possible to distinguish between different rotaviruses by CF or FA. Neutralization tests, however, detected species-specific rotavirus antigens. Any virus was neutralized by a much higher dilution of homologous species convalescent serum than by any heterologous serum. With the exception of the mouse virus there was very little cross reaction. However, in sera with a very high neutralizing titre for the homologous virus the titre was proportionately raised against heterologous virus. It is, therefore, now possible to type to species an unknown rotavirus by a neutralization test in LLC MK2 cells using convalescent serum from each species.


Preparation-conditioned changes of the antigenicity of influenza virus neuraminidases. The influenza virus strains A/Sing/1/57 (H2N2), A/Bel/42 (H0N1) and A/Bel/42 (HO)-A/Sing/1/57 (N2) were treated with bromelain under reducing conditions and with reducing agent alone, and the antigenicity of the neuraminidase (NA) of intact virus and of the split products was tested comparatively. It was found that the antigenicity of NA was influenced quantitatively and qualitatively by the preparation procedure. Antineuraminidase (AN) antibodies obtained after vaccination of guinea pigs with intact virus and with split products differed in their cross-reactivity with heterologous neuraminidases. In several cases, the quantity of AN antibody formation depended on the hemagglutinin (HA) dose present in the vaccines. The N2 NA on the recombinant virus was significantly more sensitive to treatment with reducing agent than was the N2 NA on the parent virus. AN antibodies directed against N2 NA on the recombinant differed qualitatively from that directed against N2 NA of parent virus. The results warrant the conclusion that the antigenicity of isolated NA or of NA on recombinant virus can differ from that of the NA on intact homologous virus and that such alterations could influence the determination of antigenic relationship between neuraminidases.


[Study of the innervation of blood vessels of the digestive organs by fluorescence microscopy]. The blood vessels of the samll intestine and the gallbladder were shown to possess a great amount of adrenergic nerve fibres which, when penetrating the thickness of the wall of the above organs, become thinner and the distributed between the tissue structures of the organs as the thinnest monoaxonal network. The method of Falck--Hillarp--Krokhina was used. Among the vessel nerves there are perivascular nerves accompanying the vessels along their total legnth, juxtavascular and intramural nervous bundles of the sumpathetic nature detected by the fluorescent-microscopy method. Large arteries are disposed in a considerably thicker network of specifically fluorescing fibres than veins and small arteries.


[Hypothalamo-amygdaloid connections of cat's brain]. Under study were the afferent connections of the cat's amygdala nuclei with the hypothalamus (Nauta's method) in parallel with studying geometrical parameters of the afferent fibre endings in these nuclei by the Golgi method. It has been shown that the medial hypothalamus gives the beginning to a small amount of fibres running to the medial group of the amygdala nuclei; dissipated solitary fibres run to the large- and small-cellular parts of the basal nucleus. A considerable amount of fibres run from the lateral hypothalamus to the amygdala, mainly to the medial group of its nuclei and the anterior amygdalar area, only solitary fibres were followed in the basal nuclei. We failed to observe degenerated fibres from the medial preoptical area to the amygdale. The geometry of branches of these fibre systems in the amygdala nuclei was established: they all terminate as a compact but rarely branching brush.


[Staining of the sections with mixtures of gallocyanin with picrofuchsin and eosin]. Instead of two-stage staining with hematoxylin-eosin and hallocyanin-picrofuchsin a technique for simultaneous staining in mixtures of hallocyanin and eosin or picrofuchsin is suggested. The stains-cocktails are well preserved for 4-5 weeks and may be used repeatedly.


Community education about cancer.

Community education about cancer. Telling people what they should do to guard against cancer does not necessarily produce the desired changes in attitude and behaviour. It is necessary to take account of the factors that obstruct these changes. Fear of cancer induces some people to employ psychological defences that might relieve their anxiety, but divert them from medical care. General practitioners can either "turn on" or "turn off" the community education process by the stance they adopt towards the recommendations made in educational programmes. Failur to sensitively appraise the patient's motives and feeling when seeking advice about a publicized cancer "warning sign" can both hurt the patient deter him from developing habits of early reporting. Preventive programmes of cervical cytology, instruction in breast self-examination and smoking advice can quite readily be initiated in general practice. The various media of communication in cancer education should be carefully selected and targeted. Since doctors are generally accepted as experts on health matters, their apparent undue pessimism about cancer prognosis is unfortunate. On the other hand, their low smoking rate sets a helathy example for patients to follow.


Nature of the stimulation of biogenesis of cholesterol in the liver by noradrenaline. 1. Administration of noradrenaline increased the incorporation of [1-14C]acetate into hepatic sterols and the activity of liver microsomal 3-hydroxy-3-methylglutaryl-CoA reductase. 2. The stimulation was observed at short time-intervals with a maximum at 4h and was progressive with increasing concentrations of noradrenaline. 3. Protein synthesis de novo was a necessary factor for the effect. 4. The stimulatory effect was not mediated through the adrenergic receptors, but appears to involve a direct action of the hormone within the hepatocyte.


Preliminary characterization of two thymus-dependent xenoantigens from mouse lymphocytes. Preliminary characterization of two mouse thymus-dependent (T) lymphocyte xenoantigens, T25 and T200, which are selectively labelled by lactoperoxidase-catalysed iodination of T-cells, is described. Both molecules are membrane-bound glycoproteins. Fractionation of membrane vesicles prepared from BW5147 lymphoma cells by sedimentation through sucrose density gradients show that antigens T25 and T200 are in fractions enriched with plasma membrane. Moreover antigen T200 is partially degraded when viable cells are treated briefly with low concentrations of trypsin. Both molecules are efficiently solubilized in buffers containing sodium deoxycholate or Nonidet P-40, as measured by failure to sediment at 100000g for 60min. However, gel filtration on Sepharose 6B showed the presence of aggregated material in Nonidet P-40 extracts which was not found in deoxycholate-solubilized membranes. After solubilization in detergent, antigens T25 and T200 bind to, and may be specifically eluted from, columns of pea lectin--Sepharose or concanavalin A--Sepharose. Both molecules are heterogeneous when examined by polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. As judged by its binding to columns of pea lectin, at least part of the heterogeneity of mouse thymocyte antigen T25 resides in its carbohydrate moiety.


Monocyte-reactive antibodies in patients with systemic lupus erythematosus. Cold-reactive antibodies cytotoxic for peripheral monocytes from more than half of normal donors were found in the sera of 2 of 25 patients with systemic lupus erythematosus (SLE) and 1 of 26 with rheumatoid arthritis (RA), and they were absent in 25 normal sera. In contrast, lymphocytotoxic activity for T or B lymphocytes was found in over half of the lupus sera. The antibodies to monocytes were primarily IgM and exhibited varying specificities. Some of the antibodies were directed against antigenic determinants common to monocytes, T and B cells, or against determinants shared between monocytes and one lymphocyte type. One serum possessed a high titer of antibodies that were specific for monocytes. The clinical significance of antimonocyte antibodies remains to be established.


Cathepsin D agglutinators in rheumatoid arthritis. I. Increased CDA titers in serum and synovial fluid of patients with seropositive RA. The incidence and titer of cathepsin D agglutinators (CDA) were significantly higher in seropositive rheumatoid arthritis (RA) sera than in the sera of healthy blood donors or of patients with other rheumatic diseases, including seronegative RA. A significant elevation was also found in synovial fluid (SF) samples from seropositive RA patients. CDA in the SF tended to be increased when compared with the corresponding serum. The levels of CDA correlated positively with those of rheumatoid factors (RF) when the latter were determined with IgG anti-CD Ripley-coated erythrocytes, but not when they were determined by the Waaler-Rose or latex tests. The increased CDA titers do not seem to be the result of significant amounts of IgM agglutinators or of the presence of IgM-RF. These findings suggest the existence of a link between the formation of RF and CDA, but the nature of this link cannot be fully explained.


[Textile pest control in textile stores with a combination preparation of methoxycholor and chlorpyrifos [0,0-diethyl-(3,5,6-trichloro-2-pyridyl)-monothiophosphate]]. The effect on man of a mixture of methoxyclorine and 0,0-diethyl-(o8k8l-trichloro-2-pyridyl)-monothiophosphate (chlorpyrifos) used for textile pest control in poorly ventilated textile storages were examined under realistic test conditions. The chronical exposure of the test persons to chlorpyrifos, although originally thought to be of a negligible order, surprisingly resulted in an approximately 40% inhibition of the serum chlinesterase (ChE) without any significant spontaneous recovery of the ChE activity in three out of four test subjects during the test period. On the contrary, the activity of the acetylcholinesterase of the erythrocytes (AChE), after a temporary insignificant decrease, was found to be considerable increased for the duration of the test. As a result of these examinations it is recommended not to use insecticides containing alkylphosphates for textile pest control in poorly ventilated reeom if an exposure of man during the desorption phase cannot be excluded.


Effect of temperature and caffeine on the interval-strength relationship of mammalian ventricular myocardium. In isolated cat heart papillary muscle electrically driven at the basic rate of 30 per min the effect of change in temperature (37 degrees C vs. 30 degrees C) and caffeine upon post-extrasystolic potentiation (PEP) phenomenon was studied. At 30 degrees C the basic tension developed by the regular contraction increased an average of (s +/- sm) 23 +/- 5.2% as compared to 37 degrees C. Furthermore at 30 degrees C, the curve relating the magnitude of PEP to the interval (msec) between regular and premature stimulus was significantly shifted upwards and to the right as compared to the curve obtained at 37 degrees C. The time persistence effect of PEP or at 30 degrees C. In fact, up to 5 min the corrected curve relating percentage increase of the first potentiated contraction with predetermined intervening rest period (pause) was significantly shifted upwards at the lower temperature. Caffeine (2.7 and 5.4 mM/l at 37 degrees C) produced a significant increase (s +/- sm) + 51.5 +/- 6.8% of the basic tension developed by the regular contractions as compared to the control period in the same muscles. However, caffeine decreased significantly both the relative magnitude (%) and the time persistence (corrected values) of PEP appearing on the first contraction after a predetermined interveinin pause. In control experiments in the same muscles caffeine decreased the tension developed by the first contraction following any equivalent pause during rhythmic stimulation. This relative decrease in tension of the first contraction reached a greater significance as the pause was lengthened to the limits of the rested state contraction (5 min). The results are discussed regarding the excitation-contraction coupling and calcium inactivation as the main mechanisms for positive inotropic effect during PEP. The effect of lowering the temperature could be related to the lengthening of the active state, slowing of Ca++ inactivation mechanism and/or greater stiffness of the serial elastic element. The effect of caffeine is probably related to an increase of the intracellular Ca displacement to the contractile site.


[Alcoholic hyaline-like bodies in nerve cells of the caudate nuclei in various diseases of children]. Intracytoplasmic hyaline bodies were noticed in nerve cells of the caudate nuclei of the infantile diseases: Leigh's encephalomyelopathy (12-year-old, male), Wilson's disease (14-year-old, male), Morquio's disease (12-year-old, male), pseudoulegyric type of hepatocerebral degeneration (19-year-old, male) and Schilder's disease (15-year-old, male). The hyeline bodies were noticed as linear, striate, dendritic or antler-like in form and stained pink or red with hematoxylin-eosin, orange or red with tmasson trichrome, and dark blue or purple with phosphotungstic acid hematoxylin. The characteristics of the neuronal inclusions have much resemblance to the "alcoholic hyaline-like bodies" which were described by K. Kojima in the caudate nuclei of alcoholics. The results may indicate that the presence of the hyaline bodies in the caudate nucleus is not pathognomonic for alcoholic intoxication, but may suggest the presence of a certain common metabolic disorder among the described diseases.


Radioimmunoassay of bleomycin in plasma and urine. Antibodies to bleomycin were raised by immunization of sheep and rabbits with bleomycin-albumin conjugates. The combination of a high-titre, high-avidity sheep antiserum and iodinated bleomycin produced a radioimmunoassay sensitive to 8 ng of bleomycin per ml of plasma or urine. Untreated specimens (100 microliter) of plasma or urine could be added directly to the assay tubes. The antiseerum was specific for bleomycin and showed no cross-reaction with other anticancer agents used in combination chemotherapy. Over a concentration range of 20-100 ng/ml, recovery of bleomycin from plasma was 110% and from urine, 93%. Repeated assay of plasma samples showed a decrease in bleomycin levels unless the samples were kept at 4 degrees C or below. Assay of bleomycin levels in plasma and urine from patients under treatment with bleomycin showed similarities with results reported using a microbiological assay. The radioimmunoassay offers a more reliable, rapid and sensitive method for the measurement of bleomycin.


Lymphocyte sensitization in childhood solid tumours and lymphoblastic leukaemia, measured by electrophoretic mobility test. A modified electrophoretic mobility (EM) test was performed in 150 children to examine their lymphocyte sensitization to myelin basic protein (encephalitogenic factor). Measurements in the cytopherometer were facilitated by using devitalized sheep erythrocytes as indicator particles instead of macrophages. A significant decrease in EM was found in 29/30 children with acute lymphoblastic leukaemia and in 67/75 children with solid tumours, thus giving a false negative rate in malignant disease of 9/105=8-6%, as compared to 6 false positives among 45 children with non-malignant disorders; 5 of the later "false/positive" 6 patients had autoimmune disease. Results of the EM test in the children with leukaemia were compared with those in 9 patients with non-Hodgkin's lymphoma and 2 with Hodgkin's disease at different stages, but no striking change was seen between different diseases, or after cessation of long-term immunosuppressive chemotherapy. Percentage of "slowing" ranged from 4 to 30%. These results indicate that patients with lymphoid malignancies still have lymphocytes which had been sensitized by a common antigen of the malignant cell clone at the beginning of the disease. The EM test, furthermore, could serve as an additional diagnostic aid in differentiating benign from malignant masses in the abdomen, extremities or intracranial disease.


Relationship between Escherichia coli endotoxin toxicity and the immunization status of normal adult guinea-pigs. Lipopolysaccharide extracts of E. coli (endotoxins) were toxic to normal adult guinea-pigs, yet no evidence was found of serological reactivity to endotoxins or of "immediate" dermal reactivity in vivo. In contrast, testing of the serum of experimentally immunized animals provided evidence of precipitins, agglutinins and haemolysins. It is concluded that endotoxin exerts toxic effects in the absence of significant antibody production. This suggests that endotoxin toxicity is independent of immune processes not involving cell-mediated responses.


[Mechanisms and ways of regulation of lipoic acid penetration into biological structures]. Experimental evidence of the penetration of low doses (100--120 mkM) of lipoic acid (LA) into cells and mitochondria by means of transport systems, involving proteins was obtained. The functioning of those systems is regulated by hormones, is dependent of redox states, is disturbed in the presence of energy metabolism inhibitors and is stimulated by repeated injections of LA. The penetration of LA into erythrocytes is facilitated by a concentration gradient K+ and Na+ and the high activity of transport ATPases. In case of high (over 120 mkM) content of lipoate in the incubation medium, its penetration into the cells and mitochondria occurs largely due to ordinary diffusion. Such penetration of LA predominantly occurs also under conditions of transversely directed gravitational overloading (6g). The rate of LA penetration into the biological structures of the organism is regulated by complicated and efficient mechanisms, involving hormonal control of protein biosynthesis.


Static and dynamic imaging with indium-III labelled Bleomycin in the localization of squamous cell neoplasia. Fifty two cases of squamous cell carcinoma were studied using indium-111 labelled Bleomycin. The overall accuracy of localization by static imaging alone was 80%. Detection of lung and gynaecological tumours was most consistent, while oesophageal tumours were the most commonly missed. Imaging within a few hours of administration of the radiopharmaceutical was found to be as effective as imaging at the recommended time of at least 24 hours. Inflammatory lesions giving false positive scans could be differentiated from tumour tissue by the technique of dynamic imaging. Maximum activity occurred in tumour tissue on average ten minutes after the peak for normal tissue. This difference was used to improve the detection of known tumours to 90%.


Carcinoma of the male breast: A review of 200 cases. Two hundred cases of male breast carcinoma were treated at the Christie Hospital, Manchester, between 1942 and 1971. The survival rate of the group following curative treatment is presented; the response to palliative treatment is also discussed. The survival rate was particularly good for stage I cases, with 79 per cent surviving for 5 years and 56-3 per cent surviving for 10 years. However, the later stages did less well, particularly when compared with female patients of the same age and stage. With such a rare disease it would be of help to centralize the treatment of these patients as much as possible.


Inhibition of the rapid movement of optically detectable axonal particles colchicine and vinblastine. The rapid saltatory motion of intra-axonal particles detected by dark-field microscopy in myelinated axons isolated from sciatic nerves of adult Xenopus laevis was inhibited by colchicine or vinblastine at a concentration of larger than or equal to 0.1 mM. Both the predominant somatopetal transport and the somatofugal transport of these round particles were inhibited. The reduction in numbers of moving particles was apparent first in the juxtanodal portions of the isolated axons within about 1 h. No particles could be detected moving by 3-5 h after application of the colchicine or vinblastine. During the phase of partial inhibition, those particles that were still progressing along the axon did so at apparently normal velocities while they were in motion, but remained stationary increasingly frequently and for progressively longer periods. Colchicine or vinblastine at a concentration of less than or equal to 10 micronM caused no observable inhibition within 4 h of application. Colchicine at a concentration of larger than or equal to 10 mM caused local accumulation of round particles, and vinblastine at a concentration of larger than or equal to 2.5 mM caused fragmentation of rod-shaped organelles, believed to be mitochondria. Electron microscopy of nerve fibers treated with 5 mM colchicine showed a progressive loss of microtubules from the axoplasm, such that approximately 70% of the microtubules had disappeared after 4h.


A comparison of immunochemical methods for the detection of antibodies to myelin encephalitogenic protein. The antibody titer to myelin encephalitogenic protein in rabbits and rats has been comparatively studied by double antibody radioimmunoassay, quantitative microcomplement fixation, and radioimmunoelectrophoresis. In general, these immunochemical tests quantitatively paralleled one another but minor differences were sometimes present. The desirability of using a combination of these methods in assesing the antibody response to myelin encephalitogenic protein is emphasized.


Axonal transport and axonal processing of low molecular weight proteins from the abdominal ganglion of Aplysia. Axonal transport of proteins in nerves of the abdominal ganglion of Aplysia was observed after a 2 h incubation of the ganglion in tritiated amino acids. The transported proteins migrate as a series of discrete peaks, all apparently moving at a rate of 3 mm/h. This process is sensitive to both colchicine and vinblastine, the former agent reducing the amount of transported material without affecting the transport rate. The molecular weight distribution of the transported proteins, as revealed by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate (SDS), is basically unchanged for up to 20 h after labeling. Low molecular weight species (less than or equal to 18,000 daltons) make up 10-20% of the transported protein and appear to be enriched in leucine. These proteins undergo proteolytic cleavage during transport, eventually reaching a molecular weight of 3000 daltons or lower. It is suggested that these data reflect the axonal transport and processing of neurosecretory peptides synthesized by identifiable neurons of the ganglion.


Use of sepharose-conjugated BCG antibodies for the purification of tuberculin-active components. Bacillus Calmette-Guérin (BCG) antibodies conjugated with CNBr-activated Sepharose 4B led to the isolation of tuberculin-active components from the protoplasmic materials of BCG. From these results; it is concluded that most of the tuberculin-active components (sensitins) have mycobacterial antigenic properties.


Pretreatment of hamster cells with phenethyl alcohol alters cell surface glycoproteins and inhibits vesicular stomatitis virus growth. Chinese hamster ovary cells cultured in the presence of phenethyl alcohol exhibit obvious changes in cell surface galactose and galactosamine glycoproteins as determined by the galactose-oxidase[3H]borohydride technique and SDS gel electrophoresis. Cells pretreated with phenethyl alcohol (drug was removed before infection) were not as effective as hosts for vesicular stomatitis virus as untreated cultures. A minimum pretreatment time with 0.1% phenethyl alcohol of about 8 h was required before a reduction in virus growth was observed. It is proposed that phenethyl alcohol pretreatment as outlined in this report leads to a modification of the host cellular membrane resulting in the inhibition of virus replication.


Cell cycle phase recovery from bleomycin-induced potentially lethal damage. Mammalian cells treated during mitosis with the anticancer drug bleomycin cannot recover from potentially lethal damage. G1- and S-phase cells treated in a similar manner can recover. In synchronized G1- and S-phase cells, and in asynchronous and nondividing populations, the final survival values of recovered cells have always been found to be greater than 0.2. These data suggest that a certain fixed amount of recovery can occur, regardless of the degree of initial bleomycin-induced damage. The mechanism of this particular phenomenon is unknown.


Chromosome analysis of hepatocellular carcinoma 7777 and correlation with alpha-fetoprotein production. The Morris hepatocellular carcinoma 7777 is productive of extraordinarily high levels of the oncofetal protein, alpha-fetoprotein. Its chromosome composition was examined in detail since it represents the only near-diploid tumor of such productivity and has been reported to demonstrate a single unusual chromosomal alteration. The major finding is the presence of a submetacentric marker chromosome, composed of a No. 7 chromosome and a short arm that demonstrated a poorly defined banding pattern on Giemsa staining. This marker is unique to 7777 and is of particular interest in view of recent reports of an association between such unbanded chromosome arms and supraproduction of cell products.


Immunological assay of double-helical segments in RNA fractions of different molecular size extracted from acute myeloid leukemia blast cells. Whole-cell RNA, extracted from acute myeloid leukemia blast cells, was fractionated by sedimentation through sucrose gradients. The proportion of double-helical segments present in each fraction was then determined by a quantitative microcomplement fixation assay that specifically measures double-helical RNA. Sizable amounts of double-helical segments were detected in all fractions of cellular RNA corresponding to S values higher than approximately 20. In all cell populations examined the highest proportion of double-helical segments was found in RNA fractions sedimenting faster then the 45 S ribosomal precursors RNA, i.e., in  fractions including only heterogeneous nuclear RNA.


Characterization of mouse mammary tumor viruses propagated in heterologous cells. Mouse mammary tumor viruses (MMTV) from three different strains of mice have been used to establish productive infections in feline and mink cell lines. The virions that are released by these cells compete completely in a radioimmunoassay for the major virion surface glycoprotein of MMTV (gp52), thus demonstrating that antigenic determinants of gp52 are viral coded. Competitive molecular hybridization studies have shown that the 60 to 70 S RNA's of MMTV's propagated in feline cells contain all the nucleic acid sequences found in 60 to 70 S RNA from MMTV synthesized by murine cells. The virion buoyant densities in sucrose and cesium chloride, virion sedimentation coefficient, divalent cation requirement of the virion DNA polymerase, and morphology of MMTV's synthesized in heterologous cells are similar to those of MMTV's grown in murine cells. Cultures of MMTV-infected feline cells have continuously released between 0.1 and 1.0 microgram of virus per 10(7) cells (75-sq cm flask) per day during the 60-week observation period. No detectable feline or murine type C viruses were produced by these cultures.


RNA tumor virus-like activities in human prostate: possible novel pharmacologic approaches. The cytoplasmic extracts of human prostatic tissues yield two classes of "particles" when centrifuged to equilibrium in a sucrose density gradient, one class banding at a density of 1.15-1.18 g/cm3 ("high density particles") and another at a density of 1.07-1.14 g/cm3 ("low density particles"). Both bands display endogenous DNA polymerase activity which is largely resistant to actinomycin D inhibition. The endogenous DNA products synthesized by high density particles give some indication of high molecular weight RNA:DNA complexes. The tissue extracts from normal, hyperplastic, and neoplastic prostate behave similarly in these assays. In addition, explant cultures of hyperplastic and neoplastic prostate either release, or can be induced to release, particles by treatment with bromodeoxyuridine. These particles band at a density of 1.15-1.18 g/cm3 in a sucrose density gradient and possess RNA and associated DNA polymerase activity which utilizes poly(A):oligo(dT). Our results suggest that human prostatic tissues may contain functions analogous in some ways to those of known RNA tumor viruses of other species.


Role of oncornaviruses in carcinoma of the prostate. The existence of oncornavirus genetic information in human prostatic tissue was studied by assaying tissue extracts for products of viral gene expression (ie, the p30 antigen). Tissue samples from patients with benign prostatic hyperplasia (BPH) or prostatic carcinoma (CaP) were assayed by the competetive radioimmunoassay. The competing antigens used were p30 proteins derived from the simian sarcoma virus type-1 (SSV-1) and the Rauscher murine leukemia virus (RLV). Of the 40 extracts tested, three of 20 extracts from BPH patients and one of 20 from CaP patients competed with the SSV-1 p30 antigen and only one of ten extracts from BPH patients competed with the RLV p30 antigen. The significance of these findings has yet to be established.


Search for oncogenic viruses in human prostate cancer. Electron microscopic, immunologic, and biochemical methods have been used in an attempt to detect and characterize oncornaviruses in human prostatic carcinoma (PCa) and benign prostatic hyperplasia (BPH), and in prostates of mice of high and low mammary cancer or leukemia strains. Ultrastructural examination of 37 PCa and nine BPH specimens has revealed the presence of particles resembling type C virus in five cases of PCa and one of BPH, and also two different types of intracisternal virus-like particles in seven other cases of PCa. Type B virus particles have been observed in prostate of old mice of high mammary cancer strains, while type C virus particles have been found in the prostates of most mice of all the ten strains examined. Immunofluorescence tests with sera from patients with PCa and BPH and with cells derived in vitro from PCa have shown that sera of patients with PCa contained antibodies directed mainly against Forssman-like and tumor-related antigens. In immunofluorescence tests of antisera to major proteins of oncornaviruses with cells of PCa and BPH tissues grown in vitro, positive reactions have been obtained with antisera to p30 protein of murine, feline, and simian type C viruses. Fixed immunofluorescence (FIF) tests of sera of PCa (38%) and BPH (25%) and of some normal donors (27%) gave positive cytoplasmic reaction with mouse prostate cells infected with Soehner-Dmochowski murine sarcoma virus (SD-MSV). Immunoferritin tests of 11 sera positive by FIF gave ferritin labeling of type C virus particles in the SD-MSV-infected mouse prostate cells...


Morphologic and immunologic studies of human prostatic carcinoma. Benign and malignant prostatic tissue was removed in surgery and partitioned for (a) ultrastructural study, (b) tissue culture, and (c) (c) immunochemical study. Fourteen malignant and 18 benign prostatic cancer specimens were examined by transmission electron microscopy (TEM) for the presence of viruses or virus-like particles. Viruses could not be identified with assurity in thin sections. Acinar cells of normal, benign prostatic hypertrophy (BPH), and neoplastic prostate tissue were examined in the scanning electron microscope and TEM and found to be extremely heterogenous in their surface morphologies. Three major types of surface morphologies were present: microvillous, ruffled, and bare. All three types of cells were present in normal, BPH, and neoplastic acini. A collagenase procedure was utilized to remove the stromal cells from glandular structures prior to in vitro cultivation. Partially purified extracts from 71 human urothelial tumors and 75 human urothelial nontumor tissues were used as competing antigens in competition radioimmunoassay in an effort to detect the presence of one of the structural components of type-C ribonucleic acid viruses, the p30 core protein. The urothelial tumors tested included 42 BPH specimens and 18 prostatic carcinoma specimens. Thirty-eight percent of the prostatic carcinoma tissues and 48% of the BPH tissues demonstrated the presence of a protein antigenically similar to the p30 core protein of an oncogenic RNA virus.


Cytomegalovirus and cancer of the prostate: in vitro transformation of human cells. Urogenital tissue specimens were maintained in culture for 2 years. Epithelioid growth was enhanced with use of collagenase digestion rather than trypsinization. Twenty of 34 prostate cancer cell cultures survived more than ten in vitro passages, during which time four of 20 demonstrated epithelioid morphology. One epithelioid line (T-157) survived 32 in vitro passages. The cells demonstrated lack of contact inhibition in culture, were slightly positive in acid phosphatase tests, and reacted positively with cytomegalovirus (CMV)-immune sera in indirect immunofluorescence (IF) tests. These cells, which were proven to be of human male origin, failed to yield infectious virus and could be re-isolated from a nodule induced by the cells when injected sc into weanling athymic nude mice. The serum of the patient from which the tumor cells were derived demonstrated high CMV antibody titers and reacted with the virus-specific membrane and intracellular antigens of CMV-transformed human cells in IF tests. A CMV strain isolated from one of the normal prostate cell cultures established an in vitro long-term persistent infection of human embryo lung cells which resulted in the development of two transformed cell lines. The transformed cells possessed CMV antigenic markers and induced non-differentiated tumors when transplanted into athymic nude mice. The results constitute further evidence of the transforming capacity of CMV, and suggest that the virus may be oncogenic in its natural (human) host.


Studies in the epidemiology of prostatic cancer: expanded sampling. From comparisons of prostatic cancer patients with matched control patients for selected risk variables, patients are characterized by three main trends: (a) delayed sexual drive and development, (b) early repression of sexuality, and (c) premature cessation of sexuality. Excessive numbers of patients reported occupational exposure to fertilizers and auto exhaust fumes. Diets of the patients were higher in animal fats. No differences were found between both groups for frequencies of multiple marriages or sex partners, nor for stressful effects from selected events early or late in life. Trends for circumcision and other variables are presented. The data suggest that early differences are hormonally conditioned, support a provisional endogenous rationale for initiation of prostatic cancer, and oppose a hypothesis favoring transmissible oncogenic agents. If results continue to hold up with increased sampling, limitation upon sexual activity at any time of life may increase risk.


Immunochemical studies of prostatic acid phosphatase. Immunologic specificity of the prostatic acid phosphatase (PAP) and the kinetics of the PAP-anti-PAP antibody interactions were studied in detail. Antigenic identity of electrophoretic isozymes of PAP was established in this study. Counterimmunoelectrophoretic assay, radioimmunoassay, and immunofluorescence technique were developed to detect PAP and PAP-synthesizing cells. These techniques were applied to the determination of serum PAP levels and to the identification of metastatic prostate cancer cells in biopsies.


Analysis of prostatic fluid in prostatic disease. The current studies of expressed prostatic fluid tend to confirm our previous reported pilot observations of a shift in lactic dehydrogenase (LDH) isoenzymes to a predominance of LDHV in patients with prostatic malignancy. They also suggest a decrease in concentration of acid phosphatase and an increase in concentration of protein in the presence of carcinoma of the prostate. These observations suggest a diffuse metabolic alteration of the prostate in the presence of prostatic carcinoma.


Enzyme markers in human prostatic carcinoma. In an effort to develop a sensitive and specific method for detecting human prostatic cancer at early stages, we have studied the isoenzyme patterns of acid phosphatase in patients' sera as well as in benign hypertrophic and cancerous prostatic tissues using isoelectric focusing techniques. At least eight acid phosphatase isoenzymes at pI 4.1-5.5 could be observed. The sera with highly elevated acid phosphatase activity generally contained more isoenzymes with pI values of 4.5-5.0. The purified acid phosphatase isolated from benign hypertrophic and malignant prostatic tissues showed no qualitative difference in isoenzyme patterns although quantitative variations were observed. Malignant tissue contained more isoenzymes with pI values of 4.5-4.8. Patients' sera were found to contain isoenzymes of prostate origin. We have also investigated serum ribonuclease (RNase) activity in patients with prostatic cancer. The serum RNase activity of patients was significantly elevated. No significant correlation was observed between serum acid phosphatase and RNase activity. In some instances, where acid phosphatase activity was in the normal range, RNase activity was elevated. These data suggest that simultaneous measurements of RNase and acid phosphatase activities may be of value in the diagnosis of prostatic cancer. The purified RNase has been isolated from human prostatic tissue and its immunologic properties are being studied.


Scanning electron microscopic study of prostatic cancer. Scanning electron microscopy is applied to the study of 3-dimensional surface and organization of a normal prostate gland and of samples of prostatic disease, including five cases of benign hyperplasia and 15 cases of prostatic adenocarcinoma of different degrees of differentiation. The study provided further evidence regarding the nature and origin of prostatic cancer at a cytologic level and indicated alternate pathways to the neoplastic spread within the prostate gland.


Immunochemotherapy in 34 cases of oat cell carcinoma of the lung with 19 complete responses. Thirty-four previously untreated patients with oat cell carcinoma of the lung were treated with a myelotoxic combination of cyclophosphamide, adriamycin, methotrexate, CCNU, and Corynebacterium parvum (regimen A) every 4 weeks, interspersed with a non-myelotoxic combination including bleomycin, vincristine, dehydroemetine, and Corynebacterium parvum (regimen B) weekly the other 3 weeks or when hematologic toxicity prohibited administration of regimen A. Hematologic toxicity was frequent but was never a serious problem except in two cases of profound leukopenia in which fatal supervening infection occurred. Nineteen patients in this series (56%) showed a complete response lasting from 4+ to 65+ months. Eight of these patients are still alive with a followup of 6+ to 65+ months. Nine patients (26%) showed a partial response (greater than 50%) lasting 1-10+ months. Only one patient in this group is surviving (10+ months). The overall response rate was thus 82%. It is concluded from this study that only a complete response has any significant effect on survival, the benefit of a partial response over no response being only slight. The results achieved are compared to those of available series in the literature and from this comparison strategic deductions for the treatment of oat cell carcinoma of the lung are made.


Phase I-II evaluation of cyclocytidine.

Phase I-II evaluation of cyclocytidine. A phase I-II study of cyclocytidine was conducted in 102 patients, 96 of whom had metastatic solid tumors and six of whom had acute leukemia. The drug was administered in 5- or 10-day courses of single daily iv or sc injections of 100-675 mg/m2 day. Two complete and six partial responses were observed in 64 solid tumor patients evaluable for response, 52 of whom had malignant melanoma or adenocarcinoma of gastrointestinal origin. The median duration of the responses was 6 months. An additional seven patients achieved stabilization of their disease for greater than or equal to 2 months. No responses occurred in six patients with acute leukemia. Side effects included nausea and vomiting, postural hypotension, and parotid pain, occurring in approximatley one third of patients receiving greater than 200 mg/m2/day. No myelosuppression was observed in six patients receiving 5-day courses of 100-200 mg/m2/day. Myelosuppressive toxicity became increasingly severe with doses greater than 200 mg/m2/day x 10, related at least in part to prior chemotherapy exposure including the nitrosoureas.


Tumor-specific immunity in patients with prostatic adenocarcinoma or benign prostatic hyperplasia. Twenty patients were skin tested with solubilized components of autologous prostatic adenocarcinoma or benign prostatic hypertrophy (BPH). Four of ten patients bearing adenocarcinoma of the prostate exhibited tumor-specific cutaneous responsiveness to solubilized autologous tumor-specific antigens (TSA). One responding patient also responded to solubilized allogeneic TSA. A single patient bearing prostatic carcinoma responded only to solubilized components of allogeneic BPH. Nine of ten patients with BPH exhibited no response to solubilized components of autologous BPH. The patient responding to the extract of autologous BPH, however, also had clinical stage B adenocarcinoma of the prostate. These observations suggest host responsiveness to TSA of prostatic carcinoma. Possible clinical significance and mechanisms to explain the findings are discussed.


Effect of pepsin pretreatment on pulse-cytophotometric DNA histograms. Samples of mitotic L-cells were investigated after different preparation and staining procedures using the technique of pulse-cytophotometry. It is shown that most mitotic cells which should appear in the second peak of the DNA histogram are disintegrated or separated into halves by pepsin pretreatment. Hence, the designation 'G2 + M' for the second peak is not correct for this preparative method. This should be taken into account in cell kinetic investigations performed after pepsin pretreatment.


The  formation of free axonal sprouts from a dorsal root ganglion-nerve preparation maintained in organotypic culture, and the effects of demecolcine. Nerve-ganglion preparations from rat dorsal spinal nerve roots were maintained in organotypic culture for 20 h. Free axonal sprouts formed at the cut tips. Clear and dense-core vesicles, mitochondria and smooth endoplasmic reticulum accumulated in the axons for a distance of 500  micronm behind the cut, as has previously been described in dorsal roots sectioned in vivo. Sprouting did not occur in dorsal roots maintained in culture without their ganglia attached. Sprouting was also prevented by demecolcine (3 x 10(7) M) which reduced the number of microtubules in non-myelinated, small myelinated and large myelinated axons to respectively 45, 30 and 20% of control values. The sprouts contained several types of vesicle including small clear vesicles, large and small dense-core vesicles and flattened vesicles. The possible relevance of the vesicles to transmitter mechanisms in these neurones is discussed.


Microtubules in the neurosecretory neurones of the posterior pituitary of the rat. The microtubules in the neurosecretory neurones of the posterior pituitary were studied using different electron microscopical techniques. Tannic acid staining indicated that the microtubules had a 13 protofilament substructure similar to that described for microtubules from other tissues and organisms; the dimensions of the microtubules were also similar to that previously reported. Albumen pretreatment clearly showed the microtubules running across axonal swellings, but not continuing across the nerve endings. The only organelles showing possible association with the microtubules were small vesicles and smooth endoplasmic reticulum, no association between hormone granules and microtubules could be seen.


Localization and synthesis of alpha-fetoprotein in the chicken. The localization and sites of synthesis of alpha-fetoprotein in chick embryos throughout development have been investigated using the combined techniques of immunofluorescence microscopy and tissue culture in the presence of radiolabelled amino acids, followed by immunoautoradiographic analysis. Alpha-fetoprotein is present in a range of embryonic tissues and especially concentrated in the yolk sac, liver and connective tissue. Analysis of culture fluids revealed that the yolk sac is the major site of alpha-fetoprotein synthesis with smaller, but significant quantities being produced by the liver. These results are discussed in relation to mammalian alpha-fetoprotein, and the merits of the chick embryo for studies on the biological function of AFP are considered.


Antigens of Haemophilus influenzae.

Antigens of Haemophilus influenzae. Three antigenic preparations were obtained from a non-capsulated strain of Haemophilus influenzae by ultrasonic disintegration, hot phenol extraction and from a fluid culture. They were designated H. influenzae cytoplasmic antigen (H(1-5); H. influenzae cell wall antigen (HCW); and H. influenzae culture filtrate antigen (HCF). Studies showed that H(1-5) antigen contained heat stable and heat labile components. The heat stable fraction stained positively for polysaccharide, had a positive limulus lysate test and there was immunological cross-reactivity between this and heat stable fractions of HCW and HCF. Limulus lysate assay indicated the presence of endotoxin in HCW and HCF preparations. Heat stable as well as heat labile antigens of H. influenzae should be given consideration in future studies regarding the pathogenicity of this organism in the lower respiratory tree. The specificity of the heat stable antigen of H. influenzae needs to be determined.


Characterization of human beta2-microglobulin by isoelectric focusing. b2-Microglobulin (B2M) isolated from the urine of normal subjects and patients with cadaveric renal transplantation, showed 2 homologues by isoelectric focusing, one with a pI 5.3, the other with a pI 5.7. These proteins show identical molecular weights by dextran gel filtration and sodium dodecyl sulfate acrylamide gel electrophoresis. The immunogenic reactivity demonstrates partial identity using antiserum to human B2M from 2 different sources.