[Use and evaluation of radiophotography in the ambulatory care of lung diseases].

In the methodological cabinet for pneumology of the Institute of Phtysiology, radiophotography was employed in the following fields: a) screening of acute and chronic pneumopathies as appears from : the increase in the number of cases of non-specific pneumopathies as compared with cases of tuberculosis and the quantitative contribution of the method reflected in the fact that over 80% of the cases with non-specific pneumopathies were detected by radiophotography; b) diagnosis -- by comparing with the data recorded in the files, multiple incidences (front, posterior lordosis, profile); locally pointed (targeted) photographs, rf quantified functional tests in cases suspected of C.O.B.P.: c) follow-up of the evolution of dispensary cases and of the therapeutical effect; d) scientific research and teaching activities through epidemiological and pathogenesis studies, thus allowing for a valorification of the files over a 16 years period. The use of the radiophotographic method in the activity of a cabinet of pneumology is necessary especially because it allows for an early detection, a superior morphological diagnosis, as compared with radioscopy (fluoroscopy), for an objective and economical follow-up of the cases, providing at the same time material for scientific research and teaching demonstrations.


[Organizational aspects and effectiveness of integral radiophotographic detection in a pilot area with an industrial profile].

Organizatoric and efficiency aspects are presented of five integral detections (the fifth presently in the final stage), carried out over a period of 14 years (1960--1973) in the territory of the anti-tuberculous dispensary of Turda. In the course of the four radiophotographic detections that have already been finally processed approximately 400.000 subjects have been examined. Mobilization was, in most of the cases, higher than 95% and the proportion of suspects was of 2--3.5%. The complex investigation of the suspects was higher than 95%. The index of detection of tuberculosis decreased severalfold (0.63% in the first investigation, 0.07% in the 4-th) when integral detections were repeated.


[Radiophotographic detection in evaluation of the incidence of tuberculosis].

In a territory with a population of over 120,000 inhabitants, of which 86% in rural environment, with a high tuberculosis endemic rate, four integral detections were organized in 12 districts and three in the other 12 base units of the area between 1969 and 1973. In most of the districts the incidences varied, in the years when integral detections were carried out the index being the double and in some cases 4-5 times higher, than in the years when this investigation was not performed. If annual incidences are computed for the entire area, excluding the cases detected by radiophotography the morbidity indexes appear by 50% lower. If for the whole territory anual incidences are calculated, excluding the cases that have been detected by radiophotography, morbidity indexes appear to be by 50% lower. From the viewpoint of the forms of disease radiophotographic detection brings to the dispensary two-thirds of the oligo- and asymptomatic cases. Subjects eliminating Koch bacilli, representing 44% of the patients that had been betected in a "passive" way, totalized 19% of the cases detected by radiophotography. The cost of detecting a new case was of 2210 lei and the costs for integral detections, related to the population of the area, represented less than one lei per inhabitant.


[Comparative results of total detections and detection in a group of patients with high risk for tuberculosis in an urban environment].

In the territory of 5 anti-TBC dispensaries in the area of Bucharest 2 circumscriptions have been selected at random in which radiophotographic detection was to be carried out integrally and 2 other circumscriptions were selected for the investigation of groups at high risk of developing tuberculosis. All the new cases of active pulmonary tuberculosis that have been recorded, through all the methods in these 20 circumscriptions in 1973 were analized retrospectively and the reasons appeared that had determined their existence was mentioned or was ommitted on the occasion of previous investigations. These reasons were correlated with the data concerning the method for detection that had been employed, according to the indications of the tuberculosis dispensaries. In view of the evaluation of the degree of real covering of the population in integral rf investigations, the team of the Institute of Phtysiology investigated representative lots of population from each dispensary and checked the catagraphy of the population in the field, house-by-house. It was noted that 20--21% of the subjects that had been programmed for the integral rf examination (according to catagraphic criteria) were absent when the checking in the field, that should have been programmed, were not included in the catagraphy. On the basis of this study the methodology for radiophotographic detection for groups with risk of developing tuberculosis was established.


[Long-term study of the effect of successive surveys on tuberculosis endemia].

A whole rural population of 16359 subjects was followed for a period of 24 years. This period of 24 years is well divided from the viewpoint of the succesive systematic detection three intervals being selected, as follows: a) the stage of usual anti-tuberculous assistance; b) the stage of scientific experimentation consisting in 3 radiophotographic detections repeated every two years and the annual control of groups with high risk, between 1960--1965, completed by integral biological detection in children (every year) and bacteriological controls. The population controls were followed by the diagnosis; c) the stage of discontinuing the experiment when current antituberculous assistance was resumed, between 1966 and 1974. All cases of active pulmonary tuberculosis, that have been recorded through all the methods of investigation over a period of 24 years in all these localities are correlated, on the one hand to one another, and on the other hand with objective documents obtained during the period of intensive control of the population over the 6-years interval. Thus the limits appear more correctly, within which this natural history of the disease can be detected through various types of population control, as well as some practical consequences for the improvement of the technique and of the control methodology in the future.


[20 years of experience in the use of radiophotography in the prevention of tuberculosis].

Based on a 20 years experience in the application of the pulmonary radiological control relying on radiophotography, the authors reached the following conclusions: -- 40% of subjects considered as suspect following radiophotography were confirmed to have pathological thoracic changes of which 8.5% with acitve pulmonary tuberculosis; in 1954 60% new cases were detected with 73% early forms of the disease and in 1973, 85% of new cases with 90% early forms of the disease; the effects of annual integral radiophotographic defection, correlated with other forms of anti-tuberculous fight, can be expressed in the following morbidity data : in 1954 -- 1.400.000 ; in 1956 -- 870.000 ; in 1957 -- 300.000 ; in 1962 -- 170.000 ; in 1963 -- 80.000 ; in 1966 -- 50.000. This last figure was maintained until 1969, two small increases being noted in the following two years (1970 and 1971). In the last year (1973) the figure was 40.000.


[Contribution of radiophotography in the knowledge and control of tuberculosis endemia in the area of an anti-tubercular dispensary].

After three integral detections the index of detection of active cases fell from 3.360/00 -- at the first one -- to 0.500/00 -- at the third, while the dynamics of the incidence of tuberculosis decreased in the same period from 130,950/0000 to 53.950/0000. Radiophotography brought to the anti-tuberculous dispensary 86.130/0 of the cases with pulmonary tuberculosis.


[3 successive radiophotographic surveys in a rural territory].

Three detections, carried out over a period of two years gave the following results: a high rate was obtained in the first one while the following two gave lower rates, in parallel with a decrease of the overall incidence through pulmonary tuberculosis from 326.70/0000 in 1968 to 1440/0000 in 1973. The cases were recently detected, during the last two investigations, which allowed for a wider application of the ambulatory treatment, a fact that compensated from the financial view point the cost of radiophotographic investigations. The authors suggest the maintenance of integral detection, with the same periodicity in the rural environment.


[Pulmonary tuberculosis discovered by methods other than radiophotography].

The retrospective analysis of the investigations carried out between 1969 and 1973 showed that for a total of 323 new cases of tuberculosis of the lungs recorded over this period of five years, 279 (86.37%) had been detected through radiophotography, while the remaining 13.63% were detected by other methods. Of these 67.74% were primary infection cases of tuberculosis and 32.53% were secondary tuberculosis. None of the newly discovered adults had been examined by radiophotography before (their absences were either motivated or not). Thus the cases discovered between the detections do not represent a failure of the radiophotographic method.


[Is asymptomatic pulmonary tuberculosis ever detected by radiophotography?].

Following several organized detection campaigns it was demonstrated that these did not provide valid results even when these were organized as integral detections or for groups at risk. The authors maintain that the only group in which a satisfactory result can be obtained is represented by the subjects showing symptoms evoking pulmonary tuberculosis. These are known and can be sent to investigation by the district physician. It is recommended that the radiophotographic equipments should be assimilated to radiological apparatuses, but with better accesibility which the physicians should be able to apply without difficulty in the cases with major or minor symptoms suggesting specifical pulmonary disease.


[Some tactical trends in radiophotographic detection].

The efficiency of organized detections in an area with low phtysiogenic potential fell progressively over the last five years while the efficiency of spontaneous detections rose significantly in patients with apparently non-specific respiratory symptoms. In the districts with low incidence radiophotographic actions were not very frequent and the covering of the whole population was rather low. In contrast good results were obtained in the general network in connection with subjects with respiratory symptoms. For the districts with high endemics integral detection is recommended.


Lymphographic aspects of the barrier function of lymph nodes in Hodgkin's disease.

The persistence of Lipiodol in various lymph node groups was followed up by systematic lymphographic control. Assuming a certain relationship between the barrier function of the lymph nodes and the persistence of their image on the film the authors have tried to find out whether the duration of Lipiodol persistence may be a test for the estimation of prognosis in Hodgkin's disease. The observation of such cases has shown that Lipiodol is retained for a longer period in the external iliac and lombo-aortic lymph nodes as well as in the pathologic ones, except those with lymphocyte depletion, whereas it is very rapidly eliminated from the inguinal nodes. These findings seem to prove that Hodgkin's disease is more severe in patients in whom the barrier function of the lymph nodes is defective i.e. unable to retain the foreign substances introduced in the organism. These conclusions should be further verified by comparison with other clinical and biologic factors.


[Combination of radiophotographic and tuberculin detection in groups of young people].

Tuberculin pre-testing between 1971 and 1973 in profesional schools, as well as in high schools from Brasov, showed that by the radiophotographic examination of tuberculin reactors only, all the new cases of tuberculosis were detected, as well as those requiring surveillance and chemoprophylaxis. In this way over one half of the adolescents from professional schools and one quarter of those from high schools could be excepted from radiophotography, with the corresponding effects of radiation prevention and economic efficiency.


[Indices of detection in integral radiophotographic examinations in rural areas].

Integral radiophotographic detection was carried out in the territories of 5 randomly selected village dispensaries in 5 different counties. The action was performed in strictly operational conditions, without external experimental interferences. Stress was laid on the strict following of the methodological letter concerning radiophotography. The performing of integral radiophotographic detection in strictly operational conditions in the rural environment demonstrated the utility of these examinations in the present stage. The output obtained can be considered as satisfactory; local variations can be noted and this indicates the possibility of differentiating the conduct in various geographical areas.


[Medical radiophotography in the activities of rural polyclinics].

The county polyclinic provides the radiophotographic control of a rural population of 122.741 inhabitants from the area surrounding the capital city of Bucharest. Of the total number of cases of pulmonary tuberculoses that have been recorded only 16,6% were detected in the fixed center and 61,8% by integral detections, carried out by the radiophotographic caravans. That is why the authors consider that this is not the right time to abandon integral detection. The fixed centers, by performing examinations in all those entering new jobs detect cases of tuberculosis belonging to other geographical areas. Thus, of 235 cases detected over a period of 3 years, 67% belonged to other territories and only 33% were from the population normally covered by the center. This is the filter role played by fixed centers carrying out radiophotographic detection. As compared with the 235 cases of tuberculosis there were 399 cases of non-tuberculous pulmonary diseases.


[Retrospective study of the value of radiophotographic examinations in the detection of pulmonary cancer].

Out of a total of 123 cases of centro-hilar pulmonary carcinoma and of 65 cases of carcinoma with peripheral localization changes on the previous radiophotographic images were found in 54% of the cases. The time necessary for doubling of the tumour size was of 22 months for the peripheral forms of cancer. The suspicion of pulmonary cancer was mentioned in the radiophotographic register two years before the diagnosis of the disease was made.


Studies on human serum high-density lipoproteins (HDL). IV. Isolation of lipoprotein families after incubation of HDL.

The high-density lipoproteins (HDL) of human serum appear to be unstable and easily exposed to chemical changes during isolation. In earlier studies we have isolated and purified HDL subfractions either in the presence of an SH-blocking agent, DTNB, or in the cold. By both procedures reproducible lipoprotein subfractions could be recovered by hydroxyl apatite column chromatography at the elution steps 0.03-0.05 mol/l (subfraction II) and 0.05-0.15 mol/l phosphate buffer (subfraction III). The protein moiety of both lipoprotein subfractions contained polypeptides A-I , A-II, thin line (TL), C-I and C-II, and the protein moiety of subfraction III contained also C-III. The incubation at 37 degrees C of these HDL subfractions gave reproducible daughter lipoprotein fractions that could be recovered by subsequent rechromatography on hydroxyl apatite. At each of the elution steps 0.05-0.075 mol/l and 0.075-0. mol/l one daughter fraction was recovered, the protein moiety of which was composed of polypeptide A-I, as judged by polyacrylamide gel electrophoresis, immunodiffusion, and amino acid analysis. The incubation of parent subfractions II and III caused also the appearance at elution step 0.001-0.01 mol/l of a daughter lipoprotein fraction - lipoprotein A (Lp-A) - that was characterized by a protein moiety with polypeptides A-I and A-II in equal amounts. The 'release' of lipoprotein A-I (Lp-A-I) and Lp-A was shown to be due rather to the incubation than to the column chromatography as such. The chemical changes occurring during the incubation of HDL suggested a degradation of phosphatidylcholine (PC) to lysophosphatidylcholine (lyso-PC) and glycerylphosphorylcholine (GPC). It is suggested that the degradation of PC might interfere with the interaction between the lipoprotein families composing HDL.


[Contribution of medical radiophotography in detection of non-tubercular intrathoracic diseases].

Concomittantly with the reduction of the tuberculous processes and with the transfer of the patients to pneumology sections radiophotographical detection of other pulmonary diseases has become more important. From the control of suspects the following data could be obtained: 8.5% cases of active tuberculosis, 21.46% cases with minimal lesions and with sequellae, 7,2% non-specific pneumopathies, 1.10% cardiovascular patients, 0.23% pleuro-pulmonary tumours and 0.51% cases with other affections.


Organophosphorus and methyl carbamate insecticide teratogenesis: diminished NAD in chicken embryos.

Studies with 36 organophosphorus and 12 methyl carbamate compounds establish a correlation between reduction in nicotinamide adenine dinucleotide (NAD) levels and severity of teratogenic signs in chicken embryos, a relation supported by reversal of these effects by nicotinamide derivatives. Diminished NAD occurring at organophosphorus and methyl carbamate concentrations as low as 0.6 to 2.0 parts per million in the egg constitutes a newly recognized biochemical lesion induced by the two most important classes of insecticide chemicals.


In vitro demonstration of an endothelial proliferative factor produced by neural cell lines.

Cultured endothelial cells exhibit a six- to tenfold increase in thymidine labeling index in response to a soluble factor elaborated by clonal cell lines of neural origin. This factor, endothelial proliferation factor, appears to be a unique property of tumor cells and may mediate the vascularization of these neoplasms.


Production of globules in mouse L cells penetrated with hamster sperms.

Globule formation has been observed in long-term cultures of mouse L cells penetrated with hamster spermatozoa. These numerous, uniform, and spherical structures are approximately 10 micrometers in diameter when formed, and are positive to stains specific for proteins and nucleic acids. They may be produced either by sperms within their target cells or by the cells in response to penetration by the spermatozoa.


Cyclic AMP-dependent protein kinase: pivotal role in regulation of enzyme induction and growth.

Dibutyryl cyclic adenosine 3',5'-monophosphate (cyclic AMP) produces phosphodiesterase induction, growth arrest, and cytolysis in S49 lymphoma cells. The striking parallelism between protein kinase activity that is dependent on cytosol cyclic AMP and cellular responses to dibutyryl cyclic AMP in wild-type cells and three classes of clones resistant to cyclic AMP indicates that protein kinase mediates cyclic AMP regulation of growth and enzyme induction in S49 cells.


Phosphoribosylpyrophosphate overproduction, a new metabolic abnormality in the Lesch Nyhan syndrome.

The activity of phosphoribosylpyrophosphate synthetase and the rate of phosphoribosylpyrophosphate accumulation are significantly increased in cultured lymphocytes of Lesch Nyhan patients deficient in hypoxanthine guanine phosphoribosyltransferase and in a clone of mutagen-induced, hypoxanthine guanine phosphoribosyltransferase deficient human lymphocytes. The increase in phosphoribosylpyrophosphate synthetase activity is the cause of the abnormally high cellular phosphoribosylpyrophosphate content and possibly of the purine overproduction described in this syndrome.


Adenosine 3',5'-monophosphate in reproducing and differentiated trypanosomes.

Trypanosoma lewisi, a blood protozoan of rats, undergoes differentiation from a rapidly reproducing form to a nonreproducing form in response to the host antibody ablastin. Intracellular concentrations of adenosine 3',5'-monophosphate (cyclic AMP), which has been implicated in controlling reproduction in cultured mammalian cells, was measured in the two developmental forms of T. lewisi. The concentrations were significantly different, and the results support a hypothesis under which ablastin stimulates an increase in intracellular cyclic AMP.


Diagnostic value of serum creatine phosphokinase in motor neuron disease.

In ten cases of amyotrophic lateral sclerosis, creatine phosphokinase was, without exception, elevated. In 12 cases of other diseases of the central or peripheral nervous system, values were elevated only in two cases of peripheral neuropathy.


Newer treatment in dermatology.

The future of a drug depends upon what it can do in the hands of the practitioner. Medicine is practiced on the basis of probabilities, and treatment must be selected which has the best chance of helping the patient, with the least amount of harm. There are many new drugs available for dermatologic therapy in other developed countries which are not available in this country, due to peculiarities of federal drug regulations.


Autoimmune thrombocytopenia and peripheral neuropathy heralding Hodgkin's disease.

A patient with an autoimmune thrombocytopenic syndrome was treated unsuccessfully with splenectomy. Treatment with corticosteroids and 6-mercaptopurine was partially successful, but the patient developed peripheral neuropathy and over signs of Hodgkin's disease. The latter reponded completely to radiation therapy, but the thrombocytopenia was not reversed until combination chemotherapy was given. The association of thrombocytopenia with Hodgkin's disease is reviewed.


Isolated partial deficiency of adrenocorticotrophic hormone.

A patient with tuberculous empyema who presented with severe hyponatraemia, is described. In the course of investigation, he was discovered to be suffering from isolated adrenocorticotrophic hormone deficiency.


D-Thyroxine in hyperbetalipoproteinaemia.

D-Thyroxine was administered intermittently to 11 patients with hyperlipoproteinaemia (Fredrickson type lla). To avoid possible untoward cardiac stimulation, practolol was prescribed with it. Cholesterol levels were measured regularly over a period of 4 years. A temporary drop of about 15% in the mean cholesterol level was obtained. It is, however, concluded that the over-all response is unimpressive.


Ultrastructural localisation of calcium in peripheral nerves of the rat.

An ultrastructural method which is specific for calcium was applied in a study of calcium distribution in the axoplasm of myelinated nerve fibres of rat sciatic nerves. Electron-dense deposits of calcium oxalate were seen in smooth-membraned vesicles within the axoplasm, and between the two external membranes of axoplasmic mitochondria. The significance of calcium localisation at these sites is discussed, with special reference to the role of calcium in fast axoplasmic transport.


Tinidazole for the treatment of amoebic liver abscess.

Ten patients suffering from amoebic liver abscess were treated with tinidazole (Fasigyn) 800 mg t.d.s. for 5 days. Nine were cured, and 1 patient required further treatment with other drugs. Following this, a double-blind trial was carried out to compare a group of patients treated with tinidazole with a similar group treated with metronidazole. Each series consisted of 14 patients. In the tinidazole series 13 patients were cured and for 1 patient the result of treatment was dubious. All patients in the metronidazole series were cured, but 1 patient admitted to the trial had previously not been cured by metronidazole. It appears that tinidazole and metronidazole are equally efficaceous in the treatment of amoebic liver abscess.


Alpha1-antitrypsin deficiency--an association with hepatic malignancy.

A 70-year-old man with homozygous alpha1-antitrypsin deficiency (AATD) (Pi-ZZ phenotype) at tutopsy was found to have a hepatocellular carcinoma and hepatic fibrosis, pulmonary emphysema, and cor pulmonale. Characteristic cytoplasmic inclusion bodies, with identical histochemical and ultrastructural features, were detected in both normal and malignant liver cells. It is suggested that AATD may precede malignancy, since this is the eleventh case report of this association.


Electrical stimulation of the brain. IV. Ultrastructural studies.

The ultrastructural response of tissues of the cat's central nervous system to chronic electrical stimulation with various parameters has been evaluated at four and a half days post stimulation. Cellular alterations included widespread cytoplasmic vacuolations, architectural derangement and disruption of plasmalemma and other membranes. Lipid inclusions and dense crystalline bodies were prominent in astrocyte-like phagocytic cells in the more severe lesions. Despite endothelial damage in brain parenchymal capillaries, significant extravasation of horseradish peroxidase was not observed. The ultrastructural damage observed following electrical stimulation varied from mild to severe. Although none of the parameters tested was found to be "safe" for clinical applications, it should be emphasized that the stimulations delivered in the present study were essentially continuous.


Cyclic adenosine monophosphate antagonism of prostaglandin induced vasospasm.

Prostaglandin F2alpha was applied topically to the transclivally exposed basilar artery of the cat. The resultant vasoconstriction and its reversal by dibutyryl cyclic adenosine monophosphate was recorded photographically and measured, and the results analyzed statistically. Arterial BP, pCO2' pO2 and pH were determined to insure that the vascular responses were not due to any general physiological disturbance. The results indicated that Prostaglandin F2alpha is a powerful vasoconstrictive substance and that its effects are readily reversible by dibutyryl cyclic adenosine monophosphate.


Identification and successful treatment of congenital microfistulas with the aid of directional Doppler.

Hitherto unidentifiable and therefore untreatable congenital microfistulas were detected with the aid of continuous-wave directional Doppler and a fine-beam pencil probe. The microfistulas formed part of the Klippel-Trenaunay (K-T) syndrome. The management of one case is reported in detail and in three others salient features are touched upon. Careful clinical and radiological examination failed to demonstrate any arteriovenous microfistulas. When Doppler ultrasound scanning was carried out, two discrete fistulas were discovered. Their extent and direction were mapped out accurately. Incisions were made directly over the markings displaying a pulsating capillary tuft of vessels. Further dissection exposed a feeding arteriole which was less than 1 mm. in diameter. Excision of the vascular malformations resulted in the cure of the patient. In another patient with the K-T syndrome in whom a cutaneous hemangioma involved the whole lower limb, in spite of a thorough and systematic search with a Doppler, no microfistulas could be demonstrated. It is suggested that all patients suffering from the K-T syndrome should be examined by Doppler ultrasound in the hope that microfistulas which elude radiodiagnostic techniques might be detected and treated surgically.


Growth of permanent lymphoid cell cultures from human source: tenth anniversary.

The authors developed 52 permanent lymphoid cell cultures from various human sources, mainly from neoplastic lymphoproliferative disease. These cultures are reviewed against the background of similar cultures obtained in several other laboratories. The peculiar features of these cultures are: 1) the phenomenon of lymphoblastoid transformation; 2) the production of both globulins and mediators of delayed hypersensitivity; 3) the presence of herpes type virus as related to etiology or autoimmunity; and 4) cytotoxicity and other assays for the demonstration of tumor-specific antigens.


The role of heavy metals in human health.

The article reviews the role of heavy metals in human health, including those which are biochemically essential as well as those which have no known role in the normal functioning of the organism but which are toxic. The metals discussed are: cobalt, copper, manganese, cadmium, lead, and mercury. Several are also of concern from the point of view of environmental contamination. The article describes the biochemical role for those metals that are essential, mechanisms of intoxication, intake routes and quantities, and environmental significance.


Hypertension from compression and/or enucleation of the adrenal glands in the rat.

Previos studies have shown that compression of the adrenal glands is as effective as adrenal enucleation in causing hypertension in rats. Unilateral adrenal enucleation is ineffective, however, if a normal contralateral adrenal gland is present. The studies reported herein demonstrate that unilateral compression also fails to cause hypertension in the presence of a normal contralateral gland. When present singly, either enucleate or compressed adrenals cause hypertension; when either is present with a normal contralateral gland, the blood pressure is unaffected. When compressed or enucleate glands constitute the pair, in any combination, hypertension ensues. However, whereas an enucleate gland remains extremely atrophic in the presence of a normal gland, compressed glands attain a much larger size under this circumstance. Furthermore, a compressed gland is less inhibitory to the regeneration of a contralateral enucleate gland than is a normal adrenal. Whereas enucleate glands, whether bilateral or unilateral, are always smaller than normal glands, compressed adrenals may be enlarged. The hypertensogenic function of compressed adrenals is, like that of enucleate glands, suppressed by the presence of a normal gland. The growth response of compressed or enucleate glands, whether bilateral or single, appears to depend upon the degree of injury inflicted upon them. There is a considerable discrepancy in the size of individual members of a pair when one or both have been injured, that members of a normal pair do not exhibit.


Disseminated intravascular coagulation: experience in a major cancer center.

Review of the coagulation laboratory records and medical records at Memorial Sloan-Kettering Cancer Center over a three year period (1971--1974) revealed 89 patients with disseminated intravascular coagulation (DIC). The diagnosis of DIC was made if laboratory studies showed evidence of quantitative and qualitative changes in fibrinogen and significant thrombocytopenia. The patients included 19 with leukemia (17 acute), 3 with multiple myeloma, 15 with lymphoma, 46 with metastatic solid tumors, (10 lung, 9 breast, 8 gastrointestinal, 12 genitourinary, 7 miscellaneous) 4 with vascular tumors, and 3 without tumor. Other conditions which might have precipitated or initiated DIC such as gram-negative sepsis, liver impairment, or mucin secreting tumors were present in the majority of patients. Bleeding occurred in 75% of the patients and was fatal in 36%. Thromboembolism occurred in 22.5%. Thirteen percent were asymptomatic. Serum lactic dehydrogenase was elevated in over 75% of the patients at the time of, or subsequent to the occurrence of DIC. Treatment with heparin was helpful in only three of twenty patients. Eighty percent of the patients died within one to over 30 days of the onset of DIC. Post mortem evidence of DIC was present in 18 of 43 autopsies. Results of this study indicate that DIC is a frequent complication of a wide variety of tumors and that its occurrence causes morbidity and mortality in a significant number of patients. Treatment with heparin is of little help unless remission is induced and the precipitating factor(s) are reversed.


Dependence of platelet adenyl cyclase system on oxidative phosphorylation.

The radioactive adenosine 3',5'-monophosphate (cyclic AMP) level derived from 8-14C adenine in intact rabbit platelets decreased in the presence of mitochondrial inhibitor (potassium cyanide) or uncoupler (sodium azide), and markedly increased by the addition of NaF, monoiodoacetic acid (MIA), or 2-deoxy-D-glucose. The stimulative effect of the glycolytic inhibitors was distinctly enhanced by the simultaneous addition of sodium succinate. MIA did neither directly stimulate the adenyl cyclase activity nor inhibit the phosphodiesterase activity. These results suggest that cyclic AMP synthesis in platelets is closely linked to mitochondrial oxidative phosphorylation.


Studies on gluconeogenesis, protein synthesis and cyclic AMP levels in isolated hepatocytes from alloxan diabetic rats.

Alloxan diabetic rats maintained on protamine zinc insulin for two weeks were used for these studies. Hepatocytes were isolated from these rats at various time intervals after withdrawal of insulin (0, 48, 72 and 96 hr). Gluconeogenesis with various concentrations of lactate and fructose was studied. Both lactate and fructose stimulated gluconeogenesis and showed progressive increases in glucose production up to 72 hr after the insulin withdrawal. Glucose production decreased at 96 hr. Protein synthesis in isolated hepatocytes from diabetic liver cells, as measured by the incorporation of radioactive isoleucine, valine and phenylalanine into protein, showed a decrease (5- to 6-fold) with time after insulin withdrawal. Glucagon (10(-6)M) alone increased cyclic AMP levels 10-fold in liver cells, in isolated cells from rats maintained on insulin (0 hr) or from rats withdrawn from insulin for 48 hr. The ability of glucagon to elevate cyclic AMP levels in isolated diabetic liver cells decreases 72 hr following insulin withdrawal.


Defective early phase insulin release in perifused isolated pancreatic islets of spiny mice (Acomys cahirinus).

In order to characterize pancreatic beta cell function in Geneva bred spiny mice (acomys cahirinus), the dynamics of immunoreactive insulin release were examined during perifusion of pancreatic islets isolated from normoglycemic acomys. The initial insulin response of acomys was slow: no clear-cut early (1 to 10 min) peak of insulin release was observed when glucose in the perifusion medium was abruptly raised from 2.8 mM to concentrations as high as 56 mM. This was true for islets of either young, or older more obese acomys. However, after 20 to 30 min of perifusion at the high glucose concentrations, the rate of insulin release from acomysislets became similar to that from islets of rats or mice. By contrast, glucose-induced insulin release responses observed with islets of Wistar-derived rats, Swiss albino mice, and inbred C57BL/6J lean or obese (ob/ob) mice, were clearly biphasic. Tolbutamide 1.5 mM, arginine 16 mM, and theophylline 10 mM were ineffective in stimulating insulin release from acomys islets in the presence of a substimulatory glucose concentration (2.8 mM), whereas these agents were effective in rat islets at the same substimulatory concentration of glucose. On the other hand, when these agents, as well as cyclic AMP 10 mM or cytochalasin B 10 mug/ml were applied in the presence of a stimulating concentration of glucose (16.8 mM), the glucose-stimulated insulin release from acomys islets was increased to the same or to a greater extent than from rat islets. It is suggested that the failure of all the agents tested to stimulate an early rapid phase of insulin release from acomys islets may be secondary to the observed initial insensitivity to glucose, which insensitivity may in turn reflect a selective impairment in the recognition of glucose as an insulinogenic signal in this species.


Potentiation of carbon tetrachloride hepatotoxicity in rats by pretreatment with polychlorinated biphenyls.

Pretreatment of male rats with Aroclor 1254 at a dose of 25 mg/kg i.p. for 6 days resulted in potentiation of the hepatotoxicity of inhaled carbon tetrachloride (CCl4) as evidenced by a decrease in liver glucose-6-phosphatase and elevations of serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), isocitrate dehydrogenase, and sorbitol dehydrogenase. Aroclor 1254 alone did not demonstrate hepatotoxicity. Aroclor 1254 administration resulted in large increases in cytochrome c reductase, cytochrome P-450 (448) AND P-Nitroanisole demethylation. Subsequent exposure to CCl4 vapor resulted in over 70% decreases in the latter two parameters. The potentiation was dose-dependent with a dose of 5 mg/kg or higher being effective. Aroclor 1260 administration gave results similar to those of Aroclor 1254, but Aroclor 1221 enhanced CCl4 toxicity to a lesser extent.


The effects of a polychlorinated biphenyl mixture (Aroclor 1254) on liver gluconeogenic enzymes of normal and alloxan-diabetic rats.

Normal and alloxan-diabetic rats were fed ground Purina Laboratory Chow with or without 500 ppm of Aroclor 1254 (AR) ad lib for 2 weeks. In both normal and diabetic rats, AR administration decreased food consumption, weight gain and blood glucose concentration, and increased liver weight, liver:body weight ratio, total liver lipid, liver protein and malic enzyme (ME) activity. In the normal rat, AR increased the concentrations of acetoacetate and beta-hydroxybutyrate in blood, but in the diabetic rat the concentrations were markedly reduced. AR administration decreased the activity of phosphoenolpyruvate carboxykinase (PEPck) in normal liver and the activities of pyruvate carboxylase (PC), PEPck and glucose-6-phosphatase (G6Pase) in diabetic liver.


Histopathologic changes induced in rats by localized x-irradiation of an exteriorized segment of the small intestine.

The sequence of histopathological changes was described after X-irradiation of the exteriorized segment (3 cm) of the rat ileum with  a single dose of 2200 R. A one-year follow-up was provided in rats whose exteriorized intestinal segments were irradiated. Comparisons were made between one group of animals in which the superior mesentric artery and vein were clamped during irradiation and a second group in which these vessels were not clamped. A third group of sham-irradiated controls was used for comparisons. There was a delay in the onset and progression of the radiation damage to the mucosa of the hypoxic animals in the acute post-irradiation phase. In addition, prolongation of survival in the rats with the superior mesenteric vessels clamped was observed. Mucosal regeneration was noted, occurring at 52 days post-exposure. No adenocarcinomas were found up to 354 days after irradiation. An angiofibroma and a highly differentiated osteoid lesion were described.


Radiation effects on alkaline phosphatase and glucose-6-phosphatase in anatomically different regions of mouse intestine.

The effect of gamma irradiation on alkaline phosphatase and glucose-6-phosphate has been studied in three anatomically different regions of the small intestine at a surface dose of 400 R. Both the enzymatic activities were shown to be enhanced in duodenum, jejunum and ileum 24 hours after irradiation. The activity of alkaline phosphatase on day 3 tendeed to be low as compared to day 1 post irradiation, but glucose-6-phosphatase continued to rise even after day 3. Maximum rise of glucose-6-phosphatase was observed in the jejunum. On day 9, alkaline phosphatase was diminished below the controls in the whole of intestine, but appeared to be normal on day 10. Glucose-6-phosphatase in duodenum and jejunum on the other hand was comparable to that of control mice; but in ileum, the activity of this enzyme was below the normal values. Physiological significances of these enzymes in intestine has been discussed.


Ammonium sulfate precipitation as a tool for the study of androgen receptor proteins in rat prostate and mouse kidney.

Ammonium sulfate precipitation has been used for the separation of bound and free steroids in rat prostate and mouse kidney cytosol equilibrated with tritiated androgens. A high affinity, low capacity binding protein has been identified in the 35% saturation precipitate. Biochemical and physiological data indicate that this protein is identical with the previously described 8-10 S androgen receptor. It has been demonstrated that this receptor protein binds 17 beta - hydroxy-5alpha-androstan-3-one (DHT) and testosterone in both tissues. The apparent dissociation constant (Kd) of the prostatic receptor for DHT and of the renal receptor for testosterone is 1-2 nM. The number of binding sites equals 57 and 23 fmoles/mg protein in prostate and kidney respectively. Dterminations of apparent inhibition constants (Ki) for 26 steroidal and non-steroidal compounds suggest that the binding sites in these tissues is similar or identical.


Methyltrienolone, a specific ligand for cellular androgen receptors.

Methyltrienolone (R 1881), 17beta-hydroxy-17alpha-methyl-estra-4,9,11-trien-3-one, a very active androgen, binds specifically to rat prostate cytosol with a higher affinity than androstanolone. Unlike the physiological hormone, however, it is not bound by human sex steroid plasma binding protein, SBP. This specific ligand is thus a useful tool for the detection of elusive androgen receptors and for their study, for instance, in human tumors where interference from plasma contamination has to be circumvented.


Immunochemical comparison of estradiol-binding molecules in perinatal rat brain cytosol and serum.

Estradiol-binding macromolecules in fetoneonatal rat brain cytosol and serum were compared by immunochemical techniques. When treated by a double diffusion procedure, both cytosol and serum formed precipitin lines with rabbit antiserum specific for perinatal rat serum proteins. These lines fused completely, indicating, within the limits of detection of this particular antiserum, the presence of identical antigenic determinants in the brain and serum. Prior removal of immunoprecipitable material from cytosol or serum, after incubation with the specific antiserum, prevented formation of such precipitin lines. The procedure similarly presented specific estradiol-binding to macromolecules. It was therefore concluded that the specifically perinatal, antigenically similar, components in rat brain cytosol and serum (possibly representing alphafetoprotein) are responsible for the estradiol-binding activity in these two tissue compartments. Measurements of heme concentrations indicated that the alphafetoprotein-like material in the cytosol does not reflect blood contamination, but rather a separate population of similar or identical molecules.


Gastric cancer in Sudan.

All gastric tumours received in the University Department of Pathology and the National Laboratory between 1970-1974 were re-examined. Of 35 such tumours, 28 were carcinomas, 6 malignant lymphomas and 1 leiomyosarcoma. Histological grading showed that the majority of the patients reported in the very advanced stages of the disease. Accordingly, the resectability rate was low. The incidence of primary malignant lymphoma of the stomach (16.6%) is much higher than in Western countries but is in accord with reports from countries in the Mediterranean basin.


Serological study of amebiasis and toxoplasmosis in the Lindu Valley, Central Sulawesi, Indonesia.

Results of a serology survey in April 1972 for Entamoeba histolytica and Toxoplasma gondii antibodies among 484 inhabitants of the isolated Lake Lindu Valley of Central Sulawesi (Celebes) are presented. Indirect hemagglutination antibody titers for amebiasis were found in over 10% of the population, although only 3.7% demonstrated significant titers of 1:128 or greater. There appeared to be no relationship between antibody titers and the age and sex of individuals tested, and the frequency distribution of antibody titers indicates a low prevalence of invasive amebiasis in the population. Indirect hemagglutination antibody titers for Toxoplasma gondii equal to or greater than 1:32 were found in 27.1% of the total population, and it appeared that the prevalence of titers increased with age in both sexes. More families with cats had Toxoplasma gondii antibody titers than families without cats.


[Detection of the range of cytological changes in tumors induced in rats by nitrosoamines by means of passage in the anterior chamber of the eye].

12 rat liver tumors (high, purely and low differentiated hepatomas and adenocarcinomas), 3 kidney tumors, 1 lymphosarcoma and 1 round cell sarcoma of the uterus were transplanted and passed trough anterior chamber of the allogenic rat eyes. In 8 primary transplants of the liver tumors differentiation traits increased; three of them were morphologically undistinguishable from the normal liver tissue. In some transplants of embryonic liver and kidney displasia was detected. The results obtained give evidence in favor of a very high cytological variability of tumors at the early steps of progression, and indicate that the cultivation in the anterior chamber of the eye may be a proper model for investigation of cytological variability of both malignant and normal tissues.


Interaction of ultrasound with neoplastic tissue. Local effect on subcutaneously implanted Furth-Columbia rat Wilms' tumor.

Ultrasonic irradiation was employed by direct administration to the skin overlying subcutaneously implanted Furth-Columbia rat Wilms' tumors. Treated tumors were flattened and excavated and demonstrated no stigmata of hemorrhage or infection. There was a marked decrease in growth rate of the tumors with an increase in survival time of the host. Histologic assessment with the light microscope exhibited a sharp line of demarcation between the necrosed sonicated portion of tumor and the viable intact nonsonicated area of tumor. A blackened area of skin, which was not histologically similar to a burn, was interposed betwwen the site of application of the ultrasound and the necrosed tumor.


[Surgical tactics in malignant forms of ulcerogenic tumors of the pancreas].

According to the authors' findings malignant forms of ulcerogenic tumors of the pancreas in the Zollinger-Ellison syndrome clinically show a relatively favourable course in oncological aspect. As a rule, patients die from complications of peptic ulcer before a progressive tumor growth or its metastases result in mortality. Therefore, in cases when the routine radical operators prove to be unfeasible, it is recommended to perform surgery for the purpose of liquidating ulcer and conditions for its recurrence.


[Testing of the protective effect of cell-free lyophilized vaccine against Marek's disease in field trials].

The protective effect of a lyophilized vaccine against Marek's disease ("Keramvac"--Pfizer), prepared from a cell-free turkey's herpesvirus (strain FC 126), was compared in field trials with losses in the group of non-vaccinated chickens. Under the indicated conditions, the vaccine had only a 50.86% effectiveness. The possible causes of the reduced vaccination effect are discussed with regard to the pathomorphological and virological findings suggesting, among others, an increased incidence of the symptoms of the classical form of Marek's disease in the population investigated.


Hepatic drug metabolism and adverse hepatic drug reactions.

Drugs and other chemicals are usually metabolized in the liver in the drug-metabolizing enzyme system. The metabolites sometimes bind with cellular macromolecules and injure the cell directly or serve as new antigens to create immunologic injury in a delayed fashion. The immediate or toxic injury is dose-dependent, predictable and zonal in the liver lobule, usually in the central region. Carbon tetrachloride intoxication and acetaminophen overdose are examples of injury resulting from microsomal metabolism. Other injuries related to microsomal metabolism are those produced by vinyl chloride in polymerization plant workers and by methotrexate in psoriatics or leukemic children. Most adverse drug reactions affecting the liver and producing jaundice are unpredictable, delayed in onset, and only hypothetically related to microsomal metabolism in some instances. The two main types are cholestasis and viral-hepatitis-like. The former may be in a pure form, in which case it may be partly dose-dependent, or in a form mixed with hepatitis. Many drugs produce cholestasis in a small percentage of persons, and because the reaction is benign, albeit prolonged at times, such drugs continue to be used. The viral-hepatitis-like reaction involves few drugs and affects few persons, but can be fatal. The recognition that chronic hepatitis can be caused by drugs such as oxyphenisatin, alpha-methyldopa, and isoniazid has added a new dimension to the clinical problem of adverse drug reactions, which may extend to widely used and commonly available agents like aspirin.


[Role of the virus of Aujeszky's disease in respiratory diseases of swine].

Studies carried out on pig-breeding farms have established the presence of Aujeszky's disease virus in cases of bronchopneumonia in pigs. On seven out of eight farms with bronchopneumonia the virus wad demonstrated both virologically and serologically, and nearly 50 per cent of the examined diseased pigs on these and other farms had antibodies. The individual serologic studies of pigs having antibodies revealed that the antibodies appeared in the second month of the animals' fattening. This corresponded to the manifestation of the initial symptoms of bronchopneumonia in the respective group.


[Isolation and identification of a virus causing abortions and stillbirths in swine (Preliminary report)].

A virus of the RNA type, having no lipid envelope, acid-fast and stable to heat, was isolated from an aborted fetus and from the kidney of a piglet of a lower viability at birth. It was readily cultured, multiplying quickly in primary cell cultures of pig kidney and in the SPEV cell line, producing a characteristic cytopathic effect. It gave no hemagglutination with human, chicken, and swine erythrocytes. Serologically, it was identified as a swine enterovirus of serotype I, identical with the viruses described as the etiologic agents of SMEDI.


Ultrastructural and immunohistochemical study of the human kidney in  Argentine haemorrhagic fever.

In six lethal cases of Argentine Haemorrhagic Fever (AHF) a disease caused by Junin virus, kidney samples were studied by means of immunofluorescent and electron microscopic techniques.--The ultrastructural studies showed that the distal and collecting tubes presented a large number of virus like intracytoplasmic particles. Those particles were present in the lumen of the endoplasmic reticulum cisternae and showed two distinct morphological aspects. Some of them were of high electron density and contained a few granules. The others were larger in size, electron lucid, and contained a variable number of ribosome like granules. Both types of particles originated from the endoplasmic reticulum wall by a process of budding. The presence of these particles was coincident with a severe cell damage which lead to necrosis and desquamation; and with large quantities of Junin virus antigen as demonstrated by immunofluorescence.--On the basis of these observations it is assumed that in AHF the cell damage is due to direct viral replication within the affected cells.


Ultrastructure of pulmonary granulomatosis induced in rats by intravenous complete Freund's adjuvant.

Following the intravenous injection of complete Freund's adjuvant, changes in the rat lung were studied with the electron microscope. Interstitial granulomas were produced and whereas on light microscopy these appeared to consist mainly of epitheloid cells, electron microscopy showed that the granulomas were largely made up of macrophages. Epithelioid cells were in fact few in number, atypical in appearance and limited to the periphery of some granulomas. Fenestrated capillaries were also found at the edge of the granulomas. The alveolar macrophages were increased in number and size but marked cytoplasmic vacuolation and a paucity of lysosomes are consistent with our previous suggestion that the phagocytic and migratory properties of these cells are weakened or inhibited. Alterations were found in both types of alveolar epithelial cell with the appearance of intermediate cell forms.


A light and electron microscopic study of endometrial sarcomas of the uterus.

38 endometrial sarcomas were studied light microscopically, 5 of them additionally with the electron microscope. According to their histological appearance these tumours were classified as homologous stromal sarcomas (13 cases), pure heterologous (4) and mixed mesodermal sarcomas (21).  The ultrastructure is described with reference to the cytoplasmic differentiation of the tumour cells. A basic immature cell type was present in all endometrial sarcomas irrespective whether they were of pure homologous or of mixed type. In regard to the striking similarity between this cell and cells of the early proliferating endometrium an origin of all endometrial sarcomas from immature stromal cell is suggested. The mixed tumours contain a number of highly differentiated cells like smooth muscle cells, rhabdomyoblasts, fibroblasts etc. As there was a number of cells intermediate in cytoplasmic appearances between immature and differentiated end stages it seems likely that the latter develop from the former. Thus the undifferentiated cell represents the stem cell from which the differentiation processes of all cell lines take their origin. A transition from neoplastic epithelium to neoplastic mesenchyme could not be demonstrated in thed that the mixed epithelial-mesenchymal endometrial tumours originate by a simultaneous malignant transformation of cells with a fixed differentiation potency.


[Cylindroma of the breast. A histochemical and histogenetic study (author's transl)].

The histochemical study of mucopolysaccharide components of the ground substance of the cylindroma lends force to their epithelial origine. The myoepithelial cell, which is ectodermal in origin, plays an essential role in their secretion. Silver impregnation of normal and dysplastic breast illustrates the secretory function of myoepithelial cells and their possible implication in the histogenesis of cylindroma.


[On the etiology of spindle-shaped acid-fast bodies in the human spleen (author's transl)].

Spindle-shaped acid-fast bodies have been identified only in lymph nodes till now. Their nature and their origin remained unclear. We have also found these bodies in the human spleen. Their staining reactions and their correlations to age, sex, weight of spleen, and to hemosiderin deposits were examined. They have been encountered in 50% of cases of hereditary spherocytosis and in 41.7% of cases of traumatic rupture of the spleen--but only in 2.3% of all other cases of groups of various other disorders. We conclude from our results that: 1. The spindle-shaped acid-fast bodies are made of ceroid. 2. They are not causative organisms and therefore cannot be of importance in the etiology of sarcoidosis. 3. They derive from increased destruction of erythrocytes. 4. They originate due to oxidative polymerization of membrane lipids. 5. They may also be found in absence of any fat-metabolism disturbance.


[The ultrastructure of fibrous and histiocytic skin tumors (dermatofibroma, dermatofibrosarcoma protuberans, fibroxanthoma, and histiocytoma) (author's transl)].

A report on the ultrastructure of the following skin tumors: dermatofibroma (7 cases), histiocytoma (4 cases), dermatofibrosarcoma protuberans (1 case), and fibroxanthoma (1 case). Because of their different ultrastructural characteristics a division into two groups is possible: one group of tumors would include dermatofibroma, dermatofibrosarcoma protuberans, and fibroxanthoma, where the formation of fibers is extensive and fibroblasts are suggested for its histogenesis. These types of tumor differ from histiocytoma, the cellular character of which is determined by a very pronounced phagocytosis and storage of lipid and hemosiderin; a histogenesis from histiocytes is probable. The nuclei of dermatofibroma and histiocytoma show a simple surfacedevelopment, whereas the nuclei of dermatofibrosarcoma protuberans and fibroxanthoma show multisegmented nuclei ("labyrinth nuclei"). In the case of dermatofibrosarcoma protuberans this kind of nuclear segmentation seems to be a morphologic correlate of its semimalignancy. Based on ultrastructural analysis a classification of these fiber-producing tumors into "fibrous histiocytomas" is not justified.


[Quantitative cytochemical detection of enzymes in cultured cells following infection with Rous virus].

The method of visual quantitative estimation was employed to determine the index of enzymes activity in embryonal cells cultures infected with Rous virus. In early terms (1-7 days after infection) a moderate production of diformazane was noted in the presence of glucoso-6-phosphatiosomerase, phosphoglucomutase, pyruvatoxidase, NAD. H2- and NADP. H-2-diaphorase, other enzymes showing no distinquishable deviations in the activity, as compared with the normal culture. In later terms (13-27 days) during the proliferation of the transformed cells there was found an increased level of the glycolysis enzymes activity, pentose cycle, hydrolysis of ortho-phosphoric acid monoethers and reduced lemon acid cycle and tissue respiration. Cytoplasmatic vacuoles formed in the transformed cells seem to represent hypertrophic lysosomes and phagolysosomes.


[Tumours of the corpus callosum in the anglogram (author's transl)].

On account of the median location of tumours of the corpus callosum, serial angiography reveals displacements only at an advanced stage. In many cases there is no lateral displacement of the anterior cerebral artery and a lateral angiogram of the pericallosal artery does not reveal tumours of the corpus callosum, especially if they are associated with a vascular pattern characteristic of arteriosclerosis or hydrocephalus. The deep mid-line veins are not consistently displaced. A differentiation of the vascular pattern associated with small tumours of the corpus callosum  from normal variations may be problematic. The inner veins cannot be visualised sometimes on account of increased intracranial pressure and a slowing of the circulation.


Cyclic adenosine-3',5-monophosphate concentration and enzyme activities of cerebrospinal fluid in meningitis of children.

The concentration of cyclic adenosine-3',5'-monophosphate (cAMP) and the activities of some enzymes of 29 children were measured from cerebrospinal fluid (CSF) and plasma at various stages of meningitis. The CSF cAMP values in acute untreated phase of aseptic and purulent meningitis were equal, but significantly higher than those of convalescent children with no pathological clinical or laboratory findings. During the whole course (up to 2 weeks) of antimicrobial treatment of the purulent meningitis CSF cAMP concentration was higher than in the convalescent phase. Of the CSF enzymes studied, the lactic dehydrogenase activity seemed to be the best indicator of changing stages of meningitis. It was clearly elevated in the acute, untreated phase of purulent meningitis then decreasing during the course of treatment. In aseptic meningitis this activity was at the normal level and the activities of creatine kinase and acid phosphatase behaved similarly. The plasma cAMP concentrations in the acute phase of purulent meningitis were in the same range as in the CSF. During the treatment no significant changes were seen. The enzyme activities in the plasma were normal. The CSF cAMP level seems to be a sensitive indicator of metabolic disturbances in meningitis and may serve as a diagnostic aid.


Spontaneous variations in the cell population of a T-cell lymphoma during tissue culture and transplantation.

Immunologically induced T-cell lymphomas were kept for long period fo time in isotransplantation and in tissue culture. Initially, a certain number of cells within the tumor showed differentiation towards histiocytes. These disappeared completely after about the twentieth graft generation when the tumor changed toward a more atypical and more uniform neoplasm. That change was correlated with a decrease in transplantability, a limited growth in tissue culture, and a decrease in density of theta antigens on tumor cell membranes. While the original tumor and early grafts contained occasional C-type particles, these were never demonstrated in late tumor grafts. The possible implications of these changes are discussed.


Neurocristopathy, neuroendocrine pathology and the APUD concept.

The neurosecretory cells of the hypothalamus, and the cells of the pituitary gland and the pineal, are here grouped together as a central neuroendocrine division of the APUD series. The larger, peripheral division comprises the remainder of the original series. All the cells are proven or presumptive derivatives of neuroectoderm so that, with the present exception of the parathyroid gland and its products, peptide hormone endocrinology becomes neuroendocrinology. It follows that the pathology of the APUD cell series must be regarded as neuroendocrine and it is suggested that it can best be expressed by the term neurocristopathy (Bolande, 1974). Tumours of the series, properly neurocristomas, are preferably called apudomas because their common cytochemical (APUD) and ultrastructural characteristics provide the pathologist with a ready means of diagnosis.


[The evaluation of the cyclophosphamide sensitivity of human tumours by determining the incorporation of tritiated uridine and thymidine into the nucleic acids of human tumor cells in vitro in presence of 4-hydroxycyclophosphamide (author's transl)].

A new in vitro assay for screening the sensitivity of human tumour cells against Cyclophosphamide has been developed. While biologically activated Cyclophosphamide was unsuitable because of unpurities in the material, synthetic 4-Hydroxycyclophosphamide was shown to inhibit the incorporation of tritiated uridine and thymidine into the nucleic acids of human tumour cells in vitro. 29 tumours including 14 mammarial carcinomas, 8 ovarial carcinomas and 7 other malignant tumours were tested. While 12 tumours showed a significant and 5 only a slight inhibition of the 3H-uridine incorporation in vitro. 12 tumours showed no effect. Histologically none-differentiated tumours were more sensitive against 4-Hydroxycyclophosphamide as compared with the more differentiated ones. First observations point to 4-Hydroperoxycyclophosphamide instead of 4-Hydroxycyclophosphamide as a more suitable form of activated Cyclophosphamid for the in vitro assay of Cyclophosphamide sensitiveness because of the higher stability and better availability of this compound.


[Cardiac glomus tumor. Light- and electron microscopic investigations (author's transl)].

A cardiac glomus tumor, first described by Masson, was observed in a 28 year old woman who presented symptoms of cardiac dysfunction. Electron microscopic studies disclose a wide range of differentiation of glomus cells from smooth muscle cells to epitheloid cells. The common feature of both cell types include cytoplasmic microfibrils, fusiform condensations and small vesicles. The endothelial cells also show some structural similarities to these glomus cells. The histogenesis of this cardiac tumor is discussed on the basis of its ultrastructure and its uncommon localization. It is concluded that cardiac glomus tumors arise from primitive mesenchymal cells.


Study of globular bodies found in hepatomas of Swiss mice.

In spontaneous hepatomas of Swiss mice a great number of eosinophilic globular bodies was observed without cirrhosis. Electron microscopy revealed their protein nature and origin from the rough endoplasmic reticulum cisternae.


Increasing occurence of tumour cell -- tumour cell emperipolesis in the regenerating JB-1 ascites tumour.

During the investigation of JB-1 ascites tumour cells in recurrent growth several cases of emperiopolesis were observed. Different types of emperipolesis are presented. Light microscopical serial sections, autoradiography and transmission electron microscopy indicate that the cells involved in emperipolesis are separate cells, and the authors suggest that cytopagocytosis is the initial mechanism in the development of emperipolesis.


The kininase activity of Ehrlichs' ascites solid tumor after treatment with oncolytic clostridia.

For the first time the effect of bacterial kininases of Cl. oncolyticum M 55 ATCC 13.732 could be demonstrated in the tumor itself. This is shown by an increased degradation of kinins by spore-treated tumor tissue in comparison with respective controls. The results indicate the influence of kininases on the capillary circulation of the tumor tissue as one of the fundamental reactions of oncolysis.


[Transplacental oncogenic effect of ethylnitrosourea in rabbits (author's transl)].

50 mg/kg ethylnitrosourea (ENU) per dose, diluted in a 0.9%NaCl/1%NaH2PO4 solution (pH 6.2) were administered intravenously to three pregnant rabbits. The injections were carried out on the following days of gestation: 21., 26., and 30./21., 25., and 31./22., 25., and 30. From the total offspring (22), 16 rabbits could be raised. In 12 animals, kidney tumours were observed after a latent period of 2--2 1/2 years. The induced tumours are generally composed of both epithelial and mesenchymal tissue elements. Two tumours of the series are of a pure epithelial or a pure mesenchymal nature respectively. In most of the mixed tumours, classified as Adenocarcino-Sarcomas (10), the epithelial and mesenchymal elements are closely integrated, sometimes one component predominated over the other one. Histologically the ENU-induced mixed tumours of kidney in rabbits and the "dysontogenetic" kidney tumours of children (WILMS) show comparable structural characteristics.


In-vitro demonstration of cell-mediated immunity to vaccinia virus in man.

Cell mediated immunity to vaccinia virus in man was studied by lymphocyte transformation. Vaccinia antigen, propagated on BHK-21 and Vero cells, could be used successfully for in-vitro testing after partial purification as well as crude infectious homogenates. Vaccinia antigen preparations were effective both in the infective and the inactivated state. Inactivation was usually accompanied with a certain loss of stimulating activity. Development of cell mediated immune response in-vitro after first vaccination was investigated in 17 adults. Vaccinia virus specific lymphocyte transformation was seen in the second week after vaccination in all cases. Following revaccination no increase of lymphocyte transformation ratio could be observed in 11 persons studied. At the same time the titers of humoral antibodies were elevated.


[Transferrin variants: significance and identification in paternity cases (author's transl)].

Transferrin phenotypes were determined in 3380 sera of unrelated persons of the western region of Germany with 97.60 percent for TfC and 2.40 percent for Tf variants. Identification was achieved by immunochemical means or through autoradiography. Relative mobilities in some variants were measured using Tf B2C (0.7) as reference. Application of Tf variants is demonstrated in paternity cases.


[Fibrillar and tubular fine structures in the cytoplasm of Entamoeba histolytica (author's transl)].

The electron-microscopical study of conventional fixed and contrasted Entamoeba histolytica-trophozoites from Diamonds monoxenic TTY-medium revealed "thick fibrils" in the vesicular cytoplasm of the parasites. They are 9-14 nm in diameter and are therefore considered to be myosin-like filaments, that are spread mainly in the tail or the uroid of the moving ameba. No association with microfilaments (MF) or other organelles could be observed. During the same investigation microtubules (MT) of variable length are described having a diameter of 35 nm, surrounded by a 19-25 nm wide capsule. They are distributed singly or in bundles with a maximal diameter of 350 nm. Some of the MT were coiled up to a helical shape.


Virulence of bacteria-associated, Crithidia-associated, and axenic Entamoeba histolytica: experimental hamster liver infections with strains from patients and carriers.

Experimental infections of the hamster liver were carried out with five strains from patients with clinical amoebiasis and ten strains from asymptomatic carriers. Inocula of comparatively small size (12000-36000 amoebae) were injected under the liver capsule. 1. The virulence of the patient strains varied from 21-96% (see article) and declined sharply within 7-15 weeks after elimination of the associated bacterial flora. The virulence of the carrier strains varied from 0-100%, probably fluctuating with changes in the concomitant bacterial flora (Table 1). 2. The interrelation between size of inoculum, period of bacteria-free growth, and virulence was demonstrated with a Crithidia-associated patient strains (Table 2). 3. A patient strain showed a faster decrease of virulence during axenic than in Crithidia-associated cultivation (Table 3). 4. Two successive passages through hamster liver resulted in a marked increase of virulence of two bacteria-free strains, lasting for several months (Table 4). 5. A significant enhancement of virulence of Crithidia-associated and axenic amoebae by reassociation with a mixed bacterial flora during two weeks, followed by elimination of the bacteria, was demonstrated with two strains. The restored virulence was lost again within a few weeks (Table 5). 6. The virulence of an attenuated patient strain did not become manifest by adding large numbers of dead amoebae to the inoculum (Table 6). 7. The pathology of the different lesions caused in the hamster liver by the amoebae is described, including one of a granulomatous type, frequently found after inoculation with bacteria-free amoebae. 8. In an attempt to explain the occurrence of strains differing in pathogenicity an hypothesis is put forward based on the idea of selection of virulence and avirulent amoebae.


[Secondary anemorrhea in processes in the sella region].

The authors report on 36 patients suffering from a tumor in the chiasm-sella-turcica region and their symptoms. The secondary amenorrhea and the disturbances of cycle are the first symptoms in 19 women from altogether 26 women in the stages of live from 14 to 50 years. It is commendable to take the expansive intracranial process in the chiams-sella-turcica region into consideration by the statement of the differential diagnosis of the secondary amenorrhea.


[The hidradenoma of the vulva].

The hidradenoma of vulva is a rare tumor. After description histogenesis and microscopic appearance demonstrated histological difficulties. An exact microscopic diagnois is necessary because the hidradenoma is a benign tumor.


[Comparative studies on the action of chlorine and ozone on polioviruses in the reprocessing of drinking water in Essen (author's transl)].

The present study was performed in order to evaluate comparatively the inactivation of polio virus type I strains (wild type and attenuated) by means of chlorine and ozone. Polio virus type I was chosen with regard to its epidemiological behaviour and high stability in drinking-water and sewage lines. In view of the lack of propagation techniques, hepatitis viruses A and B, unfortunately, could not be used for these experiments. The experiments were done under laboratory conditions only, and not in the water recovery plant because of hygienic reasons. Defined quantities of disinfectants were examined for their virus-inactivating effect in water without redox-potential (double-distilled water), water with low defined redox-potential (double-distilled water + KOH), previously chlorinated water with a residual chlorine content of 0.03 mg chlorine per liter (tap water) and water with a high redox-potential (well water from the drinking-water plant). Time-course studies were performed, both with chlorine and ozone, in order to evaluate the characteristics of the inactivation procedure. The experimental conditions chosen varied from experiment to experiment to obtain relevant conclusions for the practice. On the basis of our results, and taking into account the quantitative differences in effect, chlorine and ozone principially can be considered equivalent in their action of virus-disinfection. Both, the initial rate and the kinetics of virus disinfection are really identical. Both disinfectants are dependant on the condition of the water (redox-potential, pH etc.) to a great extent in their efficacy. Therefore, a decision of whether or not ozone should substitute for chlorine for the drinking-water supply in Essen cannot be drawn on the basis of virological experiments. This decision, then, depends more or less on other questions - such as relative costs and practicability of the ozonization on a large technical scale. The safety risk and technical reliability of the ozonization process is of particular significance. In the present condition of the Essen reservoir water, a good virus disinfection can be expected already with 1.0 to 1.5 mg ozone/liter (dissolved!); such a concentration guarantees very little residual ozone and, thus, makes then this procedure technically feasible. Continuous checking of the redox-potential and the amount of the ozone added is necessary. With regard to a continuous supply of ozone, the dependence on current supply must be guaranteed. Ozonization of water, probably by the cleavage of humic acid, promotes bacterial recontamination of the drinking-water in the city taps(Stalder und Klosterkötter, 45). Therefore only a combined pre-ozonization with subsequent chlorination would guarantee, both, safety and improvement of the cosmetical conditions of the drinking-water. Such a combination would be feasible with highly reduced amounts of ozone and chlorine.


[Histological diagnosis and therapy of rare breast neoplasms].

Occasional rare benign and malignant breast tumours present diagnostical difficulties, how a report on 8 rare forms of tumours among 564 breast rumors (351 benign, 213 malignant) of the years 1965--1972 at the Universitäts-Frauenklinik Greifswald shows. We found among 351 benign breast tumours 2 rare forms: 1 tubular adenoma and 1 nodular lymphoreticulosis. We diagnosed among 213 malignant breast tumours 6 rare tumour-types: one at a case an unilateral respectively a bilateral noninvasive lobular carcinoma from the carcinoma-in-situ-type, 1 spindlecell- and 2 reticulosarcoma, which in one case the starting-point of the heterogeneous differentiated reticulosarcoma was obvious situated in a teratoid tumour. Last case dealt with a real cystosarcoma phylloides, of which oncological and terminological problems were additional discussed.


[Effects of diethyldithiocarbamate on the acute toxicity and the acetylcholinesterase inhibition by methylparathion in mice].

Acute toxicity of methylparathion male mice is reduced by DET in dose-range from 50 to 300 mg/kg. Mean survival time in LD100 range of methylparathion is significantly prolonged. Inhibition of AChE in vivo is reduced, too. The observed dose-effect-relations show an approx. 10-fold increase in equi-effective doses after DET-pretreatment. DET has no protective effect both in vivo and in vitro, if methylparathion is added to the brain homogenate of mice. As probable mechanism of action a change in methylparathion-metabolism induced by DET in the system of mixed functional oxidases is discussed.


Correlation between drug induced changes of acetylcholine release and acetylcholine fractions in rat brain.

After administration of eserine, a new acetylcholine (ACh) subfraction called f+ is formed in rat brain tissue. References and methods are given for the calculation of this subfraction, which can be isolated and determined only together with the so-called "free" ACh fraction. Alterations of the f+-ACh subfraction caused by barbital, urethane, pentetrazol, arecoline and scopolamine in telencephalon, cortex and striatum of rat brain are connected with changes of ACh concentrations determined in comparable releasing tests.


[Antiviral thiosemicarbazone and related compounds. III. Quantitative relationships between structure and antiviral activity of isantin-beta-isothio-semicarbazone against mengo virus].

The virostatic activity of isatin-beta-isothiosemicarbazones can be described quantitatively by hydrophobic, electronic, and steric substituent constants using multivariate regression analysis. A preceding Free-Wilson analysis allows data smoothening, and thus improved adaptation. Predictions made on the basis of the quantitative structure-action relationships obtained could be confirmed experimentally by synthesizing and testing the corresponding compounds.


On the influence of fructose-6-phosphate, ammonium, ATP and AMP on the conformation of the phosphofructokinase from rabbit muscle.

By means of circular dichroism measurements in the range from 210-240 nm and 250-300 nm it is shown that conformational changes of the phosphofructokinase from rabbit muscle correlate with the action of effectors on the enzyme. The postulated active and inactive states differ in the secondary structure. Addition of activators causes a conformational change which is interpreted as the transition of the inactive into the active state. At 210-240 nm no reversion could be observed but at 250-300 nm there are some indications for at least partial reversion.


Serological analysis of an oncornavirus (PMF virus) detected in malignant permanent human cell lines.

Immunodiffusion analysis of the PMF virus which was detected in malignant permanent human cell lines revealed positive reactions with antisera against the Mason-Pfizer monkey virus (MPMV). No cross-reactivity was demonstrated with murine leukemia virus (MuLV), rat leukemia virus (RaLV), hamster leukemia virus (HaLV), feline leukemia virus (FeLV), simian (woolly monkey) sarcoma virus (SSV-1) and mouse mammary tumor virus (MTV). The cross-reactive antigens of the PMF virus and the MPMV are considered as evidence for the human origin of the PMF virus.


Protamine inhibition of the oxidative phosphorylation in intact, cytochrome c-depleted and restored mitochondria.

On the basis of polarographic data it is shown that protamine has a biphasic effect on the respiration of intact mitochondria. At lower protamine concentrations respiration is stimulated and this combined with a decrease of the respiratory control index; at higher ones respiration is inhibited and respiratory control is lost. In cytochrome c-depleted and restored mitochondria protamine effect on oxidative phosphorylation is only inhibitory. Increasing cytochrome c concentrations restore respiration in protamine-treated cytochrome c depleted mitochondria but not the respiratory control. Binding of cytochrome c to mitochondria is studied by determining from Scatchard plots the number of high affinity binding sites (n) and their stability constants (K). In absence of protamine in intact mitochondria n = 2.7 and K = 4.67-10(6) M-1; in cotochrome c depleted mitochondria n = 4.7 and K = 5.16-10(6) M-1. In both types of mitochondria protamine decreases significantly n as well as K. These data show that protamine may affect oxidative phosphorylation by causing desorption of cytochrome c from the inner mitochondrial membrane.


Perchloric acid-soluble proteins and protein-bound hexoses in serum and tissues of normal, hypo-and hyperthyroid rats.

The total content of perchloric acid-soluble proteins (PCA-SP) and protein-bound hexoses (PBH) were studied in blood serum and tissues (liver, kidney, lung, brain) of normal, hypo- and hyperthyroid rats. The results obtained indicate that the hyperthyroid state induced an increase in both PCA-SP and PBH in blood serum and studied tissue homogenates, and hypothyreosis causes a decrease of total glycoproteins content in all studied materials. The results were counted per 1 g of protein and in this way the nonspecific effect of thyroid hormones on the protein metabolism had no influence on the measurements.


[The effect of preparative pancreatic digestion with collagenase on the glucose stimulated insulin secretion of isolated Langerhans islets].

Pancreatic islets of wistar rats, isolated after 15 min of digestion with collagenase, secreted insulin in response to 15.0 mM glucose within 2 min and showed the typical sigmoidal glucose response during an incubation time of 15 and 60 min, respectively. Islets, isolated after 35 min of digestion with collagenase, responded with delay after stimulation with glucose (after 15 min of incubation), and are characterized by an increased "release" in the presence of 2.5 mM glucose.


Pseudomonas cytochrome c peroxidase XI. Kinetics of the peroxidatic oxidation of Pseudomonas respiratory chain components.

The steady state kinetics of cytochrome c peroxidase from Pseudomonas aeruginosa (PaCCP) has been studied by initial velocity techniques using several cytochromes c (550 and 555 P. aeruginosa; 551 P. fluorescens) and Pseudomonas azurin as electron donors and hydrogen peroxide as electron acceptor. From the initial velocity patterns a sequential mechanism with compulsory substrate-binding order is proposed for PaCCP. A comparative kinetic study of the peroxidatic oxidation of cytochrome c-551 (P. aeruginosa) by yeast cytochrome c peroxidase was made to evaluate the significance of electrostatic interactions in complex formation between the enzyme and substrates.


Subcutaneous mastectomy in 80 patients with breast tumours. Indications, surgical results and pathological findings.

Eighty patients were operated upon with subcutaneous mastectomy and reconstruction with prosthesis. Seventy operations were performed on both breasts. The indications used were carcinoma in situ in a previous biopsy, pronounced epithelial proliferations on at least two previous occasions or recurring fibrocystic disease after at least two previous biopsies. Since the autumn of 1971, the operation has been performed as a one-stage procedure and we have had few complications. The appearance of the breasts was evaluated at review 3-60 months after operation. Most patients found the results acceptable or good. The mamilla always lost its sensibility, but the sensibility of the remaining skin of the breast sometimes returned with time. Most of the patients were well satisfied with the procedure and thought it better than any other sort of treatment. The tissues removed were thoroughly studied. Changes in the breasts were often bilateral and pronounced epithelial proliferation and carcinoma in situ were fairly common. Invasive carcinoma was found in 2 instances. The importance of the histologic examination of removed tissues is stressed. A regular follow-up of these patients is important for assessing the value and the risks of subcutaneous mastectomy.


Assessment of gonadotrophin secretion in women with anorexia nervosa.

The LH and FSH secretions in 21 patients with anorexia nervosa were assessed by radioimmunoassay. On a single iv injection of 100 mug LH-releasing hormone (LH-RH), 8 patients showed LH response comparable to that of normal cyclic women in the follicular phase, and 5 patients showed excessive response. Although the remaining 8 patients showed almost no LH response, infusion of 400 mug LH-RH or daily im injections of LH-RH restored gonadotrophin responsiveness to LH-RH in all patients tested. The initial rise in LH during clomiphene citrate treatment was observed in 3 out of 5 patients, but the second peak of LH was found in only one patient. The initial suppression of LH following iv injection of conjugated oestrogen (Premarin) was observed in 9 out of 10 patients but a rebound increase comparable to that in normal cyclic women in the mid-follicular phase was found in only 3 patients. These results seem to suggest that impaired hypothalamic function is the cause of gonadotrophin deficiency and the resultant anovulation in most patients with anorexia nervosa.


Human lymphocyte binding and deiodination of thyroid hormones in relation to thyroid function.

The human lymphocyte has been investigated regarding its function as a thyroid hormone target cell. Binding and deiodination of the thyroid hormones were determined after simultaneous incubation of 131I-labelled L-thyroxine (131I-T4) and 125I-labelled L-triiodothyronine (125I-T3) with lymphocytes from healthy subjects, from hyperthyroid and primary hypothyroid patients before and after treatment. The mean percentages of binding, 8.0 +/- 0.5 (mean +/- SEM) for 131I-T4, and 9.7 +/- 0.4 for 125I-T3 in the control group, were increased in the hyperthyroids to 10.1 +/- 0.4 and 12.7 +/- 0.6 respectively, and in the hypothyroids to 10.9 +/- 0.7 and 12.8 +/- 0.6. All elevated values returned to normal with successful treatment. The mean percentage of deiodination, 12.0 +/- 1.7 for 131I-T4, and 6.5 +/- 0.9 for 125I-T3 in the control group, showed a threefold increase in the hyperthyroid patients, to 35.9 +/- 3.2 and 20.2 +/- 1.9 respectively and remained unaltered in the hypothyroid patients. The values of successfully treated hyperthyroid patients were normal and those of the treated hypothyroid patients below normal.


Oestradiol receptor levels in the human fallopian tube during the menstrual cycle.

The levels of cytoplasmic high-affinity oestradiol receptor sites were determined in the isthmus, isthmus-ampulla, ampulla and fimbria of human Fallopian tubes obtained from 23 women during the proliferative and secretory phase of the menstrual cycle and after menopause. Each segment was homogenized in 0.25 M sucrose and fractionated by differential centrifugation into an 800 g X 15 min nuclear pellet and a 100,000 g X 1 h cytoplasmic supernatant and pellet. The nuclear and cytoplasmic pellets were extracted with 0.01 M Tris/HCl pH 8.0 containing 0.25 M sucrose, 1 mM EDTA and 0.1 M KCl. The receptor levels were determined in the 100,000 g X 1 h supernatant (free receptors) and in the KCl extracts (bound receptors). Values are expressed per mug DNA. The concentration of receptors (total, free and bound) was significantly greater in the ampulla than in the isthmus in both phases of the menstrual cycle (P less than 0.001). The concentration of free receptors in the isthmus, isthmus-ampulla and ampulla obtained in the proliferative phase was not significantly different from that of the secretory phase. In the fimbria a significantly higher concentration (P less than 0.01) was observed in the proliferative phase. The bound receptors were significantly higher in all regions in the proliferative phase than in the secretory phase (P less than 0.01). As a consequence the concentration of total receptors was significantly greater along the tube in the proliferative phase (P less than 0.01). The levels of oestradiol in the nuclear pellet of each segment as measured by radioimmunoassay were significantly greater in the isthmic region (P less than 0.01) than in other regions of the tube. The inverse relationship between the concentration of oestradiol receptor sites and the nuclear levels of oestradiol along the Fallopian tube is discussed.


Hybridization of mouse leukemia virus c-DNA to mouse repeated DNA sequences.

Experiments of hybridization between mouse leukemia virus synthetic 3H-DNA probe and mouse main band and satellite DNAs indicate that there is not a higher concentration of viral sequences in the satellite DNA. On the contrary, viral sequences appear to be enriched in the fast renaturing intermediate main band DNA.


[Histochemical investigations on liver and kidney of the rat after intoxication with organophosphates (author's transl)].

Comparative histochemical investigations of the livers and kidneys of female Sprague-Dawley rats were made: 1. after intoxication with O-pinacolyl-methyl-phosphonylfluoride (Soman), O,O-diethyl-O-p-nitrophenylphosphate (Paraoxon, E 600); 2. after starvation of 24 to 36 h; 3. after hypoxia for 24 h. From the results it is concluded that the fatty degeneration of liver and kidney after PE.-intoxication is caused by intracellular hypoxia. No fatty degeneration of the organs was observed following deprivation of food for 36 h. A decreased level of cholin which might be caused by the intoxication with PE., and which could be the reason for the fatty degeneration was not found. This was indicated by the unaltered evidence of phosphatids in the intoxicated animals.


[Histochemical and histological investigations on the vagina of the beagle she-dog during various functional conditions (author's transl)].

Histotopochemistry and histology of vaginal epithelium in female beagles were studied during oestrus, metoestrus-dioestrus, post partum period and at days 20, 30, 40, 50, 60 of pregnancy. During oestrus the epithelium is uniform throughout the whole vagina: it presents itself as a high, uncornified, stratified squamous epithelium with some glycogen and lipid droplets but devoid of leucocytes. The intercellular gaps of the stratum intermedium give strong reactions for ATPase and alkaline phosphatase. The activities of oxidoreductases studied decrease continuously from basal to apical. During gravidity, post partum period and metoestrus-dioestrus distinct morphological and histochemical differences can be stated between the cranial and caudal vaginal portions. Caudal vaginal epithelium outside oestrus remains of stratified squamous type. It exhibits strong mucification during pregnancy. The PAS-positive mucous substances prefer a position in the enlarged intercellular gaps of stratum intermedium and superficiale. During pregnancy the epithelium is relatively rich in acid and completely devoid of alkaline phosphatases. Outside oestrus the epithelium of the cranial vaginal region is a relatively flat, stratified columnar one and contains leucocytes with regularity. Also the cranial vaginal portion undergoes mucification during pregnancy with a maximum about day 33. The mucous material is situated intracellularly and not within the intercellular gaps. Further, larger intraepithelial mucus cysts are observed. Alkaline phosphatase is found during gravidity in the basal region and an adluminal border of the epithelium. The reactions for oxidoreductases are strongest in the columnar cell layer which shows more functional adaptations than the remainder of the epithelium. Histochemical tests for beta-D-glucuronidase and leucine aminopeptidase give negative results in the whole vagina during all different functional stages studied.


Histochemical study of metrial gland cells through the last week of pregnancy in the albino rat.

The metrial gland cells of the rat were studied from day 16 to 21 of pregnancy through enzyme histochemistry. The following enzyme activities were tested: 2 carboxylic esterases, 4 phosphatases, 1 aminopeptidase and 10 dehydrogenases including 4 which are involved in steroid metabolism. Although acid phosphatase activity was strong in mesenchymal cells, it remained undetected in large, sometimes binucleate cells lining central and subplacental vessels of the mesometrial triangle. 5-Bromo-indoxyl acetate esterase was likewise absent from the parietal vascular cells of the central artery. The study of 6 enzyme activities, i.e., GPDH, 3-OU-BDH, G6PDH, 3-B-HSDH, primary and secondary alcohol dehydrogenases, allowed to conclude that metrial gland cells are actively involved in steroidogenesis and lipid catabolism. Maternal origin of this gland can be sustained with reference to the pattern of acid phosphatase, indoxyl-esterase and some oxidoreductases II activities distribution which appears to be different from what is found in the trophospongium area.


The effect of ACTH and cortisone on the carbohydrate-protein complexes of different types of epithelium in relation to their embryological origin.

Using histochemical methods the authors studied the effect of ACTH and cortisone on carbohydrate-protein complexes of epithelial cells derived from 3 different germ layers. It has been shown that cortisone increased the intensity of PAS reaction in all types of the epithelium investigated. Changes in acid mucosubstances after treatment with cortisone were different. After the administration of ACTH the observed changes in epithelium were not parallel to the changes seen after treatment with cortisone.


[In vitro evaluation of antiviral inhibitors by means of a turbidity method (author's transl)].

The paper presents a photometric method for the determination of virus-induced alterations (cytopathogenic effects) of cells based on nephelometric analysis. These were taken at varying time intervals after infection and with different multiplicity of infection. It was demonstrated that suppression of virus-induced CPE by the known inhibitors could also be followed by turbidity measurements. The in vitro experiments were carried out in the 2 following virus-cell-systems: Pseudorabies virus in chick-embryo cells and Mengo virus in FL-cells, respectively. According to these studies the measurements were extended to other virus strains and inhibitors (antibiotics, chemicals, and antimetabolites). The results obtained confirm the applicability of the photometric method for the screening of antiviral drugs.


Enzyme histochemistry of undecalcified bone and cartilage embedded in glycol methacrylate.

Undecalcified bone and cartilage tissue blocks were fixed for 3 h in cold formol-calcium, rapidly dehydrated with a graded series of cold ethanol, and embedded in glycol methacrylate. 2 mum sections were produced with a Sorvall JB-4 microtome using glass knives. The quality of the sections were usually excellent except for hard bone from old subjects where the bone sometimes shattered while sectioning. This method is short, relatively uninvolved and eliminates en bloc decalcification. Moreover, the method is gentle enough to allow the histochemical demonstration of alkaline and acid phosphatase by the azo dye methods, and acid phosphatase, 5'-nucleotidase and ATPase by the lead precipitation methods.


Renal transplantation in children.

From July 1967 to September 1974, 26 kidney transplantations were carried out in 16 children aged 6 to 17 years, in Gotherburg. The average age at the primary transplantation was 12 years and average body weight 29.7 kg. Five patients had familial juvenile nephronophthisis, 5 chronic glomerulonephritis, 5 chronic pyelonephritis, and one bilateral Wilms's tumour. Four patients were predialytic. Fourteen grafts came from living related donors. The surgical technique was standard as was the immunosuppression with azathioprine and cortisone; exceptionally antilymphocyte globulin was used. Thirteen patients were alive in September 1974, observed 2-65 months, 8 with a normal serum creatinine, 3 with moderately elevated serum creatinine, and 2 on hemodialysis. The 6- and 12-month survivals of patients are 100% and 93% respectively. Normal growth and full rehabilitation in recipients of functioning grafts make renal transplantation justified as a therapeutic procedure in terminally uremic children.


The long-term effects of protein energy malnutrition in early childhood on bone age, bone cortical thickness and height.

Three groups of Ugandan children, 18 in each group, and one comparison group of 18 children were examined at 11-17 years of age. The three groups had previously been admitted for treatment of protein energy malnutrition between the ages of 8 to 15, 16 to 21 and 22 to 27 months respectively. The comparison group had not been clinically malnourished throughout the period up to 27 months of age. The children came from one tribe and from similar socio-economic background, and were individually matched on age and sex. The bone age was estimated by hand wrist radiography scored for maturity by the Tanner & Whitehouse method. The metacarpal index, a ratio derived from the medullary width and full diameter of the mid-point of the second metacarpal, was used as a measure of bone cortical thickness. The three malnourished groups are significantly shorter in height than the comparison group, but are not different in bone age and metacarpal index. No differences are observed between the three groups of children who had been admitted for protein energy malnutrition at different ages. The findings are discussed as they relate to the existing literature.


Focal nodular hyperplasia of the liver, benign hepatomas, oral contraceptives and other drugs affecting the liver.

Due to the claim of an association between focal nodular hyperplasia of the liver, benign hepatomas and oral contraceptives, the files in the departments of pathology at the university hospitals in Lund and Malmö were examined for these two diagnoses made since 1945 and 1957, respectively. 26 cases of focal nodular hyperplasia of the liver and 7 benign hepatomas were found, 18 and 2, respectively, in women. Since 1963, the year before oral contraceptives were introduced in Sweden, focal nodular hyperplasia has been diagnosed in 8 women in the reproductive period of life; 4 of these had taken oral contraceptives. The 4 diagnoses were established in 1972-1974. At most, 25 per cent of Swedish females between the ages of 15 and 44 years have been on oral contraceptives. The Swedish series of 28 patients with focal nodular hyperplasia comprised 3 epileptics and 3 diabetics. At least two of the epileptics had been treated with barbiturates and/or hydantoins. The prevalence of drug-treated epilepsy in Sweden is 0.4-0.5 per cent, and of diabetes about 2 per cent. The possible aetiological role of drugs provoking an increase of the smooth-surfaced endoplasmic reticulum of the liver and proliferation of vascular fibrous tissue in a part of the liver which preveiously may have been damaged by vascular disturbances or trauma, is considered. No relationship between benign hepatomas and drugs was found. The observations support the notion that oral contraceptives may be of aetiological importance in the development of focal nodular hyperplasia of the liver, although the material is too small for epidemiological and statistical analysis.