Selective localization of 4'-(9-acridinylamino)-methanesulfon-m-anisidide in B 16 melanoma. The acridine derivative 4'-(9-acridinylamino)-methanesulfon-m-anisidide (AMSA, NSC-141549), a new antitumor agent undergoing phase I clinical evaluation, is highly active against B16 melanoma in vivo. AMSA was found to be concentrated in B16 melanoma cells in vivo and remained at high concentrations for at least 72 h. Subcellular fractionation of B16 melanoma cells revealed the drug to be bound to melanin granules. The results suggest the possible use of AMSA in human melanoma and the design of other antimelanoma agents that would exploit the affinity of the acridine nucleus for melanin.


Application of EEG sleep for the differential diagnosis and treatment of affective disorders. In the last decade all night EEG sleep research has attempted to delineate the sleep features most characteristics of depressive states occurring in adult life. We have reported that EEG sleep variables could be used to verify a diagnostic classification for affective syndromes. This EEG sleep generated schema significantly dichotimized each major clinical category using only two or three EEG sleep measures. REM latency and REM density were sufficient to separate out primary from secondary depressed patients. Sleep efficiency, REM sleep percent, and delta sleep percent discriminated between the psychotic and nonpsychotic subgroups in the primary depressive group. Furthermore, EEG sleep variables separated secondary depression with concurrent medical disease from secondary depression without medical disease using REM activity and intermittent nocturnal awakening as the requisite variables of discrimination. Other ongoing investigations have established that the REM intensity of the first REM period is increased in primary depression. The search for EEG sleep correlates of clinical response in depressed patients receiving tricyclic antidepressants has suggested that, the more rapid the suppression of REM sleep, the more likely that the patient will respond to tricyclic antidepressants. Finally, clinical response appears to be associated with a period of sustained elevation of REM latency.


Functional aspects of the norepinephrine receptor coupled adenylate cyclase system in the limbic forebrain and its modification by drugs which precipitate or alleviate depression: molecular approaches to an understanding of affective disorders. The results provide evidence for a central postsynaptic regulatory mechanism involving the noradrenergic receptor coupled adenylate cyclase system. This particular system in the limbic forebrain displays properties of an adrenergic receptor with partial beta characteristics. Drugs which either can precipitate or alleviate depression in man cause time dependent opposite changes in the reactivity of this receptor system. It is tempting to speculate that depression-prone patients may have catecholamine receptors in limbic and possibly other brain structures with heightened responsiveness and that successful treatment requires desensitization of enhanced noradrenergic receptor function thus causing a reduction in the postulated amplificational mechanism that translates sensory input eventually into physiological and behavioral events.


Tryptophan and depressive illness.

Tryptophan and depressive illness. Plasma free tryptophan is significantly decreased in monopolar, depressed patients. No evidence was found to suggest that poor nutritional history prior to hospital admission was responsible for these low levels. Factors known to influence tryptophan-albumin binding in plasma, e.g. concentration of plasma proteins, albumin and non-esterified fatty acids, did not account for the low levels of free tryptophan in depressed patients. A significant decrease in plasma free tryptophan levels was found in perimenopausal but not in pre- or post-menopausal female controls. This mirrors the decrease in circulating oestrogens. Although exogenously administered oestrogens do not have any therapeutic efficacy in relieving mild residual depressive symptoms of lithium treated patients, they increased the levels of plasma free tryptophan. Clofibrate also displaces tryptophan from plasma protein binding sites in both depressed patients and controls. Utilization of the increased levels of plasma free tryptophan is reduced in depressed patients. A situation therefore exists in depressed patients where the plasma free tryptophan is not only reduced but also leaves the plasma less readily than in control subjects.


Prostaglandins and sleep. Awaking effect of prostaglandins and sleep pattern of essential fatty acids deficient (EFAD) rats. The experiments were carried out to investigate the effects of prostaglandins (PGs) on the sleep pattern in the cat, and in normal and EFAD rats. The data indicate that the duration of slow wave sleep (SWS) was significantly longer in EFAD rats compared with the normal rats. However, no difference in the REM sleep was observed between the two groups. Intraventricular (i.vc. )administration of PGE1, PGE2 and PGF2alpha increased wakefulness without a significant alteration of REM sleep. PGE1 administered i.vc. did not alter the duration of SWS or REM sleep in the chronic cat, but induced ponto-geniculo-occipital (PGO) waves (spikes) which are the phasic phenomenon of REM sleep. The fact that previous administration of 5-hydroxytryptophane abolished the PGE1-induced PGO spiking, might indicate that this drug triggered the spikes mainly via the functional inhibition of the serotonergic system.


The effect of 7-oxa-13 prostynoic acid on the mechanism of action of bradykinin in human synovial fibroblasts. Bradykinin, a potent inflammatory mediator, induces an increment in intracellular cyclic AMP concentrations of human synovial fibroblasts and evokes the synthesis and release of 3H-arachidonic acid and 3H-E prostaglandins from these cells pre-labeled in their phospholipids. Fetal calf serum in the media also stimulates the synthesis and release of these labeled lipids from pre-labeled human synovial fibroblasts and potentiates the bradykinin-induced cyclic AMP response. The PGE1 analogue, 7-oxa-13 prostynoic acid, completely abrogates both the bradykinin-induced cyclic AMP response and the bradykinin- and fetal calf serum-evoked release of labeled E-prostaglandins from pre-labeled cells. In serum-free media, the prostaglandin antagonist stimulated the release of 3H-arachidonic acid from pre-labeled human synovial fibroblasts and did not inhibit the bradykinin-induced release of this lipid.


Use of isoproterenol infusion to study intrapulmonary gas mixing in man. In the present investigation, the effect of an increased cardiac output on intrapulmonary gas mixing was studied in healthy male subjects. Increase of heart rate and cardiac minute output was induced by infusion of isoproterenol, intrapulmonary gas mixing was analyzed by simultaneous washout of inert gases widely differing in molecular weight (helium and sulfur hexafluoride). Parameters, appropriate to indicate quality of gas mixing, have been crossover point (COP) and separation index (SI). During isoproterenol-induced tachycardia, the COP occurred earlier and the SI decreased. Both changes then demonstrate an improved gas intrapulmonary mixing. The movement of the heart reduces stratified inhomogeneity.


[Intermittent chemotherapy from the beginning or only after a period of daily administration? Quantitative bacteriological study at the initial phase of chemotherapy with INH + RMP + EMB in daily or intermittent administration]. A number of 75 adults with pulmonary tuberculosis (M. tuberculosis positive at microscopy and in cultures) were randomly selected for one of the following therapeutical regimens, administered under close surveillance in hospital during 3 months: --INH5 mg/kg body weight+RMP10 mg/kg body weight+EMB25 mg/kg body weight daily; --INH15 mg/kg body weight+RMP10 mg/kg body weight+EMB40 mg/kg body weight, intermitent administration (2/7). Disappearance of the Mycobacterium from the sputum was studied quantitatively both by microscopy and in cultures; the sputum samples were collected in the morning three days running every week during the period of 13 weeks surveillance. Processing of the results showed that in the material studied the initial intermittent administration of the drugs was just as efficient as daily administration irrespective of the criterion used for comparison (moment of negativation, rate of disappearance of the Mycobacterium and/or proportion of negative cases, dynamics of the decrease in the number of bacilli eliminated in the course of the treatment, regression of the radiologic alterations).


[Epidemiological study of chronic cough and obstructive ventilatory dysfunction in a rural area]. An epidemiological study (MRC--Questionnaire and spirography) has been carried out on a population aged between 40 and 69 years living in a rural area (Costeşti, district of Buzău). 440 subjects (202 men and 238 women; 83% of the population in this age group) were examined. Chronic productive cough in subjects with no other respiratory diseases was found in 8,9% of the examinated males and in 5.0% of the females. The figures are lower than those found in an urban population and in a previous survey in an other rural area. Obstructive syndrome (reduced FEV 1.0/VC ratio) was found in 5.0 and in 2.9%, respectively. More than half of the patients with obstructive syndrome had no cough; the lung function alterations found in these subjects may be due--at least in some cases--to the obstruction of distal airways which have no clinical manifestations in the early stages.


[Post-tuberculosis syndromes in a pneumology unit]. With reference to 156 patients with a post-tuberculous syndrome, admitted to a pneumology unit, the authors discuss the anatomoclinical aspects of the primary disease and morbid entities developing against the background of the sequelae. The circumstances in which chronic bronchitis develops and post-tuberculous bronchopulmonary suppuration, frequently encountered in the pathology secondary to stable tuberculosis are analyzed. The necessity of preventing potential unspecific diseases and insuring an optimal complex treatment is emphasized.


[Statistico-mathematical appraisal of the length of the pretherapeutic interval in the prognosis of tubercular meningitis in children]. The data obtained concerning the two main parameters for the prognosis of tuberculous meningitis: onset-admission interval, assessed anamnestically and electtoencephalogram performed on admission, were processed mathematically by computer. The EEG is a more reliable parameter for assessing the gravity of the lesions on admission that the anammestic data regarding the onset, at a signficance threshold of 10.48% as against 5.23%. For 11.3 days there was a close correspondence between the two parameters, after which the onset-admission variable became aleatory, the only objective index of gravity being the EEG. Statistico-mathematical processing increases the objectivity and precision of the prognosis.


[Treatment for spontaneous pneumothorax]. The present study refers to 67 cases of spontaneous pneumothorax admitted to intensive care unit. Symptomatic therapy and treatment of the pneumothorax is efficient. Minimal thoracotomy with continuous aspiration drainage indicated in severe pneumothorax and relapses after exsufflation, was considered the basic procedure in the symptomatic treatment.


[Bronchiectasis in advanced old-age. Etiopathogenetic and diagnostic considerations and medico-social implications]. A study was carried out on the etiopathogeny and socio-medical implications in 18 cases of bronchiectasis, without a typical clinical symptomatology before admission. All the patients were over the age of 60 years. The bronchographic examination was performed in all the cases. In 8 of the cases bronchiectasis was interpreted as a post-tuberculosis syndrome and in the other 10 cases bronchiectasis was attributed to pulmonary sclerosis of different origin (acute unsuppurated pneumopathy). The gradual changes in pulmonary mechanics, the organic and functional deficiences developing with age lowered the resistance of the body to viral and bacterial infection, contributing to the onset of bronchiectasis in the older group. The suppurative episodes were curred by treatment in all the cases.


[Evaluation of the epidemiological potential of patients eliminating Koch bacilli demonstrable by direct microscopic examination]. A retrospective epidemiological study was carried out on the patients in evidence since 1972-1973, following up the contacts from that time. From the data obtained it results that the proportion of contacts who contracted the disease was of 1.06% of the subjects coming in contact with cases negative at the direct microscopic examination and in cultures, 1.1% of the subjects in contact with cases negative at the direct examination but positive in cultures, and 3.9% (four times greater proportion) of the subjects in contact with bacilli eliminators, at the direct examination. The authors emphasize the simplicity and greater output of the microscopic examinations in tuberculosis.


[Technic, indications and value of pulmonary decortications (615 operated cases)]. On the basis of their experience in 615 cases of pleuropulmonary decortication, the authors discuss the indications, contraindications, approach and procedure in pleuropulmonary decortication. Surgery has the double purpose of suppressing the empyema cavity and recovering most of the functional pulmonary parenchyma. A personal procedure was applied consisting of thoracotomy through the sixth intercostal space, then along the cleavage lines outside the limits of the empyema pouch, from the periphery towards the center at the level of the pulsatile organs, zones called the key points of pleuropulmonary decortication. Very good results were obtained in 80--50% of the tuberculous empyema cases and in 90--95% of the non-tuberculous diseases. The authors consider that pleuropulmonary decortication is a widely applicable surgical method in pleural empyema, being one of the few surgical methods used for redressing the function of an organ.


B-cell activating properties of polymyxin B. Polymyxins are known to be inhibitors of certain polyclonal B cell activators such as lipopolysaccharide and dextransulphate. However, increased specific responses to hapten-coupled mitogens have been reported after the addition of polymyxins to superoptimal conjugate doses. In this paper we have studied the effect of polymyxin B on superoptimal polyclonal doses of lipopolysaccharide. Results similar to those reported for hapten-lipopolysaccharide conjugates were obtained. Polymyxin B was also found to exert adjuvant properties for a primary immune response to sheep erythrocytes and to be a thymus-independent antigen.


Central nervous system involvement in patients with rotavirus gastroenteritis. Two children with rotavirus gastroenteritis are presented. The first case developed a fatal Reye's syndrome and the other one encephalitis with slow recovery. The rotavirus diagnosis was made in both cases by electron microscopy and a significant rise in antibody titres to Nebraska calf diarrhea virus was seen in one of the two patients.


Surgical treatment of simple syndactyly. During the period 1963--74 a total of 20 operations for simple syndactyly were performed on 34 fingers. A dorsal rectangular flap and thick split skin grafts were regularly used except in 2 cases where full thickness grafts were used for covering the skin defects. There were no secondary operations. The period of observation after 13 operations was 4 years or more. It is concluded that the dorsal rectangular flap technique combined with thick split skin grafts give satisfactory results.


Autonomic receptor functions of the human ureter: an in vitro study. The autonomic receptor functions of ureteral smooth muscle were studied in vitro on strips of human ureter obtained at surgery. A dose-dependent, reproducible, contraction response to 5-hydroxytryptamine (Serotonin, 5-HT) was demonstrated. This response could be blocked by methysergide. Responses to acetylcholine and to drugs stimulating adrenergic receptor functions were also found, but they were weak and inconsistent. This suggests that contraction of ureteral smooth muscle is mediated through receptors which are sensitive to 5-hydroxytryptamine.


Urinary excretion of cyclic AMP in hyperparathyroidism. The urinary excretion of adenosine 3', 5'-monophosphate (cAMP) was investigated in 15 subjects with primary hyperparathyroidism prior to parathyroidectomy and in 13 of them also after the operation. In comparison with healthy control subjects the cAMP excretion was raised in 8 of the patients pre-operatively and after operation all values had become normal. The discriminatory value of the cAMP analyses seemed to be increased by relating the cAMP values to the urinary excretion of calcium. With the applied methods determination of urinary cAMP was superior to a radioimmunoassay of parathyroid hormone in recognizing patients with primary hyperparathyroidism. In normal subjects it appeared that the cAMP excretion expressed per gram creatinine was somewhat higher in women than in men.


[The malignant neoplasm in pediatrics].

[The malignant neoplasm in pediatrics]. A summary of diagnostic and therapeutic progress in pediatric oncology is presented. The results are impressive, in that at least 1 child in 3 may be successfully treated. A truly effective treatment for the individual child requires the close cooperation of specialists on a national, regional and local scale. Pediatricians and general practitioners who suspect neoplasm are required, on the one hand, to ensure speedy and adequate clarification of the case, and, on the other, to cooperate in the treatment and care of children with cancer. Briefing and instruction of parents is of great practical importance.


Preferential utilization of free cholesterol from high-density lipoproteins for biliary cholesterol secretion in man. High- and low-density lipoproteins carrying free cholesterol labeled with 3H or 14C were administered to a patient with a bile fistula. The free cholesterol from high-density lipoproteins was more rapidly incorporated into biliary cholesterol than the free cholesterol from low-density lipoproteins. These findings show that the liver in man selectively utilizes and secretes the free cholesterol from a particular lipoprotein.


Prostaglandin E1 inhibitis platelet aggregation by a pathway independent of adenosine 3',5'-monophosphate. Aggregation of human blood platelets induced by adenosine diphosphate or 1-epinephrine was inhibited when the platelets were suspended in plasma which had been previously exposed to an insolubilized omega-aminohexylagarose derivative of prostaglandin E1. This decrease of platelet aggregation was not accompanied by a change in the concentration of adenosine 3',5'-monophosphate (cyclic AMP) in platelets. The results demonstrate the existence of an alternative pathway independent of cyclic AMP for the inhibition of platelet aggregation by plasma.


Different brain areas mediate the analgesic and epileptic properties of enkephalin. Single injections of 120 micrograms of methionine-enkephalin were made into various midbrain and forebrain structures in the rat. Analgesia was observed after injections into or near the ventral, caudal midbrain periaqueductal gray matter. Seizures and other pathological electroencephalogram (EEG) changes were seen with injections into or near the forebrain dorsomedial nucleus of the thalamus. No animals with midbrain injection sites showed EEG changes, and none with forebrain injection sites were analgesic. These data, taken together with other lines of evidence, suggest that enkephalin-induced analgesia and enkephalin-induced seizures are mediated by opiate receptors that are located in different brain areas and that are pharmacologically different.


Atypical lobular and papillary lesions of the breast: a follow-up study of 30 cases. Sections from 879 consecutive breast biopsies performed for clinically and grossly benign disease between 1962 and 1966 were reviewed. Twenty-four cases of undiagnosed lobular carcinoma in situ or atypical lobular hyperplasia and six cases of intraductal papillary carcinoma were found. Only one patient later developed invasive carcinoma, an infiltrating lobular carcinoma in the ipsilateral breast, which was diagnosed seven years after the biopsy containing lobular carcinoma in situ. Invasive cancers have not been found in other patients who have a median follow-up period of eight years.


Idiopathic neurotrophic feet in Blacks: a pathological study. The pathological findings in tissues obtained from 6 patients with idiopathic neurotrophic feet are described. The salient features were those of a neuropathy characterized by gross demyelinization and marked changes in the distal blood vessels. The vascular changes included medial and intimal hypertrophy with luminal narrowing. It is proposed that both the neural and the vascular changes were secondary to chronic alcoholism.


The effect upon the liver of evisceration with or without hormone replacement. All, or nearly all, of the nonhepatic splanchnic viscera were removed in dogs. In most untreated dogs, the liver cells underwent changes similar to those caused by portacaval shunt, including structural deterioration of organelles and fatty metamorphosis. The rate of division of the hepatocytes, as measured by the mitotic index and by autoradiography, was depressed as were deoxyribonucleic acid synthesis and adenylate cyclase activity. These changes were restored to, or toward, normal with the intraportal administration of commercial or purified insulin but not with glucagon or epidermal growth factor. The results of both the pathologic and biochemical studies were consistent, except for an incongruity in some of the dogs in which the colon was retained.


Middle cerebral artery occlusion within an irradiated glioblastoma multiforme. It is rare for gliomas to involve adjacent intracranial arteries. A case of middle cerebral artery occlusion within a glioblastoma multiforme is presented.


Fine structure of rabbit articular chondrocytes in tissue culture during logarithmic and confluent stages of growth. Ultrastructural changes in cultured articular cartilage chondrocytes from rabbit, during two growth phases were examined by transmission and scanning electron microscopy. Cells in logarithmic growth are characterized by an abundance of intracellular lipoid bodies, little development of rough endoplasmic reticulum (RER), and few cytoplasmic microfilaments. As the cells reach confluency there is a concomitant development of RER, organization and abundance of microfilaments, loss of lipoid bodies, and increase in the number of mitochondria. The fine structure of cultured chondrocytes is very similar to that of rabbit cartilage cells in situ, in that numerous lipoid bodies and microfilaments are prominent features in both cases.


Scanning electron microscopy of induced cell rounding of mouse adrenal cortex tumor cells in culture. The surface topologies of mouse adrenal cortex tumor cells of primary or clonal origin grown as monolayer cell cultures were observed by scanning electron microscopy following their exposure to substances that effect steroid release and/or cell rounding. ACTH induced cell rounding with a concomitant profuse development of fine microvilli in a non-synchronously dividing cell population. This was less pronounced with other steroidogenic substances and absent in EGTA or trypsin-treated cells. Morphological alterations occurred most rapidly with cAMP and least rapidly with dbcAMP. The rapid development of fine microvilli with ACTH is proposed to be a specific hormone mediated response.


Ultrastructure of leydig cells as revealed by secondary tissue treatment with a ferrocyanide-osmium mixture. Leydig cells prepared routinely (glutaraldehyde--osmium) for ultrastructural studies are generally found to be lacking in subcellular detail as a result of poor membrane preservation and a dense cytoplasmic matrix. A method modified after that of Karnovsky (1971), utilizing a ferrocyanide--osmium mixture for post-treating glutaraldehyde fixed tissued, was found to yield routinely excellent preservation of Leydig cells. The primary advantages of this method were the enhancement of contrast within the Leydig cell and greatly improved membrane preservation. In addition, the smooth endoplasmic reticulum always appeared as an extensive network of interconnected tubules of uniform diameter; mitochondria, lysosomes, peroxisomes, multivesicular bodies, and Golgi were especially prominent. Glycogen and microfilaments, not readily seen in routine preparations, were found to be abundant in these cells. New observations on the numbers and distributions of subcellular organelles are described and are discussed in relation to their possible role in the steroidogenic process. In view of the greatly improved tissue preservation observed in this study, it is suggested that this treatment be used routinely for preservation of rat Leydig cells.


Effect of cyclic AMP on placental active transport of amino acid in rats. In pursuit of the probable relationship of cAMP to the placental active transport of amino acids as suggested by our previous human data, experiments were done in this study with dibutyryl cAMP and theophylline loaded in pregnant rats to examine the changes in level of 14C-lysine in the maternal liver, placenta and fetus. The results are: (1) Loading of dibutyryl cAMP had no effect on the uptake of 14C-lysine in the maternal liver, placenta or fetus, except that the correction of the values with its concentration in the maternal blood revealed only a slightly significant elevation in the value in each of them 30 min after the loading. (2) Loading of theophylline significantly increased the uptake of 14C-lysine in all these organs. (3) The content of cAMP in the placenta significantly increased with the loading of theophylline. These results have led the authors to believe that endogenous cAMP is significantly linked with the placental active transport of amino acids, though there is no apparent contribution to it by exogenous cAMP.


Potential role of amphotericin B methyl ester in the prevention and therapy of herpetic keratitis. Amphotericin B methyl ester (AME), a semisynthetic derivative of amphotericin B, was studied in the rabbit cornea for its potential role in prevention and therapy of HSV, vaccinia virus, and vesicular stomatitis virus. It was effective in the prevention of lesion formation by these three viruses and dose-related antiviral effects were shown. Of these viruses HSV was the most sensitive to AME. The antiviral effect of AME was additive with those of IDU and ribavirin. However, it was not effective in treating established lesions due to HSV and vaccinia virus. Since its mode of action is to bind to the sterol sites of the viral envelope, it is suggested that AME should also be effective against other enveloped DNA and RNA viruses. A new method of therapy for epithelial herpetic keratitis in humans using a combination of AME with MWD is proposed.


Prophylactic adenine arabinoside following marrow transplantation. Interstitial pneumonia is a major cause of morbidity and mortality following allogeneic marrow transplantation for hematologic malignancy. In this prospective randomized study, 22 of 40 patients received prophylactic adenine arabinoside (Ara-A) at a dose of 5 mg/kg/day administered intravenously on an intermittent schedule. Thirteen episodes of interstitial pneumonia occurred among treated patients, including three cases associated with cytomegalovirus (CMV) in the lung. Ten episodes of interstitial pneumonia were seen in the untreated group, with CMV cultured from five. Surveillance viral cultures were positive from 18 different sites in 12 treated patients compared to 10 sites from 7 patients in the untreated group. No significant toxicity from Ara-A was encountered, and no difference in overall survival between the two groups was detected. Ara-A did not reduce the frequency of interstitial pneumonia or viral isolation from routine cultures.


[The cancerologically correct operation for nephroblastoma (author's transl)]. The following methodology is suitable for increasing the radicality of and the safety of the vessels during a transperitoneal operation for nephroblastoma and simultaneously for sparing the necessity of postoperative radiation: 1. primary exposure of the renal vascular cross, the vena cava, and the aorta through incision of the plica duodeno jejunalis together with mobilization of the duodenum to the right, the mesocolon to the left; 2. primary ligature of the a. renalis in front of the v. renalis (no problems on either side); 3. systematic retroperitoneal en bloc lymphodissection from the a. mesenterica superior to the forking of the aorta, laterally to the diaphragm, probative at the adnexa; 4. subsequent lateral release of the left-sided tumorous kidney, medial release of the right-sided tumorous kidney after mobilization of the cecum.


[A new method of lymphadenography of the regional lymph nodes of the human urinary bladder. Findings relevant to cancer of the bladder (author's transl)]. Experience with and findings of a new method of indirect lymphography (endovesical lymphography) for roentgenologic visualization of lymph nodes and lymphatic vessels of the human urinary bladder are presented. After injection of Lipiodol Ultrafluid into the submucosal layer of the bladder wall all regional lymph node groups could be demonstrated. In cases of carcinoma of the bladder, endovesical lymphography provides early evidence of beginning carcinomatous infiltration of regional lymph nodes. Pedal lymphography as used thus far, provides information only about advanced lymphatic metastatic spread. It is possible that endovesical lymphography will yield new information leading to more accurate treatment of vesical carcinoma in terms of tumor staging.


Multiple endocrine cell types in thyroid medullary carcinoma. Evidence for calcitonin, somatostatin, ACTH, 5HT and small granule cells. 10 cases of thyroid medullary carcinoma (TMC) have been studied ultrastructurally and histochemically. Well differentiated calcitonin-producing C cells were present in all tumours, being prevalent in 9 cases. 5-Hydroxytryptamine (5HT) storing cells were found in two cases, somatostatin immunoreactive cells in at least 5 cases and ACTH-immunoreactive cells in 4 cases. Ultrastructurally, at least 3 types of apparently non-C cells were observed. Type 1 cells with large, poorly osmiophilic granules resembling those of gastroenteropancreatic D cells, were present in 6 cases; they appeared to correlate well with somatostatin immunoreactive cells. Type 2 cells with large osmiophilic granules were found in 5 cases; they resembled ACTH-MSH cells of the human pituitary and may correspond to the ACTH-immunoreactive cells of light microscopy. Type 3 cells with small granules and an unknown function were found in 6 cases, always in scarce number. It is concluded that TMC, although mainly made up of C cells, usually contains large proportions of other endocrine cell types.


A morphologic and morphometric study of the mitochondria in several hepatoma cell lines and in isolated hepatocytes. Some characteristics of the mitochondria of hepatocytes and of three hepatoma cell lines have been compared. By means of stereologic analysis of electron micrographs of cross-sections through cells the volume of mitochondria per unit volume of cell cytoplasm and the surface areas of the mitochondrial envelope and cristae membranes have been measured. The relative mitochondrial volume in the cytoplasm decreases with increasing growth rate but the surface area of outer and cristae membranes per unit volume of mitochondria is not altered. The internal organization of hepatoma mitochondria, however, differs distinctly from that of normal liver mitochondria as evident from electron micrographs; the hepatoma cells contain mitochondria in which parallel cristae appear to cross the whole mitochondrial profile unlike the irregular, short cristae seen in normal liver mitochondria. Furthermore, in the fast-growing hepatoma cells the mitochondrial matrix appears less dense than in the hepatocyte. Hepatoma cells contain less organized rough endoplasmic reticulum than normal liver cells and the spatial relationship of the mitochondria to the rough cisternae, seen in the hepatocyte, is absent in the fast-growing hepatoma cell lines. It is concluded that hepatoma cells have fewer mitochondria than normal liver cells, but that the organelles have a normal content of inner membranes.


Electron Microscopy of Nephropathia Epidemica. Glomerular changes. Electron microscopical changes in the glomeruli in 20 kidney biopsies from 18 patients, who were suffering from or had lately suffered from Nephropathia epidemica were studied. Various kinds of deposits were seen. Under the endothelial cells there were collections of light flocculent material. Small dark deposits were seen in the mesangium at the mesangial cell processes, inside the thickened basement membrane, and occasionally on the epithelial side of the membrane. Large deposits were seen around mesangial cells in the mesangium. Deposits were less numerous than in chronic immune complex diseases. The intramembranous or subepithelial deposits were associated with "moon craters", membranous convoluted structures or membrane debris. Granular extracellular mesangial material, round extracellular particles and intraendothelial microtubular inclusions were occasionally seen. In two of our cases occasional capsular epithelial cells showed numerous myelin bodies. Typical viruses were not seen in the glomeruli. The findings are in accord with the short period of scanty immune complex deposition in the glomeruli in the clinically active phase of Nephropathia epidemica.


Immunoelectrophoretic study of Sendae virus envelope antigens with hyperimmune sera prepared in different laboratory animals. At similar HAI titers rabbit sera reveal a larger number of fractions (ten) in immunoelectrophoretic analysis of Sendai virus envelopes than do guinea pig sera, which only yield three distinct fractions. These differences are observed in both rocket and crossed immunoelectrophoresis, and are more marked in the latter. The number of fractions revealed does not differ in relation to the antigen used for hyperimmunization (intact Sendai virus, Triton-disrupted virus or envelope fractions extracted by Triton or Tween-ether). Solubilized Sendai virus envelopes obtained by Tween-ether or Triton treatment contain host antigens in their structure, the same as intact virus.


Chromosome abberations in rat embryo cells transformed after infection with ultraviolet-irradiated herpes simplex virus. Two rat embryo cell lines (TR1 and TR2) transformed after infection with ultaviolet-inactivated herpes simplex virus type 2 showed modal chromosome numbers in the tetraploid range. In the TR1 cell line a near-diploid cell population replaced during subcultivation the hypotetraploid cells thus explaining the loss of immunofluorescent viral antigens. Both transformed cell lines showed frequent achromatic gaps. In the TR1 cell line such gaps were preferentially located in specific chromosome regions. The occurrence of achromatic gaps is presumably associated with the activity of a viral gene.


[Spontaneous tumors in rats from the Rappolovo Breeding Nursery of the Academy of Medical Sciences of the USSR]. The authors report the data on the incidence of neoplasms in rats of the "Rappolovo" nursery breeding (USSR Acad. Med. Sci.) and their offsprings during 4 sequential generations kept in the vivarium of the N. N. Petrov Research Institute of Oncology of the USSR Ministry of Health. The frequency of spontaneous tumors in 213 male and 230 female rats was 25.8 and 35.7% accordingly. Totally, male animals developed 65 tumors, females--114. over 80% of all neoplasms developed in animals older than 18 months. The frequency of neoplasms of separate localizations in males and females was as follows: the hypophysis--7.0 and 12.6% correspondingly; the mammary gland--0.5 and 11.7%, the thyroid (thyroidal epithelium) - 1.4 and 3.0% and (light cells) 5.6 and 8.3%; the adrenal cortex--0.5 and 1.3%; the hematopoietic system --7.0 and 5.6%; parasitic sarcomas of the abdominal cavity --5.6 and 3.0%; the skin --0.4 and 0.4%; soft tissues --0.9 and 0%; the liver--0.4 and 0.4%; the kidneys --0.4 and 0.4%. Moreover, one male showed seminal vesicle tumor, and females-solitary neoplasms of the pancreas and salivary gland, the dura mater, the ovary and uterus. Significant differences were revealed in the frequency of spontaneous neoplasms in separate rat generations.


The presence of complement fixing antibodies to the avian group-specific ("gs") sarcoma-leukosis antigen in the human population and in cancer patients. Antibodies to the avian group-specific "gs" sarcoma-leukosis antigen were made evident by complement fixation reaction in human sera collected from apparently healthy subjects and from patients with different forms of cancer and non-neoplastic diseases. The number of sera investigated was of 2,123. The possible mechanisms that might account for this paraimmune response of the human organism and the prospects of developing prophylactic steps against cancer are discussed.


Investigations on the incidence of complement fixing antibodies to the avian group-specific ("gs") sarcoma-leukosis antigen in fowl farm workers. The presence of complement fixing antibodies to the avian "gs" sarcoma-leukosis antigen is reported in the personnel of five different fowl farms. Seroconversion was observed in the workers from one of the farms, where the initial antibody incidence was very low.


Separation of a glycoprotein antigen for the diagnosis of bovine leukemia and some of its biochemical properties. Data are presented on the separation and on some biochemical properties of an antigen to be used in the immunodiffusion (ID) test for detection of bovine leukemia virus. The antigen obtained proved to have the same efficiency in the ID test as a commercially available standard antigen. Experimental results suggest that the antigen is released into the culture fluid in the form of a glycoprotein molecule consisting of two subunits with a molecular weight of 60,000 linked by--SH bonds.


[Clinical x-ray characteristics of oat cell lung cancer]. The analysis of the case reports of 116 patients with oat-cell cancer of the lung, treated at the N. N. Petrov Research Institute of Oncology of the USSR Ministry of Health from 1952 to 1971, has revealed some features of the clinico-roentgenological picture of the disease: a short-term anamnesis, prompt development of the symptoms with predominant pains in the involved thoraic portion and retorsternally, a prevailing peribronchial growth (76.6%), early and extensive metastasization revealed in 84.5% of cases. The detection, on roentgenograms and tomograms of the chest organs, of the block of enlarged lymph nodes in the lung hilus and mediastinum in the presence of a small tumor in the lung allowed oat-cell cancer to be suspected. The roentgenological picture of median oat-cell cancer is characterized by the presence of tumor conglomerate in the lung hilus, which consisted of the primary tumor penetrating in lymph nodes adjacent to the bronchus in 66.6% of canses.


[A case of Klippel-Trenaunay syndrome].

[A case of Klippel-Trenaunay syndrome]. The case of a 33-year-old woman suffering from the Klippel-Trenaunay-syndrome which belongs to the syndromes of dysplasia is discussed. The cases in question is an anaeviformous variant. Apart from this there exists a renal hypoplasia which is to be seen within the Klippel-Trenaunay-syndrome. This renal hypoplasia has led to a terminal renal insufficiency and has made necessary a chronic haemodialytic treatment.


Interaction between ceruloplasmin and Sendai virus envelope components. Note VI. Effect of ceruloplasmin on the antigenicity of Sendai virus and subviral fractions. The results obtained by immunization of rabbits with different Sendai virus antigens (whole virus, envelope fragments and partially purified nucleoprotein) previously incubated with homologous ceruloplasmin confirm the hypothesis of a common protein support for both hemagglutinin and neuraminidase activities, demonstrate the participation of ceruloplasmin in the immune mechanism and reveal the role of the carbohydrate moiety of the glycoprotein in immune response. The probable mechanism of interaction between ceruloplasmin and Sendai virus envelope glycoprotein is discussed.


[Seasonal changes in soil biological activity of two different forest association (author's transl)]. The biological activity of the soil under a beech forest and a spruce forest was examined in respect to the CO2-production of the soil samples, the speed of vanillin decomposition, as well as the activity of the soil enzymes catalse, saccharase and phosphatase. Both soils indicated an indentical course of seasonal activity.


A new technique of heterogenous enzyme-linked immunosorbent assay, stick-ELISA. II. Application of stick-ELISA to antigens of various infective agents. Stick-enzyme-linked immunosorbent assay (Stick-ELISA) was applied to antigens of a variety of infective agents. An acceptable reproducibility in a series was reached, the variation coefficient being twelve percent. Preliminary results revealed that ready coated sticks could be stored at 4 degrees C for at least two to three weeks.


[Evaluation of the alginat membrane filter method for the Enterovirus concentration in water (author's transl)]. It is bound to use a concentration method for the research of enteroviruses in water. One of the concentration methods, the filtration on alginat membranes, avoids the problem of the virus elution from the filter, then the membrane is soluble in a sodium citrat buffer. This method was studied with different types of water (synthetic water, tap water and wastewater). -The recovery efficiency of Poliovirus I in clear waters (synthetic water and tap water) was poor, unsatisfying reproducible; the results are better for small virus concentrations. This efficiency may be slowly enhanced by the addition to the sample of aluminium chlorid at a final concentration of 5.10(-4) M. -The technical problems (brittleness of the membranes, slow filtrations speed, small sample volume), soon noticeable with clear waters, are more important in the case of trouble waters. Meanwhile the use of this filtration method gives better results for the recovery of Poliovirus I in wastewaters than the direct inoculation to cells cultures.


[Spontaneous intracerebral hematomas].

[Spontaneous intracerebral hematomas]. Within a period of five years, the authors observed 31 patients with spontaneous non-traumatic intracerebral haemorrhages. Seventeen of them were hypertensive patients. In four cases, tumour haemorrhages were found, especially in glioblastomas. In two cases, the basic disease was haemophilia and in another two cases cerebral aneurysms were found. There was one case of haemorrhagic encephalitis and one patient was being treated with anticoagulants. Eight patients died within ten days after the operation, two patients died later. The haematomas were mainly located in the temporal and parietal regions; one haematoma was found in the cerebellar hemisphere. One haematoma was detected in connection with an inoculation against influenza. In the therapy, preference is given to osteoplastic trepanation, in rare cases puncturing through a drill-hole is employed. The operation is carried out in the early phase as soon as the patient can be operated on.


[Antiviral therapy of herpetic lesions of the nervous system]. The authors discuss some results of their study concerning the therapeutical effectiveness of different drugs and methods in treating herpes. A total of 194 patients were observed. In 73 cases desoxyribonuclease, interferon, inductors of interferon were used (viruses of ECHO of type 1 and 12, polyomyelitis vaccine, yeast ribonucleinic acid were used as inductors). Antiviral therapy permitted to prevent the development of postherpetic neuralgia, decrease the duration of hospitalization and in cases of remittent development either arrest or significantly reduce the number of relapses and clinical signs. The authors propose a scheme in the treatment of neurological forms of herpes. Further search for effective treatment is discussed.


[Familial peroxidase-deficiency and acute myeloic leukemia (author's transl)]. A complete lack of myeloperoxidase (MPO) was demonstrated in a boy suffering from acute myeloic leukemia during the acute phase of the disease and after a remission was achieved. A partial defect of MPO was demonstrated in the patient's father, no further abnormalities were seen in other members of the family. The fine structure of the patient's neutrophils and monocytes appeared normal, no activity of MPO was demonstrated on the fine structural level. In the father's neutrophils transitional forms between cells exhibiting a normal MPO activity and those without activity were demonstrated. The neutrophil bactericidal activity was strongly inhibited in the patient and decreased in his father. Normal values were found in: NBT test, chemotaxis, serum-dependent phagocytosis, number of B and T lymphocytes, serum immunoglobulins, and complement. A possible connection between MPO deficiency and leukemia is discussed.


Regional distribution of prostaglandin-metabolizing enzymes in the mucosa of the human upper gastrointestinal tract. The occurrence of three enzymes of prostaglandin metabolism, 15-hydroxy-prostaglandin-dehydrogenase, delta13 -reductase and prostaglandin E-9-keto-reductase was investigated in gastroscopically obtained biopsy specimens of human upper gastrointestinal mucosa. All three enzymes could be found in the mucosa of oesophagus, gastric fundus, corpus and antrum and duodenum. While the specific activity of 15-hydroxy-prostaglandin-dehydrogenase was highest and the specific activity of prostaglandin E-9-keto-reductase was lowest in all regions studied, differences of the specific activities of the enzymes between the regions are remarkably small. These results are discussed with respect to possible functions of endogenous prostaglandins in human gastrointestinal mucosa.


[Incorporation of radioactive calcium and technetium pyrophosphate in to bones]. A method is given for simultaneous in vivo measurement of mineral and collagen metabolism of the bone. Accretion rates of 47-calcium as a chlorid into the bone are representative for bone mineralisation and of 99m-technetium labelled pyrophosphate for collagen metabolism. Compartmental models used for analysis are presented. Bone accretion rates are given in mg, or mMol respectively per unit time for the skeleton, by computation of the specific activity of 47-calcium and 99m-Technetium pyrophosphate and rational bone accretion as registered by total body profile scanning technique. The results obtained in five normal volunteers are presented.


[Chronic hypophosphatemic osteopathy ("rachitis"). Clinico-osteological review]. Chronic hypophosphatemia is the most common type of "resistant" rickets. Bone deformities, dwarfism and X-chromosomal dominant heredity, are regular findings in this "inborn error" of phosphate metabolism. Continumous administration of high dosage of vitamin D results in some improvement of the rickets-like bone lesions. Oral administration of phosphate seems to improve longitudinal growth. A summary of our experiences in 44 patients is presented.


[Chronic hypophosphatemic osteopathy (rachitis). Orthopedic review]. Origanized collaboration between the osteologist and the orthopaedic surgeons in diagnosis and treatment of this disease, is basically important for a successful orthopaedic approach and for the maintenance of stabile long-time healing-results. From a total of 48 patients, in 25 cases an operative treatment was necessary. The relationship between the biochemical distrubance of bone metabolism and biomechanical factors in the progressive development of articular and diaphyseal axis deformities, especially of the weight bearing lower extremities, was determined. The indications and mechanical conditions with relation to conservative and operative therapeutic procedures are analyzed and the praeoperative biomechanical and biochemical therapeutic approach is described in detail.


Glial-mesenchymal tropism of in vivo avian sarcoma virus neuro-oncogenesis in rats. Intracerebral inoculation of avian sarcoma virus (ASV) in postnatal animals induces gliomas and sarcomas but no neuronal tumors. High titer Bratislava-77 strain ASV was inoculated intracerebrally in fetal F-344 rats between 17 and 20 days of gestation: a time of active neuronal proliferation. Following birth inoculated rats developed gliomas and sarcomas but no neuronal tumors. The results are evidence that the glial-mesenchymal tropism of in vivo ASV neuro-oncogenesis is independent of stage of neurocytodifferentiation at inoculation.


Cell membrane structure of human giant-celled glioblastoma. A giant-cell glioblastoma was examined by electron microscopy and by the freeze-fracture technique. The cell membranes bordering the extensive extracellular space often showed complicated undulations and peripheral vacuoles as well as occasional microvilli or filopodia. The undulations were mainly composed of plasmalemmal vesicles as well as of large (400--800 nm in diameter) and small (30--50 nm in diameter) localized protrusions and invaginations of the cell membrane. Deep invaginations of the cell membrane apparently resulted in two separate cytoplasmic portions. Locking of protruded cytoplasmic tongues and adherens junctions were sometimes seen in closely approximated cell membranes. The average number of membrane particles per micrometer2 was 630 +/- 130 on the P face and 180 +/- 30 on the E face. The membrane particles were occasionally aggregated to form clusters about 30 to 150 micrometer in diameter. Gap junctions were occasionally found, but there were no tight junctions. Large particles about 30 nm in diameter were found in places.


Endoneurial pressure in hexachlorophene neuropathy. Increased endoneurial pressure of up to 17.0 cm H2O was recorded in the peripheral nerves of rats fed hexachlorophene in their laboratory diet. The pressure was measured using a micropressure transducer developed for recording pressure in the microcirculation. The results were correlated with morphologic findings. Teased nerve fibers and araldite-embedded specimens of hexachlorophene damaged sciatic nerve revealed the characteristic severe intramyelinic edema due to splits in the minor dense lines of compact myelin giving rise to wide interlamellar spaces as shown in previous studies. The endoneurial pressure of rats exposed to hexachlorophene for 11 days and subsequently fed a normal diet returned to normal (0.2-3.0 cm H2O) after 12 days, and morphologic examination showed few residual abnormalities. Prolonged exposure to hexachlorophene for up to 4 weeks caused widespread axonal degeneration in addition to intramyelinic edema. Animals treated with hexachlorophene for 21 days followed by a normal diet for 14 days showed degenerated axons, phagocytosis of myelin as well as interstitial edema and elevated endoneurial pressure. It is suggested that axonal degeneration in hexachlorophene neuropathy is caused by increased endoneurial pressure.


No demonstrable accumulation of 14C-vitamin D3 in developing rat teeth and bones. The distribution of 14C-vitamin D3 administered subcutaneously in arachidic oil to 6-day-old suckling rats has been examined autoradiographically. The animals were sacrificed 1, 2, 4 and 8 days after injection. The autoradiographic exposure time was 4 months. The sectioning and exposure was performed in a freeze-room. Radioactivity was found mainly in the liver, kidney, intestines and fat depots. No uptake was found in developing teeth or bones.


Idiopathic Parkinsonism with Lewy-type inclusions in cerebral cortex. A case report. A case of idiopathic parkinsonism showed specific neuropathological findings, namely, the diffuse appearances of intracytoplasmic inclusions of Lewy type in the cerebral cortex in addition to many Lewy bodies in the pigmented brain stem nuclei. The staining properties and the ultrastructure of the inclusions in the cerebral cortex had a strong resemblance to those of the Lewy bodies in the substantia nigra, though a few electron microscopical differences were observed. Almost all of these 'cortical inclusions' were homogeneous or had an obscure core in their center, and they gave the impression of immature Lewy bodies.


Subacute sclerosing panencephalitis with special reference to the ultrastructure of inclusions in the brain and lung. A 7-year-old boy, who was diagnosed as typical SSPE by clinical data and laboratory findings, was autopsied and observed by immunofluorescent techniques, light and electron microscope. The morphological characteristics in the brain were perivascular cuffings with plasma cells, lymphocytes and mononuclear cells, gliosis and a large number of intranuclear and intracytoplasmic inclusions in the neuroglias and nerve cells. Various kinds of intranuclear inclusions were elucidated by electron microscopy and the fin structures of these inclusions were described in detail. At least five types of intranuclear inclusions were regarded as specific in SSPE. The presence of intranuclear inclusions of mononuclear cells in the lungs resembling the inclusions in the neuroglias suggested that the disease was not localized in the brain but could be disseminated throughout the body.


Childhood coronary sclerosis.

Childhood coronary sclerosis. Childhood coronary sclerosis was studied histologically, histochemically immunohistochemically and biochemically on 60 autopsy cases aged from new-born to 20 years. Intimal thickening often started even in the newborn babies particularly at branching or bending points of the arteries, where fibrocellular proliferation with acid mucopolysaccharide accumulation was the main histological feature. Microthrombi were occasionally demonstrated even in infants, and fatty streaks appeared generally in the second decade. Microthrombi were usually smaller and fewer than fatty streaks. Beta-lipoprotein and fibrinogen infiltrations into intima were proven in some cases. Mural vascularization was occasionally observed especially in the areas beneath intimal thickening. Pressure effect of the blood stream and anatomically specific points in the arteries seemed to be important as initial factors of coronary sclerosis, where plasma constituents might pass in an easier manner into intimas by increased permeability. Secondarily mural capillaries might play some role in developing atheromas which would produce an eccentrically located luminal obstruction later in adulthood, by local circulatory disturbances within the arterial walls.


Trophoblastic pseudotumour of the uterus. A case report. A 52-year-old woman with vaginal bleedings had hysterectomy because curettings prompted suspicion of malignancy. A uterine tumour with deep infiltration of trophoblastic cells in the myometrium was revealed. Postoperative quantitative analysis for urinary human choriongonadotropin gave 1500 IU/1. The patient got no other treatment and is well 3 years after operation. The histopathological picture and the clinical course were consistent with the recently introduced diagnosis of benign "trophoblastic pseudotumour", which should perhaps replace the old terms "syncytioma" and "chorionepitheliosis".


An analysis of 38 malignant fibrous histiocytomas in the extremities. All the malignant soft tissue tumours in the extremities and limb girdles reported to the Finnish Cancer Registry between 1960-1969 were reviewed. From a total of 246 sarcomas, 38 were diagnosed as malignant fibrous histiocytoma. There was an equal number of male and female patients with the median age of 67 years. The thigh was the most frequent site, and the majority of the tumours originated in the deep soft tissues. The predominant treatment was excision followed by radiation therapy. In 17 patients there were one or more recurrences and in 21 patients there was a metastatic spread ascertained by biopsy, autopsy or clinical or radiographic evidence. There were 11 survivors with a minimum of 5 years' follow-up; seven patients died of an intercurrent disease and the remaining 20 patients were considered victims of their tumour. The findings that seemed to favour a poor prognosis were higher age and female sex of the patient as well as deep location, large size, necrotic areas, and high mitotic activity of the tumour.


Biochemical and morphological characterization of subcellular fractions isolated from rabbit colon muscle. From a homogenate of rabbit colon muscle subcellular fractions were isolated by differential centrifugation. The crude microsomal fraction could be separated into subfractions, a fraction of vesicular microsomes at 35% sucrose, a fraction containing sarcolemma, mitochondrial fragments and microsomal vesicles at 35--45% sucrose and a small protein fraction at 45--55% sucrose. Their biochemical properties and their morphological characterization were investigated. The cholesterol and the phospholipid content was equally distributed between the microsomal fractions 35% and 35--45% while the RNA was localized to the mitochondria and the microsomal fraction 35%. The enzyme cytochrome c oxidase was found to be concentrated in the mitochondria while a high contamination was found in the microsomal fractions 35--45%. The NADH-oxidase activity was highest in the 35% fraction and the 5'-nucleotidase activity in the 40,000 X g supernatant. The microsomal subfractions contained the enzymes ATPase, adenylate cyclase and phosphodiesterase. In the 35% fraction Ca stimulated the hydrolysis of ATP. The binding of [3H]-ouabain and the incorporation of [3H]-leucine was most pronounced in the 35% fraction. In a K+-free Krebs Ringer medium the binding of the glucoside was stimulated in all the fractions. From these results we concluded that the fraction 35% sucrose may be mainly derived from the endoplasmic reticulum and the plasma membrane while the 35--45% originates from the plasma membrane, mitochondria and to a lesser extent the endoplasmic reticulum.


Primary culture of adult rat liver cells. I. Preparation of isolated cells from trypsin-perfused liver of adult rat. Isolated hepatic cells from adult rats were prepared by perfusing the livers with trypsin. The highest yield of viable cells was obtained by perfusing the liver with 0.1% trypsin, pH 7.0, at 37 degrees C for 30 min. Following this treatment about 70% of cells excluded trypan blue. The isolated cells contained many binucleate cells. Between 60 and 70% of DNA present originally in the liver was recovered from the isolated hepatic cells, which had higher glucose 6-phosphatase activity than the liver. Thus the resulting cell population seems to be rich in hepatocytes. The isolated hepatic cells, however, lost some of their cellular proteins such as alanine and tyrosine amino-transferases. It was suggested that the membranes of isolated hepatic cells might be damaged by both enzymatic digestion and mechanical destruction.


A clinical pilot study on preformed autologous ossicles. II. A research project concerning performed autologous ossicles has been going on for more than ten years. Animal experimental studies were followed by a clinical pilot study which showed that bone could be produced in a titanium mould placed in the proximal tibia metaphysis. In the present investigation, in which another five patients were operated on, the experimental design was changed compared to the first pilot study and bone production was improved. In addition to the tibial moulds ten titanium cylinders were placed around a bony bridge prepared in the linea temporalis of the ear to be reconstructed. Nine out of ten of these cylinders contained bone suitable for ossiculoplasty. Histology showed higher osteocyte density and a higher proportion of vital looking osteocytes in the performed grafts compared with a peroperatively sculptured graft of cortical bone. On histochemical investigation the performed graft cells seemed viable at the time of transplantation. The technique for obtaining a preformed autologous ossicle through the titanium cylinders in the temporal bone was easy to perform and the patients did not experience any discomfort. The risk of infection in this area was judged to be small.


Simian virus 40 chromatin showing nucleosomes in linear bead-like arrangements along extended closed circular DNA. Viral nucleoprotein complexes were extracted from nuclei of permissive cells (CV-1) infected with simian virus 40 (SV40) and examined by electron microscopy. SV40 nucleoprotein complexes (SV40 chromatin) showed nucleosomes in linear bead-like arrangements along the extended closed circular DNA. The contour length of the SV40 chromatin was only 1.0-1.8 times shorter than that of viral DNA obtained after deproteinization. The data suggest that the circular DNA in SV40 chromatin can be extended to nearly its full length without detachment of the histone complexes.


Regulation of macromolecular synthesis in Morris hepatomas. In this review, some studies are discussed in which an attempt has been made to determine the nature of changes in macromolecular synthesis in Morris hepatomas. The incorporation of isotope labeled precursors into nucleic acids and proteins has suggested greatly increased rates of DNA synthesis in comparison with rat liver of normal and tumor bearing rats, but for RNA and proteins the changes may be impressive for individual macromolecular species but total synthesis is not greatly changed. Fractionation of nuclear proteins has indicated altered patterns of synthesis which are related to the growth rates of the tumors and are much more pronounced than in regenerating liver despite a growth rate similar to that of the most rapidly growing hepatomas. Investigations with drugs which inhibit synthesis of macromolecules has suggested that liver neoplasia may be accompanied by changes in response which may make the tumor less sensitive or more sensitive to regulation than the tissue of origin.


The receptor concept: prejudice, prediction, and paradox. Major  progress has been achieved in understanding the chemical nature of receptors for certain hormones and neurotransmitters. Some of these units have been obtained as homogenous proteins; concept and technology are adequate to permit the detailed chemical and structural analysis of these macromolecular units. The critical problem which now arises is to define how a receptor once "occupied" and "activated" serves to initiate action. Elucidation of details of receptor structure, in of itself, will not solve the "coupling problem" in hormone action. New concepts, as well as new technics, will probably be necessary. In this discussion I have raised the possibility that metals coordinated to hormone receptor complexes may be the "trigger" element involved in initiating action, serving to alter the state of functional units in binary fashion. In effect, the metal determines whether the "state" of the system is active or inactive. As stated previously in connection with the action of steroid hormone receptor complexes, the specific suggestions made relating metals to the hormone coulping process have been advanced primarily to illustrate the conceptual gap which exists with respect to "coupling." The present suggestions may prove to be correct or untenable, in whole or in part. If it turns out that metals play a central role in the coupling process of hormone action, perhaps via completely different mechanisms than those suggested here, one of the central ideas of receptor action developed by the pioneers who created the receptor concept will have been resurrected in principle, if not in detail. In science, as in life generally, conceptual progress once achieved sometimes turns out to be the rediscovery of the past.


The synthesis and secretion of serum albumin in Morris hepatomas 5123tc and 9121. In vivo, Morris hepatomas 5123tc and 9121 do not secrete serum proteins into the bloodstream. However, they synthesize albumin, at a reduced rate, if compared with liver. The produced albumin accumulates, leading to an enlargement of the Golgi apparatus and the appearance of intracellular vesicles. The proportion and the absolute amount of albumin found within the hepatoma cells is increased compared with liver. As described recently for liver in vivo and for hepatocyte suspensions, albumin is synthesized also in hepatoma cells via a precursor protein. Hepatoma cells in culture secrete albumin into the medium. However, albumin accumulates in the cells with time in culture, indicating again a limited secretory capacity of the hepatoma cell.


Components of the renin-angiotensin system in the plasma of Bothrops jararaca. By means of high voltage electrophoresis experiments it could be demonstrated that the dipeptide hydrolase present in the plasma of Bothrops jararaca is similar to the angiotensin I converting enzyme of human plasma. Therefore, angiotensin I can be considered as a probable natural substrate for this potent snake peptidase in contrast to bradykinin, which is excluded in that case, since this snake plasma was previously found to be deficient in intrinsic kinin releasing system. On the other hand, the presence of angiotensinase activity in this snake plasma could also be demonstrated. Through the pharmacological comparison of angiotensin II with the pressor peptide released from the Bothrops jararaca plasma by chymotrypsin, an indirect indication of the presence of angiotensinogen in the plasma of this reptile was obtained.


Cellular control of collagen breakdown in rheumatoid arthritis. Remodelling of connective tissue and its destruction in rheumatoid arthritis is related to collagenolysis. Study of collagenase released by rheumatoid synovial cels has indicated that the enzyme is released as latent form from adherent synovial cells in culture. As a latent enzyme it is protected from complexing with alpha2 macroglobulin, the principal proteinase inhibitor. Activation in vivo is very likely caused by proteases which destroy or complex with a portion of collagenase responsible for its latency. Recent data suggest that the latent collagenase is an enzyme-inhibitor complex and not a true zymogen.


Percutaneous needle biopsy of bone in the cancer patient. Needle biopsy of skeletal lesions is easily accomplished by the percutaneous technique. Although this approach has been utilized for many years, the frequency has definitely increased of the 91 cases performed at M. D. Anderson Hospital and Tumor Institute from September 1976 to September 1977, adequate material was obtained in 92.3% of the patients, and the diagnosis was established accurately in 83.5% of the cases. No complications were encountered. The technique, indications, and contraindications are discussed and illustrated with representative cases. The contribution of this technique to the management of patients with malignant disease is significant. The benefits include rapid and accurate establishment of a tissue diagnosis, avoidance of a surgical procedure with its associated risks and cost, and simplicity and safety of the procedure facilitating its repetition if needed.


Sonography of the common bile duct: value of the right anterior oblique view. The common hepatic and proximal common bile ducts (common duct) lie anteriorly and generally to the right of the portal vein in the porta hepatis. This constant anatomic relationship can be used to demonstrate the common duct and to differentiate it from the portal vein by gray scale ultrasonography. The patient is scanned longitudinally from the right anterior abdominal wall with the ultrasound beam directed posteromedially until two tubular structures are demonstrated in the porta hepatis. The more anterior tubular structure in this projection is the common duct. If the common duct is less than 3 mm in diameter, it may not be clearly delineated. In these cases the absence of common duct dilatation can be inferred. The usefulness of this view for detecting common duct dilatation was evaluated in a series of 101 consecutive cases proven by surgery, autopsy, or cholangiography. The overall accuracy was 96% (four false negative studies; no false positives). We conclude that sonography should be the imaging procedure of choice for suspected extrahepatic biliary obstruction if the serum bilirubin level precludes intravenous cholangiography.


Diagnostic accuracy of CT in circumscript liver disease. To evaluate the accuracy of CT in diagnosing circumscript liver disease, CT findings in 105 patients were compared to the results of invasive diagnostic procedures (laparoscopy, laparotomy, and autopsy). In all patients at least one of these procedures was performed in addition to CT. CT proved to be a valuable noninvasive method in detecting and differentiating circumscript liver lesions such us metastases, primary liver tumors, solitary cysts and polycystic disease, abscesses, and echinococciasis. The 10% rate of false positive and false negative diagnoses indicates the limitations of the method.


[Prostaglandins and bronchial asthma (author's transl)]. Prostaglandins (PG) show different effects on the bronchomotoric excitability depending on the fact to which group they certain. The best investigated PG are PGE1, PGE2 (bronchodilators) and PGF2a (bronchoconstrictor). It is possible that PG play a certain role in the pathogenesis of bronchial asthma. Among other hypotheses, the influence upon adenylate cyclase - cAMP systems (without affecting the adrenoreceptors) is evident. Probably, PG exert a regulatory function on bronchial tone. The pathogenetic imporatnce of PG metabolites for bronchial asthma is discussed. A therapeutical influence upon bronchial asthma is theoretically possible on four ways: by 1) stimulation of partial endogenous synthesis of PGE, 2) inhibition of the biotransformation of PGE, 3) exogenous application of PGE, i.e. development of PGE derivatives indifferent to bronchial mucosa, stable in solution and relatively resistant to biotransformation and 4) inhibition of biosynthesis of PGF2a. The development of synthetic PGE1 derivatives (15-methyl-11-desoxy-PGE1) appears to be of future importance. Summarizing we can say that, at the present stage of development, a directed therapeutic utilization of PG for bronchial asthma seems to be of low probability yet. The problem of aspirin-induced asthma including all its practical consequences is discussed.


Synergistic effects of dietary carbohydrate and cholesterol on serum lipids and lipoproteins in squirrel and spider monkeys. Serum lipid and lipoprotein responses to diets with a high level of simple carbohydrate (69% w/w sucrose) and a low level of saturated fat (5% w/w butter-coconut oil, polyunsaturated/saturated fatty acid ratio 0.03) containing 0, 0.1, and 1.0 mg/kcal added cholesterol was studied in five squirrel (Saimiri sciurea) monkeys. Variations in response produced by altering the nature of dietary carbohydrate (sucrose versus dextrin) and the fat (polyunsaturated/saturated fatty acid ratio, 0.03 versus 1.5) in the above diets were studied in three groups (five per group) of spider monkeys (Ateles sp.). In the absence of exogenous cholesterol, feeding a sucrose-saturated fat diet for 6 weeks produced a consistent increase in serum cholesterol in both species and an increase in serum triglycerides only in squirrel monkeys. Exogenous cholesterol had a remarkable synergistic effect on the high carbohydrate diet in increasing the serum cholesterol and had a suppressing effect on serum triglycerides in both species. Polyunsaturated fat reduced the hypercholesterolemic effect of sucrose with or without exogenous cholesterol. Dextrin diets resulted in lower serum cholesterol responses than sucrose diets when the diets contained 0 or 0.1 mg/kcal added cholesterol. Serum cholesterol response was reflected in beta- and alpha-lipoproteins. These results emphasize the varied response of serum lipids and lipoproteins to dietary changes in carbohydrate, fat, and cholesterol that might have a bearing on experimental atherosclerosis.


Extrauterine mesodermal (müllerian) adenosarcoma: a clinicopathologic analysis of five cases. Five extrauterine examples (three pelvic and two ovarian) of a distinctive mesodermal (müllerian) mixed tumor previously described to occur in the uterus and designated müllerian adenosarcoma are reported. The tumors were diagnosed during the fifth to eight decades of life. They usually formed very large, partly cystic masses, which had occasionally spread to adjacent organs by the time of operation. On microscopic examination the tumors consisted of benign-appearing neoplastic glands lying in a sarcomatous stroma. The glands were lined by a variety of müllerian epithelial cell types, and the stromal element resembled endometrial stromal sarcoma. Three patients had malignant courses manifested by intrabdominal recurrence, distant metastases, or both. This tumor should be clearly distinguished from the more common forms of mesodermal (müllerian) mixed tumor in which the epithilial as well as the stromal component is malignant and the prognosis is much more grave.


Immunoglobulin inclusions in non-Hodgkin's lymphomas. The occurrence and characteristics of intracellular immunoglobulin inclusions in non-Hodgkin's lymphomas are described. Lymphoma cells from three patients with immunoblastic sarcoma contained classic cytoplasmic, periodic acid-Schiff (PAS)-positive Russell bodies. Immunoperoxidase staining revealed monoclonal IgG (k) in two cases and a polyclonal pattern in the third case, where the tumor evolved from a reactive lesion. Unusual cytoplasmic inclusions were observed in the neoplastic cells of two patients with follicular center cell lymphoma. In one case large globular structures lacking a distinct limiting membrane were seen, while the cells of the other patient contained "signet-ring-like" vacuoles filled with microvesicles. Both were PAS-negative and showed monoclonal immunglobulin staining. In two other cases PAS-positive intranuclear inclusions consisting of monoclonal immunoglobulin IgM(k) could be demonstrated. The possible significance of these findings in B-lymphocyte derived neoplasms is discussed.


Poland syndrome in British Columbia: incidence and reproductive experience of affected persons. Patients with Poland syndrome were ascertained through the British Columbia Health Surveillance Registry, through hospital records, and through practicing plastic and orthopedic surgeons. Of 44 patients who were ascertained, 28 had family histories taken and were examined. Physical findings were: absence of the sternal head of the pectoralis major in all patients, symbrachydactyly in most patients, and infrequent other associations such as ipsilateral undescended testis, Möbius syndrome, clubfoot, and submucous cleft palate. Family histories were "negative" in all cases. The 8 affected adults had 24 reportedly normal children. Mean paternal age was significantly higher than the paternal age in the population. The incidence was 1/32,000 livebirths in British Columbia. It was concluded that in the British Columbia population the syndrome is usually a sporadic event.


Gestational trophoblastic neoplasms: morphologic correlates of therapeutic response. GTN were evaluated histologically in reference to biologic behavior and response to chemotherapy. GTN requiring more intensive, multiple drug chemotherapy usually exhibited increased mitotic activity, nuclear atypias, compact growth of cytotrophoblast, and little maturation, as compared to lesions that responded more favorably. Fibrinoid at the interface of tumor and host tissues was associated with a favorable response to drug therapy. Patients requiring more intensive chemotherapy were more likely to present with distant metastases and high levels of hCG prior to treatment and to reach remission only after many courses of treatment. The clinical and morphologic features of fatal cases suggest that these represented the extreme of a biologic continuum, with collapse of defense mechanisms despite chemotherapy. The early recognition by the pathologist of those lesions that may be resistant to chemotherapy is important to the clinician in selection of an optimal treatment protocol.


Current concepts in the management of small cell carcinoma of the lung. Small cell carcinoma of the lung should be viewed as a widely disseminated disease in all patients. Therefore, systemic treatment with intensive combination chemotherapy should now be considered as the primary and initial treatment modality. The role of radiation therapy for local or involved-field needs to be re-examined to determine if such localized therapy following intensive combination chemotherapy offers any benefits in response rate or survival duration. The role of immunotherapy is not established, and further controlled studies are necessary to define such a role, if any does exist. Prophylactic whole brain irradiation may be useful to avoid neurologic complications, however, it does not appear to improve response rate or survival duration. A randomized study needs to be done to see whether prophylactic whole brain irradiation following complete remission alters the occurrence rate of brain metastases. Response rates up to 100% and disease free survivals greater than one year have been reported. Therefore, a realistic potential for cure exists for some patients with this particular type of lung cancer.


Estimation of age from the pubic symphysis by means of multiple regression analysis. This study has been carried out to assess the age from the pubic symphysial surface employing a multiple regression analysis and a quantification theory model I analysis. Using partial regression coefficients and/or normalized scores obtained from the analyses, ages of skeletal remains can be quantitatively estimated with a fairly high reliability. The use of this method is, however, limited to the samples between 18 and 38 years of age, because age changes in the symphysial surface show large variations after about 40 years. The reliability of this method was also examined.


Glomangioma of the lung.

Glomangioma of the lung. An unusual pulmonary tumor was identified on the basis of light and electron microscopic findings as glomangioma. The ultrastructural findings of intracytoplasmic fibrils with dense bodies, electron-dense plaques, pinocytotic vesicles, and basement membranes are consistent with smooth muscle origin. The differential diagnosis between our tumor and other unusual tumors is discussed. The occurrence of a glomangioma in the lung may indicate the existence of pulmonary glomera.


Relationship of necrosis and tumor border to lymph node metastases and 10-year survival in carcinoma of the breast. The pathologic findings of 330 patients with invasive carcinoma of the breast who were followed for 10 years after radical mastectomy was reviewed. The presence or absence of necrosis and the character of the border of the tumor were two factors which were observable in all cases. Necrosis in the carcinoma was associated with a higher mortality rate, a higher incidence of axillary node metastases, and a higher mortality rate in patients with axillary node metastases than were primary carcinomas without necrosis. Tumors with necrosis and a root border showed significantly more aggressive behavior than did those tumors with a rounded border and no necrosis.


[Opiate receptors and endorphines (author's transl)]. Recent progress in narcotic drug research is briefly reviewed. Several investigators were able, independently to identify stereospecific opiate receptors, which mediate the specific effects of narcotic analgesics. A possible physiological importance of opiate receptors is likely, since endogenous ligands could be detected. Especially from brain and from pituitary glands of several species, quite a number of peptides with morphine-like effects could be isolated. The chemical structure of some of these endorphines could be analyzed. Endorphines are suggested to be involved in pain perception, electroanalgesia, acupuncture analgesia, psychiatric disorders, synthesis and release of pituitary hormones.


The freeze-fracture study of alveolar type II cells and alveolar content in fetal rabbit lung. Freeze-fracture replication technique was utilized to study the morphology of type II alveolar epithelial cells and alveolar contents in the late gestation of rabbit fetuses. It was shown that the lamellar inclusion bodies of type II cells were enveloped by the usual type of unit membrane with membrane-associated particles of 15 nm diameter. The interior of the inclusion bodies was composed of multiple stacks and/or whorls of membranes which were devoid of membrane-associated particles. Small vesicles within the inclusion were found more frequently with this technique than in chemically fixed thin-sectioned preparations. The intra-alveolar contents were comprised of two components; sperical bodies, which were identical to the internal contents of the lamellar bodies of type II cells, and tubular elements. These tubules most often appeared rectangular on cross-fractured faces. Triangular hexagonal fracture faces were also noted. The tubules were seen to rest on the surfaces of the spherical components. Our observations suggest that the tubular element of alveolar contents is formed through the interaction between the discharged lamellar body content and the alveolar fluid, and further suggest that at least the major constituent of type II cell lamellar bodies is lipid not bound to protein. Three new observations were made in this study; the absence of membrane-associated particles on the interior of the lamellae of the inclusions, the cross-fractured profiles of tubular elements of the alveolar contents, and the occasional multicompartmental nature of type II cell inclusions.


Induction of a cell membrane antigen by equine infectious anemia virus. Equine fibroblasts persistently infected with equine infectious anemia virus acquire a new cell membrane antigen demonstrable by indirect radioimmunoassay, using infected horse serum as an antibody source.


Burro aortic collagen: platelet aggregating activity and ultrastructural changes induced by plasma. A fibrillar collagen molecule was extracted from the upper thoracic aorta of an old burro (Equus asinus). Presence of the collagen in the extract was determined by amino acid analysis, scanning and transmission electron microscopy, incubation with collagenase, and assays of its platelet-aggregating capacity by "aggregometry". Based on the amino acid rations of proline/hydroxyproline and lysine/hydroxylysine, the collagenous protein most nearly resembles type I of 4 main published types of collagen. Quantitative assays of the collagen as a mediator of platelet aggregation showed human platelets more sensitive and sheep platelets slightly less sensitive than burro platelets. Incubation with collagenase abolished platelet aggregation  capacity and converted the fibrillar collagen to a gel-like mass. Incubation with galactose oxidase neither lessened nor intensified the collagen-mediated platelet aggregation. Incubation with burro plasma decreased platelet aggregating activity and changed the collagen ultrastructure (demonstrated with scanning electron microscopic imaging). The significance of a naturally occurring plasma (protein) factor(s) which may have a regulatory role in reducing the chemical activity of the fibrillar collagen molecule with platelets is also discussed.


An immunofluorescence diagnostic test for feline viral rhinotracheitis. Hyperimmune serum against feline viral rhinotracheitis was produced in a goat and conjugated with a fluorescent dye. Cell cultures infected with rhinotracheitis virus had positive immunofluorescence. Cell cultures infected with other feline viruses and herpesviruses of other species did not fluoresce. In cats experimentally infected with rhinotracheitis virus, the virus was isolated from nasal and conjunctival swabs 1 to 9 days after inoculation. Nasal smears stained with the conjugated antiserum fluoresced 1 to 9 days after inoculation when clinical disease was most apparent. Conjunctival smears had positive immunofluorescence 1 to 6 days, but not 9 days, after inoculation. On postinoculation day 23, rhinotracheitis virus was not isolated from nasal or conjunctival swabs and nasal and conjunctival smears did not fluoresce. Rhinotracheitis virus or feline calicivirus was isolated from naturally infected cats with upper respiratory tract disease. Nasal and conjunctival smears from rhinotracheitis virus-infected cats had positive immunofluorescence in all cast showing clinical illness. Smears from 1 clinically normal cat from which rhinotracheitis virus was isolated did not fluoresce. Nasal and conjunctival smears from calicivirus-infected cats did not fluoresce.


Pancreas-passaged avian encephalomyelitis virus and its immunogenicity. A serial 34-chicken pancreas passage of avian encephalomyelitis virus by oral administration was successful. Oral inoculation test with 4 passaged viruses showed rapid infection of the duodenal wall and unchangeable infection of pancreas diminishing the viral invasiveness to other organs. The passaged virus caused neither detectable viremia nor clinical avian encephalomyelitis signs and produced neutralizing antibody of high titers.


Diagnosis of avian viral diseass by electron microscopy. Clinical material from avian species was examined directly by electron microscopy for the presence of viruses. Mycoplasma-like and coronavirus-like particles were found in chicken feces. These particles did not appear to be associated with disease and were not propagated in the laboratory. Infectious bursal disease virus was readily detected in impression smears of bursas from experimentally infected birds. Poxviruses were demonstrated in smears made from canarypox lesions. Difficulty in distinguishing intact particles of Newcastle disease virus from mycoplasmas and orthomyxoviruses was resolved by treating viral preparations with deoxycholate. After treatment, Newcastle disease virus was lysed, rendering the nucleocapsid visible, whereas influenza virus was mainly unaffected. Viral particles that were recognized only with difficulty by direct elecron microscopic examination were more easily identified using immunoelectron microscopy.


Parainfluenza-3 virus exposure of beef heifers prior to natural breeding. Ninety-six Hereford heifers (approximately 7 months of age) were randomly divided into 2 equal groups and housed 1.6 km apart (with 2 replications in time, 1 year apart). At 15 months of age, 1 group/replicate was inoculated with parainfluenza-3 virus, and the other group was given virus-free spent culture medium. Twenty-four hours later, 2 virgin bulls (2 years old) were placed with each group (24 cows) for natural breeding. Viral inoculation caused a twofold increase in parainfluenza-3 titer and a 0.3 C body temperature increase. There was no effect recognized from the virus on natural breeding efficiency.


Hand-to-hand transmission of rhinovirus colds. Rhinovirus was transmitted from experimentally infected volunteers (donors) to susceptible recipients and the efficiencies of spread by hand-to-hand contact and large- and small-particle aerosols compared. Transmission of infection was very efficient by the hand route: 11 of 15 hand-contact exposures initiated infection, compared with one of 12 large-particle (P less than 0.005) and none of 10 small-particle (P less than 0.005) exposures. Rhinovirus was present in nine of 18 (50%) nasal swab specimens, 28 of 43 (65%) hand rinses, and seven of 18 (39%) saliva specimens of donors; geometric mean titers of positive specimens were 10(1.5), 10(1.4), and 10(1.2) tissue culture infectious dose 50/ml (TCID 50/ml), respectively. Rhinovirus was present in 20 of 43 (46%) recipient hand rinses, with a geometric mean titer of 10(1.4)TCID50/ml. Virus on donors' hands was transferred to recipients' fingers during 20 of 28 (71%) 10-second hand-contact exposures. These findings support the concept that hand contact/self-inoculation may be an important natural route of rhinovirus transmission.


Small-cell carcinoma of the lung: therapeutic management. Although bronchogenic carcinoma generally remains a tumor resistant to treatment, marked progress in the therapy of the small-cell undifferentiated subtype has occurred in the past 5 years. Many aspects of its growth and metastatic spread are such that it is not satisfactorily treated surgically. However, it is sensitive to both radiation and a variety of chemotherapeutic agents. Use of these agents in combination seems to produce a greater antitumor effect than single drugs. The combination of radiation and chemotherapy results in marked tumor regressions. Untreated, this carcinoma has a very short median survival (2 months). Administration of current "aggressive" combination therapy regimens has resulted in median survivals of nearly 1 year with some patients still living 3 years after therapy.


Rubella vaccine. Recommendation of the Public Health Service Advisory Committee on Immunization Practices. Center for Disease Control, U.S. Department of Health, Education, and Welfare; Atlanta, Georgia. Rubella infection may be subclinical or overlooked because of the nonspecificity of its most frequent manifestations. Joint involvement is most frequent in women but can occur in men and children. The most serious complication is induction of fetal anomalies in infected pregnant women. This paper reviews the proper use of live rubella virus vaccine for prophylactive immunization and the postexposure treatment with immune serum globulin for modification or suppression of symptoms.


Recent progress in the development of radioimmunoassays for human serum lipoproteins. A review of radioimmunoassays for measuring human apolipoprotein B (apo B), the A apolipoproteins of high density lipoprotein (apo A-I and apo A-II) and apolipoprotein C-II (apo C-II) in human plasma and in isolated lipoproteins is presented. The sensitivity, specificity and validity of each of these assays is discussed. In normolipidemic subjects the reported serum apo B concentrations ranged between 0.83 +/- 0.16 and 0.92 +/- 0.21 g per l (m +/- SD). Serum apo B concentrations were highest in Type II subjects (Type IIa homozygotes 3.83 +/- 0.43 g per l; Type IIa heterozygotes 2.37 +/- 0.47 g per l) and were less elevated in patients with Type IV and Type V disorders (1.32 +/- 0.21 g per l and 1.26 +/- 0.30 g per l, respectively). Preliminary data on the relationship between plasma apo B and cholesterol, the distribution of apo B amongst the lipoprotein classes and a comparison of the lipoprotein lipid-apo B ratios in the various hyperlipidemic disorders are summarized. In contrast to apo A-II, the immunoreactivity of apo A-I was not fully exposed in whole sera and in isolated lipoproteins. The different methods used to measure the apo A-I immunoreactivity are discussed. In normolipidemic subjects the serum apo A-I concentration in males and females was 1.13 +/- 0.061 and 1.24 +/- 0.068 g per l (m +/- SD), respectively, while the corresponding serum apo A-II values were 0.35 +/- 0.038 g per l and 0.41 +/- 0.046 g per l. In subjects with Tangier's disease, the serum apo A-I and apo A-II concentrations were less than 1 percent and 5 to 7 percent of that found in controls. The serum apo A-I level was also reduced in two subjects with abetalipoproteinemia (0.38 g per l and 0.30 g per l) and Tye II hyperlipoproteinemia (range 0.54 to 0.86 g per l). In normotriglyceridemic subjects and those with Type IIa hyperlipoproteinemia, the total plasma apo C-II concentrations were 0.0497 +/- 0.0040 g per l and 0.0562 +/- 0.0054 g per l (m +/- SE). Plasma apo C-II levels in Type IIb, Type IV and Type V lipoproteinemic subjects were 0.0899 +/- 0.0046, 0.0854 +/- 0.0069 and 0.1328 +/- 0.0021 g per l, respectively and were significantly higher than in the normotriglyceridemic subjects. An analysis of the relationship between the apo C-II content and the lipoprotein lipase activator properties of VLDL isolated from normo- and hypertriglyceridemic plasma samples is presented.


Plasma lipoproteins and coronary heart disease. Both plasma low-density (LDL) and high-density lipoproteins (HDL) have been associated with the genesis of cardiovascular disease. Recent studies with cells grown in culture have suggested a regularory role of these lipoproteins in cellular cholesterol metabolism and pointed at abnormalities resulting from deviations of these regulatory processes. The precise relationship between these observations in vitro and the atherogenic process remains open to investigation.


[Effect of penicillin on the antigenic properties of serum beta-lipoproteins]. Peculiar characteristics of the antigenic properties of penicillin compounds with heterological and homological beta-lipoproteids of the blood serum were investigated. The beta-lipoproteids isolated from the blood serum of humans (donors) and rabbits were mixed with potassium benzylpenicillin (10000 and 50000 gamma/ml). Twenty seven rabbits were immunized with such compounds and solutions of beta-lipoproteids without addition of the antibiotic. The antisera obtained from the animals were used in the reaction of precipitation and immunoelectrophoresis, the results of which were densitometrized. Some physico-chemical properties of the preparations, such as pH, electrokinetic features were also studied. It was shown that the immunochemical properties of heterological beta-lipoproteids, i.e. precipitation bands changed due to the effect of penicillin. They differed from the control by compactness and contrastness, their amounts decreased, a separate band not identical to that of the control antigen appeared. A separate or intermediate antigen was found in the experiments with serum exhaustion. The peculiarities of the precipitation reaction were confirmed by the immunoelectrophoregrams. These differences were also registered on the densitograms. The compounds of penicillin with homological beta-lipoproteids of the rabbit blood serum induced formation of specific precipitins in the animals. Some physico-chemical properties of beta-lipoproteids also changed under the effect of penicillin.


Enhanced virus replication in mammalian cells exposed to commercial emulsifiers. Mammalian cell cultures were used to show that a variety of commercial emulsifiers are capable of enhancing the sensitivity of these cells to infection with several viruses. Some emulsifiers were not active as enhancers, and those viruses that responded to the enhancing emulsifiers were single-stranded ribonucldic acid viruses. The double-stranded viruses that were tested were nonresponders.


Comparison between adsorption of poliovirus and rotavirus by aluminum hydroxide and activated sludge flocs. Adsorption of poliovirus and rotavirus by aluminum hydroxide and activated sludge flocs was studied. Both aluminum hydroxide and activated sludge flocs adsorbed greater amounts of poliovirus than rotavirus. Aluminum hydroxide flocs reduced the titer of poliovirus in tap water by 3 log10, but they only reduced the titer of a simian rotovirus (SA-11) in tap water by 1 log10 or less and did not noticeably reduce the number of human rotavirus particles present in a dilute stool suspension. Activated sludge flocs reduced the titer of added poliovirus by 0.7 to 1.8 log10 and reduced the titer of SA-11 by 0.5 log10 or less. These studies indicate that a basic difference in the adsorptive behavior of enteroviruses and rotaviruses exists and that water and wastewater treatment processes that are highly effective in removal of enteroviruses may not be as effective in removing other viral groups such as rotaviruses.


Thalamic lesions during the development period and their clinical correlation. 28 autopsy cases were investigated in which the thalamus was impaired in early life, i.e. prenatal, perinatal, and postnatal (under 1 year of age). The thalamus is vulnerable to brain damage in the perinatal and early postnatal period. Lesions in the thalamus are severe in the DM, PL and VPL, and moderate in the VL and pulvinar thalamus. The anterior nuclei and center median show little change. Many of the cases with athetoid movements have complicated thalamic lesions in addition to those of the basal ganglia. In one patient who showed athetosis as a sequela of encephalitis japonica, the VL and PL in the thalamus were involved severely; in contrast the basal ganglia revealed very slight changes.


Observations on toxin and hemagglutinin produced by Clostridium botulinum type C. In the culture fluid of a hemagglutinin-positive strain of Clostridium botulinum type C, two toxins of different molecular size, hemagglutinin positive and negative, were separated by sucrose density gradient centrifugation.


Concentration of enteroviruses from large volumes of tap water, treated sewage, and seawater. Methods are described for the efficient concentration of an enterovirus from large volumes of tap water, sewage, and seawater. Virus in acidified water (pH 3.5) in the presence of aluminum chloride was adsorbed to a 10-inch (ca. 25.4 cm) fiberglass depth cartridge and a 10-inch pleated epoxy-fiberglass filter in a series at flow rates of up to 37.8 liters (10 gallons) per min. Adsorbed viruses were eluted from the filters with glycine buffer (pH 10.5 to 11.5), and the eluate was reconcentrated by using a combination of aluminum flocculation followed by hydroextraction. With this procedure, poliovirus in large volumes of tap water, seawater, and sewage could be concentrated with an average efficiency of 52, 53, and 50%, respectively. It was demonstrated that this method is capable of detecting surface solid-associated viruses originating from sewage treatment plants. No difference in virus recovery between laboratory batch studies and a set-up with acid-salt injection was found. This unified scheme for the concentration of viruses has many advantages over previously described systems. These include: high operating flow rates, low weight and small size, effectiveness with a variety of waters with widely varying qualities, and filters with a high resistance to clogging.