Lung biopsy in Pneumocystis carinii pneumonia: a histopathologic study of typical and atypical features. This study of 36 patients with Pneumocystis carinii pneumonia emphasizes a spectrum of histopathologic changes that have not been classically considered features of the infection. These atypical microscopic findings were present in 69% of the cases as defined in this retrospective examination. As expected, the suggestion of the correct diagnosis of Pneumocystis carinii pneumonia on the basis of a frozen section and without the aid of appropriate special stains was extremely difficult in the majority of biopsies. It is important for the pathologist to maintain the possibility of this infection in his differential diagnosis when he examines a pulmonary biopsy from a patient who is immunologically compromised.


Detection of hepatitis B surface antigen by means of orcein staining of liver. Paraffin-embedded sections of liver biopsies from 65 patients and 16 autopsies were stained by a modified orcein method as described by Shikata, to appraise the efficacy of the method in detecting hepatitis B antigen, (HGsAg). Of the liver biopsies from patients with chronic hepatitis, 55% were positively stained. Staining was observed in the cytoplasm of liver cells but was frequently irregular in distribution. The technic is simple and may be used for evaluation of fresh or stored liver. The positive stain is of value in the diagnosis of chronic hepatitis with minimal or absent histologic changes, as well as the distinction of chronic from acute hepatic disease. The method may be useful for detecting asymptomatic carriers. However, weak positive staining of hepatic parenchyma should be evaluated with caution when serologic tests for HBsAg are negative. It may warrant repeated serologic testing. Evaluation of stored autopsy material suggests that Shikata's stain may also be used in determining the etiology of cirrhosis. Inclusion bodies seen in hepatomas stain positively with orcein, suggesting that they contain, or are related to, HBsAg.


Human nucleolus organizers: the satellites or the stalks? A silver-staining technique specific for demonstrating nucleolus organizer regions (NOR) showed that the achromatic stalks of the 10 acrocentric autosomes of the human complement represent the NORs. Some variability in number of stained stalks is observed from cell-to-cell and from individual-to-individual. The silver-stained masses may extend beyond the stalks and cover the satellites, especially in chromosomes with short stalks or minute satellites.


Exocrine pancreatic insufficiency syndrome in CBA/J mice. II. Biochemical studies. Premature activation of proteolytic zymogens (trypsinogen, chymotrypsinogen) as an early step in the pathogenesis of exocrine pancreatic insufficency (EPI) syndrome in CBA/J mice was investigated in electrophoresed pancreatic homogenates. Polyacrylamide gels containing extracts from control pancreas required prior activation of trypsinogen and chymotrypsinogen (with exogenously added enterokinase and trypsin, respectively) to produce activity staining with specific synthetic substrates. On the contrary, bands of activity staining in gels containing homogenates from mice with EPI syndrome could be readily detected without trypsin or enterokinase preincubation. Subcellular fractionation of control and diseased pancreas revealed that the premature intracellular proteolysis was confined to the zymogren granule fraction, which, even in very moderately affected pancreases (10 to 30% acinar cell autolysis), was very labile in vitro. These proteolytic events reflect the biochemical consequences of zymogen granule destabilization that were observed at the ultrastructural level.


Chemical and histochemical studies of human alveolar collagen fibers. Light and electron microscopic studies have established that the normal human alveolar argyrophilic (reticulum) fiber is collagen fiber. The silver impregnation method is highly sensitive and specific for histologic demonstration of the elaborate collagen fiber network of alveolar septa. The argyrophilic alveolar collagen fiber does not stain with the periodic acid-Schiff (PAS) or periodic acid-thiocarbohydrazide-osmium tetroxide (PTO) reaction. The materials positive for the PAS and PTO reactions in alveolar septa are epithelial and endothelial basal laminas, which are nonargyrophilic. Chemically, lung collagen fibers are composed of Type I and Type III collagens, which differ in amino acid composition, chain composition, and carbohydrate content. The chemical heterogeneity of lung collagen may have important biologic implications in the maintenance of normal structure and in the repair of lung injury.


View box exercises for teaching problem solving in radiology. An organized radiologic problem-solving system is presented for developing improved view box exercises for students and residents. It is based on six components: (1) problem sensing, (2) problem hypothesizing, (3) problem searching and definition, (4) problem identification, (5) resolution, and (6) verification. Since all examinations by the practicing radiologist involve these components, worthwhile simulated clinical management games should also incorporate them. A simulated radiologic exercise should be a valid measurement of the resident's ability to manage a wide range of clinical situations and techniques and should improve problem-solving strategies. Use of simulated clinical cases eliminates risk to patients during the educational process.


Chronic rotator cuff impingement in the throwing athlete. Compromise of the space between the humeral head and the coracoacromial arch may be a source of chronic shoulder pain associated with rotator cuff impingement in the athlete participating in throwing sports. In certain carefully selected individuals, surgical decompression may alleviate these symptoms. The surgical procedure can be done under local anesthesia and may enable the athlete to return to his previous level of performance without disability.


[Centrifugal fibers in the human retina]. The examination of 16 human retina stained in toto according to the Gallego method (1953) demonstrated the presence of centrifugal optic fibers. These fibers appear as large argyrophilic axons and can be traced as of the papille, amongst the centripetal optic fibers. The centrifugal fibers show a high degree of ramification which may extend over a quarter of the total retinal surface and terminate in the internal plexiform layer. Elsewhere the existence of perivascular and intravascular axon terminals as well as short axon ganglion nerve cells were demonstrated.


Urticaria. An updated review.

Urticaria. An updated review. Urticaria can result from many different stimuli, and numerous factors, both immunologic and nonimmunologic, are involved in its pathogenesis. Most commonly considered of immunologic mechanisms is the type I hypersensitivity state mediated by IgE. Another immunologic mechanism involves the activation of the complement cascade, which produces anaphylatoxins that can release histamine. Immunologic, nonimmunologic, genetic, and modulating factors converge on mast cells and basophils to release mediators capable of producing urticarial lesions. In addition to the clinical and laboratory diagnosis and treatment regimens, we review such mediators as histamine, kinins, serotonin, slow-reacting substance of anaphylaxis, prostaglandins, acetylcholine, fibrin degradation products, and anaphylatoxins that increase vascular permeability and can thereby produce wheals. Special consideration is given to histamine and the factors that regulate is secretory release from mast cells and basophils, including the modulating role of intracellular levels of cyclic adenosine monophosphate.


Comparative studies of the incorporation inhibition of radioactive nucleotides and amino acids in vitro under the influence of adriamycin, bleomycin, and sodium arsenate. The incorporation of 14C-marked nucleotides and amino acids into the nucleic acids and into the cellular protein of PHA-stimulated human lymphocytes was inhibited variably by increasing doses of Adriamycin, Bleomycin and Na2HAsO4. The findings, which were obtained with the aid of the liquid scintillation counter and partly by means of 14C-thymidine-marked autoradiographies shows clearly that Adriamycin causes the strongest incorporation inhibition. In contrast to this, the inhibition caused by Bleomycin and arsenate is considerably less destructive. It was shown by means of cytophoto metrical examinations that Adriamycin is capable of fixing cells in the G2 phase and in the S phase. Cells react similarly to Bleomycin and arsenate. The differential inhibition of nucleic acid and protein metabolism induced by Adriamycin, Bleomycin and arsenate is correlated with a varying responsiveness of lymphocytes to the cytostatically effective substances.


Detection by electron microscope of rod-shaped organisms in synovial membrane from a patient with the arthritis of Whipple's disease. Rod-shaped organisms identical to those present in the jejunal mucosa have been found in the synovial membrane of a patient with Whipple's disease. These probably caused inflammatory changes which sere reflected in an increase of the cellular content and high enzyme levels (acid phosphatase and 5-nucleotidase) of the synovial fluid. Tetracycline was effective in controlling the bowel lesion but only had a temporary effect upon the arthritis. Erythromycin controlled both the bowel lesion and the arthritis.


CEA monitoring of palliative treatment for colorectal carcinoma. Palliative treatment was applied to 131 cases of unresectable or palliatively resected colorectal carcinoma being monitored with serial CEA determinations. There were 84 instances of disease progression with 67 (80%) of them showing an increase in CEA above pretreatment levels or maintaining high levels, and 17 (20%) showing a fall when compared to pretreatment values or maintaining low initial values. There was a clear-cut regression of the disease in only 9 instances. In all 9, the CEA clearly dropped or maintained low valles throughout the period of regression. No patient in regression had a rise or maintained an elevated CEA level. These changes in CEA followed closely the clinical response of our patient to the use of a particular agent, although for the Nitrosourea compounds there may be a tendency to lower the CEA regardless of the patient's tumor response to the drug. This could be due to the fact that the Nitrosoureas produce a diffuse block of cellular activity, both at the nucleous and cytoplasm; while other compounds act as alkylating agents or by inhibition of enzymes involved in the metabolism of nucleic acids (i.e., 5-FU inhibiting thymidylate synthetase). In general, longer survival was found in those patients who had initially lower levels of CEA as compared to those with high initial levels. The patients with a favorable CEA response to the treatment (falling CEA or maintained low value), even in many who did not show a clinical response had a longer survival than the group with rising or stable high levels. The main value in CEA monitoring of patients resides in its correlation with the amount of disease present and then its ability to detect progression of tumor mass which is not clinically measurable.


Palliation of malignant esophago-respiratory fistulae by permanent indwelling prosthetic tube. Malignant esophago-respiratory fistula is an incurable condition calsing severe distress to those patients suffering from it. Sixty two successive patients with esophago-respiratory fistulae, secondary to squamous cell carcinomas of the esophagus, were intubated for palliation. The first 14 were intubated by a traction technique using the Celestin tube, and the remaining 48 were intubated by the Procter-Livingstone tube inserted by a pulsion method. Celestin intubation had a mortality of 64.3% but 75% of those intubated by the Procter-Livingstone tube were discharged from hospital, swallowing satisfactorily and relieved of their respiratory distress. In our experience the insertion of the Proctor-Livingstone tube by a pulsion technique, can be performed in a few minutes, with little morbidity and allows the patient to be discharged from hospital within 3-4 days of the procedure. It is a successful and acceptable method of treating malignant esophago-respiratory fistulae.


Effects of citrulline administration on enzymes of liver and brain in rats. Intraperitoneal administration of citrulline (30 mg/kg body weight) for three days to rats brought about an increase in the activity of hepatic ornithine-aminotransferase without any change in glutamine-synthetase activity. In the brain of the same animals, the activity of the glutamine synthetase in cerebellum and brain stem increased significantly. In cerebral hemispheres the activity of ornithine aminotransferase was increased without a change in glutamine-synthetase activity. Under these conditions, there is a rise in the content of glutamine, citrulline, arginine and ornithine in all the three regions of the brain.


[Metabolism of glucosamine in the liver of Scyliorhinus canicula (selachian)]. (1) The metabolism of the glucosamine was studied in the liver of S. canicula, after injection of D-(1-14C) glucosamine into the animal. (2) The labelled acid-soluble derivatives were separated by ion exchange columns and characterized by chromatography and electrophoresis, and were identified as glucosamine, glucosamine 6-P, N-acetylglucosamine, N-acetylmannosamine, N-acetylneuraminic acid, N-acetylglucosamine 6-P, N-acetylglucosamine 1-P, N-acetylmannosamine 6-P, UDP-N-acetylglucosamine, UDP-N-acetylgalactosamine. (3) The variation with time after glucosamine injection of the radioactivity of the fractions separated on Dowex 1-X4 was investigated. This study showed a decrease of the radioactivity in the fraction 1 (glucosamine and glucosamine 6-P), an increase in the fraction II (N-acetylneuraminic acid) and the fraction IV (UDP-N-acetylhexosamines), and a stability in the fraction III (phosphorylated N-acetylhexosamines). (4) The absence of label in neutral hexoses and their phosphorylated derivatives was interpretated as due to the weak activity of the glucosamine 6-P isomerase, which is positively modulated by the N-acetylglucosamine 6-P.


Oral fructose tolerance, gastric emptying and absorption: a compartmental model. Gastric emptying and intestinal absorption regulate transfer of ingested fructose from stomach to plasma. Using conscious rhesus monkeys we have developed a compartmental model which describes this system. Fructose tolerance tests were performed in groups of monkeys by intragastrically administering 2 g/kg of 10.5% D-fructose solution; fructose concentration in arterial plasma, [fructose], and intragastric volume were measured at intervals afterward. One group was pretreated with atropine; stomachs imptied with a time constant, tau, of 67 min. Another group received fructose solution with trisodium citrate added; tau was 18 min. Another group received only fructose; tau was 30 min. Using these constants, a model was developed to describe the [fructose] data. In this model k1 related amount of fructose in intestine to absorption rate and Ae represented absorption efficiency. K1 = 0.03 and Ae = 89% provided a good fit for data from the atropinized group. k1 = 0.018 and Ae = 56% provided a good fit for data from the other groups. Differences were explained by considering effects of atropine on gastrointestinal secretion. The model adequately describes our [fructose] data and may be adapted for tests utilizing other substances.


[Biochemical polymorphism in the red partridge (Alectoris rufa)]. Egg white proteins, hemoglobin, serum proteins and enzymes from Alectoris rufa have been examined by starch gel electrophoresis. All three genetic parameters, mean proportion of loci polymorphic per population (P), mean numbers of alleles per locus (A), and mean proportion of loci heterozygous per individual (H) are given for Alectoris rufa, and comparison were made between the proteins of the related species Coturnix coturnix japonica.


On the induction of the hepatic tyrosine aminotransferase by quinolinic acid. The induction of tyrosine aminotransferase by quinolinic acid is inhibited completely by cycloheximide and by alpha-amanitin, but only partially during the first 3 hours by 5-azacytidine and 8-azaguanine; longer treatment with 8-azaguanine, however, also prevents the major increase in enzyme activity. The hepatic concentration of cyclic AMP does not change after administration of quinolinic acid. Insulin, like hydrocortisone, acts additively to qlinolinic acid. The isoenzyme pattern of tyrosine aminotransferase is not changed cosniderably during induction of quinolinic acid. Most likely, quinolinic acid acts through its own mechanism of induction.


Purification and properties of human placenta arylsulphatase A. 1. Arylsulphatase A (arylsulphate sulphohydrolase E.N. 3.1.6.1) has been purified 7200-fold from human placenta using concanavalin A Sepharose chromatography. 2. Ultracentrifugation studies indicated that the purified enzyme was homogenous with respect to sedimentation coefficient and molecular weight and has a molecular weight of 102000. 3. The purified enzyme could hydrolyze cerebroside 3-sulphate, seminolipid and sulphogalactosylsphingosine under identical conditions. 4. The kinetic parameters for the hydrolysis of all sulphate esters used in the present study were the same. 5. Both seminolipid and sulphogalactosylsphingosine were competitive inhibitors for the hydrolysis of cerebroside-3-sulphate with an inhibition constant of 0.2 mM. 6. Kinetic parameters, metal ion effect and heat inactivation profile of enzyme suggest that the same active site of enzyme is responsible for the hydrolysis of cerebroside 3-sulphate, seminolipid and sulphogalactosylsphingosine.


A duplex retina and the electroretinogram in the nocturnal Perodicticus potto. The presence of cones in potto's retina has been proved beyond doubt although they are very restricted in number (1 cone for 300 rods). Morphologically, speaking there is no point in calling these cones "rudimentary" except for their slender outer segment. There are red sensitive elements in that retina at wavelengths beyond the spectral sensitivity of visual purple and it is tempting to assume that these elements are cones. The ERG evoked from these elements by red light differs from that in response to white and blue light. They dark-adapt faster than the receptors sensitive to blue and white flashes. However in some of their properties, for example fusion frequency, these cones behave like rods in other species. As these few cones seem to activate the bipolar cells nearly as effectively as the numerous rods, it is suggested that these cones may be responsible for day vision in the potto.


Changes in blood glucose, blood and muscle lactate,and plasma lactic dehydrogenase levels in the pigeon on acute exposure to cold. Adult pigeons were subjected to acute cold exposure (-25 degrees C; 30 min) after which the levels of blood glucose, blood and muscle lactate and plasma lactic dehydrogenase were measured. Partially defeathered (dorsum and pectoral regions) birds, following exposure to cold, showed marked reduction in blood glucose and blood and muscle (pectoralis) lactate. Fully plumed birds, in contrast, showed no significant reduction in body temperature or blood glucose and only moderately reduced lactate levels indicating the effectiveness of the insulative feather coat in maintaining thermal and metabolic homeostasis. The partially-defeathered pigeons exposed to cold showed a two-to-three-fold increase in plasma lactic dehydrogenase activity, which may reflect a molecular adaptation in their calorigenic response to cold.


Influence of aminooxyacetate administration on ammonia-induced metabolic disturbances in the rat liver. The purpose of the present report was to investigate the effects of aminooxyacetate administration to rats on the ammonia-induced disturbances in the substrate levels and in the activities of the enzymes involved in glutamine metabolism. 1.--Aminooxyacetate enhances the accumulation of ammonia following an ammonia load and prevents the other substrate level changes induced by ammonia. Thus, this transaminase inhibitor suppresses ammonia detoxication by formation of aminoacids as well as by urea synthesis. 2.--A significant decrease of glutamine synthetase activity is observed only after administration of both aminooxyacetate and ammonium chloride. 3.--Like in rats injected with ammonium chloride alone, an ammonia-induced activation of liver glutaminase I is found in inhibitor-pretreated rats. This result confirms the specific enhancement of glutaminase I activity by ammonia in excess.


[Treatment of rhythm disorders by fenoxedil hydrochloride]. Fenoxedil chlorhydrate (FC), which is used as a treatment for cerebral circulatory failure and peripheral vascular disease, has been given to 100 patients with a cardiac arrhythmia: atrial fibrillation (78 cases), atrial flutter (4 cases), atrial tachysystole (2 cases), ventricular extrasystoles (12 cases), and supraventricular extrasystoles (4 cases). FC has been prescribed alone, or as a complement to current anticoagulant or digitalis treatment; combination with prenylamine, amiodarone, dysopyramide or a drug of the quinidine group must always be avoided, and the potassium level checked and corrected if necessary before treatment. In 78 cases of atrial fibrillation, the authors found that sinus rhythm was restored in 58 (74.4%); four cases of flutter were restored, and one case out of two of atrial tachycardia. In case of supraventricular and ventricular extrasystoles the results are less clear, and merit a further study with a larger number of cases. The electrocardiographic disorders encountered in this series have been evaluated: lenghthening of the QT interval, disorders of atrioventricular conduction, sinus inhibition. They were either produced by or aggravated by the FC. No cases of axis deviation were encountered. The authors make mention of the complications observed by other authors, but draw a distinction between the prescription of FC in cases of cerebral vascular insufficiency, without previous knowledge of the exact cardiac status of the patient (otherwise there is a risk of severe accidents), and the use of FC in cases of arrhythmia which have undergone full assessment before the drug is used. According to this study, FC appears to be a very effective anti-arrhythmic agent, but its use demands very rigorous clinical and electrocardiographic supervision.


Pharmacokinetics of a neurotoxic oral dose of leptophos in hens. A pharmacokinetic profile of [14C] leptophos was determined in laying hens following a single oral dose of 400 mg/kg (0.58 muCi). Most of the radioactivity was excreted into the urine and feces. After 15 days, the total radioactivity recovered in the combined urinary-fecal excretion was 73.5% of the administered dose. A major part of the absorbed leptophos was concentrated in the eggs. The total 14C radioactivity in egg albumen was 7.29% of the administered dose as compared to 4.67% in egg yolk. The half-life for the disappearance of radioactivity from the birds' bodies following the administration of [14C] leptophos was 11.55 days. A correlation between the pharmacokinetics of leptophos and the susceptibility of the hen to delayed neurotoxicity is discusses.


[Feeding rhythms and the diurnal rhythm of cell proliferation in pharmacologically induced liver growth (author's transl)]. Stimulation of hepatic DNA synthesis can be achieved in the intact rat by alpha-hexachlorocyclohexane (alpha-HCH = alpha-benzene hexachloride). The extent of stimulation is high in the morning and low in the evening. These rhythmic variations in the rate of DNA synthesis are synchronized indirectly by the light-dark rhythm, but directly by the animal's feeding habits: Rats eat preferentially during the night. If the diurnal rhythm of food intake is abolished, the rhythmic fluctuations in the rate of DNA synthesis are no longer detectable; if rats are adapted to daily feeding periods of only 5 h, these fluctuations are pronounced and almost synchronized. Further experiments show that the time of feeding determines the time of DNA replication. It is concluded that food intake provides a "2nd stimulus" or permissive factor, which is required for the induction of DNA synthesis in a certain critical stage of the prereplicative phase. Labelling experiments with orotic acid suggest that foot intake initially induces an increase of RNA synthesis. The results indicate that controlled feeding schedules provide the possibility to synchronize, in the living animal, a proliferating population of hepatocytes. A hypothesis is derived which offers an explanation for the generation of the diurnal rhythm of cell proliferation in the liver.


Double-exposure duplication of preoperative and postoperative 2 X 2 transparencies. Before and after photographs in plastic surgery are an essential part of the patient's record. They also provide visual data to supplement both primary and continuing education lectures. When successive photographs are used in lectures, a sharp visual memory is required to compare effectively the preoperative and postoperative photograph. The method presented in this article uses a specially constructed frame used as an accessory for one of the common commercial slide copiers. This device makes it possible to copy, duplicate, and frame preoperative and postoperative 2 X 2 transparencies onto a single 2 X 2 transparency without any additional work on the original, such as framing, cutting, and remounting. This technique leaves the original preoperative and postoperative 2 X 2 transparency slides intact for possible use elsewhere in the same lecture or subsequent lectures on the same subject.


Properties of erythrocyte catalase from homozygotes and heterozygotes for Swiss-type acatalasemia. The unstable catalase variant found in the blood of individuals homozygous for Swiss-type acatalasemia and the enzyme species present in heterozygous carriers of this rare defect have been further characterized. The mutant enzyme isolated from acatalasemic red cells is considerably more heat labile and differs in electrophoretic mobility from the normal enzyme. Catalase preparations obtained from heterozygotes consist of an apparently uniform enzyme species, probably representing a molecular hybrid, with properties intermediate to those of the normal and the variant enzyme. However, antigenic identity of catalase from all three sources is observed. Model experiments indicate that hybrid catalase molecules can be produced by recombining normal and variant dimer subunits. Fractionation of erythrocytes according to density and age shows that most of the residual catalase activity is localized in juvenile acatalasemic cells, whereas in normal and heterozygous individuals the catalase activity level does not alter significantly during the life span of the red cells. These findings agree with the observation that there is no gene dosage in heterozygotes, their catalase activity values falling within the normal range.


The alpha macroglobulins of rat serum.

The alpha macroglobulins of rat serum. A three-stage method for isolation of alpha1 macroglobulin and alpha2 macroglobulin from the serum of normal and injured rats is described. The methods successively used, namely gel filtration, ultracentrifugation and chromatography on DEAE-cellulose, were chosen to minimize loss of tryptic esterase-protecting activity. The two proteins differed slightly with respect to the following properties: mol.wt., alpha1 macroglobulin 7.46 X 10(5), alpha2 macroglobulin 7.16 X 10(5); isoelectric focusing, alpha1, macroglobulin pI 4.4, alpha2 macroglobulin pI4.5. Amino acid analyses were identical, except with respect to tyrosine: alpha1 macroglobulin 3.96 +/- 0.24, alpha2 macroglobulin 3.16 +/- 0.32 mol/100 mol of total amino acids. When isolated from the serum of uninjured rats, alpha1 macroglobulin retained the capacity to bind 1.05 mol of trypsin/mol. However, if isolated from serum 2 days after injury only 0.78 mol of trypsin/mol of alpha1 macroglobulin was bound. alpha2 macroglobulin isolated from this latter serum bound on average 0.97 mol of trypsin/mol. When reduced with N-acetylcysteine, both molecules formed subunits of size corresponding to that expected for quarter molecules. When alpha2 macroglobulin was reduced with dithiothreitol, quarter molecules were again produced. alpha1 macroglobulin, however, when thus treated gave a more complex mixture, containing a component having a mol.wt. of less than 6 X 10(4). Antisera raised against the two proteins permitted estimation of the concentration of each protein in the plasmas or sera of normal and injured rats. Plasma from normal male rats contained 3.76 +/- 0.56 mg of alpha1 macroglobulin/ml (n = 33) and 0.016 +/- 0.001 mg of alpha2 macroglobulin/ml (n=33). After injury by injection of turpentine and cortisone, the concentrations in plasma were at 3 days 5.19 +/- 0.81 mg of alpha1 macroglobulin/ml (n = 12) and at 2 days 1.38 +/- 0.35 mg of alpha2 macroglobulin/ml (n = 12). Antisera to the two proteins did not cross-react with one another. The quarter molecules formed by reduction of both proteins showed increased antigenicity.


Rat alpha2 acute-phase macroglobulin. Isolation and physicochemical properties. 1. Rat alpha2 acute-phase macroglobulin was isolated from turpentine-injected rats by Sephadex G-200 chromatography and ion-exchange chromatography on DEAE-cellulose. This method, since it does not include (NH4)2SO4 treatment, allows the study of the physicochemical as well as the biological properties of the molecule. 2. The purity of the preparation was demonstrated by ultracentrifugation, polyacrylamide-gel electrophoresis, fused "rocket" immunoelectrophoresis as well as double immunodiffusion. 3. The rat alpha2 acute-phase macroglobulin was characterized in terms of its main physical and chemical properties. Its isoelctric point was determined by isoelectrofocusing to be 4.55; s020,w was 18.4S and E1%/1cm at 278 nm was 6.8. The mol.wt. was determined by light-scattering to be 770000. 4. The amino acid content was compared with that of rat alpha1 macroglobulin and was found very similar. The carbohydrate composition of alpha2 acute-phase macroglobulin was determined to be: hexose, 4.25%; glucosamine, 3.4%; sialic acid, 2%; fucose, 0.2%. From these results it was concluded that alpha2 acute-phase macroglobulin, although a typical acute-phase reactant, possesses the characteristic physicochemical properties of alpha macroglobulins.


Hepatic synthesis of carnitine from protein-bound trimethyl-lysine. Lysosomal digestion of methyl-lysine-labelled asialo-fetuin. The biosynthesis of carnitine in the rat was studied by following the metabolism of two radioactive derivatives of asialo-fetuin. The first contained 14C-labelled methyl groups covalently bound to the 6-N-amino fraction of its lysine residues as 6-N-monomethyl- and dimethyl-lysine. By treating this protein with iodomethane, a second derivative was produced in which the radioactivity was preferentially incorporated as 6-N-[Me-14C]-trimethyl-lysine. These desialylated glycoproteins, like other asialo-proteins, were immediately cleared from the blood by rat liver. Within hepatocyte lysosomes, the 14C-labelled proteins were rapidly hydrolysed, producing free amino acids containing the various 6-N-[Me-14C]methylated lysine residues. The radioactive amino acids crossed the lysosomal membrane and were further metabolized in the cytosol. Carnitine was the major radioactive metabolite detected in extracts of the rat carcass and liver after intravenous injection of 6-N-[Me-14C]trimethyl-lysine-labelled asialo-fetuin. Within 3h, at least 34.6% of the trimethyl-lysine in the administered protein was converted into carnitine. Similarly, an isolated perfused rat liver converted 30% of the added peptide-bound trimethyl-lysine into carnitine within 90 min. On the other hand, in numerous attempts we failed to detect radioactive carnitine in both rat liver and carcass between 20 min and 22 h after injection of 6-N-[Me-14C]-monomethyl- and -dimethyl-lysine-labelled asialo-fetuin. These data provide evidence for a pathway of carnitine biosynthesis that involves trimethyl-lysine as a peptide-bound precursor as proposed by R.A. Cox & C.L. Hoppel [(1973) Biochem. J. 136, 1083-1090] and V. Tanphaichitr & H.P. Broquist [(1973) J. Biol. Chem. 248, 2176-2181]. The findings also show that rat liver can synthesize carnitine without the aid of other tissues, but cannot convert free partially methylated lysines into trimethyl-lysine.


His bundle recordings in diagnosis of impulse formation in Kent and Mahaim tracts. His bundle electrograms were recorded in 2 patients with ectopic beats arising in accessory atrioventricular tracts. Case 1 had Wolff-Parkinson-White (WPW) type A and a left-sided Kent tract with a short effective refractory period. Though ectopic impulse formation most probably occurred within the Kent tract itself, a vulnerability-related origin in the ventricular muscle close to the distal end of the Kent tract could not be excluded. In Case 2, with a Mahaim tract extending from His bundle to ventricles, there were three types of QRS morphologies resulting from : (a) atrioventricular conduction exclusively through the normal pathways; (b) atrioventricular conduction through both, normal pathway, and Mahaim tract; and (c) ectopic impulse formation in the Mahim tract. Specialized electrophysiological studies were essential to diagnose these unusual arrhythmias.


Excretion of alpha-foetoprotein in the urine of rats during exposure to 3'-methyl-4-dimethylaminoazobenzene. Female rats were maintained on standard laboratory diet, Miller's diet or Miller's diet containing 3'MeDAB. Animals fed standard or Miller's diet did not excrete alpha-foetoprotein (AFP) in their urine. Early appearance of AFP was demonstrated by examining the urine of rats on the 3'MeDAB regimen. The incidence of positive urine samples was high between the 5th and 7th week of the experiment. It thereafter declined, but from the 3rd month it steadily rose and reached a maximum of 80% at about 10 months. Though urinary excretion of AFP was irregular in individual animals, several positive urine samples were obtained from all rats followed for more than a few months. The urine of 90% of hepatoma-bearing rats contained AFP at the time of killing. The incidence of elevated serum AFP levels as determined by immunodiffusion, increased with the duration of the experiment, but was still only 70 percent in rats fed 3'MeDAB for over 34 weeks. The severity of the hepatic alterations, as well as hepatocytic uptake of [3H]thymidine, increased with time. The serum of animals fed the standard diet was negative, whereas AFP was very infrequently detected in the serum of rats given Miller's hypoprotein diet. The results demonstrate that, in a population exposed to hepatocarcinogenic agent, the recurring detection of urinary excretion of AFP is a useful indicator of the high risk of developing hepatomas.


Serum alpha1-foetoprotein levels in 153 male patients with germ cell tumours. --alpha1-Foetoprotein (AFP) levels have been measured by radioimmunoassay in the serum of 153 male patients with gonadal and extragonadal germ cell tumours. Thirty-five patients with pure seminoma, and 34 patients with teratoma but without any postoperative evidence of residual or recurrent tumour, consistently had normal serum AFP levels (less than 25 ng/ml). Of 84 patients with active teratomas, 56 (67%) had serological evidence of AFP production. Ten patients with histological evidence of pure yolk sac (endodermal sinus) tumours all had raised levels. Teratomas containing yolk sac (elements may or may not be associated with raised serum levels. Trophoblastic (choriocarcinomatous) elements in a teratoma were not normally associated with high values. Fourteen patients with teratomas had elevated levels in the absence of histologically detectable yolk sac elements. Serum AFP levels often became elevated before clinical evidence of recurrence, so that AFP can act as an effective marker of the course of the disease and its response to therapy in many patients, but recurrent or progressive disease may be present in the absence of raised levels.


Oral anticoagulation in the treatment of a spontaneously metastasising murine tumour (3LL). The effects of long-term anticoagulation with phenprocoumon on growth of the Lewis lung carcinoma (3LL) were studied. Oral anticoagulation initiated at the day of i.m. transplantation of the 3LL into C57BL mice significantly inhibited primary tumour growth and reduced the number of spontaneous metastases to the lungs. Intermittent anticoagulation was without effect on metastasis formation but still retarded primary growth. There was no influence of anticoagulation on the mean survival time (MST) of tumour-bearing animals. Phenprocoumon appears to improve the results of cyclophosphamide of 5-fluorouracil treatment, but there were no statisticially significant differences. In contrast, bleomycin treatment in combination with adjuvant anticoagulation suggested a possible drug synergy. No significant influence of anticoagulation on the response of the primary tumour to irradiattion was found, though the MST of irradiated and anticoagulated animals was greater than in the solely irradiated controls. The present investigations suggest that coumarin derivatives have some direct tumour-inhibiting capacities, but exert their antimetastatic action via deceleration of the blood clotting mechanism.


Airborne contact dermatitis from Compsoitae oleoresins simulating photodermatitis. American ragweed (Ambrosia) dermatitis has an airborne pattern and is caused by lipid soluble oleoresins of pollens. A similar weed dermatitis has been described in India and Australia. The weeds involved were all of the Compositae family and contain sesquiterpene lactones with one common antigenic determinant. This study reports seven Danish patients treated for many years under the diagnosis of photodermatitis, who eventually proved to suffer from Compsoitae oleoresin dermatitis. Probably, Compsitae dermatitis is a world-wide disease, although aften misdiagnosed as has happened in Scandinavia.


Sequential studies on components of the haemostatic mechanism in pregnancy with particular reference to the development of pre-eclampsia. Components of the haemostatic mechanism were studied at intervals in 60 primigravidae over the course of pregnancy and the puerperium; 12 of these developed pre-eclampsia. During pregnancy there was a fall in fibrinolytic activity and fibrinolytic capacity and a rise in fibrinogen, FR-antigen, alpha 1-antitrypsin and alpha 2-macroglobulin. The women who subsequently developed pre-eclampsia could not be identified on the basis of these measurements. Following delivery there was a more rapid return of fibrinolytic activity and capacity towards normal in the women who had not had pre-eclampsia. The urinary FR-antigen level was higher in the women with pre-eclampsia.


Biochemical changes in Bifidobacterium bifidum var. pennsylvanicus after cell wall inhibition. IX. Metabolism and release of cellular lipids in the presence of antibiotics. Inhibiton of cell wall synthesis caused simultaneously an increase in cellular phospho-and glycolipids and a marked release of these compounds to the medium. The composition of the cellular and the released glyco-and phospholipids was almost the same. Antibiotics, which inhibit cell wall synthesis, did not influence glycolipid composition, but increased the relative and absolute amounts of disphosphatidylglycerol and its lysoderivatives. Incorporation and chase experiments demonstrated a considerable stimulation of phospholipid metabolism, and of diphosphatidylglycerol synthesis especially. Release of lipids was not accompanied by loss of cellular protein. Omission of Tween 80 from the medium decreased the release by about 50% and increased the relative amounts of the phosphogalactolipids in the cells and in the culture fluid. Inhibitors of protein synthesis and valinomycin caused a decrease in cellular lipidphosphorus content, and a relative increase of the phosphogalactolipids. No release of lipids was observed under these conditions.


Immunochemical study of beta-glucuronidase inhibitor from porcine sublingual gland. Relationship between the antigenic determinant and the active site of the inhibitor. Following removal of sialic acid by neuraminidase treatment the activity of the beta-glucuronidase inhibitor was remarkably decreased, but the antigenic determinant was not affected. A partial common antigen to the inhibitor was isolated from porcine small intestine, by successive fractionation of trypsin extraction of the latter on Sephadex G-150, DEAE-cellulose and Sepharose 4B column chromatography. The immunologic and characteristic properties of the common antigen were compared with those of the beta-glucuronidase inhibitor is not identical with its antigenic determinant.


Photooxidase system of Rhodospirillum rubrum. I. Photooxidations catalyzed by chromatophores isolated from a mutant deficient in photooxidase activity. The aerobic photooxidations of reduced 2,6-dichlorophenolindophenol and of reaction-center bacteriochlorophyll (P-870) have been investigated in membrane vesicles (chromatophores) isolated from a non-phototrophic Rhodospirillum rubrum strain. In aerobic suspensions of wild-type chromatophores, continuous light elicits an increase of the levels of 2,6-dichlorophenolindophenol and of oxidized P-870, which reach steady-state values shortly after the onset of illumination. In contrast, light induces in mutant suspensions a transient increase of the levels of 2,6-dichlorophenol-indophenol and of oxidized P-870, which fall to low steady-state values within a few seconds. These observations suggest that the mutation has altered a redox constituent located on the low-potential side of the photochemical reaction center, between a pool of acceptors and oxygen. Since endogenous cyclic photophosphorylation is catalyzed by mutant chromatophores at normal rates, it appears that the constituent altered by the mutation does not belong to the cyclic electron-transfer chain responsible for photophosphorylation. However, the system which mediates the aerobic photooxidations and the cyclic system are not completely independent: endogenous photophosphorylation is inhibited by oxygen in wild-type chromatophores but not in mutant chromatophores; in addition, the inhibitor of cyclic electron flow, 2-heptyl-4-hydroxyquinoline-N-oxide, enhances the aerobic photooxidation of reduced 2,6-dichlorophenolindophenol by chromatophores from both strains. These results support a tentative branched model for light-driven electron transfer. In that model, the constituent altered in the mutant strain is located in a side electron-transfer chain which connects the cyclic acceptors to oxygen.


Influence of membrane  thickness and ion concentration on the properties of the gramicidin a channel. Autocorrelation, spectral power density, relaxation  and single-channel studies. The properties of the gramicidin A channel in membranes made from a series of monoglycerides have been studied. In agreement with previous studies, the dissociation rate constant kD of the dimeric channel was found to increase strongly with increasing chain length of the monoglyceride, corresponding to a decrease of the mean life-time of the channel. The value of kD, however, was not strictly correlated with the membrane thickness, as seen from a comparison of membranes with different solvent content. Furthermore, the life-time of the channel increased with the concentration of the permeable ion. This effect was tentatively explained by an electrostatic stabilization of the channel. The single-channel conductance lambda was found to decrease with increasing membrane thickness d, if d was varied by increasing the chain length of the lipid. On the other hand, if d was changed by varying the solvent content of the membranes formed from one and the same lipid, lambda remained constant. These observations were explained by the assumption of local inhomogeneities in the membrane thickness. A striking difference between the lambda values obtained from autocorrelation analysis in the presence of many presence of many channels (lambda a) and those obtained from single-channel experiments (lambda sc) occurred with membranes from longer chain-length monoglycerides. This difference disappeared at low ion concentrations. Electrostatic interactions between channels in local clusters were proposed for an interpretation of these findings.


The influence of phospholipid polar groups on gramicidin channels. The influence of well-defined changes in the polar part of phospholipid molecules on the properties of black lipid membranes was studied using a series of phospholipids with identical hydrocarbon chains, but systematically changed polar groups. The hydrocarbon tails of the lipids under study were composed of 1,2-dipentadecylmethylidene glycerol. The polar parts differed in the degree of N-methylation and comprised phosphocholine, -N,N-dimethylethanolamine, -N-methylethanolamine and ethanolamine. Stable black lipid membranes could be formed with the solvents octane, decane, dodecane, tetradecane and hexadecane. The properties of gramicidin-induced single ionic channels changed systematically in membranes from the phosphatidylcholine to the phosphatidylethanolamine analogue, as indicated by an increase in the amplitude lambda of the unit conductance step and a decrease in the average channel life-time or duration tau. The series of tau-values was opposite to that expected from hydrocarbon thickness (specific capacitance). It is suggested that the surface tension gamma is a relevant parameter for the prediction of tau-values.


Raman spectroscopic investigation of the interaction of gramicidin A with dipalmitoyl phosphatidylcholine liposomes. The interaction of gramicidin A with dipalmitoyl phosphatidylcholine liposomes is investigated by Laser-Raman spectroscopy. As revealed by the methylene C-H stretching mode the phase transition of the hydrocarbon chains near 40 degree C is eliminated in the presence of gramicidin A. Liposomes prepared from a mixture of lecithin and cholesterol seem to be unaffected by gramicidin A and show only the normal broadened phase transition.


Factor VIII coagulant activity and factor VIII-related antigen released from isolated perfused human spleens. Eight human spleens were perfused for up to 65 h at normothermia and the coagulant Factor VIII activity measured in the perfusate. In addition, in three experiments Factor VIII-related antigen was determined in the perfusate. Although the spleens were pathologically enlarged and the normal structure involved by different diseases, all spleens released Factor VIII coagulant activity and Factor VIII-related antigen. On average the total amount of Factor VIII coagulant activity released was equivalent to that of 3.5 l of human plasma.


Audiovisual materials: a survey of bibliographic controls in distributors' catalogs. The current pattern of bibliographic control in audio-visual distributors' catalogs is described. Eight bibliographic control elements are defined, and the criteria for evaluating the occurrence of these elements in sixty-four sample catalogs are specified. When the distributors are grouped according to category, such as educational or commercial, the pattern of bibliographic control has three distinct clusters of elements. When the distributors are grouped by the number of titles handled, there is no clear pattern. The implications of these patterns are discussed in terms of practical library reference services. A solution to the problem of bibliographic control of health science audiovisual materials is proposed.


A two-phased model for library instruction. This article describes two methods of library orientation and instruction: self-paced audiotapes and computer-assisted instruction (CAI). The tapes are used to orient the user to the libraries' physical facilities, policies, services, and tools, while CAI is used to provide detailed library information in an interactive mode.


Testosterone metabolism in benign prostatic hypertrophy: in vivo studies of gestonorone caproate and cyproterone acetate. 18 patients with obstructive benign prostatic hypertrophy were studied. A 5-day treatment with gestonorone caproate (200 mg daily and 200 mg on alternate days) and cyproterone acetate (300 mg daily) suppressed the plasma LH and serum LH levels. Subsequently, H3-testosterone was injected intravenously and its elimination from plasma and uptake and metabolism in the BPH tissue studied. The elimination of total radioactivity and H3-testosterone from plasma was not altered after the 3 treatment regimens as compared to the control group. The uptake of total radioactivity into BPH tissue and its intraprostatic metabolism particularly to dihydrotestosterone was significantly suppressed in the patients with daily injections of gestonorone. Cyproterone acetate and gestonorone caproate on alternate days did not cause this effect.


Detrusor and urethral dysfunction in prostatic hypertrophy. Assessment of bladder and urethral function in 9 patients with prostatic hypertrophy before and after transurethral resection of the prostate was performed utilising gas cystometry, detrusor reflex activating procedures, combined electromyographic and gas urethral pressure profilometry and uroflowmetry. A high incidence of detrusor hyperreflexia was found preoperatively indicating neurogenic dysfunction of the bladder. Removal of the obstructive tissue implied a change in detrusor reflex function in a part of the patients confirming the findings from a larger series studied with watercytsometry. Decompression or injury of sensory nerve endings in the prostatic urethra thus seem to determine detrusor function after surgery to the prostate. The impact of the resection upon urethral function was an increase in maximum urinary flow due to a significant shortening of the functional urethral length. No change in maximum urethral intramural pressure could be demonstrated.


A simple method for the introduction of an oesophageal tube in advanced carcinoma of the oesophagus. A simple technique is described which facilitates the introduction of an oesophageal tube in cases of advanced carcinoma of the oesophagus. The method has proved satisfactory in cases with the tightest of strictures.


Fetal proteinuria in diagnosis of congenital nephrosis detected by raised alpha-fetoprotein in maternal serum. High concentrations of alpha-fetoprotein (alpha-FP) were found at 14, 19, and 21 weeks gestation in the serum of a woman with a history of unexplained fetal death in her previous pregnancies. The alpha-FP concentration of the liquor also was high at 21 weeks and the pregnancy was terminated. Though the fetus was macroscopically normal, measurement of albumin, alpha-FP, IgG, and alpha2-macroglobulin in the fetal urine showed a selective proteinuria, and congenital nephrosis was diagnosed after examination of the fetal kidneys by electron microscopy. Possibly some fetuses reported to be "false-positive for neural tube defect" may have had renal lesions of this nature. Examination of fetal urine may be the simplest initial diagnostic procedure in any future case.


Radiofrequency thermocoagulation of Gasserian ganglion and its rootlets for trigeminal neuralgia. Thirty-nine patients with trigeminal neuralgia, not controlled by medical treatment, were treated by radio-frequency thermocoagulation of the Gasserian ganglion and its posterior rootlets. Thirty-six received satisfactory pain relief. In 30 patients touch sensation in the treated territory was preserved. The corneal reflex was affected in only six patients, two of whom subsequently developed keratitis. There were no other complications apart from a minor unpleasant sensation in eight patients. By selectively destroying pain fibres this technique offers the scope of preserving touch sensation in the treated area. Moreover, the zone of analgesia can be restricted to the affected region by sensory mapping through electrode stimulation before thermocoagulation. Its simplicity, low morbidity, associated short hospital stay, and the increased ability to preserve touch sensation, especially of the cornea, seem to make it preferable to other forms of surgical management for trigeminal neuralgia.


Studies on the encephalitogenic effects of purified preparations of human and bovine oligodendrocytes. Bulk-isolated human and bovine oligodendroglia, practically free from myelin, have been used in attempts to elicit an autoimmune response which has been compared with acute experimental allergic encephalomyelitis (EAE). For these experiments, a total of 20 Hartley guinea pigs, 33 Lewis rats and 16 rabbits have been studied. Animals were inoculated with a range of doses of purified preparations of both human and bovine oligodendroglial cells in complete Freund's adjuvant (CFA) and compared with others challenged with whole white matter in CFA. The latter animals all developed clinical and histological signs of experimental allergic encephalomyelitis (EAE) 2-3 weeks post-inoculation. In general, oligodendroglial cells were encephalitogenically less potent than white matter. Guinea pigs were the most susceptible to inoculations of oligodendroglia. In several given human oligodendroglia 14 days earlier, a paraparesis indistinguishable from conventional EAE was seen. Animals receiving bovine cells showed no clinical signs. Histologically, the CNS of afflicted guinea pigs displayed severe inflammation but, in contrast to conventional EAE in the same species, demyelination was rare in the small group of animals tested. After sensitization with oligodendroglia, rats displayed no clinical disease. Histologically, some given human cells had positive evidence of disease while bovine cells in others gave a mild response. Rabbits showed no clinical and very little histological disease. Although more extensive studies are needed to confirm the findings, from the animals studied it appears that (1) variation in response to inocula containing oligodendroglia exists among the species tested, (2) that human oligodendroglia are more potent immunologically than bovine cells, (3) that CNS lesions produced by these cells in guinea pigs, lack a strong demyelinative component and (4) a specific antigen might exist in oligodendrocytes which is distinct from myelin basic protein. The possible reasons underlying our findings are discussed.


Dimethylsulfoxide action on fast axoplasmic transport and ultrastructure of vagal axons. The axonal microtubules (MT) are believed to be involved in fast axonal transport (FAXT). Dimethylsulfoxide (DMSO) has a strong stabilizing action on MT in vitro which may account for some of its reported biological effects. DMSO at concentrations of 5% disrupts the FAXT in a high percentage of axons emanating from the nodosum ganglion in the cat vagus nerve. Whereas 5% DMSO does not affect the FAXT in all axons, 10% DMSO blocks all the FAXT. The blockage is substantially, but not completely, reversed by washing the vagus for 2 h. DMSO at 2% caused no discernible change in either the FAXT or the axonal morphology, but some swelling of glial cells occurred. Ultrastructurally, 10% DMSO caused some axons to swell and others to shrink. The MT appeared normal and their total number per axon did not change. The spatial relationship of the axonal constituents is clearly altered by the DMSO and this may have contributed to the failure of the transport. It is suggested that the DMSO, through strengthening the forces involved in polymerization, renders them non-functional for FAXT.


Axoplasmic transport of norepinephrine in the locus coeruleus-hypothalamic system in the rat. The axoplasmic transport of norepinephrine (NE) between the nucleus locus coeruleus (LC) and the hypothalamus has been measured by three methods which employ the stereotaxic injection of [3H]catecholamines in the rat brain. [3H]NE is synthesized from [3H]dopamine (DA) injected into the LC and transported at a rate of 0.8-0.9 mm/h. This rate is probably an underestimate since it includes the time required for uptake and conversion of [3H]DA to [3H]NE prior to transport. Measurement of transport of [3H]NE between the posterior and anterior hypothalamus gives a rate of 2 mm/h which is independent of [3H]DA uptake and [3H]NE synthesis. This rate is in good agreement with the 1.9 mm/h figure calculated for [3H]NE transport in the system after LC injection of [3H]NE and represents a closer estimate of the true rate of axoplasmic transport than the 0.8-0.9 mm/h estimate. Transport of [3H]NE occurs through primarily ipsilateral NE fibers running in the median forebrain bundle and is blocked by 6-hydroxydopamine lesions in the bundle. Early appearing [3H]NE in the hypothalamus forms a relatively stable pool which is unaffected by median forebrain bundle lesions and is essentially unchanged by [3H]NE transported from the LC. This pool appears to be derived from non-specific spread of [3H]DA after injection, probably through the cerebrospinal fluid.


Intraaxonal transport of horseradish peroxidase in the sympathetic nervous system. Following a single injection of horseradish peroxidase (HRP) into the superior cervical ganglion (SCG) of the rabbit, the uptake and anterograde transport of this label was confirmed in the ganglion cell bodies, postganglionic axons, and preterminal and terminal ending axons in the ciliary processes of the eye. From the same injection site the intraaxonal HRP reaction product was demonstrated in myelinated axons, presumably by retrograde transport. Intracytoplasmic HRP was identified in large, single membrane-bound, dense vesicles predominantly in perinuclear orientation. Intraaxonal HRP appeared throughout, either within single membrane-bound round or oblong vesicles of variable sizes and densities. Frequently, the HRP vesicles in the axons revealed elaborate membranous subunits. A limited number of whole axons or axon fascicles were diffusely stained with HRP reaction product at or near the injection site. This phenomenon may be the result of membrane injury to neurons. The HRP label was found in small amounts in axons and terminals in the ciliary processes of the eye as early as 4 h following injection into the SCG, indicating a rapid anterograde transport of HRP from a single extracellular source. Likewise the HRP label disappeared from the ganglion cell bodies and processes by the 6th day following injection. Presence of numerous HRP-labeled myelinated and non-myelinated axons in the SCG confirms the bidirectional transport of HRP in the sympathetic nervous system.


The seventh cranial nerve of the rat. Visualization of efferent and afferent pathways by cobalt precipitation. The cobalt sulphide precipitation technique, in conjunction with Timm's intensification procedure, was used to delineate the afferent and efferent intramedullary pathways of the seventh cranial nerve complex in the rat. The branchial motor nucleus with the accompanying first part, genu, and second part of the root are described. The motor branches to the superficial facial musculature do not contain fibres of geniculate ganglion origin or fibres which terminate in the spinal trigeminal nucleus. The motor branches to the deep facial muscles arise from the dorsal part of the branchial motor nucleus and traverse to the midline medial to the genu, then project under the genu into the lateral reticular formation before exiting with the facial nerve. The salivatory and lacrimal nuclei and their intramedullary pathways are described. Sensory fibres from the cutaneous auricular branch enter the spinal trigeminal tract and most of the chorda tympani gustatory fibres enter the fasciculus solitarius. A smaller number of gustatory fibres extend medially to the region of the salivatory nucleus. Fibres of greater superficial petrosal origin also enter the fasciculus solitarius as well as the medial reticular formation. These findings are discussed in relation to previous anatomical, physiological and clinical reports.


Rapid axonal transport of tyrosine hydroxylase in rabbit sciatic nerves. We compared the axonal transport of tyrosine hydroxylase with that of dopamine-beta-hydroxylase by means of an in vitro stop-flow technique. Proximal to a locally cooled nerve region, the activity of both enzymes increased linearly for 3 h. Internal standards of partially purified adrenal enzyme showed that the increased activity of tyrosine hydroxylase was not due to changes in activators or inhibitors. Furthermore, this increased activity represented increased V max, unaccompanied by changes in Km for tyrosine; probably, therefore, it reflected increased concentrations of the enzyme. From the rates of increase of enzyme activity, we calculated that, on the average, tyrosine hydroxylase was transported at 0.78 mm/h, and dopamine-beta-hydroxylase at 2.4 mm/h. Much less tyrosine hydroxylase than dopamine-beta-hydroxylase seemed free to move in the nerves, suggesting greater similarity between true transport velocities than between average velocities of these enzymes. When nerves were rewarmed after local cooling for 3 h, waves of accumulated enzyme activity moved distally. The wave of dopamine-beta-hydroxylase activity had a single peak moving at about 14 mm/h. The wave of tyrosine hydroxylase activity had a small component moving this fast, but more of it moved slower, at velocities down to 5 mm/h...


Differences in the composition of the polypeptides deposited in the axon and the nerve terminals by fast axonal transport in the garfish olfactory nerve. Proteins transported by the fast wave of axonal transport have been shown to be deposited both in the axon and in the nerve terminals. Differences in the nature of the molecules deposited in these two areas were studied in the garfish olfactory system. In order to avoid analysis of transported molecules in two different types of tissue like the olfactory nerve and the olfactory bulb, the study was conducted (1) by comparing the composition of the moving crest of radioactivity at two different points along the nerve: when the crest enters the axon and when it reaches a distance of approximatively 5 cm from the nerve endings, (2) by determining the composition of the molecules remaining in the axon behind the moving crest. Three subcellular fractions (two membranous fractions and a mitochondrial pellet) were investigated. In both membranous fractions the majority of the polypeptides deposited in the axon ranged from 50 to 150,000 daltons. No outstanding peak of radioactivity was found in either fraction. Radioactivity was relatively evenly distributed among the various polypeptides. In the lightest membranous fraction, however, a peak (mol. wt., 54-58,000) was more particularly deposited in the axon. The opposite situation was found for the molecules moving toward the synapses: transported radioactivity was concentrated in a few distinct polypeptides, while the others were significantly less labeled. Three peaks were found in the lightest membranous fraction (mol. wt., 35,000, 54-58,000 and 126,000). Only two peaks were determined in the heaviest fraction (mol. wt., 58,000 and 126,000). The 126,000 mol. wt. peak increases with distance in both membranous fractions from 9 to 12% of the total radioactivity and moves mainly toward the synapses. The 35,000 mol. wt. polypeptide presented some interesting properties: it was found in larger quantities in the lightest membranous fraction; labeling was very poor in the heaviest membranous fraction, and finally this polypeptide appeared to be largely transported to the synapses. Results concerning the polypeptide composition and the composition of the transported molecules indicated that the lightest fraction may contain more synaptosomal material. From this study it appears that most transported polypeptides are distributed in both the axon and the nerve terminals, but that the percentage delivered to each area varies. A few distinct polypeptides on the contrary are more selectively transported to the synapses and are even differently localized in subcellular fractions.


Effect of current palliative treatment on the survival of patients with breast cancer. The length of survival of 302 patients with breast cancer first treated between 1946 and 1949, who had mostly only contemporary radiotherapy for metastases, has been reviewed and compared with that of 578 patients, first treated between 1966 and 1969, who had modern endocrine therapy, cancer chemotherapy and radiation therapy. Although patients in the latter group demonstrated a significantly increased length of survival after the first metastases appeared, these differences were not substantial. In spite of impressive regressions in some patients with metastatic breast cancer after modern palliative therapy, the median survival after the first appearance of metastases has been increased only by about 6 months.


The role of IgE in the immune response to neoplasia: a review. The role of IgE in the immune response to neoplasia has received little attention despite suggestive evidence for an IgE response to tumor specific antigens. A complex interrelationship is known to exist between basophils, eosinophils, histamine, complement, and T cells. The latter cells are known to play a central role in the immune response to neoplasia and, in addition, are now considered important in the production and regulation of IgE, the molecule that may supply an important link between pharmacological and cellular dynamics of a successful anti-tumor response. The evidence for an IgE role in the immune response to tumors, the relationship between atopy and cancer, and the possible mechanisms whereby IgE could enhance tumor rejection are discussed in this review.


Clinical aspects of intrahepatic bile duct carcinoma including hilar carcinoma: a study of 57 autopsy-proven cases. The clinical features of 57 autopsied cases of intrahepatic bile duct carcinoma including 28 cases of the peripheral type (cholangiocarcinoma in the narrow sense) and 29 cases of the hilar type are described in comparison with those of hepatocellular carcinoma, with a review of the literature on the clinicopathological aspects of intrahepatic bile duct carcinoma. As compared with hepatocellular carcinoma, the average age of the patients was older; the male predominance was not obvious, chronic parenchymal liver disease was infrequent in the past history, association of primary cirrhosis was seldom, cholestatic features were frequently the early signs and more pronounced during the course, the liver was enlarged to a lesser extent, ascites was less common, signs of portal hypertension were absent or minimal, and extrahepatic metastases were less frequent. In many respects, the hilar type resembled extrahepatic bile duct carcinoma, and the peripheral type was somewhat between it and hepatocellular carcinoma. Although the overall survival was not much different from that for hepatocellular carcinoma, early diagnosis is emphasized; this would make surgical management possible. Differential diagnosis from hepatocellular carcinoma may be possible in the majority with direct cholangiography, liver scan, celiac angiography, determination of alpha-fetoprotein and hepatitis B antigen, and blood chemistry such as SGOT, SLDH, serum bilirubin and alkaline phosphatase. Illustrative cases are given including one patient with a hilar carcinoma who survived for more than 2 years after transhepatic biliary drainage.


Biological characterization of a prolonged antileukemic effect of 5-azacytidine. A prolonged cytotoxic effect of 5-azacytidine (aza-CR) on leukemic colony-forming units (LCFU) was observed in mice with transplanted L1210 leukemia. LCFU showed rapid reaccumulation in the marrow 12 hr after injection of 0.1 mg of aza-CR per mouse. However, after 0.5 mg of aza-CR, repopulation was delayed for at least 6 days. Experiments were performed to determine the mechanism of this prolonged antileukemic effect. Suspensions of leukemic marrow prepared from mice treated 4 days previously with 0.5 mg of aza-CR were exposed to [3H]thymidine in vitro in order to kill cells in S phase. Suspensions exhibited a 40% reduction in LCFU, indicating the prolonged effect was not due to cell cycle progression delay. Mice given whole-body irradiation prior to receiving L1210 demonstrated the same delayed repopulation following the high dose of aza-CR as nonirradiated mice, suggesting that the effect was likely not due to an immune reaction. aza-CR, when given to normal mice as long as 2 days prior to leukemic transplantation, was able to prolong the survival of leukemic mice, but not when given at longer intervals. Administration of aza-CR to mice 1 day or 1 hr prior to leukemic transplantation resulted in decreased LCFU survival as well as delayed repopulation of LCFU; the rate of repopulation was not changed. This indicated a prolonged residual activity of the drug, but not sufficient to explain the total in vivo suppression. In contrast, administration of aza-CR to leukemic mice suppressed repopulation of a subsequent leukemic transplant for 4 days, even when the cells were given 2 days after the aza-CR. Cytidine was partially able to reverse the delayed repopulation of LCFU when given 1 day after aza-CR, but it was unable to reverse the phenomenon 2 days after aza-CR. Therefore, a high dose of aza-CR produces a prolonged antileukemic effect which is probably mediated by continued availability of an aza-CR metabolite. Since this effect is more pronounced in leukemic mice than in nonleukemic mice, the pharmacokinetics of high doses of aza-CR probably differ in normal and leukemic mice.


Comparison of 2,2'-anhydro-1-beta-D-arabinofuranosyl-5-fluorocytosine and cytosine arabinoside in the treatment of murine brain tumor. 2,2'-Anhydro-1-beta-D-arabinofuranosyl-5-fluorocytosine (anhydro-ara-FC) was compared with cytosine arabinoside (ara-C) in the treatment of ic implanted murine Glioma 261. Both drugs given in ip doses of 500 mg/kg immediately inhibited the uptake and incorporation of tritiated thymidine into the DNA of brain tumor, small intestine, and spleen. Inhibition of DNA synthesis in the tumor recovered within 12 hours of anhydro-ara-FC administration, yet it remained depressed greater than 50% of control 12 hours after ara-C administration. Inhibition in the small intestine recovered within 24 hours of drug administration with either agent while inhibition in the spleen remained depressed greater than 24 hours. Anhydro-ara-FC administered ip in single doses less than or equal to 1500 mg/kg or in multiple doses less than or equal to 200 mg/kg three times a week for ten doses failed to prolong the survival of tumor-bearing mice, and minimal increased survival followed drug administration of 200 mg/kg every 24 hours for five doses. In contrast, ara-C in doses of 50, 100, or 200 mg/kg three times weekly for ten doses significantly increased the survival of tumor-bearing animals between 17% and 36%.


Comparative ultrastructure of submaxillary salivary glands from mice treated with cytosine arabinoside, cyclocytidine, and anhydro-ara-5-fluorocytidine. The effects of cytosine arabinoside (ara-C), cyclocytidine (cyclo-C), and anhydro-ara-5-fluorocytidine (AAFC) on the ultrastructure of the serous and mucous cells of the submaxillary salivary glands were evaluated in normal BDF1 mice. Rapid loss of zymogen granules from serous cells and a discharge of mucous cell contents were observed within the first hour after administration of a single iv dose of cyclo-C. Serous cells were essentially devoid of granules (1-3 mum) within 3 hours; regranulation observed initially at 6 hours produced a population of microgranules (approximately 0.8 mum) by 24 hours; most serous cells contained a reduced complement of small granules through 96 hours after cyclo-C. Mucous cells recovered secretory content within 3-6 hours after drug administration. Neither ara-C nor AAFC produced zymogen-granule or mucous discharge or other cytopathologic effects in the murine submaxillary salivary glands. Thus, it can be postulated that cyclo-C itself is the secretogogue. The ultrastructural changes observed in this study provide a cytopathologic correlate of the salivary gland dysfunctions reported to follow the administration of cyclo-C to man.


Influence of ventricular conduction defects on ventricular repolarisation and coupling intervals of ventricular extrasystoles. In all conduction disorders of the left ventricle the Q-T interval is prolonged in relation to the prolongation of the QRS duration, but the S-T interval (measured from the end of the S wave) is within normal limits. Right ventricular conduction defects are associated with prolongation of the Q-T interval, but the S-T interval in incomplete and complete right bundle branch block is subnormal. In the absence of a broad QRS, the Q-T and S-T intervals are not prolonged in left anterior hemiblock. However, an associated non-specific left intraventricular conduction defect or right bundle branch block does prolong the QRS and thus the Q-T interval. The S-T interval is normal or subnormal in the presence of right bundle branch block and left anterior hemiblock confirming that left anterior hemiblock does not effect the Q-T interval and repolarisation. In the presence of any conduction defect which prolongs the QRS duration, extrasystoles have longer coupling intervals. The coupling intervals are longer in the presence of left bundle branch block than right bundle branch block. It is postulated that this is due to the differences in the time of depolarisation and thus repolarisation of the left ventricle.


Effect of dietary cholesterol on the pattern of osmium deposition in the symbiote-containing cells of the pea aphid. Pea aphids left for 48 h in unbuffered osmium tetroxide show heavy staining of many organelles in the symbiote-containing cells (mycetocytes and sheath), embryos and oenocytes very similar to that characteristic of mammalian sterol-synthesizing cells. However, the staining of the per-aphid cells is, to a large extent, dependent on the presence of cholesterol benzoate, or free cholesterol, in the aphid's diet. In aphids cultured in vitro with 3H mevalonate in the presence of added cholesterol, the incorporation of label into the cholesterol and lanosterol fractions is significantly reduced. If the dietary cholesterol effects a similar inhibition in vivo, the cholesterol-dependent osmium staining could be due to precursors(s) of cholesterol accumulating in the intracellular sites described. There is also osmium staining of large (normally electron-transparent) vacuoles in mycetocytes, gut and fat body, irrespective of dietary cholesterol.


Transport adenosine triphosphatase activity in the rat cornea. The sodium-potassium activated adenosine triphosphatase (NaKATPase) activity of the rat cornea was investigated histochemically using a Pb2+-precipitation technique in which adenosine triphosphate (ATP) is used as substrate and two methods for potassium-dependent para-nitrophenyl-phosphatase (K-NPPase) activity. With all the three techniques used it was demonstrated that the sodium-potassium-activated adenosine triphosphatase (NaK-ATPase) activity is localized in the cell membranes of the endothelium whereas a much weaker activity was observed in the epithelium. When the Pb2+-technique was used, the epithelial cell membranes showed a weaker reaction in the presence of ouabain. This activity was only Mg2+-dependent and was presumably due to an Mg2+-dependent ATPase. The validity of the histochemical techniques for NaK-ATPase activity is discussed. The results emphasize the importance of the endothelium as the main site of Na+ transport in the cornea. Small amounts of the enzyme are also present in the epithelium, which seems to be rich in Mg2+-ATPase. Provided that careful controls are performed, all the methods give consistent results in the cornea.


A core polyprotein of murine leukemia virus on the surface of mouse leukemia cells. A polypeptide of molecular weight approximately 75,000 daltons, p(75), was identified on the surface of AKR spontaneous leukemia cells by lactoperoxidase-catalyzed radio-iodination. This protein was shown by immunoprecipitation to have antigenic determinants of MuLV p30, p15, and p10, but not gp70, suggesting that p(75) represents a polyprotein composed of virion core components. As evidenced by studies on incorporation of radioactive glucosamine, p(75) is probably glycosylated. No p(75) was found on 2 month old AKR thymocytes, and only a small amount of p(75) was detectable of thymocytes from 4 month old animals. However, substantial quantities of p(75) could be found on thymocytes from 6 month old, yet still preleukemic mice.


Palliation of cyanotic congenital heart disease in infancy with E-type prostaglandins. Prostaglandin-E (PGE) infusions have been used in an attempt to increase ductal patency in 11 infants aged one to 99 days with cyanotic heart disease. PGE1 was used in nine infants and PGE2 in two. Five patients had pulmonary atresia, four extreme pulmonary stenosis, one Ebstein's anomaly and one simple transposition of the great arteries. All but the oldest infant showed a satisfactory increase in oxygen saturation (average 36%) attributed to dilatation of the ductus. The failure in one infant may have been due largely to hypoplasia of the left pulmonary artery. The only important side effect was apnea in one infant receiving PGE2. The efficacy of this form of treatment is confirmed in infants dependent on ductal patency for survival. PGE is an important asset in saving the lives of neonates requiring an aorticopulmonary shunt operation. The recommended starting dose is 0.1 mug/kg/min of PGE1 given by constant infusion.


Tachycardia and bradycardia-dependent bundle branch block alternans: clinical observations. Eleven patients with tachycardia-dependent, bradycardia-dependent, or "pseudobradycardia-dependent" bundle branch block (BBB) alternans were studied. This classification is based on the following criteria: 1) When alternans is initiated by a sudden acceleration in ventricular rate, or it appears with aberration of the second beat after a pause, the alternans is tachycardia-dependent and results from a 2:1 bidirectional block in the affected bundle branch. 2) When alternans begins with the aberrant complex terminating a pause it is bradycardia-dependent; such an alternans results from alternating bundle branch cycle lengths and refractoriness, possibly produced by alternating transseptal retrograde penetration of the affected bundle branch. 3) In cases referred to as "pseudobradycardia-dependent BBB" alternans, a change from alternans to persiscardia-dependent BBB" alternans, a change from alternans to persistent BBB occurs as the cycle lengthens; however, the disappearance of BBB with further increase of the cycle length proves the tachycardia-dependence of the conduction defect.


Atrial tachycardia without P waves masquerading as an A-V junctional tachycardia. Two patients who presented by scalar ECG with an A-V junctional tachycardia were demonstrated during an electrophysiologic evaluation to have an atrial tachycardia without P waves in the surface ECG. Case 1 had an atrial tachycardia that conducted through the A-V node with a Wenckebach block. Atrial activity was recorded only from the proximal portion of the coronary sinus and from right atrial areas near the tricuspid valve. Case 2 had an atrial tachycardia that abruptly began and terminated following carotid sinus massage. Atrial activity was recorded only in the coronary sinusos, and pacing at that site resulted in atrial capture, with Wenckebach conduction to the ventricles. These observations demonstrate that an atrial tachycardia without P waves can simulate A-V junctional tachycardia with or without Weckebach block. Such findings may have a bearing on some important electrophysiologic concepts such as the origin of A-V junctional rhythms and the need for atrial participation in A-V nodal re-entry.


Effects of cycle length on atrial vulnerability. The effect of cycle length on atrial vulnerability was studied in 14 patients manifesting reproducible repetitive atrial firing during atrial extra-stimulus (A2) testing. Repetitive atrial firing was defined as the occurrence of two or more premature atrial responses with return cycle (A2-A3) of 250 msec or less and subsequent mean cycle length of 300 msec or less, following A2. The zone of repetitive atrial firing could be defined in terms of its longest and shortest A1-A2 coupling intervals. Each patient was tested at a long cycle length (CL1) (mean 884 msec) and a short cycle length (CL2) (mean 557 msec). CL1 was sinus rhythm and CL2, an atrial paced rhythm. Repetitive atrial firing occurred in two patients at CL1 and in all patients at CL2. Of the former two patients (group 2), the zone of repetitive atrial firing was markedly widened in one at CL2 due to a shortening of atrial functional refractory period (FRP) at CL2. In the other, zone of repetitive atrial firing could not be totally defined due to induction of sustained atrial flutter preventing definition of atrial FRP. The occurrence of repetitive atrial firing at only CL2 in 12 patients (group 1) reflected: 1) a shortening of atrial FRP from 294 +/- 11 msec at CL1 to 242 +/- 10 msec at CL2 (mean +/- SEM; P less than 0.01), allowing delivery of A2 at shorter coupling intervals (9); 2) the new occurrence of repetitive atrial firing at A1-A2 coupling intervals achievable at both cycle lengths (1); or 3) both effects (2). In conclusion, decrease of cycle length potentiated atrial vulnerability. This demonstration implies that atrial pacing could potentiate occurrence of paroxysmal atrial fibrillation or flutter.


Studies on vasculitis. VI. Antiglobulins or rheumatoid-like factors in cutaneous vasculitis lesions detected by an improved immunofluorescence procedure. Human cutaneous vasculitis lesions tend to be chronic in contrast to ephemeral experimental Arthus responses. Human lesions were examined for fixed antiglobulin antibodies, as occur in rheumatoid joint synovia, which could bind globulins to form tissue-damaging complexes and perpetuate the inflammation. The immunofluorescence procedure was modified by pretreating sections with 5% bovine serum albumin, and by using fluorescein conjugates of F(ab)2 portions of antibodies to avoid the antigen-nonspecific binding that sometimes occurs in inflamed or necrotic tissue. Previous findings of immunoglobulins in lesions were confirmed by the more discriminating technique. IgG and IgM was present more frequently in lesions with mainly mononuclear cell changes, than in those with mainly neutrophil changes, leucocytoclastic or necrotizing vasculitis. Fab occurred in some lesions without Fc of IgG or IgM. Three lesions containing IgM or IgM and IgG, specifically bound heat-aggregated whole IgG or Fc of IgG. None bound IgM. The results indicate that the immunoglobulin in some cutaneous vasculitis lesions is locally formed or fixed antiglobulin, which will bind aggregated IgG possibly forming complexes perpetuating the lesion.


Comparison of double-antibody radioimmunoassay with Farr-technique radioimmunoassay and double-antibody enzyme immunoassay for alpha-fetoprotein. We describe double-antibody procedures for determining alpha-fetoprotein in human serum. An equilibrium procedure can be done in 24 h with a sensitivity of at least 4 mug/liter and coefficient of variation of 5.5%. There are no interferences from normal human sera or sera with certain commonly seen chemical abnormalities. We also describe and discuss sequential procedures that range in sensitivity from 250 ng to 1mug/liter and require 24-48h incubation. The precise (mid-range)portion of the dose/response curve for sequential procedures can be shifted to higher or lower values by an adjustment of the time of preliminary incubation of antibody with unlabeled antigen. With a 37 degrees C incubation, a sequential procedure can be completed in 7 h. Sensitivity is 1 mug/liter, and coefficient of variation 8.0%. The relative merits of the above assay procedures are discussed. The double-antibody redioimmunoassay is twice as sensitive as the Farr procedure [J. Infect. Dis. 103, 239 (1958)], and it is free of the large and variable nonspecific precipitation that accompanies the precipitation of bound antigen with sodium sulfate solution. Double-antibody radioimmunoassay is superior to enzyme immunoassay in both sensitivity and precision.


Immunoelectrophoretic quantitation of alpha-fetoprotein. We describe an immunoelectrophoretic method for alpha-fetoprotein quantitation. The sensitivity of the method, which is easy to perform in the routine laboratory, is under the best conditions 50 mug/liter, but 83 mug/liter can always be detected. With this test, sera from patients with various hepatic diseases and from pregnancies can be tested.


[Inventory of oligoclonal fractions of subacute sclerosing panenephalitis cere-brospinal fluid in Africa with a specific immuneserum: first results (author's transl)]. The oligoclonal gamma-fractions in the cerebrospinal fluid (C.S.F.) from one case of subacute sclerosing panencephalitis (S.S.P.E.) have been studied by means of immunolectrophoresis. The gamma-zone consisted of IgG and free kappa and lambda chains. Besides that, a rabbit immune serum against S.S.P.E. C.S.F. has been prepared. This immune serum did reveal in the gamma-zone one additional protein which is different from IgG and normal tissue proteins. The possibility for this additionnal protein to be of myelinic origin is postulated, because of the demyelinisating nature of the lesion.


Peripheral blood B-lymphocyte abnormalities associated with hyperthyroidism of Graves' disease. Proportions of peripheral blood thymus-derived T lymphocytes (T cells) and bone-marrow-derived B-lymphocytes (B cells) were studied in twelve hyperthyroid patients and ninety-nine non-hyperthyroid control subjects including thirty-nine healthy individuals and sixty patients with various disorders. All hyperthyroid patients had Graves' disease and eight were untreated. The sheep erythrocyte (E)-rosetting technique was employed for enumeration of T cells and the immunofluorescent technique was used for identification of lymphocytes with surface immunoglobulins (SIg), a marker for B cells. The results showed that hyperthyroid patients had higher percentages of lymphocytes stainable for SIg, whereas their T-cell proportions were the same as our control values. In addition, approximately half or more of the fluorescein stainable lymphocytes reacted with each of the five antisera against individual heavy chain determinants, including the epsilon chain, indicating the presence of more than three Ig determinants on the same cell. The fluorescein-stainable cells did not form E rosettes. Blocking of the Fc receptor on lymphocytes by incubating the patients' cells with heat-aggregated human IgG or heated goat anti-bovine serum albumin (anti-BSA) failed to abolish the subsequent fluorescent staining of the cells. Incubation of patients' lymphocytes with non-fluorescent anti-epsilon inhibited the subsequent staining of cells with fluoresceinated anti-epsilon but not staining with fluoresceinated anti-mu or anti-gamma. Thus, the study revealed B-cell abnormalities associated with hyperthyroidism, manifested by the simultaneous presence of multiple Ig classes, including IgE, on a single B cell. Results of studies of incubation of the patients' plasmas with lymphocytes from health individuals and studies of SIg by overnight culture of the patients' lymphocytes with or without prior trypsinization suggested that the SIg was generated endogenously by the cell on which it resided.


Inhibition of human lymphocyte transformation by human alpha-foetoprotein (HAFP); comparison of foetal and hepatoma HAFP and kinetic studies in vitro immunosuppression. Five pure isolates of human alpha-foetoprotein (HAFP) from adults with tumours of the li er or stomach, as well as HAFP isolated from foetal liver, inhibit in vitro human lymphocyte transformation induced by phytomitogens, anti-human thymocyte serum, and the mixed lymphocyte culture. Foetal HAFP produces 50% inhibition at concentrations of 1-5 mug/ml. The HAFPs isolated from tumour-bearing adults are 1-3 orders of magnitude less potent (50% inhibition achieved at approximately 20, 130, 500, and 2000 mug/ml, respectively). In order to achieve maximum inhibition HAFP must be present at the time of mitogen addition; pre-exposure of lymphocytes to HAFP, followed by washing, does not result in lymphocyte suppression. The inhibiting effect of HAFP cannot be overcome by a ten-fold increase in mitogen concentration implying that HAFP does not act by simple competition with the lymphocyte membrane for the mitogen combining site. HAFP may play an immunoregulatory role during foetal development.


Maintenance of immunologic self-tolerance by nonimmunogenic forms of antigen. Immunologic tolerance to EAE in guinea-pigs appears to be a function of a determinant distinct from the encephalitogenic region of the myelin basic protein molecule. In Lewis rats (in which species the molecular sites for disease-induction and tolerance have not been completely characterized) the mechanism underlying this state of immunologic tolerance involves suppressor cell regulation of the autoimmune response. On the basis of these experimental findings we postulate that natural self-tolerance is maintained by suppressor T cells which are stimulated by nonimmunogenic fragments of self-antigen released during protein turnover.


Pregnancy zone protein analogue in pregnant and non-pregnant primates, and its decrease during pregnancy in some monkey species. Rabbit antiserum to human pregnancy zone protein (PZP) cross-reacted with analogous proteins in several species of primates. The chimpanzee PZP showed reactions of identity with human PZP, while the PZP analogue in the orangutan, in four species of old world monkeys (pig-tailed, rhesus, cynomolgus and stump-tailed) and in a species of new world monkey (squirrel) showed equivalent reactions of partial identity with human PZP. In the chimpanzee and orangutan, the PZP analogue was present in low concentrations in non-pregnant animals, but as in the human, it increased quite appreciably during gestation. In the chimpanzee, this increase in pregnancy was about four-fold greater than in the human. In sharp contrast, in the old and new world monkeys, the PZP analogue was present in much higher concentrations in non-pregnant animals than it is in humans. In addition, during pregnancy the PZP analogue in these monkey species actually decreased during pregnancy. In the few cases studied, normal levels were regained about 1 month after delivery. A normal plasma protein, alpha2-macroglobin, was also studied in these primate species, because this protein shares some characteristics with PZP. Analogous alpha2-macroglobulin serum proteins were found in all the primates tested, but the observed gel diffusion identity patterns suggested that this protein was phylogenetically older than PZP. alpha2-macroglobulin increased slightly during human pregnancy, but in all the other primates studied, the alpha-macroglobulin analogue was either unchanged or slightly decreased during gestation.


Treatment of cancer of the ovary.

Treatment of cancer of the ovary. This chapter has stressed the importance of early diagnosis in the treatment of cancer of the ovary with suggestions as to achieving this goal by a more aggressive approach to the accurate diagnosis of pelvic tumours. The combined use of surgery with radiation therapy and/or chemotherapy has also been discussed with the definition of the functions of the surgeon, radiotherapist and chemotherapist. The place of surgery in the staging and initial treatment of this disease is outlined and the indications for surgery for advanced and recurrent disease are demonstrated. The use of the various modalities of ionising radiation has been outlined and the place of chemotherapy and selection of appropriate drugs are also discussed.


Treatment of cystic ovarian disease in dairy cattle. Comparative observation of the effects of an intramuscular injection of corticosteroids and an intravenous injection of a combination of human chorionic gonadotropin and progesterone. Of 67 cows with cystic ovarian disease (COD), 34 were injected intramuscularly with 20 mg of betamethasone of 10 mg of dexamethasone (CC) and 33 intravenously with a combination of 3,000 IU of human chorionic gonadotropin and 125 mg of progesterone (HCG -P). Pregnancy rates and intervals between treatment and conception were 32.4% and 32.1 +/- 30.5 days, respectively, in the CC-treated cows and 30.3% and 51.6 +/- 29.5 days in the HCG -P-treated ones. Cows which had not responded to gonadotropin treatment showed a considerably higher pregnancy rate when treated with CC and a lower pregnancy rate when administered with HCG -P than those which had received no treatment before. There was a trend that the earlier a cow was treated, the more readily she recovered. CC injection gave a satisfactory result even when performed long after calving. The estrous behaviour seemed to be related with prognosis in cows with COD. In both CC-treated and HCG -P-treated cows, the pregnancy rate was the highest in cows showing anestrus and the lowest in those exhibiting irregular estrus.


Contraceptive steroid toxicology in the Beagle dog and its relevance to human carcinogenicity. Problems associated with the use of the Beagle dog in chronic toxicological studies of contraceptive steroids are described. A short review is presented on the occurrence of spontaneous tumours in dogs and in bitches of various breeds. The current status of knowledge of canine reproductive hormones and endocrinology is outlined, together with effects of contraceptive steroids. The pathology and histological classification of spontaneous and induced mammary neoplasia in the dog is discussed and compared with breast cancer in women. A series of recommendations are included for future research in this field which it is hoped may resolve some of the outstanding issues and lead to a more suitable toxicological model for contraceptive steroids.


On the influence of task relevance and stimulus probability on event-related-potential components. Fifteen subjects were presented with series of tones. Any one tone was either loud or soft, and in any one series the probability of one tone intensity was either 0.9 or 0.1. Subjects were instructed to count the frequent tones or to count the rare tones. The stimuli were also presented while the subjects were solving a word-puzzle. Event-related potentials (ERPs) were recorded from 9 scalp locations (F3, C3, P3, FZ, CZ, PZ, F4, C4, P4) referred to linked mastoids. ERP components were measured with a Principal Components analysis and the relations between these measures and the independent variables were evaluated with the ANOVA procedure. This paradigm allowed an evaluation of the effect of stimulus probability, stimulus relevance, and task relevance on the waveform of the ERPs. We conclude that the P350 component is enhanced whenever the eliciting stimulus is both rare and in some sense relevant to the subject's task and the degree of enhancement is greatest when the rare--relevant tone is loud. A "slow wave" component which follows P350 is related to the same variables but has a scalp distribution quite different from that of P350. The slow wave shows a progressive shift in polarity from negative to positive from the frontal to the parietal sites, while the P350 is of nearly equal amplitude (and positive) at the central and parietal sites and has a smaller (positive) and amplitude at FZ. A third prominent component, negative in polarity, peaking at about 210 msec, is most pronounced following rare stimuli, whether or not they were task relevant. The amplitude of N210 tended to be largest at the frontal electrode. This study then demonstrates that when suitable measurement techniques are used, multiple endogenous ERP components can be observed, each related to distinct aspects of cognitive behavior.


Effects of voluntary isometric and isotonic activity on late transcortical reflex components in normal subjects and hemiparetic patients. When the median nerve is stimulated at the wrist during voluntary contraction of m. abductor pollicis brevis (APB) EMG activity of this muscle contains different distinct responses: a direct muscular response (M response), a spinal reflex response (S response) and a third late reflex response, first described by Upton et al. (1971) as a second volitional reflex response (V2). Comparison of this very likely long-loop reflex involving pathways to and from the cortical level (therefore labelled C response) under isometric (hold) and isotonic (move) contraction revealed a strong facilitation of the response under the latter condition. Repetitive trains of stimuli had stronger facilitatory effect on the occurrence of this late reflex response than single stimuli. Cutaneous stimuli of the median nerve afferents did not exhibit M and S responses but definite late excitatory responses with similar latencies to the C responses. In cases of hemiparesis (mild to severe loss of sensorimotor control of finger movements) the C response was diminished, delayed or absent. These findings together with recent primate and human experimental work support the  hypothesis of a transcortical stretch reflex. On the premise that muscular as well as cutaneous afferents contribute to the afferent cortical input the late C response can be interpreted as the efferent component. The C response may be a valuable aid in the diagnosis of small lesions of the sensorimotor cortex and internal capsule.


Micro-tremor of the eyes of comatose patients. An electronic method has been used to record the micro-tremor of the eyes of a group of comatose patients. Changes in the micro-tremor waveform patterns have been observed in successive records taken over a period of several days. These changes have been associated with changes in the depth of coma.