Serological diagnosis of gonorrhoea by an enzyme-linked immunosorbent assay (Elisa).

IgG antibody to an outer membrane protein extracted from Neisseria gonorrhoeae was measured in patients with gonorrhoea. The level in such patients was significantly higher than in normal controls or in patients with other conditions who were attending the clinic for sexually transmitted diseases. Significantly higher antibody levels were detectable in half the patients within a few days of infection and in a similar proportion of carriers--both male and female. Men with rectal gonorrhoea had particularly high antibody levels. Sixteen per cent of presumptively normal men and 11% of normal women gave positive results but the actual false positive rate could be lower.


Ultrastructure of supraspinal dorsal root projections in the toads. I. The obex region.

The ultrastructure of the dorsal column nucleus (DCN) has been investigated at the level of the obex region in normal and experimental toads. Large 'isolated' neurons (greater than 20 micrometer) and clusters of small neurons (less than 20 micrometer) have been identified in this region. Synaptic profiles have been classified into three types: large 'en passant' LR boutons, containing round synaptic vesicles and neurofilaments, small R boutons with round vesicles and F boutons with pleomorphic vesicles. The axon terminals exhibited synaptic contacts with cell somata, with dendrites of varying calibers and with other axons. The terminals involved in the axo-axonic contact were the F boutons which were presynaptic to the LR boutons, thus representing the morphological basis for presynaptic inhibition. Transection of the second dorsal root was performed in order to identify the terminals of the primary afferents to the DCN, after different survival periods (16 h--50 days). Only the LR boutons underwent degeneration, thus representing the central endings of the primary dorsal root afferents. The functional significance of these findings was discussed.


The effects of chronicity on burst structure in epileptogenic foci.

Pyramidal tract neurons (PTNs) from tungstic acid, cobalt and alumina gel foci in cat were studied for spontaneous and antidromically-evoked firing patterns. Specifically, the structured long-first-interval (LFI) burst was looked for. The LFI burst did occur spontaneously from PTNs in tungstic acid foci but could not be antidromically evoked. The LFI burst did not occur as often as would have bee predicted from cobalt and alumina foci, but, in foci older than 60 days, antidromically-evoked activity could be a burst which was structurally identical to those which occurred spontaneously. This data, in addition to that from acute penicillin foci, would indicate that the ability for single antidromic APs to evoke burst activity in PTNs is a function of the chronicity of the epileptic focus rather than the agent used to produce the focus.


A comparative study of the polypeptides of mammalian peripheral nerve myelin.

Polypeptide components of peripheral nerve myelin prepared from sciatic nerves of mouse, rat, rabbit, cat, guinea pig, monkey, dog and chicken were analyzed using a 20% polyacrylamide slab-gel electrophoresis system. Using this technique, we have demonstrated that there are at least two polypeptides present in the region of P1 protein (mol. wt. 18,000 and 16,000), and two closely moving components in the region of P2 protein (mol. wt. 13,500). A polypeptide (mol. wt. 10,500) is present in significant amounts only in mouse sciatic nerve myelin. Staining with periodic acid-Schiff reagent shows that in addition to P0 protein (mol. wt. 28,000), the major glycoprotein of peripheral nerve myelin, there are several minor glycoprotein components in both the high and low molecular weight regions.


An autoradiographic, semistereotaxic mapping of major projections from locus coeruleus and adjacent nuclei in Macaca mulatta.

The autoradiographic method was used to trace projections from the monkey locus coeruleus (LC) and adjacent nuclei (nn. parabrachiales, n. tractus mesencephalicus nervus trigemini, substantia grisea centralis). Pathways attributed to LC are presented diagrammatically in a set of 26 coronal sections. They include a descending pathway along the tractus tegmentalis centralis, a caudal pathway entering the corpus medullaris cerebellaris via the lateral wall and roof of ventriculus quartus, and an ascending pathway along the tractus tegmentalis centralis giving off branches to the commissura posterior, tractus habenulo-interpeduncularis, centrum medianum and n. ventralis posteromedialis thalami, fasciculus lenticularis, lamina medullaris thalami lateralis, capsula interna, commissura supraoptica dorsalis, tractus supraoptico-hypophyseus, stria terminalis, laminae medullaris interna and medialis and pars interna of globus pallidus, corpus subfornicale, capsula externa, stria longitudinalis, cingulum, and gyrus rectus. A contribution to the branches entering n. ventralis posteromedialis thalami and the commissura supraoptica dorsalis was attributed to the nn. parabrachiaels. Axons entering trigeminal structures via the tractus mesencephalicus nervus trigemini were attributed to labeling of cells in the nucleus of that tract. Terminal areas attributed to labeling of LC axons were evident in decreasing order of density in the bed nucleus of stria terminalis, substantia innominata, nn. amygdalae anterior, centralis and basalis (dorsal portion), nn. paraventricularis, supraopticus and dorsomedialis hypothalami, and n. antero-ventralis thalami.


Synthesis of thymidine nucleotides in Bacillus subtilis.

To investigate the synthesis of thymidine nucleotides in Bacillus subtilis, mutants that carried various combinations of thyA, thyB, and other mutations affecting pyrimidine metabolism were isolated. It was found that exogenously supplied deoxycytidine was converted to thymidine nucleotides. The present data suggest that deoxycytidine nucleotides are first deaminated to yield deoxyuridine nucleotides which can serve as substrates for both thyA- and thyB-coded synthetases. A deaminase activity for dCDP was found in crude extracts of B. subtilis. A mutant lacking the deaminase activity was unable to convert deoxycytidine nucleotides to thymidine nucleotides.


Relative positions of chromosome 1 loci Fy, PGM1, Sc, UMPK, Rh, PGD and ENO1 in man.

Ongoing linkage studies of red cell antigens and enzymes in many families along with concentration on a large Mennonite kindred segregating for Sc have resulted in lods, recombinant: nonrecombinant counts and multi-point information which support an order with approximate recombination fractions as measured in the male as follows: Fy--.25--PGM1--.20--Sc--less than .05--UMPK--.15--Rh--.20--PGD, with ENO1 close to PGD. The insertion of Sc and UMPK between PGM1 and Rh allows the recognition of double crossing-over between the latter pair; indications are that this is not a rare event in the female. In the male no evidence of double crossing-over was found in the similar distances PGM1--Rh and Sc--PGD in 13 and 19 opportunities respectively.


The TRH test: its value in the diagnosis of Graves' ophthalmopathy.

When a goiter or hyperthyroidism is absent, the diagnosis of ophthalmic Graves' disease is often difficult. We evaluated the thyrotropin (TSH) response to intravenously administered thyrotropin-releasing hormone (TRH) in fourteen patients presenting with proptosis or lid retraction. All of them had normal results with routine thyroid function tests and in most a T3 suppression test and orbital ultrasonography were performed. We found an absent or impaired response to TRH in the patients with Graves' ophthalmopathy which correlates well with their having a non-suppressible thyroid gland. Patients with orbital tumours, pseudotumours or congenital lid retraction responded normally to TRH. The TRH test was easier and as reliable as the T3 suppression test in the investigation of a patient with suspected Graves' disease.


Intensity of stimulation and rod and cone response in clinical electroretinography.

We exposed adult Rhesus monkeys who were fully dark adapted to paired flashes of white light which increased in intensity by increments of 0.1 log. units. As intensity increased, the amplitudes of both the cone and rod systems increased while the implicit times decreased so that the responses overlapped. High intensities produce a complex waveform which prevents separation of the rod and cone components or timing of the peaks. On the other hand, low intensities separate the early and late receptor potentials (L.R.P.) of cones and rods well and make it easy to time normal and pathological variations.


Laser iridotomy and trabeculotomy in monkeys. A morphological study.

We performed laser iridotomy and trabeculotomy on Rhesus and Cynomologous monkeys with a Britt Model 152 repetitively pulsed argon laser. The total energy delivered varied from 2 to 6 joules. The easiest sites for laser iridotomy were at 3 and 9 o'clock. The iridotomy remained open for at least 2 months. Scanning electron microscopy confirmed that no damage occurred to the lens. After laser burns to the trabecular meshwork light microscopy showed anterior synechiae, corneal endothelial swelling and trabecular coagulation. Scanning electron microscopy showed that only a few holes were made in the trabecular tissue, even after a massive dose; some of them appeared to lead directly to the canal of Schlemm. We feel that although this machine can be used successfully to perform iridotomy in humans, it cannot replace the current surgical procedures in glaucoma.


Vasoactive intestinal polypeptide excitation of central neurons.

Vasoactive intestinal polypeptide (VIP) was tested on neurons in the rat sensory motor cerebral cortex and on the isolated hemisected toad spinal cord. Iontophoretically applied VIP excited deep, spontaneously active cortical neurons, including identified corticospinal neurons. The excitation had a latency of onset varying from several seconds to over 1 min and often lasted for a minute or longer after cessation of the application. Desensitization of the effect occurred with repeated applications. VIP caused a depolarization of motoneurons and dorsal root terminals in the isolated amphibian spinal cord. Threshold for this effect was about 10(-6) M. The effects of VIP on both preparations were comparable with those of another peptide, substance P.


Effects of growth temperature on protoplast membrane properties in Bacillus megaterium.

Changes in the protoplast membrane of the KM strain of Bacillus megaterium were assessed after growth at 20, 30, or 37 degrees, C. Although the overall membrane concentrations of lipids and proteins were virtually unchanged, increased culture temperature resulted in cells with membranes that contained relatively more unbranched and long-chain fatty acids and more acidic phospholipids, as well as different proportions and numbers of individual proteins. Electrophoretic analysis revealed 23, 31, or 29 protein bands, respectively, in membranes from cells grown at the three temperatures. Protoplasts from cells grown at higher temperatures were considerably less susceptible to lysis by shearing forces. As judged by passive leakage at 30 degrees C, intact cells from cultures grown at 37 degrees C were the least permeable to erythritol. Relatively low ambient concentrations of Ca2+ or Mg2+ protected protoplasts from osmotic lysis but even much higher concentrations left erythritol leakage virtually unaffected. Thus, growth temperature affected not only membrane lipis but also membrane proteins and these changes resulted in membranes with altered mechanical properties and permeabilities.


A cytochrome b-like pigment with a peak at 567 nm in Pseudomonas aeruginosa.

A cytochrome b - like pigment with an absorption peak at 567 nm was detected in Pseudomonas aeruginosa irrespective of whether the organism was grown aerobically or anaerobically under denitrifying conditions. This pigment has not been reported previously for P. aeruginosa but it has been detected in other denitrifying bacteria including closely related Pseudomonas species.


New presentation of alpha heavy chain disease: North American polypoid gastrointestinal lymphoma. Clinical and cellular studies.

Alpha Heavy Chain Disease has generally been described in the Mediterranean area in young people with a diffuse gastrointestinal lymphoma and malabsorption. We describe a patient from the United States with polypoid lymphoma of the gastrointestinal tract and a prolonged clinical course, who had the characteristic alpha heavy chain disease protein. He did not have malabsorption, and the gastrointestinal tract, though containing multiple discrete lymphomatous polyps had little plasmacytic reaction. Lymphosarcoma cell leukemia developed late in the course and the malignant cells had the characteristics of B lymphocytes but did not contain alpha heavy chains. The data support the contention that the lymphoma in this form of alpha heavy chain disease may involve B lymphocytes but that the abnormal protein may be produced by other cells. Polypoid varieties of gastrointestinal lymphoma in North America must now be considered part of the spectrum of alpha heavy chain disease and the diagnostic protein searched for diligently.


The use and abuse of CEA test in clinical practice.

Charts of 437 patients having plasma carcinoembryonic antigen determinations during the period January 1, 1976 through April 30, 1976 were reviewed to determine whether CEA results led to clinical decisions altering management patterns. Data analysis disclosed that CEA test results did not result in any change in management in 167 patients with non-neoplastic disease. Most had single determinations. In 270 patients with neoplastic disease, CEA results led to changes in management in one patient with lung cancer and two patients with colon cancer, which may have altered prognosis. In a fourth patient, CEA results led to discovery of unresectable pancreatic cancer at laparotomy. Cost benefit analysis indicated a CEA test cost of $5,047.50 per patient benefitted in 299 patients eligible for analysis. We conclude that maximal benefit to the patient results from serial CEA test use in follow-up of colon cancer patients after curative therapy.


Pregnancy outcome of patients treated for Hodgkin's disease: a controlled study.

Normal reproduction prosepcts for Hodgkin's disease patients are unknown. This study compares the outcome of 93 pregnancies in 48 patients with 228 pregnancies in 69 sibling controls. No statistically significant differences for  spontaneous abortions or abnormal offspring were noted comparing all patients with all controls or 35 irradiated patients with all controls. Pregnancy outcome of 13 patients who received both irradiation and chemotherapy prior to pregnancy appeared to be compromised compared to controls. Wives of male patients in this category were more likely to have spontnaeous abortions than  wives of male controls; female patients in this category were significantly more likely to produce abnormal offspring than were female controls (p = 0.047). In this series of patients therapeutic irradiation alone did not appear to jeoparadize posttreatment reproduction in fertile Hodgkin's disease patients but in the smaller group of patients who received both irradiation and chemotherapy the reproduction picture was statistically not as good.


"Mediterranean abdominal lymphoma" or immunoproliferative small intestinal disease. Part II: pathological aspects.

The pathology of 25 cases of Mediterranean abdominal lymphoma, better designated as immunoproliferative small intestinal disease (IPSID), are reported from the American University of Beirut Hospital. The series includes nine cases with documented alpha heavy chain disease (alpha-HCD). The disease is characterized by the presence of a diffuse and compact bandlike lymphoplasmacytic infiltration of the proximal small intestinal mucosa. The presence of a concomitant malignant lymphoma in the intestine and/or mesenteric lymph nodes, and of alpha-heavy protein in the serum is commonly encountered. Two histopathologic variants of IPSID are present. The first is characterized by the diffuse infiltration of the mucosa, at sites away from tumoral masses,  by either pure plasmacytic infiltration, or mixed lymphoplasmacytic infiltration. This variety is associated with the immunoblastic sarcoma type of malignant lymphoma, and with alpha chain disease (alpha-HCD). The second variant is characterized by a diffuse follicular lymphoid hyperplasia pattern in the small intestinal mucosa. The associated malignant lymphoma is  diffuse and undifferentiated often having a starry-sky pattern. This variety is not associated with alpha-HCD. Both histologic variants share the same clinical antecedents. In five patients, mesenteric lymph nodes harbored immunoblastic sarcoma while the intestinal mucosae of the same patients were involved with a benign appearing lymphoplasmacytic infiltration. This finding stresses the need for staging laparatomy. Three patients, with alpha-HCD, had peripheral lymph node involvement with immunoblastic sarcoma. The disease apparently evolves in two stages: an immunoproliferative phase, probably reversible, and a later development of malignant lymphoma. The term immunoproliferative small intestinal disease accurately describes the nature of the entity.


Metabolism of 7,12-dimethylbmethylbenz(a)anthracene by macrophages and uptake of macrophage-derived metabolites by respiratory tissues in vitro.

Cultured mouse macrophages and tracheal and lung tissue each produced the same ethyl acetate-soluble derivatives of 7,12-dimethylbenz(a)anthracene (DMBA). The derivatives produced in the different cultures were indistinguishable by thin-layer chromatography and by high-pressure liquid chromatography but differed in their relative proportions. The greatest difference was seen between lungs and macrophages. The predominant metabolite produced by lungs was 8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz(a)anthracene, while macrophages produced equal quantities of both 8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz(a)anthracene and a second uncharacterized derivative, Metabolite B, at low DMBA doses (less than 0.05 microgram/ml medium) and primarily Metabolite B at higher DMBA doses (greater than 0.05 microgram/ml medium). Macrophages released the majority of the ethyl acetate-soluble metabolites that they produced into the surrounding medium. With the exception of 8,9-dihydro-8,9-dihydroxy-7,12dimethylbenz(a)anthracene, these derivatives were accumulated within tracheal and lung tissue when these organs were cocultivated with macrophages in the presence of DMBA.


Chemical and biological adjuvants capable of potentiating tumor cell vaccine.

With an L1210 tumor vaccine model, three biological and two chemical agents were tested for their ability to act as adjuvants. Adjuvant was administered with irradiated L1210 cells to immunize mice against this poorly immunogenic tumor. Two chemicals, pyran copolymer and glucan, and one biological, Brucella abortus strain 456 ether extract, were shown to be strong stimulators of antitumor immunity. Vaccination with irradiated tumor cells or adjuvant alone did not produce host resistance. Optimal immunity to challenge was produced by concomitant administration of either pyran copolymer, glucan, or B. abortus strain 456 ether extract with L1210 vaccine. Antitumor immunity was maximally expressed when vaccine and adjuvant were administered i.p. Evidence for systemic immunity was demonstrated when challenge was at a distal s.c. site. Mice immune to challenge were found to be refractory to a later rechallenge.


Inhibition of polycyclic aromatic hydrocarbon-induced neoplasia by naturally occurring indoles.

Indole-3-carbinol, 3,3'-diindolylmethane, and indole-3-acetonitrile, three indoles occurring in edible cruciferous vegetables, have been studied for their effects on 7,12-dimethylbenz(a)anthracene-induced mammary tumor formation in female Sprague-Dawley rats and on benzo(a)pyrene-induced neoplasia of the forestomach in female ICR/Ha mice. When given by p.o. intubation 20 hr prior to 7,12-dimethylbenz(a)anthracene administration, indole-3-carbinol and 3,3'-diindolylmethane had an inhibitory effect on mammary tumor formation, but indole-3-acetonitrile was inactive. Indole-3-carbinol when added to the diet for 8 days prior to challenge with 7,12-dimethylbenz(a)anthracene inhibited mammary tumor formation, whereas indole-3-acetonitrile did not. Dietary administration of all three indoles inhibited benzo(a)pyrene-induced neoplasia of the forestomach in ICR/Ha mice. The identification of dietary constituents that can inhibit chemical carcinogens ultimately may be of value in understanding the balance of factors that determines the neoplastic response to these cancer-producing agents in the environment.


Separation of glutathione S-transferase activities with epoxides from the mouse liver h-protein, a major polycyclic hydrocarbon-binding protein.

The C3H mouse liver h-protein is a cytoplasmic protein to which metabolites of carcinogenic polycyclic hydrocarbons bind covalently following i.p. injection. It has a number of physical properties similar to those of the glutathione S-transferases (EC 2.5.1.18). These properties include molecular weight (40,000), number of subunits (2), basic isoelectric point around 8.0, sedimentation coefficient (3.5S), and subcellular localization. In this communication, we have shown that glutathione S-transferase activities with 1,2-epoxy(3-p-nitrophenoxy)propane and benz[a]anthracene 5,6-oxide as substrates were separated from the h-protein on carboxymethylcellulose and isoelectrofocusing columns. The purification of the mouse h-protein as a [3H]-7,12-dimethylbenz[a]anthracene conjugate or as the free form is also described.


Surface processes of olfactory receptors.

The free surface morphology of olfactory receptor cells from the nasal mucosa of Cynomolgus monkeys was studied electron microscopically. The receptor cell, in addition to showing characteristic cilia, possess several branched or unbranched shorter elevations or spiny processes covered by numerous delicate lace-like filaments not previously described. These filaments diminish in length and number toward the base of the microvillous protrusions.


The termination of the central microtubules from the cilia of Tetrahymena pyriformis.

In frayed axonemes of cilia isolated from Tetrahymena pyriformis, observed in negative stain, the central apparatus remains intact, stabilized in part by the sheath projections that encircle the two singlet central microtubules. The projections terminate ca. 1.5 +/- 0.5 micron before the microtubules themselves end. The microtubules are capped together at their tips by a distinct structure, the central pair cap. The cap, ca. 50 nm across and 90 nm long, consists of a stack of two disks and a ball, similar in shape to a finial. The cap is the only part of the axoneme that extends to the distalmost point of the ciliary membrane and, therefore, it may be of significance in length determination or in shaping the ciliary tip.


Template activity of macronuclear and micronuclear chromatin of the ciliate Stylonychia mytilus.

Template activity of macronuclear and micronuclear chromatin of the ciliate Stylonychia mytilus was studied under in vitro conditions. Micronuclear chromatin has a template activity which is about 50% of that of the macronucleus. The relative number of initiation sites is much smaller in micronuclear chromatin.


Vectorcardiographic quantification of infarct size in baboons.

A vectorcardiographic method has been developed for determining the absolute size of myocardial infarcts in baboons resulting from coronary artery ligation. Spatial area (mvolt . msec) and voltage (mvolt) difference-vectors were obtained for 8 animals by measuring the voltage loss and temporal deviation from pre- to post-ligation McFee scalar leads. The difference vectors were then correlated with the absolute infarct volumes, which were derived by histological assessment 10 days after ligation. Absolute lesion sizes ranged from approximately 2 cc to 14 cc, involving 10-30% of ventricular muscle mass. The correlation coefficient, r, for the area deviation index was 0.98 (SEE = +/- 0.24 cc); and for the voltage deviation index, r was 0.92 (SEE = +/- 0.51 cc). These results demonstrate that the severity of infarction can be accurately determined if prepathological vectorcardiograms are available.


Regional myocardial wall thickening response to nitroglycerin. A predictor of myocardial response to aortocoronary bypass surgery.

The peak rate of systolic wall thickening (p +/- dTw/dt) in regions of the left ventricle (LV) was determined preoperatively by biplane roentgen videometry in 18 patients before and after sublingual administration of nitroglycerin (NTG) and 3-23 months (median 12) after aortocoronary bypass surgery. The regional LV response to NTG was a reliable predictor for postoperative improvement in regional wall dynamics after successful aortocoronary bypass grafting. The ejection fraction response to NTG or surgery will not predict the regional myocardial response to NTG or surgery, nor will the regional response predict the global response. Subendocardial myocardial infarction is another cause of unimproved regional myocardial function after NTG and aortocoronary bypass surgery.


Conditions for vasodilator-induced coronary steal in experimental myocardial ischemia.

The conditions for coronary steal were determined using the two vasodilators--dipyridamole and nitroglycerin--in anesthetized dogs after ligation of the left anterior descending coronary artery (LAD). Previous studies have shown that when the non-ligated coronary arteries are normal, collateral flow increases after dipyridamole. This study utilized a model in which the distal LAD was ligated and the proximal LAD and left circumflex (LC) arteries were stenosed. Heart rate and blood pressure were kept constant. In 20 dogs, 1-1.5 mg/kg dipyridamole caused a decrease in flow to the ischemic region as measured by radioactive microspheres (0.19 to 0.14 ml/min/g, P = 0.05) while flow increased four-fold to surrounding nonischemic myocardium. The decrease in collateral flow was confined to the epicardial half of the ischemic region (0.26 to 0.14 ml/min/g, P less than 0.001) and was associated with an increase in sigmaST from 30.9 to 44.7 mV (P less than 0.01). In five dogs nitroglycerin, 5 microgram/kg/min, produced no significant changes in collateral flow or flow to other parts of the LV, and sigmaST was unchanged. Vasodilator-induced coronary steal therefore appears to require 1) an arteriolar-type dilator like dipyridamole and 2) stenoses of the arteries supplying collateral flow to the ischemic region. The steal phenomenon is probably caused by a decrease in pressure distal to the stenoses in these vessels, resulting in reduced driving pressure for collateral flow.


Radioimmunoassay of calcitonin in the plasma of rhesus monkey and man.

We describe a radioimmunoassay for rhesus monkey and human immunoreactive calcitonin, in which a selected goat anti-human calcitonin antiserum, 131I-labeled synthetic human calcitonin tracer, and purified synthetic human calcitonin standards were used. The mean basal concentration of calcitonin in normal monkey plasma (254 microgram/liter) was not significantly different from that in normal human plasma (217 microgram/liter). The data indicate that the method is sensitive (lower limit of detection, 5 ng/liter), specific, accurate, and reproducible (coefficient of variation, 1-11% over a wide range of concentrations). Monkey calcitonin response to changes in plasma calcium concentration is similar to that in man, with significant correlation between calcium and calcitonin concentrations. Use of this radioimmunoassay for monkey and human calcitonin allows the monkey to be used in further studies of factors regulating secretion, function, and metabolism of calcitonin under various experimental conditions that would not be feasible in man.


Response to thyrotrophin releasing hormone in Klinefelter's syndrome.

In eleven patients with Klinefelter's Syndrome TSH, T4 and T3 levels have been measured after stimulation with TRH. The eleven patients included three who had been noted to have a low radioactive iodine uptake and two of these also had abnormally low T4 levels. Three of the patients were receiving androgen replacement therapy. A normal response to TRH was observed in all cases.


Evidence for thyroidal secretion of 3,3',5'-triiodothyronine in man and its control by TSH.

Thyroidal secretion of 3,3',5'-triiodothyronine (reverse T3, rT3) and its control by TSH was assessed by measuring (1) arterio-venous hormone gradients in patients undergoing surgery, (2) changes of hormone concentrations after induction of anaesthesia, and (3) changes induced by TRH administration. In ten patients in whom thyroid activity was under TSH control (parathyroidectomy and non-toxic goitre) increased thyroid vein/carotid artery ratios (TV/CA) for rT3 (mean TV/CA ratio 2.53) were found when compared to six patients with non-toxic goitre on suppressive doses of T4 (mean TV/CA ratio, 1.27) (P less than 0.05). The mean calculated operative secretion rate of rT3 was 12.5 microgram/day but only 2.4 microgram/day in patients receiving T4. In thirteen patients undergoing elective surgery induction of anaesthesia significantly increased rT3 levels. In nine euthyroid adults intravenous TRH (200 microgram) increased peripheral venous rT3 levels between 3 h (P less than 0.005) and 8 h (P less than 0.05) after the injection. It is concluded that significant amounts of rT3 are secreted by the thyroid gland at operation and this is, in part, under TSH control.


Recessive spondylocostal dysostosis: two new cases.

Two sisters with spondylocastal dysostosis are presented. Clinical findings are: short neck, short trunk, decreased upper to lower segment ratio, vertebral and costal malformations and normal intelligence. Both the clinical aspects and the family history are suggestive of the autosomal recessive form of the disease.


Beta-galactosidase deficiency: prolonged survival in three patients following early central nervous system deterioration.

Three adult patients from two families have shown slowly progressive neurologic deterioration since the age of 3 years, associated with profound beta-galactosidase deficiency. Although affected individuals from the two different families differ in degree of intellectual deficit, facial coarseness and spondyloepiphyseal dysplasia, all lack visceromegaly and macular red spots. The diversity of phenotypic expression in these patients and others previously reported suggests the existence of composite genotypes (compound and double heterozygosity).


Localization of a conformational anomaly to the Fabmu region of a monoclonal IgM cryoglobulin.

The hydrodynamic (gel filtration and sedimentation) properties of an isolated monoclonal IgM-K cryoglobulin (McE.) and five non-cryoglobulin cold-soluble proteins, as well as their constituent monomeric subunits and (Fc)5mu and Fabmu fragments, are compared under both native and partially denaturing conditions. It is concluded that the cryoimmunoglobulin exhibits a significantly greater Stokes radius than the non-cryoglobulin reference proteins, and that this difference arises in the Fabmu region of the McE. molecule. When the proteins and their fragments are analysed by circular dichroism in the far u.v. region, an atypical conformation is again detected in the Fabmu region of the cryoglobulin. These findings are the first demonstration and partial structural localization of a conformation anomaly in a monoclonal cryoimmunoglobulin.


Circulating thyroid hormone levels and adequacy of dialysis.

In vitro thyroid function tests were performed in three groups of patients with chronic renal failure who were receiving, on average, 15, 18 and 27 hours of maintenance hemodialysis per week. Total thyroxine levels were low and total triiodothyronine levels low to normal in those receiving the least dialysis (15 hours), and were significantly higher in those receiving longer dialysis. Free thyroxine levels, as measured by the effective thyroxine ratio, were normal and similar in all three groups, as were serum thyrotrophin levels. All patients were clinically euthyroid. As total hormone levels showed a significant inverse relationship to both urea and creatinine, this study suggests that there is a dialyzable metabolite retained in uremia which competes with thyroid hormones for protein-binding sites.


Genetic studies on heterochromatin in Drosophila melanogaster and their implications for the functions of satellite DNA.

In Drosophila melanogaster the centromeric heterochromatin of all chromosomes consists almost entirely of several different satellite DNA sequences. In view of this we have examined by genetic means the meiotic consequences of X chromosomes with partial deletions of their heterochromatin, and have found that the amount and position of recombination on each heterochromatically deleted X is substantially different from that of a normal X. It appears that the amount of heterochromatin is important in modifying the "centromere effect" on recombination.--In all the deleted Xs tested, chromosome segregation is not appreciably altered from that of a nondeleted control chromosome. Thus satellite DNA does not appear to be an important factor in determining the regular segregation of sex chromosomes in Drosophila. Additionally, since X chromosomes with massive satellite DNA deficiencies are able to participate in a chromocenter within salivary gland nuclei, a major role of satellite DNA in chromocenter formation in this tissue is also quite unlikely.--In order to examine the mechanisms by which the amount of satellite DNA is increased or decreased in vivo, we have measured cytologically the frequency of spontaneous sister chromatid exchanges in a ring Y chromosome which is entirely heterochromatic and consists almost exclusively of satellite DNA. In larval neuroblast cells the frequency of spontaneous SCE in this Y is approximately 0.3% per cell division. Since there is no meiotic recombination in D. melanogaster males and since meiotic recombination in the female does not occur in heterochromatin, our results provide a minimum estimate of the in vivo frequency of SCE in C-banded heterochromatin (which is predominantly simple sequence DNA), without the usual complications of substituted base analogs, incorporated radioactive label or substantial genetic content.--We emphasise that: (a) satellite DNA is not implicated in any major way in recognition processes such as meiotic homologue recognition or chromocenter formation in salivaries, (b) there is likely to be continuous variation in the amount of satellite DNA between individuals of a species; and (c) the amount of satellite DNA can have a crucial functional role in the meiotic recombination system.


Effects of Fructus gardeniae extract on hepatic function.

This article discusses the effects of Fructus Gardeniae extract on hepatic function. Fructus Gardeniae extract manifested no hepatotoxic effects on rats, as shown by alkaline phosphatase, aspartate aminotransferase, and lactate dehydrogenase studies. Fructus Gardeniae extract failed to activate the UDP-glucuronyltransferase system; whereas in hyperbilirubinemic state the enzyme was activated, presumably by substrate induction. Fructus Gardeniae extract increased the activity of UDP-glucose dehydrogenase, which would result in an increase in availability of UDP-glucuronic acid intracellularly, BSP clearance study showed an unexpected impairment of hepatic uptake of the dye after extract treatment. The action mechanism involved in lowering of serum bilirubin level by Fructus Gardeniae extract may well be complex; it is probably acting on a locus other than glucuronyl transferase.


Endocrine regulation of fetal development and its relation to parturition in the rhesus monkey.

Rhesus monkey fetuses were surgically prosencephalectomized (Type 2) or functionally hypophysectomized (Type 1) at 75 days gestation, then returned to the uterus until elective Caesarean section on day 145--150 (term 167 days). Deprivation of fetal hypothalamic releasing factors in Type 2 and fetal pituitary tropic hormones in Type 1 significantly delayed the ontogeny and functional development of fetal endocrine tissues. Bone ossification and growth were significantly retarded in Type 1 only, not in Type 2. In Type 1 the body and all organs except the endocrine glands were about half normal weight. The adrenals, thyroids, ovaries and testes were histologically abnormal and about one-tenth normal weight. Non-endocrine organs were histologically similar to 110-130-day fetuses. Thyroxine (T4) concentrations were significantly depressed in Type 1 fetal and maternal plasma at Caesarean section but normal in Type 2. Cortisol concentrations were normal in Type 1 fetal and maternal plasma. Types 1 and 2 plasma oestradiol concentrations were significantly lower in mothers but normal in fetuses. Type 1 placentas produced significantly less progesterone in vitro than normal. Fetal endocrine autonomy is indicated (thyrotropin-releasing factor excepted). Many of the hypothalamic and anterior pituitary hormones do not pass in effective amounts from mother to fetus. Fetal endocrine autonomy is a prerequisite for the control of both development and parturition.


Human decidua and uterine contractility.

Physiological saline solution injected into the uterus by the extraamniotic route was found to damage the decidua and rupture its lysosomes. The mechanism by which this procedure provokes abortion may be through the release of lysosomal phospholipase A2 (EC 3.1.1.4), an enzyme thought to regulate the formation of polyunsaturated fatty acids utilized for prostaglandin synthesis. A similar sequence of events may be involved in the initiation of spontaneous labour, since decidual cells obtained at elective Caesarean section at term exhibited degenerative changes and signs of release of a lysosomal marker enzyme. The cause of this release is unknown.


[Comparison of the effects of digitalis and nitroglycerine in coronary heart disease with cardiac failure on exercise (author's transl)].

The effects of moderately rapid oral digitalization and sublingual nitroglycerine were studied in 13 patients with coronary heart disease without signs of manifest heart failure but definite rise in pulmonary artery pressure on ergometric exercise. Digitalis had no effect on exercise-induced rise in pulmonary pressure. In the individual case there may be a clear-cut deterioration in exercise response. This possible unfavourable digitalis effect cannot be predicted in a given case from the clinical state and thus one must critically assess digitalis treatment in coronary heart disease without manifest heart failure. On the other hand, the favourable effect of nitroglycerine in lowering pulmonary arterial pressure at rest and preventing an abnormal pressure rise on exercise underlines its value in the treatment of both compensated and uncompensated coronary heart disease.


Immunobiology and pathogenesis of alpha chain disease.

alpha chain disease, the most frequent of the heavy chain diseases, is a proliferative disorder of B lymphoid cells involving primarily the small intestine and mesenteric nodes. The characteristic immunoglobulin, whose detection by immunochemical techniques may present some difficulties, consists of incomplete alpha chains devoid of light chains. The deleted portion of the alpha chain is located in the Fd segment and involves both the variable and first constant domains. In both of two proteins for which structural data are available, normal sequence resumes at the beginning of the hinge region. The absence of L chains is due to a failure of synthesis. alpha chain disease appears to proceed in two stages. The early stage is characterized by a possibly non-malignant diffuse and extensive plasma cell infiltration which may be reversible after administration of antibiotics. The later stage is characterized by overt neoplasia (immunoblastic lymphoma). The socio-geographic distribution of the digestive form of alpha chain disease shows a clear predilection for underpriviliged populations living in areas with a high degree of infestation by intestinal pathogens which play presumably a crucial role in the pathogenesis of the disease.


[Qualitative and quantitative EEG-findings in schizophrenia (author's transl)].

The results of the qualitative but particularly the quantitative EEG-studies indicate that 1. The EEG of adult schizophrenics is characterized by an appearance of excessive fast activity along with some slow waves and the lack of alpha-activity. 2. Excessive fast activity and lack of alpha-waves have also been found in the EEGs of psychotic children and most interestingly in children whose parents (particularly the mother) are schizophrenic (high risk children). 3. Based on the studies during sleep and investigations with neuroleptics, it was established that the origin of the excess fast activity in schizophrenia cannot be the muscle potential. Particularly the excess fast activity in high risk children for schizophrenia goes against the muscle potential hypothesis. 4. The quantitative EEG changes seen in schizophrenia show similarity to those seen after hallucinogenic compounds particularly after anticholinergic hallucinogenics. 5. All neuroleptics (major tranquilizers) produce quantitative EEG alterations which are almost diametrically opposite to those seen in schizoprenia.


[Influence of uncorrelated noise sources in parallel signal processing chains on the coherence function (author's transl)].

When linear relationships between bio-electrical signals have to be established, it is important to consider the possible influence of noise added to these signals during recording and processing. Using a model for the signal generation (Fig. 1A) and one for the signal processing (Fig. 1B), the influence of uncorrelated noise in parallel signal processing chains on the coherence function can be quantified (Fig. 2). This is illustrated by the results of electrophysiological experiments, in which field potentials have been recorded simultaneously by two electrodes in different parts of the rat brain.


Intestinal secretion of IgA and IgM: a hypothetical model.

The secretory component (SC) has recently been found to be associated with IgM in external secretions, although in a less stable complex than secretory IgA. Moreover, SC combines spontaneously in vitro with both IgA and IgM. A prerequisite is that the immunoglobulins contain the J chain, which is present only in dimers and polymers. This polypeptide is essential for the formation of an SC-binding site which appears already at the cytoplasmic level in IgA- and IgM-producing immunocytes. Locally formed J-chain-containing immunoglobulins are therefore readily available for complexing with SC present in the membranes of columnar secretory epithelial cells of glandular sites. This complexing initiates pinocytosis and external transport. Immunohistochemically the gland cells are shown to contain SC, IgA and IgM in identical locations, except that SC alone appears in the Golgi zone. Locally formed IgA and IgM antibodies are thus efficiently transferred to the mucosal surface where they exert an immunological exclusion of antigens. Conversely, IgG antibodies, which are not actively drained away from the lamina propria, may rather become engaged in complement activation and cell-mediated cytotoxicity with potentially deleterious effects on the tissue. Secondary to severe inflammatory reactions, secretory epithelium may show decreased production of SC; the selective external transport of SC-stabilized secretory IgA and IgM is thus jeopardized, and a vicious circle may be set up in the mucosa.


[Changes in the spontaneous EEG-activity before and during voluntary self-paced movement. New ways of investigation of the central mu-activity (author's transl)].

Movement-related desynchronization was investigated in the EEG from central region in human subjects, during voluntary self-paced movement of the thumb. The average dynamic time-behaviour of the power in the alpha band was calculated from 4 sec before to 2 sec after voluntary movement. In all investigated subjects (9 students and 7 patients with several forms of hemiplegia) a significant power reduction before voluntary movement of the thumb was found. This power decrease can be interpreted as desynchronization of the central mu activity. Therefore, it appears that in all subjects a mu activity can be demonstrated. In most cases, a short-lasting desynchronization of central mu activity occurred about 2 sec before movement onset and was followed by a second one, about 1 sec before movement onset which reached a maximum during initiation of movement. Frequently the first desynchronization occurred in parallel but often also before the Bereitschaftspotential.


[EMG-findings in typ-II-glycogenosis (Pompe's disease, acid maltase deficiency) (author's transl)].

EMG findings of two patients (one 43 years old male; one 47 years old female) with Typ-II-glycogenosis are referred. The diagnosis is proofed by enzym histochemical, ultrastructural and biochemical investigations. The EMG findings were characterized by vivacious spontaneous activity and the high rate of different EMG pattern in one patient. Beside myopathic patterns existed neurogenic patterns and spontaneous activities as pseudomyotonic discharges, fibrillations and positive sharp-waves. Case I showed myotonic discharges too. These EMG findings are compared with the histological findings. Signs of differentiation between myotonic and pseudomyotonic discharges especially in view of Typ II glycogenosis is discussed. The EMG findings of the two investigated patients are compared with others of the literature.


[EEG after sleep deprivation in patients with unequivocal and equivocal epileptic seizures, as well as no epileptic patients (author's transl)].

In 107 patients the EEG after sleep deprivation was performed. The patients have been divided in three groups: 1) with clinically unequivocal, 2) equivocal and 3) no epileptic seizures. All the patients where subdivided in those with and those without anticonvulsive medication. In patients with a previous normal EEG, sleep deprivation had the most activating effect regarding focal or generalized spikes or spike wave complexes in group one. However, patients without medication showed more often activation compared with untreated patients. In the second group the activation was less pronounced, again presenting the same relation between treated and untreated patients. Patients with no seizures as well as a control group of 20 volunteers had no activation at all.


[Evaluation of blocking and activation response of focal EEG abnormalities by opening and closing the eyes (author's transl)].

Blocking and activation of constant focal EEG abnormalities by opening and closing the eyes were assessed by visual analysis in 173 EEG recordings of 173 patients. Correlations between single variable were weak in general and did not gain statistical significance in any case. The blocking response had similar extent on both hemispheres. There was no sign of direct dependence from extra- or intracerebral localisation of the causal process. However, the biplot method of computing the results discovered several constellations of variables responsible for blocking and activation. Two of them are reported here. 1) Both responses were more prominent at frontal than at occipital areas. 2) A prodominant slowing localized in mainly frontal regions on the left hemisphere and caused by a process extending from extracerebral or cortical to subcortical showed the greatest tendency to be blocked by opening the eyes while the cause of the focus had no influence.


[EEG in Parkinson's disease and cerebral hypoxia (author's transl)].

EEG-findings of a group of 95 patients suffering from Parkinson's disease were related to accompanying diseases inducing cerebral hypoxic hypoxidosis. The EEG in 59 to 74 per cent of our patients was abnormal but the changes were not specific. There was a correlation between age and EEG-abnormalities. On the other hand no association could be seen between EEG-changes and duration of the Parkinson's disease. At least 74 per cent of the patients suffered from concomitant cardiovascular complications and 36 of them had a severe pathologic EEG as well as a pathologic ECG. The results lead to the conclusion that in treatment of parkinsonian patients attention is to be paid to accompanying diseases as heart failure, angiopathy or anemia.


Effects of TRH on circulating growth hormone, prolactin and triiodothyronine levels in the bovine.

The effects of administration of synthetic thyrotropin-releasing hormone (TRH) on circulating growth hormone (GH), PROLACTIN (PRL) and triiodothyronine (T3) levels of lactating dairy cows, non-lactating dairy heifers, and beef cows were studied. Intravenous administration of 0.1, 1, and 5 microgram of TRH per kg of body weight (bw) elevated plasma GH and PRL levels of lactating cows within 5 min. The plasma GH and PRL levels increased in proportion to the dose of TRH and reached a peak 10 to 30 min after TRH injection. Intravenous administration of 1 microgram of TRH per kg of bw to 7 non-lactating heifers, 14 lactating dairy cows, and 5 non-lactating beef cows elevated plasma GH level to peak values after 15 min, the increase rates being 6.9, 5.6, and 3.8 times as high as those in the pretreatment levels. The mean maximum vale was also in that order. Plasma T3 levels of non lactating dairy heifers at pre- and post-injection of TRH were significantly higher than those of lactating cows. The peak values of plasma PRL were obtained between 5 to 30 min after TRH administration. The increase rates of lactating dairy cows, heifers, and beef cows were 19.2, 13.9, and 20.9 times as high as those in the pretreatment. In contrast to GH and T3, plasma PRL levels of both pre- and post-injection with TRH in lactating cows and heifers were significantly higher in May than in October, though the increase rates were similar. Plasma PRL levels of lactating dairy cows at pre- and post-injection with TRH were significantly higher than those of non-lactating heifers. Subcutaneous administration of TRH was also effective to increase plasma TH, rl, and T3 levels in lactating cows. No significant change of GH or PRL response to TRH was observed after a short-term pretreatment of thyroid hormones.


Obesity and thyroid function. 3. Relationship between some indicators of thyroid function and the energy metabolism of striated muscle in obese women.

1. In a group of 23 obese women the relations between some indicators of thyroid function (thyroxine-binding globuline--T4BG, triiodothyronine-binding globuline--T3BG, Achilles tendon reflex--ART) on the one hand and activities of enzymes of the energy metabolism (hexokinase--HK, triose phosphate dehydrogenase--TPDH, lactate dehydrogenase--LDH, glycerol-3-phosphate dehydrogenase--GPDH, citrate synthease--CS, malate dehydrogenase--MDH, hydroxyacyl--COA dehydrogenase) in the quadriceps femoris muscle on the other hand were investigated. 2. Correlations were found between T4BG and TPDH, LDH and GPDH activities, between T3BG and TPDH and GPDH activities and between the value of the Achilles tendon reflex and TPDH activity. Functionally these enzymes activities are associated with glycolysis and hydrogen transport from cytoplasmatic NADH2. No correlations were found between enzymes of the aerobic metabolism incl. enzymes of fatty acid oxidation and indicators of thyroid function. 3. The results indicate a relationship between thyroid function and enzymes involved in glycolysis and hydrogen transport from cytoplasmatic NADH2. They do not suggest, however, the unequivocal conclusion that in obese women with reduced thyroid function there is a generally reduced energy supplying metabolism in skeletal muscle.


Acute prolonged confusion in later life as an ictal state.

Six patients ranging in age from 42 to 69 with no prior history of seizure disorder presented an acute prolonged or intermittent confusional state, with or without psychotic symptoms, as an ictal manifestation. The EEGs demonstrated protracted generalized spike and wave discharges, but full diagnostic evaluation disclosed no evident cause for the seizures. All promptly responded to small amounts of intravenous diazepam and subsequent oral phenytoin and phenobarbital. Three of the six patients had focal spike or sharp wave discharges on EEGs recorded subsequently, suggesting that the episodes may reflect secondary generalized seizures in some cases. These cases do not fit in the classic category of petit mal status and appear to be a distinct entity.


Neuropsychological performance in posttraumatic epilepsy.

Performances on the Wechsler-Bellevue Intelligence Scale and on Halstead's neuropsychological measures were investigated in two groups of adult subjects with posttraumatic seizures. One of the groups, in addition to seizures, had abnormal and persistent focal cortical signs. The other group had seizures only and no other known deficits or complications. The results suggest that posttraumatic epilepsy, whether or not accompanied by abnormal and persistent focal cortical signs, is associated with significant psychological impairment. Patients with posttraumatic epilepsy alone perform somewhat better than those whose epilepsy is accompanied by independent evidence of cortical damage. However, the performance difference between such patients is not major, nor is it statistically significant on most measures such as those used in the present study. Possible reasons for the performance deficit in this group were discussed.


Regulation of hepatic drug metabolism by elaidic and linoleic acids in rats.

Elaidic and linoleic acids were administered at doses of 40 and 200 mg/kg i.p. every second day for 4 weeks to rats fed a fat-free diet. The fatty acids had only a slight effect on the weight gain of the animals. The amount of microsomal protein was slightly decreased with the higher dose of linoleic acid. The higher dose level of both fatty acids decreased the microsomal phospholipid content. The relative amounts of microsomal phospholipid fatty acids were also altered due to fatty acid administration. The activity of microsomal NADPH cytochrome c reductase and microsomal cytochrome P-450 contents were decreased by the higher dose of linoleic acid. The hepatic aryl hydrocarbon hydroxylase and p-nitroanisole O-demethylase activities decreased in fatty acid-treated rats. The UDP-glucuronosyltransferase activity was also lowered after the fatty acid administration. The results suggest that fatty acid-induced changes in the activities of drug-metabolizing enzymes may be due to the microenvironmental changes of membrane-bound enzymes.


Properties of the high-molecular-weight deoxyribonuclease of Bacillus subtilis degrading single-stranded DNA.

We have studied the properties of the high-Mr DNAse degrading single-stranded DNA which is present in extracts of Bacillus subtilis. This enzyme is a heterogeneous aggregate of identical subunits with an Mr of 36 000, as measured in dodecylsulfate/polyacrylamide electrophoresis. The aggregate can be disassembled by the presence of Triton X-100, but reforms spontaneously following removal of the detergent. A mild proteolytic treatment of the aggregate causes the irreversible and nearly quantitative conversion into the free subunit. The modified subunit has identical properties (in terms of size, chromatographic adsorption and catalytic activity) as the small DNAse previously described by Ciarrocchi et al. [Eur. J. Biochem. 61, 487 (1976)], i.e. an endonuclease highly specific for single-stranded DNA and producing 5'-P and 3'-OH ends.


Isolation and characterization of free cytoplasmic messenger ribonucleoproteins from rabbit reticulocyte.

Free cytoplasmic messenger ribonucleoproteins have been prepared with a high yield in a zonal rotor. They are rapidly labelled by [3H]uridine. Their sedimentation coefficients are 14.6 S and 19.4 S. Their protein contents are higher than in ribosomes, as indicated by a shift towards greater wavelength in their ultraviolet spectra and a buoyant density of 1.39 g cm-2 in CsCl. They do not cross-react with antiribosome antibodies and their protein patterns in sodium dodecylsulfate and two-dimensional polyacrylamide gel electrophoresis are different from ribosomes'. They may contain up to 30 proteins. The proteins are acidic and their molecular weights range from 22 000 to 100 000. When compared to chromatin they behave more like non-histone proteins than histones.


The binding site of ribosomal protein L1 from Escherichia coli on the 23-S ribosomal RNA from Bacillus stearothermophilus. A possible base-pairing scheme differing from that proposed for Escherichia coli.

The region of Bacillus stearothermophilus strain NCA 1503 23-S ribosomal RNA protected from T1 ribonuclease digestion by the 50-S ribosomal subunit protein L1 from Escherichia coli has been established. The sequence of 115 nucleotides is compared to the analogous region in E. coli. The similar behaviour of the RNA towards the recognition of protein L1 may be explained in terms of secondary base-pairing, even though there exists almost 40% difference between the primary nucleotide sequences.


Role of IgD in the immune response and tolerance. II. Precursor analysis of murine B cells separated on the basis of surface IgD or treated with an anti-delta serum.

Precursor analysis of the function of murine B cells with surface IgD has been accomplished using an alloantiserum directed against a delta allotype and cellular affinity chromatography. Spleen cells from 3-week-old C57BL.Ige mice were treated with a TNP-labeled anti-delta allotype serum, washed and passed through an anti-TNP affinity column. The cells passing such a column were depleted of IgD-bearing lymphocytes by immunofluorescence and also showed a greatly reduced ability to develop into specific antibody-forming cell clones vs. the fluorescein (FL) hapten in a limiting dilution microculture system in vitro. In contrast, the IgD-bearing cells eluted from such columns were slightly enriched in precursor activity compared to the original population. Moreover, brief treatment with anti-delta serum alone produced a partial reduction in the precursor frequency vs. FL with C57BL.Ige spleen cells (which bear the appropriate delta allotype) but not C57BL/6 spleen cells (which are negative for this delta allotype). This effect varied with the age of the spleen donor, but was most dramatic with splenocytes from 2 to 3-week-old mice. This contrasts with the effect of anti-mu pretreatment, which only inhibited neonatal precursors. The results are interpreted in terms of the maturation of murine B cells and the function of IgD and IgM receptors in triggering an immune response.


Effects of methysergide, pizotifen and ergotamine in the monkey cranial circulation.

Internal and external carotid vascular resistances were measured, in anaesthetized monkeys, to asses the direct cranial vascular effects of i.v. methysergide, pizotifen and ergotamine, and their effects on the cranial vascular responses to the constrictors 5-hydroxytryptamine and noradrenaline and the dilators histamine, prostaglandin E1 and bradykinin. Methysergide reduced responses to 5-HT, and tended to potentiate the external carotid responses to noradrenaline. Pizotifen blocked responses to histamine; it tended to reduce internal carotid responses to 5-HT, but it potentiated external carotid 5-HT responses. Ergotamine reduced responses to 5-HT and noradrenaline, but this was probably related to its cranial vasoconstrictor effects, especially in the external carotid circulation. Methysergide induced weak transient cranial vasoconstriction and pizotifen had no direct effects. These findings may be relevant to the therapeutic actions of these drugs in migraine, since the doses used approximated to those used clinically.


Studies on the neuropharmacology of thyrotropin releasing hormone (TRH) and a new TRH analog.

TRH and a new TRH analog (all L-pyro-2-aminoadipyl-histidyl-thiazolidine-4-carboxamide, MK-771) have been compared with several other peptides for their "analeptic" activity and their ability to enhance the excitatory actions of microiontophoretically applied acetylcholine (ACh) on cerebral cortical neurons of rats. TRH and MK-771 offset the narcosis induced by pentobarbital in mice, whereas the C-terminal free acid derived from TRH, melanostatin, somatostatin and pyroglutamyl-histidineamide have been found inactive. Similarly, of these peptides only TRH and MK-771 induced a tremor of the forepaws in pentobarbital-anesthetized mice. Employing comparable ejection currents and durations, only TRH and MK-771, applied by microiontophoresis, enhanced the excitatory actions of ACh on spontaneously active cortical neurons in anesthetized rats. Based on these findings and other recent data, it is suggested that the interactions of TRH and MK-771 with cholinergic mechanisms may underlie some of the actions, including their anti-anesthetic effects, of these peptides.


Distribution of calcitonin cells in the thyroid glands of normal adult rhesus monkey Macaca mulatta.

The calcitonin cells of adult rhesus monkey Macaca mulatta are located in the central region of thyroid along the median axis. The anterior and posterior poles, the isthmus and peripheral regions of thyroid are completely devoid of C cells. The parathyroid also lacks C cells.


Innervation of the renal cortex.

Morphologic studies of renal innervation have utilized the methods of histochemistry and electron microscopy. Much information has been derived from examination of the renal cortex in monkey and rat. Fluorescence histochemistry shows a rich adrenergic innervation. Acetylcholinesterase can be demonstrated histochemically in the renal nerves by light and electron microscopy. Studies in the rat using 6-hydroxydopamine, a drug that selectively destroys adrenergic nerves, indicate that the glomerular arterioles and surrounding tubules are innervated by adrenergic nerves containing acetylcholinesterase. Distinct neurovascular and neurotubular junctions are observed the electron microscope. They are anatomically consistent with being the sites of synaptic transmission. Ultrastructural analysis of serial sections reveals that single individual axons contact multiple vascular cells and renal tubules. We now have a considerable body of information concerning the morphology of renal innervation are are beginning to appreciate the role of the renal nerves in kidney function.


The activity of purine salvage pathway enzymes in murine and horse models of congenital and acquired dysimmunity.

Previous studies of human congenital immunodeficiency states and in vitro observations of lymphocyte response to mitogens have implicated two purine salvage pathway enzymes, andenosine deaminase (ADA) and nucleoside phosphorylase (NP), as critical in the normal maturation and/or function of the immune system. Based on this information, ADA and NP activities were examined in a variety of congenital and acquired animal models of dysimmunity. The animals studied herein included: congenitally athymic (nude) mice; congenitally asplenic mice; congenitally athymic-asplenic mice; motheaten mice; New Zealand mice; and Arabian foals with severe combined immunodeficiency. No significant differences in the activities of ADA and NP were observed in any of these animals when compared with either normal littermates or animals with intact  immune function. Major species differences were apparent when erythrocyte ADA acitivty was compared between mice and horses. In contrast, only minor strain alterations in ADA or NP activity were noted between several inbred groups of mice.


Small dose anti-Rh therapy after first trimester abortion.

The standard prophylactic dose of anti-Rh immunoglobulin used in the United States is 300 microgram. For use after spontaneous or induced abortion and diagnostic amniocentesis, this dose represents immunological "overkill". A 50 microgram dose has been effectively used for these patients in other countries but the specific products used were not equivalent to the products available in the USA. No evaluation of this 50 microgram dose has been conducted in the USA. This is a pilot study of 315 patients given a 50 microgram dose or a 300 microgram dose of anti-Rh immunoglobulin after first trimester abortion. No patient in either treatment group developed atypical blood group antibodies within 6 months. This finding confirms that 50 microgram of the American product is protective after first trimester abortion.


Pituitary-adrenal response to separation in mother and infant squirrel monkeys.

Pituitary-adrenal response in mother and infant squirrel monkeys following brief separation was assessed. Each mother and infant pair was tested under each of 3 conditions: (1) Basal; (2) Separation-Reunion; and (3) Separation. Samples were obtained from mothers and infants in the Separation and Separation-Reunion conditions 30 min following the initial disturbance. A similar paradigm was used to assess the effects of separation in surrogate-reared animals. The results indicate that mothers, infants, and surrogate-reared infants respond to 30-min separation with a substantial increase in plasma cortisol. The values obtained in the Separation-Reunion condition did not differ significantly from Basal values in any of the 3 groups, suggesting that the effect of separation on the pituitary-adrenal system is not due to the disturbance involved in the separation procedure. The response of surrogate-reared infants suggests that these infants develop similar attachments to the surrogate as normal infants to their own mothers.


Insular amyloidosis and diabetes mellitus in Macaca nigra.

Amyloid in the islets of Langerhans increases with increasing severity of diabetes mellitus in Macaca nigra. The amount of insular amyloid was quantified, and diabetic monkeys averaged eight times more islet amyloid than did normal monkeys. The quantity of insular amyloid correlated significantly with glucose clearance in intravenous glucose tolerance tests and with serum glucose, triglycerides, immunoreactive insulin, and prebetallipoprotein measured after an overnight fast. As with human beings, insular amyloid appeared to be more prevalent in aging monkeys. The results support the hypothesis that the interrelated islet pathologic and metabolic events, which result in the appearance of insular amyloid concomitant with islet cell necrosis, may contribute more to maturity-onset diabetes in aging individuals than has been heretofore realized.


Suppression of autochthonous tumors by mixed implantation with Nocardia rubra cell-wall skeleton and related bacterial fractions.

Antitumor activities of the cell-wall skeleton of Nocardia rubra and related bacterial fractions in autochthonous tumor-host system were tested on autografts of spontaneous mammary adenocarcinoma in SHN mice and of 3-methylcholanthrene-induced fibrosarcoma in ICR/JCL mice. The oil-attached cell-wall skeleton of N. rubra was the most effective in suppressing the autografts of the mammary adenocarcinoma but less of the fibrosarcoma, when the autografts were mixed with oil-attached preparation and implanted subcutaneously in the original host, while peptidoglycolipid of Mycobacterium tuberculosis Aoyama B was the most suppressive on the autografts of the fibrosarcoma but not on the mammary tumor autografts. The cell-wall skeleton of Mycobacterium bovis BCG slightly suppressed the autografts of the fibrosarcoma. Presensitization of tumor-bearing mice with the cell-wall skeleton of N. rubra resulted in a more marked suppression on autografts of both tumors than without the presensitization, but local destruction of these tumor autografts did not induce recognizable systemic immunity to the respective tumors. Intralesional injection of cell-wall skeleton of N. rubra showed prolongation of survival days of mice with fibrosarcoma.


Base and base sequence specificity of the binding of 4-hydroxyaminoquinoline 1-oxide to DNA.

Synthetic and natural DNAs we;e reacted with 4-hydroxyaminoquinoline 1-oxide (4-HAQO) in an in vitro enzyme system. The amount of 4-HAQO bound to DNA varied significantly depending on the DNA used. The base sequence as well as the base composition affected the binding. Optical melting profiles of 4-HAQO-modified DNAs were examined. Decrease in the melting temperature and broadening of the transition width were commonly observed. Melting fine structure of lambda-phage DNA became less clear according to the modification. The shape of the melting curves of synthetic polynucleotides was little affected by binding, which suggests that the binding sites are distributed randomly along a DNA molecule. Binding of 4-HAQO to a purine base may distort the secondary structure of neighboring base pairs in a DNA molecule. Degree of the distortion can be estimated as a free energy increment associated with the binding. It was found that the free energy increment differs considerably among the polynucleotides with different base sequences.


Effect of a lactobacilli preparation on traveler's diarrhea. A randomized, double blind clinical trial.

The effectiveness of prophylactic ingestion of a commercial preparation of lactobacilli (Lactinex) for the prevention or modification of traveler's diarrhea was tested in a randomized double blind clinical trial in 50 volunteer travelers to Mexico from the United States. Twenty-six subjects received the lactobacilli preparation and 24 received placebo. The incidence of diarrhea and its duration during the 4 weeks of observation were quite similar for the two preparations: 35% for lactobacilli-treated subjects and 29% for placebo subjects. Typically, the diarrhea was mild, lasting 2 days. From the observations during this study we conclude that prophylactic ingestion of lactobacilli for 1 week does not reduce the incidence or duration of traveler's diarrhea either during the period of ingestion or during the following 3 weeks.


Primate mesenteric blood flow. Effects of vasopressin and its route of delivery.

The effects of vasopressin on blood flow in the superior mesenteric artery and on mean arterial pressure and portal venous pressure were measured in 7 rhesus monkeys. Vasopressin was injected, as either a bolus, or infused both intravenously and intraarterially to assess the influence of the route of administration upon hemodynamic responses. Dose-dependent decreases in superior mesenteric arterial flow were observed during both intraarterial and intravenous injections of vasopressin. No statistically significant differences between the two routes of administration, the decrease in flow, and changes in pressure were observed. Based upon these observations, one might anticipate that intravenously administered vasopressin will be as effective as intraarterially administered vasopressin in reducing mesenteric blood flow, and thus portal venous pressure, in man.


[A contribution to the problem of heterologous insemination (author's transl)].

The problem of a heterologous insemination must occasionally be dealt with. The conditions for such treatment are not good in the Federal Republic of Germany. This, however, should not negatively influence the quality of the therapy. At least the serologic characteristics of the donor should be known. The impetus for this article was provided by the unsuccessful course of a pregnancy after heterologous insemination in a patient with an established, severe Rhesus incompatibility.


Cytogenetic localization of the acid phosphatase-1 gene in Drosophila melanogaster.

A translocation in which a segment of chromosome 3 is inserted into the Y chromosome was found to contain the acid phosphatase-1 gene (Acph-1). In flies hyperploid for that gene, acid phosphatase-1 levels are proportional to the dose of the gene. The locus is placed within the salivary chromosome subdivisions 99D and 99E on the basis of its inclusion in the translocated segment and on the previous placement of the claret locus. Several chromosomal rearrangements involving heterochromatic breakpoints and euchromatic breakpoints adjacent to 99D-99E were tested for possible postiion-effect variegation of acid phosphatase-1. No decrease in the synthesis of the electorphoretic subunit encoded by the relocated gene was observed within any of the rearrangements.


Electronmicroscopic histochemical investigation of the surface of the cell membrane of the renal tubules with the use of ruthenium red and lantanum nitrate.

The renal tubules were investigated with the use of ruthenium red and lanthanum nitrate to titrate the carbohydrate groups which are localized on the differentiated surface of the cell membranes and intercellular spaces. Ruthenium red visualized the surface coat which is tightly bound to the outer lamellae of the cell membrane. Lanthanum nitrate used in this investigations is a valuable marker of the intercellular spaces. The applied markers have visualized in the kidney the canals which are originated from the foldings of membranes of the tubular cells which adhere to the basal membrane. The markers used in combination with the fixative glutaraldehyde-paraformaldehyde give an electrondense envelope of the cell membrane which is more distinct as compared with specimen treated with glutaraldehyde and markers only.


Contribution to the problem of cyst-producing coccidians.

The problem of life cycles of cyst-producing coccidians, mainly those of the genus Sarcocystis, from carnivorous birds has been discussed. Oocysts of the "sarcocystic" type have been recovered from 9 species of birds of prey and owls from Czechoslovakia. The course of experimental infection in a group of birds consisting of the species Tyto alba, Asio otus, Strix aluco, Buteo buteo has been described. We inoculated these birds with cystic stages of the genus Sarcocystis obtained from white laboratory mice (Mus musculus) infected previously with oocysts from Tyto alba. The nomenclature of heteroxenous coccidians of the genus Sarcocystis has been discussed and suggestions have been made for the use of simple, one-word specific names. A description is given of a new species of the genus Sarcocystis--Sarcocystis dispersa sp. n. Its asexual development and cyst production in Mus musculus (intermediate host), and cyst production in Tyto alba and Asio otus (definitive hosts) have been studied.


[Studies on the antigenicity of swine arterio graft (author's transl)].

To obtain better arterio grafts, we prepared three samples from adventitia of swine carotid arteries, and their antigenicity was studied with immunological procedures. Sample I was prepared from swine carotid arteries, by eliminating the extraneous fat and connective tissues. Sample II was prepared from Sample I by treatment with chymotrypsin, and Sample III was prepared from Sample II by treatment with 3% glutaraldehyde for 14 days. From the three samples, the water soluble protein fractions were extracted, and abbreviated as E-I, E-II and E-III, respectively. Immunopharmacological tests in guinea pigs and rabbits including active and passive anaphylaxis, passive cutaneous anaphylaxis, Schultz-Dale test and Arthus's phenomenon among these extracts revealed cross reactions between E-I and E-II. Also, precipitin test and Ouchterlony's method, precipitation was observed between E-I and E-II, and it was suggested that there might be at least a common antigen between E-I and E-II. The rabbits which had been implanted subcutaneously at the back with the minced Sample I evoked severe reactions and died after intravenous injection of E-I at the 3rd or 5th month after implantation. No reaction was observed between Sample III and E-III in the same experiment. From the above results, it was suggested that the antigenicity of swine carotid arteries could be eliminated by the treatment with chymotrypsin and glutaraldehyde.


Facial expressions in captive squirrel monkeys (Saimiri sciureus).

The facial expressions of captive, group-living squirrel monkeys are described. Elements of facial expressions, the occurrence of these expressions and accompanying vocalizations are detailed. The range of facial expressions recorded for this species is similar to that previously reported for other simian primates.


Annual reproductive strategy of the squirrel monkey (Saimiri sciureus).

The physiological and behavioral factors underlying the annual reproductive cycle of the squirrel monkey were evaluated under controlled laboratory conditions. Mating activity following the formation of two social groups served to synchronize the reproductive phases during the subsequent year of observation. Changes in male and female reproductive status were assessed during four designated phases: breeding, pregnancy, lactation and fatting. Behavioral and somatic changes in gonadectomized subjects, living in the social groups, were also evaluated. The variations in behavior and physiology across the year were considered in terms of factors constraining the timing of the natural reproductive pattern.


Home range, activity pattern, and agonistic encounters of a group of night monkeys (Aotus trivirgatus) in Peru.

Findings are presented from a 9-week field study on Aotus trivirgatus in continuous primary, tropical forest in Peru. One group of 2 adults and 2 juveniles utilized the same lodge area in the center of a home range of 3.1 ha for the duration of the study. The group utilized eleven fruit trees of nine different species during the 9 weeks. The home range overlapped extensively with that of other Aotus groups.


The taste responses in primates to the proteins thaumatin and monellin and their phylogenetic implications.

Electrophysiological and behavioural methods have been applied to 34 species of the primates and, for comparison, to the Madagascan hedgehog to determine their responses to the proteins thaumatin and monellin. These substances elicit an intensely sweet taste sensation in man. All Catarrhina prefer monellin to water. The responses of the Prosimii as well as those of the South American primates to monellin are different, some species show a reaction, other species are not sensitive. In the case of thaumatin neither the Prosimii--including Tupaia and Tarsius--nor the South American primates show any response to this protein. Only the Cercopithecidae, the Hylobatidae and the Pongidae respond to this protein like man and prefer this substance to water. This physiological aspect of taste constitutes a clear dichotomy within the order Primates. This capability to taste thaumatin probably developed as long as 38 million years ago.


Composition of the milk of the common marmoset (Callithrix jacchus) and milk substitutes used in hand-rearing programmes, with special reference to fatty acids.

Analyses of marmoset (Callithrix jacchus) milk were carried out to determine values for crude protein, lactose, total lipids, major minerals, and osmotic pressure. Mean values were (g/100 ml): protein, 3.6; lactose, 7.5; total lipids, 7.7; minerals (mg/100 ml): sodium, 21.4; potassium, 54.3; calcium, 92.2; phosphorus, 22.8; magnesium, 5.0; chloride, 52.2; osmotic pressure, 354 mosm/kg water. Similar analyses were conducted on 2 milk substitutes used in hand-rearing programmes. Fatty acid analyses were carried out on natural milk, the milk substitutes, and the marmoset diet. For hand-rearing C. jacchus it is recommended that a human milk substitute is modified by increasing the levels of protein, carbohydrate, and total lipids, and that a small amount of fish oil is added.


[Indications for central veinous catheterism in psychiatric patients (author's transl)].

Based on cases of a Psychiatric Intensive Care Unit specific indications and applications of catheterism of central-veins in these special instances are presented, the psychiatric indications and contraindications for such measures are submitted in addition to those known from other medical fields. The mode of insertion, duration, infusionregimen and rates of complications are reviewed in 102 cases. Two of the common veinous-catheter systems are compared as for practicability.


[Clinical, preclinical and prenatal diagnosis of congenital sphingolipidoses by determining lysosomal hydrolases (author's transl)].

Sphingolipidoses in infancy and adulthood and associated metabolic disturbances are caused by a recessively inherited, circumscribed lysosomal enzyme deficiency in the catabolism of various structural tissue substances. After presenting detailed methods for the quantitative assay of activities of lysosomal hydrolytic enzymes in leukocytes, serum , fibroblasts, urine and organ tissue with the aid of synthetic chromogenic and fluorescent substrates the signigicance of these methods for clinical diagnosis, for the detection of homozygote persons before developing clinical symptoms (preclinical diagnosis), for the preventive prenatal diagnosis and forthe detection of heterozygote carriers is described for the following diseases: Deficiency of hexosaminidase A and B, deficiency of beta-glucosidase, deficiency or arylsulfatase A, deficiency of alpha-galactosidase, deficiency of alpha-glucosidase.


On the linkages between chromophore and protein in biliproteins, VII. Amino acid sequence in the chromophore regions of C-phycoerythrin from Pseudanabaena W 1173 and Phormidium persicinum.

Bilipeptides from all chromophore regions were prepared by trypsin digestion of C-phycoerythrin from Pseudanabaena W 1173 and Phormidium persicinum. Analytical separation and quantitative determination of bilipeptides was achieved by isoelectric focusing, preparative isolation by gel chromatography and ion-exchange chromatography. Amino acid analysis revealed cysteine as the only amino acid common to all chromopeptides. Amino acid sequences were determined by Edman degradation and the dansyl-Edman technique. Sequences are different in all 5 and 6 chromophore regions, respectively. Possible homologies are discussed. A thioether linkage between ring A of the chromophore and cysteine was found in the bilipeptides (as before in biliproteins). A second linkage (serine ester) was found in only one peptide (CM 4.I from Pseudanabaena W 1173). This peptide absorbs as cation at a longer wavelength (559 nm) than the other bilipeptides (542 - 550 nm).


Free light chain synthesis by neoplastic cells in chronic lymphocytic leukaemia and non-Hodgkin's lymphoma.

Cell populations from twenty-two cases of B-cell neoplasia reflecting various stages of B-lymphocyte maturation were investigated for their ability to synthesise immunoglobulin (Ig) in vitro. All surface Ig positive neoplasms studied synthesised labelled Ig of the same light chain class as that expressed at the cell surface. Immature B-cell neoplasms, chronic lymphocytic leukaemia (CLL) and CLL-type lymphoma, synthesised only a minor proportion of their total protein as Ig; labelled free light chain was the only detectable secreted Ig product in thirteen cases and was in excess in the remaining four. Labelled heavy chain was detected in cell lysates in all but one case. Follicular centre cell lymphomas, neoplasms of more mature B-lymphocyte types, synthesised more of their total protein as Ig and showed a more balanced synthesis of heavy and light chains compared to the other neoplasms studies. The Ig synthesis patterns and, in particular, free light chain production, are discussed in relation to normal B-lymphocyte maturation.


Inhibition of C5 convertase by epsilon amino caproic acid (EACA): a limiting factor in the generation of C5a anaphylatoxin.

The effect of EACA on spontaneous C5 consumption and on the mechanisms of C5 activation through the alternative pathway of complement were analyzed. In contrast to the effect upon C3, ADDITION OF 1 M EACA to normal human serum (NHS) did not enhance spontaneous consumption of C5, but augmented its haemolytic efficiency. In the presence of 1 M EACA, activation of serum with zymosan (Z), resulted in inhibition of the formation of C5 convertase, and thus of C5 cleavage and C5a anaphylatoxin release. The generation of a C5 convertase on activated zymosan (Z) was inhibited when Z was formed at 17 degrees with NHS containing 1 M EACA. In contrast, if Z was formed in the absence of EACA the C5 convertase could be regenerated with fresh serum containing 1M EACA. Nearly maximal C5 consumption was obtained if 5 mM EGTA and 10 mM MgCl2 were added to the mixture. These conditions are considered optimal for generation and maximum recovery of fully active anaphylatoxin.


Characterization and localization of secretory component in the chicken.

A component found free in intestinal contents and caecal contents of conventional and germ-free chickens (lacking IgA producing cells) was found to have similar characteristics to mammalian secretory component (SC). Free secretory component (FSC) showed a classic reaction of partial identity with secretory IgA (SIgA) from bile, intestinal contents and cystic oviduct fluid. Furthermore, there was demonstrable cross-reactivity between FSC and a low molecular weight component released from SIgA by mild reductive dissociation, confirming the presence of a disulphide-linked accessory polypeptide chain. Fractionation of serum IgA revealed two molecular classes of IgA, a high molecular weight 15S IgA which possessed SC and could not be differentiated antigenically from SIgA and a low molecular weight 7S IgA which showed a reaction of partial identity with 15S IgA and non-identity with FSC. Fluorescent localization of SC in young germ-free chicks demonstrated its presence in the supranuclear golgi zone, apical cytoplasm and basement membrane of crypt epithelial cells. It is concluded that the characteristics of chicken SIgA are closely aligned with those of its mammalian counterpart and are consistent with a system in which SIgA is the wynthetic product of two distinct cells, final assembly occurring in the crypt epithelium.


Antigen dose and strain variation as factors in the genetic control of the immune response to sperm whale myoglobin.

The primary and secondary immune response to the antigen sperm whale myoglobin was investigated in DBA/2, 129 and B10.BR mice over a dose range of immunization from 10 to 2000 microgram. Using an antigen excess technique, the quantity of antibody produced after secondary immunization followed a sigmoidal dose-response curve and the maximal plateau level was found to be different for each strain of mice. Furthermore, the genetic control of the immune response was investigated in twelve different inbred strains of mice following secondary immunization with 500 microgram of myoglobin. A continuous distribution for the mean antibody responses was obtained for the twelve different strains of mice. High responsiveness was associated with H-2 haplotypes d, f and k located on chromosome 17, the non-agouti gene 'a' located on chromosome 2 and the chinchilla gene 'c(ch)' located on chromosome 7. It is concluded that either a large number of IR-genes to myoglobin are present in many loci located on different chromosomes or the antibody differences could be explained by a cross-tolerance mechanism requiring no IR-genes at all.


Vole agent identified as a strain of the trench fever rickettsia, Rochalimaea quintana.

The vole agent described by Baker in 1946 was studied as an example of a bacterium that has been mistakenly regarded a rickettsia. Unlike rickettsiae, the vole agent killed chicken embryos with great irregularity, multipled primarily at the surface of avian or mammalian cells and not intracellularly, produced colonies rather than plaques on chicken embryo monolayers under agar, and developed small colonies after 4 to 7 days of cultivation on blood plates. It was most conveniently cultivated on monolayers of irradiated L cells and was purified by minor modifications of the Renografin gradient procedure used for rickettsiae. It actively catabolized glutamate, glutamine, succinate, and pyruvate, but not glucose or glucose-6-phosphate. Enzymatic activities of cell extracts were consistent with above findings. The base ratio (molar percent guanine plus cytosine) of its deoxyribonucleic acid was shown to be 39, which was identical to the base ratio of the deoxyribonucleic acid of Rochalimaea quintana tested simultaneously. Serological studies indicated no cross-reactivity with Rickettsia tsutsugamushi, but strong cross-reaction with R. quintana was observed when a hyperimmune rabbit serum and a convalescent human serum were tested. We conclude that the vole agent is a strain of the trench fever rickettsia, R. quintana.


Experimental infection of mouse peritoneal mesothelium with scrub typhus rickettsiae: an ultrastructural study.

The infection cycle of Rickettsia tsutsugamushi in mouse peritoneal mesothelial cells, observed late in the course of an established infection, intimately involved the host cell plasma membrane. Organisms multiplied in the cytoplasm, moved to the cell periphery, and acquired a host-membrane coat as they budded from the cell surface. Rickettsiae enveloped by this membrane entered other mesothelial cells, apparently by a phagocytic mechanism. Organisms escaped from the phagocytic vacuole as the vacuole membrane and host membrane coat disintegrated. Free rickettsiae replicated by binary fission in the cell cytoplasm. Rickettsial infection of mesothelial cells induced conspicuous cellular hypertrophy with increased numbers of unaltered cytoplasmic organelles.


Toxicity of Pseudomonas aeruginosa exotoxin A for human macrophages.

Pseudomonas aeruginosa exotoxin A was toxi in vitro for human peripheral blood macrophages. Cytotoxicity, manifested by morphological evidence of cell death and inhibition of [3H]thymidine uptake, followed exposure to as little as 10 ng of exotoxin per ml for 1 h. In addition, phagocytosis of heat-killed Candida albicans by macrophages exposed to sublethal concentrations of exotoxin was impaired. This cytotoxicity was neutralizable with antiexotoxin serum.


Resistance and susceptibility of mice to bacterial infection: course of listeriosis in resistant or susceptible mice.

Resistance and susceptibility to Listeria monocytogenes in mice was found to be related to (i) the innate ability of the nonimmune macrophages to kill or inhibit the growth of the organism during the first 24 to 48 h after infection, and (ii) the time of onset of acquired cell-mediated resistance. Resistant C57Bl/6 mice were 10 times more efficient than susceptible BALB/c mice at suppressing the early growth of Listeria in the liver. Furthermore, the onset of acquired immunity occurred 24 to 48 h earlier in C57Bl/6 than in BALB/c mice. Acquired immunity was measured by (i) fall in bacterial numbers in spleen and livers of infected mice (ii) adoptive transfer of immunity to normal mice by using spleen cells from infected mice, (iii) delayed-type hypersensitivity skin testing, and (iv) uptake of tritiated thymidine by lymphocytes in the spleen.


Effect of iron on yields of exotoxin A in cultures of Pseudomonas aeruginosa PA-103.

The yields of exotoxin A in Pseudomonas aeruginosa cultures were influenced by the concentration of iron in the culture media. When the iron concentration of the culture media was increased from 0.05 to 1.5 microgram/ml, there was at least a 90% decrease in exotoxin A (measured both by enzymatic activity and by mouse lethality) and a slight increase in the growth of the bacteria. The addition of iron as late as 13 h after initiation of growth repressed further measurable increases of exotoxin A within 3 h. Intracellular toxin levels were also reduced by increasing the iron concentrations of the culture media. The addition of 3.0 microgram of iron per ml did not significantly alter either the enzyme activity of preformed crude or purified exotoxin A or the mouse toxicity of the pure toxin. Thus it appears that either the rate of production or the rate of intracellular degradation of exotoxin A is regulated by the concentration of iron in the culture media.


Role of exotoxin and protease as possible virulence factors in experimental infections with Pseudomonas aeruginosa.

Evidence is presented which suggests that both the proteases and the exotoxin produced by Pseudomonas aeruginosa multiplying in situ in a burned mouse model are virulence factors. A 50% decrease in functional elongation factor 2 (EF-2) was seen 16 h postinfection in the liver of mice infected with the toxigenic, protease-producing P. aeruginosa strain M-2; at the time of death EF-2 was depleted by 80%. This correlates with a reduction in the level of protein synthesis in the liver of infected animals. Treatment with specific antitoxin extended the mean time to death and blocked depletion of EF-2. Administration of gentamicin 24 h after infection caused rapid clearance of bacteria and extended the mean time to death, but all animals treated with either antitoxin or gentamicin eventually died. In contrast, treatment with both antitoxin and gentamicin provided virtually complete protection. Infection of mice with P. aeruginosa WR5 (protease-producing, nontoxigenic) or with P. aeruginosa PA103 (toxigenic, slow protease producer) required several logs more bacteria and did not result in the same extensive depletion in EF-2 content. When challenge with PA103 was supplemented by injection of purified Pseudomonas protease, the mean time to death was shortened and significant reduction in liver EF-2 was observed. It is suggested that both toxin and proteases are required for the full expression of virulence in Pseudomonas infections.


Rat model of experimental endocarditis.

A simple model of infective endocarditis was produced in rats. With the aid of a guide wire, polyethylene catheters were passed into the left ventricle through the right carotid artery of Sprague-Dawley rats weighing 300 to 350 g. A volume of 1 ml of an overnight culture of Streptococcus mitis, Staphylococcus aureus, or Streptococcus faecalis was intravenously injected 1 to 2 days after catheterization. Bacterial titers of Streptococcus mitis in vegetations were about 10(4)-fold greater than in other tissues. Blood cultures were always positive after 6 h. Mortality was 19% at 1 week and 82% at 2 weeks. Catheters were pulled 24 h after infection, and vegetation titers of greater than 7.0 log10 colony-forming units per g were sustained at 5 days. In intravenously infected rats without catheters, blood and tissues were sterile after 3 to 5 days. With Staphylococcus aureus, vegetations had greater than 9.0 log10 colony-forming units and with Streptococcus faecalis 8.8 +/- 0.3 log10 colony-forming units per g at 2 days. The rat model of infective endocarditis should prove to be suitable for further pathological and therapeutic studies.


Antibody-dependent cytotoxicity against Trypanosoma rhodesiense mediated through an alternative complement pathway.

A quantitative in vitro method was used to examine the role of classical and alternative pathways of complement activation in cytotoxicity against African trypanosomes by immune serum. This assay is based on the estimation of the extent of antibody-mediated cytotoxicity by measurement of inhibition of incorporation of [(3)H]leucine as an indicator of trypanosome metabolic integrity. To determine which pathway(s) is activated during cytotoxic events, complements sufficient in all components (C4S) and deficient in C4 (C4D) were used. Immune inhibition of [(3)H]leucine uptake by trypanosomes was observed in the presence of both complement sources. Treatment of C4S or C4D serum with cobra venom factor or disodium ethylenediaminetetraacetic acid abolished antibody-mediated cytotoxicity as well as immune hemolysis, thus suggesting the requirement for late-acting complement components. Ethyleneglycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid had no effect on inhibition of leucine incorporation, whereas immune hemolysis was inhibited, suggesting that cytotoxicity did not require C1 activation, a Ca(2+)-dependent event. The dependence of the cytotoxic process on Mg(2+) and not Ca(2+) ions and the fact that C4D guinea pig serum is fully active in trypanosome cytotoxicity indicate that an alternative pathway of complement activation is sufficient for activity.


Suppression of delayed hypersensitivity to the hapten by induction of tolerance to the carrier.

Delayed hypersensitivity reactions (DHR) and anaphylactic reactions to carrier and hapten determinants were studied in guinea pigs immunized with DNP-mycobacterium and rendered partially tolerant to the carrier by a single intravenous injection of mycobacterium prior to immunization. The results clearly show that the induction of depressed DHR to mycobacterium leads to a suppression of DHR to the hapten while no depression of anaphylaxis to the hapten is observed. It is proposed that the tolerogenic treatment acts at the macrophage level rather than at the T cell level.


The urban fiscal crisis in the United States, national health insurance, and municipal hospitals.

The fiscal stress which many U.S. cities are currently experiencing, the persistent problems of large-city local government hospitals, the recent decisions for selected public hospital closings in New York City and Philadelphia, and the prospective enactment of a program of national health insurance collectively raise questions about the viability of the nation's major municipal hospitals. While the majority of the nation's 40 largest cities are in a state of economic and demographic decline, the diversity which characterizes their fiscal conditions and their responses to fiscal stress suggests caution in generalizing from the highly publicized New York City experience in asserting the ability of cities to continue to maintain public hospital activities. Indeed, there is considerable evidence to indicate that the staying power of municipal hospitals is quite substantial even in circumstances of severe fiscal stress. Further, analysis of the effect of Medicaid implementation on municipal hospital utilization and of the impact of prospective national health insurance programs on the demand for and supply of medical services suggests that municipal hospitals will continue to be important providers of health care services for many years to come.