[On the mode of action of bradykinin on smooth muscle (author's transl)]. At extremely low concentrations, in the picomole and the nanomole range, bradykinin produces contraction and relaxation of smooth muscle in the gastrointestinal and the urogenital tract. At the target organ, bradykinin interacts with discriminator proteins of the plasma membranes and triggers, via changes in certain membrane functions, its biological response:--The binding to the discriminator makes specific conformative and constitutional demands on the nonapeptide. The binding results from an angular conformation which exists in the solution. The complete sequence is responsible for this specific conformation. Consequently, the biological activity of partial sequences is low. The conformational analysis of analogues used in studies on the mechanism of action showed but slight differences from bradykinin. The interaction of these analogues with the discriminator protein is disturbed to a varying extent by modifications at positions 1, 5, 8 and 9 in the side chains. The affinity for the discriminator is affected, dependently on the respective configuration, by substitution on the beta-C atom in the two phenylalanine residues.--Bradykinin is not only bound to, but also degraded at, the plasma membranes of the rat uterus and duodenum. The bradykinin-degrading enzyme has been characterized as a kininase II with the aid of various inhibitors. The conformative and configurative prerequisites decisive for enzymatic degradation are others than those decisive for binding to the discriminator.--The changes in the activities of the membrane-bound adenylate and guanylate cyclases (produced by the bradykinin-discriminator complex) that take place at the rat duodenum and uterus in the presence of extracellular calcium ions contrast with each other: At the duodenum, the ratio between these two cyclic nucleotides is changed in favour of adenylate cyclase; and at the uterus, in favour of guanylate cyclase; Substances which increase or decrease the cAMP level may also potentiate or inhibit the relaxation of the duodenum. These bradykinin-induced changes in enzyme activity must be considered in connection with other effectors, e.g. prostaglandins and calcium ions.--The calcium-ion-dependence of the effect of bradykinin on the guinea-pig ileum and the rat uterus indicates the importance of these ions as additional second messengers. Bradykinin stimulates the influx of calcium ions into the ileum; it is ineffective if no extracellular calcium ions into the ileum; it is ineffective if no extracellular calcium ions are available. It seems that intracellular and membranal calcium is mobilized in the uterus, which is evidenced by results from experiments with EGTA on the isolated organ and by the release of calcium from plasma membranes after application of bradykinin. It is assumed that the observed changes in membrane functions are induced by the peptide-discriminator complex simultaneously and not in the form of a causal chain.


Synthesis and antimicrobial action of some bis-thiazolidines. alpha, delta-Bis(thiazolidinidione-2,4-hydrazone-4-yl-3)butane (1) was reacted with heterocyclic and aromatic aldehydes in boiling glacial acetic acid, where the corresponding analogs of alpha, delta-bis (thiazolidindione-2,4-N-arylidenehydrazone-4-yl-3)butane (2) were separated. While with some other heterocyclic and aromatic aldehydes, and under the same conditions, the corresponding analogs of alpha, delta-bis(thiazolidinidione-2,4-N-arylidenehydrazone-4-arylidene-5-yl-3) butane (3) were obtained. The synthesized compounds exhibit antimicrobial activity.


[The use of spray drying in pharmacy (author's transl)]. Owing to the favourable physical conditions of the evaporation process, the technique of spray drying has been used for some time to obtain dried products from solutions, suspensions, emulsions and fluid extracts. In the pharmaceutical industry, it may be utilized as a -drying technique, -micronizing procedure, -procedure for the manufacture of polymorphic or amorphic forms of active substances, -technique for producing microcapsules and spray embeddings, -method for manufacturing direct-tablettable active substances. The technical development which ranges from spray dryers for laboratory experiments to industrial plants, and the continuous operation are favourable prerequisites for research and use on an ever greater scale.


Synthesis and antimicrobial testing of 2-substituted styryl-6-nitro-4-quinazolones. Condensation of 2-methyl-6-nitro-4-quinazolone with different aldehydes was achieved by fusing the reactants in the presence of zinc chloride, affording 2-substituted styryl-6-nitro-4-quinazolones. 2-(3-substituted aminomethyl)-4-hydroxystyryl-6-nitro-4-quinazolones were also prepared through the Mannich reaction. The antimicrobial testing of five of the compounds prepared showed that some of them produce promising effects.


[Animal experiments on the pharmacokinetics of ocrase (author's transl)]. The blood level, distribution and elimination of ocrase, a protease from Aspergillus ochraceus, were determined in rabbits after application of the 131I labelled enzyme in therapeutic doses.


Long-term effect of relaxation on blood pressure and anxiety levels of essential hypertensive males: a controlled study. The long-term effect of relaxation in lowering blood pressure and anxiety was evaluated in this study. Eighteen male Caucasian essential hypertensives with moderate elevations in blood pressure were studied. Relaxation significantly reduced both blood pressure and anxiety. Control procedures had no significant effect. The reductions lasted for 12 months after training. However, there was no statistical relationship between reduction in blood pressure and anxiety.


The stress response: a new perspective.

The stress response: a new perspective. A theory of the response to chronic intermittent stress, intergating many diverse studies, is presented. Chronic intermittent stress is presumed to be the type of stress most frequently encountered and most likely to cause physiological changes which predispose an organism to tissue damage. The theory states that all organisms are genetically predisposed to adapt to stress and that the physiological pattern of adaptation is similar across species. This pattern consists of a conditioned endocrine response before the stressor is presented accompanied by a decrease in arousal during the stress. These changes occur because the organism is predisposed to learn cues predictive of stress and to assess the threat potential of the stressor. This pattern is adaptive because it conserves resources and promotes homeostasis. Maladaptation is discussed in terms of failure to learn situational expectancies and appropriate responses. Implications of this theoretical perspective are examined.


Activation of human B lymphocytes (the in vitro polyclonal B cell activator-induced plaque-forming cell system). The characteristics of human B lymphocyte triggering, differentiation, and regulation are described using the polyclonally induced anti-sheep red blood cell hemolytic plaque-forming cell assay system. Technical and methodologic considerations, cellular requirements and mechanisms of regulation including suppressor and helper influences are discussed. Also considered are theoretical concepts regarding normal immune response versus pathologic immune states and the potential biologic role of polyclonal activation in these human immune mechanisms.


Left-to-right shunts. (Quantification, mathematical methods and their statistical comparison). This work describes a non-traumatic technique for quantitative determination of left-to-right shunts. Various mathematical methods to evaluate the radioisotope concentration lung curve are considered. Data were collected with a gamma camera system connected to a computer. The first results were obtained from 18 patients at the Ospedali Riuniti in Parma, Italy. All the mathematical processes are described. The three methods used were based on: 1. the count ratio (C2/C1) between two pulmonary activity concentrations, 2. the gamma function fitting, 3. decreasing exponential. A comparison of the three methods shows that the gamma function method is the most reliable. In this kind of investigation the patient's radiation dose is low enough for it to be repeated so that the course of the disease can be followed.


Von Willebrand's disease in pigs and atherosclerosis. There is experimental evidence that platelets, by interacting with the arterial wall may be important in the initiation of atherosclerosis. This paper describes the results of consecutive experiments indicating that pigs with impaired platelet-blood vessel interaction in the form of von Willebrand's disease are resistant to the development of atherosclerotic plaques. Ongoing experiments in these pigs are providing significant insight into the relationship of the circulating platelets, the endothelial cell and circulating von Willebrand factor, and the reactivity of the arterial wall in the process of atherosclerosis.


Clinical quality of amalgam restorations. The clinical quality of 203 mesio-occlusal Class II and 127 buccal Class V restorations of 246 persons aged 25 years were studied. One third of the amalgam restorations were considered to be unacceptable. Marginal overhang was the prevailing type of failure (17%), recurrent caries occurred at 12% of the restorations, unacceptable proximal contact at 10%, unacceptable marginal adaptation at 8% and isthmus fractures at 2%.


The role of renin in the control of the circulation and in hypertensive disease. Renin is a hormone secreted by the juxtaglomerular cells of the kidney; it interacts with a plasma protein substrate to produce a decapeptide prohormone angiotensin I. Converting hormone located on vascular endothelium converts the decapeptide to an octapeptide, angiotensin II, which effects vasoconstriction, the secretion of aldosterone by the adrenal cortex, and retention of sodium by the kidney. The biosynthesis and control of renin secretion are not well understood, and the question as to whether renin is synthesized and stored in a larger precursor form is as yet unresolved. Whether or not higher molecular weight or inactive forms of renin in plasma have a role in controlling renin activity or whether they simply represent a degradative pathway for renin is as yet uncertain. The availability of several inhibitors of the renin-angiotensin system has served to define the role of renin both in normal cardiovascular homeostasis and in renovascular hypertension. It appears that renin plays an important role in maintaining blood pressure in the salt- or volume-depleted state and that it is responsible for the initial phases of renovascular hypertension in any model of this disease process. Renin's part in chronic renovascular hypertension depends on whether or not sodium is permitted to accumulate. If sodium intake is restricted or if sodium excretion is unimpaired (such as in two-kidney renovascular hypertension models), renin continues to play a significant role during the chronic phase.


Effect of different types of anaesthesia including percutaneous local anaesthesia on survival of experimental skin flaps. Local anaesthesia by epicutaneous application of the ketocaine solution A2358 gave survival of experimental skin flaps in the guinea pig which corresponded on average to 71% of the total flap. The survival after pentobarbitone anaesthesia, general anaesthesia with ether, and infiltration of prilocaine without and with adrenalin varied between 41 and 53%. The difference in effect between percutaneous anaesthesia with A2358 and the other procedures was statistically significant (p less than 0.001). Epicutaneous application of A2358 followed by one of the other forms of anaesthesia gave a flap survival that did not differ from that following local anaesthesia with A2358 alone, except when followed by injection of prilocaine with adrenalin. The improved survival after epicutaneously applied A2358 is probably attributable to an effect on the peripheral vascular bed resulting in increasing blood supply and nutrition. It may be possible that A2358, for example, could be used in man as a complement to other forms of anaesthesia to provide enhanced tissue survival in skin flaps.


The effect of zinc tape upon wound healing. A biochemical, histochemical and histological study in rats. The healing of excisional wounds in rats, which were treated with zinc tape, gauze sponge or porcine skin, was studied. Wound closure was completed earlier in zinc-tape-treated wounds than in wounds treated with a gauze sponge or porcine skin. Wound contraction was more pronounced in gauze- and porcine skin-treated wounds than in zinc-tape-treated wounds. More foreign body giant cells were seen 14 days after operation in gauze-treated contra zinc tape-treated wounds, whereas hydroxyproline concentration was higher in tape-treated wounds. Histochemically the acid phosphatase activity was pronounced in macrophages, foreign body giant cells and fibroblasts. The alkaline phosphatase activity was pronounced in granulocytes and fibroblasts. Quantitatively a reduction in alkaline phosphatase activity was seen in gauze-treated wounds from 7 to 14 days. A decrease was seen in albumin concentration in gauze- as well as zinc-tape-treated animals which was most pronounced after 7 days in the gauze-treated animals.


Treatment of pilonidal sinus by radical excision and reconstruction by rotation flap surgery of Z-plasty technique. Defects after excision of large pilonidal sinuses were reconstructed by either rotation skin flaps or a Z-plasty technique. Altogether, 16 patients were operated on, 10 with a rotation flap and 6 with a Z-plasty technique. All the patients except one underwent a radical operation. The patient not having a radical operation had a recurrence. Two cases in the Z-plasty groups acquired an infection in the distal part of the wound necessitating reoperation on the resultant sinus. The disability after this more extensive surgery was not more pronounced than after ordinary surgical procedures. For large recurrent pilonidal sinuses, radical excision and primary suturing of the wound using a rotation flap is recommended as the method of choice.


Freeze-fracture studies of the plasmalemma of Candida albicans after treatment with econazole-nitrate. In electron microscopic studies the interior of the plasmalemma of Candida albicans was revealed by means of the freeze-fracture technique. The superficial structures of the extracellular (E) and protoplasmic (P) fracture faces differed negligibly from structures on the corresponding fracture faces of Saccharomyces cerevisiae. Following treatment with 2.2 x 10(-5) M econazole nitrate a layer, present on the P face in the form of a tight matrix of globular proteins, dissolved into isolated groups of particles whose globular elements sometimes formed hexagonal patterns. As the damage progressed, fissure-shaped membrane invaginations on the P face disappeared. Parts of the outer lipid layer of the plasmalemma were torn off the cell wall and adhered in fragments to the P face. The ultrastructural changes in the plasmalemma induced by econazole nitrate temporally correlate with an increase in the permeability of the cell envelope found in physiological studies performed by other authors.


Survey of Cryptococcus neoformans in the respiratory tract of patients with bronchopulmonary disorders and in the air. Cryptococcus neoformans was cultured from 9 (1%) of 835 clinical specimens examined from the respiratory tract of patients. These isolations came from 3 (0.4%) of the760 patients; 8 isolates were from sputum and one from urine. The fungus was not demonstrable in the air at a selected site during a 2-year study although other species of Cryptococcus, namely, C. albidus, C. ater, C. flavus, C. laurentii, C. magnus, C. terreus and C. uniguttulatus were isolated. The three C. neoformans positive patients were males, with pulmonary tuberculosis as the primary disease and history of repeated exposure to pigeon excreta in two. None of these patients manifested any overt signs and symptoms specificially attributable to cryptococcosis, nor did they receive any antifungal therapy. Repeated isolations of C. neoformans from sputum, a positive urine culture and demonstration of cryptococcal antibodies in a serum specimen, followed by negative cultures and serology, suggested that patient 1 had spontaneously recovered from an episode of benign, minimal pulmonary cryptococcosis. Patients 2 and 3 probably carried the fungus as a transient resident of the respiratory tract. The results suggest that C. neoformans is of uncommon occurrence in the respiratory tract of patients with bronchopulmonary disorders and that the isolation of the fungus from this site may not necessarily imply an etiologic relationship.


Transformation of the gene for hypoxanthine phosphoribosyltransferase. Purified DNA from wild-type Chinese ovary (CHO) cells has been used to transform three hypoxanthine phosphoribosyltransferase (HPRT) deficient murine cell mutants to the enzyme positive state. Transformants appeared at an overall frequency of 5 x 10(-8) colonies/treated cell and expressed CHO HPRT activity as determined by electrophoresis. One gene recipient, B21, was a newly isolated mutant of LMTK- deficient in both HPRT and thymidine kinase (TK) activities. Transformation of B21 to HPRT+ occurred at 1/5 the frequency of transformation to TK+; the latter was, in turn, an order of magnitude lower than that found in the parental LMTK- cells, 3 x 10(-6). Thus both clonal and marker-specific factors play a role in determining transformability. The specific activity of HPRT in transformant extracts ranged from 0.5 to 5 times the CHO level. The rate of loss of the transformant HPRT+ phenotype, as measured by fluctuation analysis, was 10(-4)/cell/generation. While this value indicates stability compared to many gene transferents, it is much greater than the spontaneous mutation rate at the indigenous locus. The ability to transfer the gene for HPRT into cultured mammalian cells may prove useful for mutational and genetic mapping studies in this well-studied system.


Transvesical Harris-Hryntschak prostatectomy with primary bladder closure and local vasoconstriction. The simple, rapid and satisfactory method of the transvesical Harris-Hryntschak open prostatectomy is described. When this technique is used bleeding is reduced to an average of 85 ml. and visibility is improved by the local injection of a synthetic vasoconstrictor, ornithine-8 vasopressin, before enucleation. Hermostasis is obtained by tamponade with fine sutures occluding the bladder neck. Bladder closure is with heavy watertight, purse-string sutures. A "time and motion" study has reduced the usual operating time to 15 to 20 minutes with an intraoperative transfusion rate of 2.3%.


Renal autotransplantation for recurrent renal colic. Renal autotransplantation as an alternative to ileal interposition has been done successfully in patients with repetitive episodes of renal colic. Urinary tract continuity has been re-established by anastomosis of a Boari tube directly to the renal pelvis. This has resulted in easy egress of recurrent calculi without pain. Furthermore, the musculature of the Boari tube seems to be adequate for prevention of vesicorenal reflux. The procedure has been devoid of electrolyte and mucous urinary retention problems associated with ileal interposition and it is advocated as an alternative in the management of such patients when medical therapy fails.


Evaluation of patients for secondary hypertension. The recognition of secondary causes of hypertension, such as renovascular disease and aldosteronism, can be enhanced by stimulation and suppression of the 2 limbs of the renin angiotensin system. Normal values have been established in unstimulated and stimulated conditions. Saline infusion suppresses plasma aldosterone normally. Patients with proved adenomas do no suppress renin and are outside the well established ranges of normal suppression. Likewise, furosemide will stimulate renin release. Patients with proved aldosteronism are outside the normal ranges of plasma renin activity. These maneuvers also are useful in discriminating renovascular hypertension, particularly when achieving differential renal venous collections under stimulated conditions (after furosemide and tilting). By stressing this system (with furosemide stimulation or saline suppression) one can discriminate better secondary hypertension by the failure to respond normally.


The eighth Frederick H. Verhoeff Lecture. presented by saiichi mishima, MD Behçet's disease in Japan: ophthalmologic aspects. The problems of Behçet's disease in Japan have been reviewed with particular emphasis on the ophthalmologic aspects: the historical background for the Japanese works, diagnostic critieria, epidemiology, some statistics, ocular symptomatology, ocular histopathology, etiology, pathophysiology, and treatment. Behçet's disease is the most frequent entity in endogenous uveitis in Japan. Patients are found throughout the country, and the prevalence rate averages seven to eight per 100,000 population: the rate is higher in the northern than in the southern districts. The diagnosis is made on the basis of a combination of clinical symptoms that are divided into the major and minor criteria symptoms. The major criteria comprise the ocular involvement, aphthous ulcers of the oral mucous membrane, genital ulcers, and skin lesions. These symptoms recur often as attacks and the disease follows a chronic course. The ocular involvement is found in 83% to 95% in males and 67% to 73% in females; the male  to female ratio in the number of patients is 1.78. Both into the anterior segment type and the fundus and panophthalmic types. The anterior segment type shows serous iridocyclitis with the classic type of hypopyon appearing in about 12% of the attacks. This type is found in about 20%, more often in females than in males, and the visual prognosis is more favorable than in the fundus and panophthalmic types. In the latter two types, attacks of retinal angitis resulting in intensive retinal edema, yellowish-white exudate, and hemorrhages recur particularly in the macular region, and the visual prognosis is poor. More than 50% of male patients lose visual acuity to less than 0.1 in five years, but this is the case in only 10% of female patients. Consequently, Behçet's disease is the cause of blindness in about 12% of acquired blindness in adults. The ocular histopathology during the attack is characterized by severe angitis with intensive infiltration of neutrophil leucocytes largely in the uveal tract and the retina; the latter is severely affected and loss of visual cells and other neural elements results. The etiology of this disease still remains unknown but genetic predisposition is suggested since this disease is strongly linked with HL-A-B5. Environmental factors are also considered. Various abnormalities are found in the blood chemistry, blood cells (particularly in neutrophil leucocytes), immunologic mechanism, fibrinolytic and blood clotting system, and hormonal system. Chemotractic factors are found in the aqueous humor. These changes are particulary enhanced just before and during the ocular attacks. Systemic corticosteroids are deleterious to the visual prognosis, but cyclophosphamide and colchicine appear to suppress attacks and help patients maintain the visual acuity. However, these drugs are toxic, particulary to the reproductive organs, and the patients must be informed of this side effect and be allowed to make a decision before they are used.


Long term followup of cataracts in children after renal transplantation. In reviewing the course of 218 renal transplantation recipients 55% have developed PSC of which eleven patients have had surgery on one or both eyes; The operations in general have been uncomplicated, and the visual results have been excellent with the exception of one case that had a detached retina. The cataracts were probably induced by heavy corticosteroid therapy as the larger the dosage and the younger the recipient, the more prone were they to the development of lens changes. Phacoemulsification was preferred in this series as the more expeditious technique, leading to a clearer anterior chamber with less chance of developing a secondary cataract.


The natural course of active choroidal lesions in the presumed ocular histoplasmosis syndrome. Eighty-two patients and 106 eyes with the POHS have been followed for one year or longer. Untreated active choroidal lesions were divided into groupings based on the distance from the center of the CFZ and the reltionship to the border of the CFZ. Twenty-three percent of untreated active choroidal lesions that were located inside the CFZ achieved 20/20 to 20/40 vision. Sixty-three percent of untreated active choroidal lesions that were located outside of the CFZ achieved a vision of 20/20 to 20/40. The active choroidal lesions with the best visual prognosis were 0.25 to 0.5 disc diamterers, demonstrated no growth, and had little or no associated choroidal bleeding. Activation of choroidal lesions in the fellow eye at the site of preexisting atrophic scars was documented in 21% of the eyes. One fellow eye developed a de novo active choroidal lesion. Eighteen percent of the cases had structurally congested nerve heads characterized by slight elevation of the disc and no physiologic depression; 3% of the eyes had drusen of the optic nerve. A relationship may exist between peripapillary scarring in the POHS and these nerve head changes.


[Finding of the staphyloccoi and streptococci of mastitis on the udder after various ways and means of cleaning]. The presence of mastitis staphylococci and streptococci on the udder's surface of 400 cows was studied following application of various ways and means of cleaning. The presence of agents causing mastitis was determined before and after cleaning the udder. On uncleaned udder surfaces presence of mastitis staphylococci was observed in 52.5% and of mastitis streptococci--39.5% of udders studied. After washing with water mastitis staphylococci--on 12-20% of the udders. Following udder cleaning with solutions of antigerm 50 (0.04%) or yozan CCT (4%), mastitis staphylococci were found on 4% and 6% of the udders, respectively, while mastitis staphylococci--on 2% and 6%, respectively. Udder surface staphylococci belong in 2.2% to II phagous group, in 46.6%--to the III group, and in 37.7% -- to mixed groups. The most frequently encountered phagous types were 6 and 42D.


[Use of the pyruvate test for determining the bacterial activity in milk]. Comparative studies were carried out on the pyruvate and reductase tests applied in milk of varying hygienic properties. It was established that: just after milking the pyruvate and reductase tests have a low correlation with bacterial infestation of milk; in milk cooled at 3--5 degrees C for a longer period (72 h) the pyruvate test has a good correlation with bacterial infestation of milk; following storage of milk at temperature above 10 degrees C the reductase test with methylene blue is better correlated with bacterial infestation of milk; the pyruvate-test is appropriate for evaluation of bacterial activity in milk cooled at low temperature and transported every second day; the reductase test is appropriate evaluation of bacterial activity in not well cooled milk which is transported one a day.


[Comparative studies between different methods for demonstrating blocking antibodies in experimental Br. melitensis infection in sheep and goats]. In the course of 4 years 4624 serums of 34 sheep and 4 goats experimentally infected with Br. melitensis biotype 1 and biotype 3 in a chronic phase of the Brucella infection process and 2792 serums obtained from part of the same sheep in acute and subacute phase of Brusella infection were investigated. In was established that Coomb's test and the cysteine test show greater constancy in proving the existence of blocking antibodies. They are followed by the Brucella blocking test after Renoux and the mercaptoethanol test. In the complement binding reaction participate mainly mercaptoethanol-sensitive antibodies, while in the presence of blocking (mercaptoethanol resistant) antibodies the complement binding reaction is characterized by binding a smaller amount of the complement. Cold complement binding leads to increased titers of complement binding antibodies mainly in respect to blocking antibodies. Positive hemocultures are established more often in case of mercaptoethanol-sensitive agglutinins in high titers, while positive urocultures--in case of high titer reaction of complement binding, in case of higher titers of blocking antibodies or in case of positive complement binding reaction and higher content of blocking (mercaptoethanol resistant) antibodies.


[Influenza in man and animals].

[Influenza in man and animals]. A review of references found in World literature concerning the present day problem of grippe virus participation in man's and animals' pathology is made. New aspects of the relations between grippe viruses in man and in the animals, strain circulation, changes in their antigenic structures and the arisal of spontaneous mutations as well as the possibility for preserving human grippe strains in animals during interepidemical periods are revealed. Various hypotheses confirming this possibility are discussed. Results obtained in this field are summed up and an attempt to compare and analyse them is made in view to construct all-round conceptions and elaborate a strategy related with the study of grippe viruses also in animals and birds as their eventual biological reservoir. Data presented are of interest not only for etiology and epidemiology but also for the ecology of viral infections. Conclusions concerning the need to study grippe virus interrelations in man and animals in an all-round aspect, including the participation of various specialists, are made.


[Enterococci and coliforms in yellow sheep's milk cheese]. Ninety-two samples of sheep milk yellow cheese were investigated 30 and 180 days after its production. The content of enterococci varied within a wide range--from 100 to 1,9 million per g. In 14.28% of the samples more than 10 000 enterococci per g were found. No correlation between salt content, acidity and pH and number of enterococci in the yellow cheese samples studied as well as between quantity of enterococci, period of cheese ripening and storage and the organoleptic evaluation of the product's ripeness was established. In 100% of the samples studied coli titer was above 0.1. Of the 137 differentiated enterococci strains 67.1% belonged to the species Str. durans, while 32.8%--to Str. faecium.


[Hemagglutinating activity of enterotoxic strains of E. coli isolated from calves]. The manose-resistant hemagglutination activity of 272 E. coli strains isolated from calves sick or dead of colibacteriosis, 43 of which were enteropathogenic, was assessed. Strain enteropathogeneity was determined after the method of Smith and Halls (1967). It was established that 38 (88.3%) of the 43 enteropathogenic strains cause full or partial hemagglutination of horse or pig erythrocytes. Manose-resistant hemagglutination was not observed in the non-enteropathogenic E. coli strains. Manose-resistant hemagglutination of enterotoxic E. coli strains is in relation with their enteropathogeneity.


[Growth characteristics of mutant strains of Escherichia coli isolated from poultry in the presence of streptomycin]. Three Escherichia coli strains--302(O111), 311(O78), and 331(O2) as well as streptomycin sensitive and streptomycin resistant mutants obtained from them by mutagenesis were studied. The sensitivity of all strains to streptomycin was tested in dilution series on hard and fluid medium. Growth curves were worked out by the biophotometer of Bonet, Maury and Jonan, adding various streptomycin concentrations to the medium at the very beginning of the experiment and 90 min after that. It was established that streptomycin concentrations above 15 microgram/cm3 added to bacteria sensitive to it at the beginning of their log-phase, shortens its duration by about 40%.


Studies of colicin action on wall-less stable L-forms of Escherichia coli. I. Degree of attachment and of killing effect on rods and stable L-form cells. Escherichia coli strains B and K12 W 1655 F+ are able to bind more lethal units of colicins E2, E3, G, H, Ia, and K+ X per one stable L-form cell (of the protoplast type) than per one rod cell; colicin D is bound in a higher amount on E. coli B rods. This pattern remains unchanged, if the same colicins are attached on chloroform-killed cells of both forms. Rods of both E. coli strains are more sensitive to colicins D, E2, E3, K + X (as--in the strain B--to colicin Ia) than cells of the respective L-forms. In the strain W 1655 F+ both cell forms are equally highly sensitive to colicin Ia. The stable L-forms of both strains are much more sensitive to colicins G and H than the rods. Thus the Gram-negative cell wall decreases the probability of a colicin molecule to get attached to its receptor in the cytoplasmic membrane. On the other hand, in E. coli cells the attachment of most colicin molecules to the wall receptors increases the probability of their biological effect. There is no such effect of the wall-attachment on the action of colicins G or H. The strain B is tolerant to colicin E2, while being resistant to E3; thus the cytoplasmic membrane receptor sites for them are not identical.


Factors influencing the copy number of F-like plasmids in Escherichia coli and Salmonella typhimurium. The copy numbers of Flac, four F-like plasmids and pLT2 were estimated in two strains of Salmonella typhimurium and (for all except pLT2) one strain of Escherichia coli. For organisms grown in casamino acids minimal medium, the plasmids spanned a 7--8 fold range of copy number with ColB-K98 having the highest copy number in each strain and R124 the lowest. The copy number of ColB-K98 was substantially greater than 1 in each of the strains tested. There was no clear relation between the plasmid size and copy number, although the plasmids studied spanned only a narrow size range. The copy number of individual plasmids was slightly reduced or not affected at all by the presence of a second plasmid in the same strain. Derivatives harbouring each of the plasmids were grown in three different media to ascertain how plasmid copy number responds to changes in growth rate. For each plasmid, the copy number increased with decreasing growth rate. Extracts from each of the three strains harbouring ColB-K98 contained two distinct plasmid species. One appeared to be about twice as large as the other and both were absent from Col- segregants.


[Study of a Pseudomonas mutant altered in methanol metabolism]. A glycine-resistant mutant was isolated from a methylotrophic strain of Pseudomonas species possessing serine pathway. This mutant presents some improvements in regard to growth parameters, and is able to excrete a fluorescent pigment under certain culture conditions. This pigment is capable of accelerating the reduction rate of formaldehyde to formate coupled with NAD. The same cannot be said for the wild type.


[Modes of entry of Toxoplasma gondii trophozoites into normal mouse peritoneal macrophage and HeLa cell monolayers. A phase-contrast microcinematographic study (author's transl)]. The mode of entry of living trophozoites of Toxoplasma gondii (RH strain) into normal mouse peritoneal macrophage and HeLa cell monolayers was studied by phase-contrast microcinematography. The results have shown that Toxoplasma can enter into macrophages either by phagocytosis (Figs. 1 and 2) and/or by active penetration (Fig. 3). Only the latter process was observed with normally non-phagocytic HeLa cells (Fig. 4). During this process the parasites actively moved towards the host-cells by flexion and penetrated them always through their sharpest end. Active penetration was a rapid phenomenon (about 20 s at 37 degrees C) and was accompanied by a series of morphological changes, i.e., elongation of the anterior end, contraction and swelling of the parasite body. Contrasting with phagocytosis, toxoplasmas which had penetrated into the cell were not immediately isolated from the host-cytoplasm by a microscopically discernable vacuole. The nature of the process of penetration (pressure and/or perforation of the plasma membrane) is discussed.


Course of antibiotic sensitivities in Escherichia coli and Staphylococcus aureus from animals. In order to establish the evolution of resistance against the common antibiotics from the beginning of their use up to the present time, the sensitivity of Escherichia coli isolated from the cecum of wild boars was determined. The MIC's of E. coli from these animals in a zoological garden was examined for comparison. The samples from the wild boars were collected in five forests in the Belgian Ardennes. The MIC's obtained (Table 1) are comparable to the mean values given in the early literature concerning strains of human origin (Table 7). E. coli from wild boars in a zoological garden has less sensitivity than from domesticated animals. However, the MIC's of staphylococci from fecal matter of the animals in captivity were not markedly enhanced except for streptomycin (Table 3). It was striking to find that staphylococci were absent in all the fecal samples from the wild boars living in their natural environment. The specific habitat of staphylococci is in man. Wild boars are the ancestors of domestic pigs. The MIC's of E. coli from the latter were determined for evaluation of altered resistance. All isolated strains were fairly resistant to the six substances tested (Table 2). Chloramphenicol was still the most active antibiotic. Staphylococci from some domestic animals (pigs, cattle, chicken) were sensitive to all the substances tested except the aminoglucosides and ampicillin (Table 3). E. coli from pigs bred on large farms in Spain (Toledo and Badajoz Provinces) were also highly resistant (Table 4) to five compounds and sensitive to cephalotin, polymyxin B, furoxone, and Carbadox. The samples obtained from family farms also contained unsensitive strains (Avila Province). These animals had never been given antibacterial feed additives as was confirmed by examination of feed samples (Table 6). Staphylococci when present in the Spanish samples can be considered to be antibiotic sensitive with the same exceptions as in the Belgian samples and also unsensitive to chloramphenicol. The use of antibiotics in animal feed was very common in Spain as was shown by feed analysis (Table 6). The risk of transferable resistance by plasmids between animal species must not be very high. In some cases where resistance formation could be mediated by R-factors, sensitive E. coli or staphylococci were isolated. Resistance was not generalized among animals from the same farm or in adjacent sties. No explanation for this discrepancy was found.


[The occurrence of salmonellae in drinking water (author's transl)]. A total of 7187 samples of drinking water from different areas of the Lower Saxonian District of Braunschweig was investigated according to regulations of the Trinkwasser-Verordnung during June 1977 and May 1979. The bacteriological results are given in Tab. 1 and 2. Salmonellae were isolated in three samples of drinking water and in one sample of sludge from a municipal pipe of drinking water (see also Tab. 2). Additional experiments confirm that growth of salmonellae and other enterobacteria is possible in that sludge (Fig. 1 and 2). These findings implicate some considerations: E. coli and coliforms are the most important microbial water quality indicators of the Trinkwasser-Verordnung. It is presupposed that, when the indicator density is low (less than 1 per 100 ml) the probability that pathogen are present also will be very low. But the question is how low. The risk factor may be estimated on the base of the E. coli-Salmonella ratio in raw sewage of about 10(6). But this relation lessens already in effluents of sewage treatment plants to 10(3) and it seems to be often 10(2) in inadequately disinfected drinking water. For example, we have found four Salmonella serotypes and 408 E. coli during two years. Therefore, the judgement of the presence of E. coli or coliforms in samples of drinking water must impact highly on the improvement of the water quality by disinfection in future.


Partial purification and characterization of the oxytocin-inactivating enzymes from chicken liver. 1. Two enzymes acting on the linear portion of oxytocin: carboxamidopeptidase (releasing Gly . NH2) and prolyl peptidase (releasing Leu-Gly . NH2) were identified in the cytoplasmic fraction of chicken liver. 2. Carboxamidopeptidase was purified 134-fold with a 23% yield, and prolyl peptiase 71-fold with a 20% yield. The specific activity of the final preparations was 181 and 96 microU/mg protein, respectively. 3. The optimum pH for carboxamidopeptidase was 6.0--6.5 and for prolyl peptidase, 7.5. Carboxamidopeptidase activity was inhibited by Mn2+, Zn2+, Ca2+, Co2+, and stimulated by EDTA; the activity of prolyl peptidase was inhibited by Zn2+ and Mn2+. The Km value of both enzymes for oxytocin was 1.5--2.4 microM.


Significance of the immunological factor in the sterility of cervical origin. Clinical data and terapeutic trends. In 40 couples with negative penetration test in vivo and in vitro we have looked for abSA, abSI and abIF. We discuss the usefulness of the condom protected intercourse and the artificial insemination with husband's sperm as therapeutic approaches.


Testing twin means and estimating genetic variance: basic methodology for the analysis of quantitative twin data. Twin methodology for the analysis of continuously distributed traits is presented as a guideline for initial steps in the analysis of twin data. Tests for heterogeneity of twin means and variances are reviewed along with estimates of genetic variance. Analysis of twin data appears on the surface to be a rather simple task, but investigators may well be confused by the wealth of choices available for hypothesis testing. This paper is designed to help the less experienced investigator, with perhaps a modest amount of data, begin analysis with maximum attention to testing all testable assumptions of the twin model, and using recent examples of applications of the methods.


Blood coagulation abnormalities in the Schönlein-Henoch syndrome in adults. 23 adult patients with Schönlein-Henoch's syndrome were observed between 1965 and 1976. Nephropathy was noted in 18, gastrointestinal bleedings in 13, thrombosis of legs in 4, cases. Haemostasis was studied in the successive phases of the process on 185 occasions altogether. The studies included four different capillary tests, thromboelastography, the Gerendás coagulogram, determination of partial thromboplastin time and two platelet-function tests. Additional renal biopsy was performed in 10 cases, mesocolon and skin biopsy in one case each. The results of at least one of the capillary tests were found positive in each of the patients in some stage of the process. The coagulation status was marked by hyperocagulability either in itself or combined with laboratory signs of hypocoagulability. Immunohistological study of the biopsy specimens revealed glomerular fibrin deposits in 7 cases. On the evidence of the follow-up studies the laboratory tests may be used for the assessment of the activity of the process. The alternatives of local intravascular coagulation (LIC) or of compensated diffuse intravascular coagulation (DIC) are offered for the interpretation of hypercoagulability.


Comparison of the analgesic dose-effect relationships of nefopam and oxycodone in postoperative pain. The analgesic dose-effect relationship of nefopam was compared in a double-blind randomised trial with that of oxycodone in immediate postoperative pain. Nefopam 15 mg or oxycodone 4 mg was given every 10 min i.v. (maximum six times) to patients in pain after upper abdominal surgery until their wound pain (scored 0-3) disappeared. The mean pain intensity (PI), initially 2.2 in both groups, descreased by approximately the same extent for up to two doses in both groups (to 1.5 after nefopam 30 mg and to 1.1 after oxycodone 8 mg). Thereafter PI was significantly less in the oxycodone group and diminished almost linearily to 0.1 after the sixth dose (24 mg). In the nefopam group, the PI score fell to 1.1 after the fourth dose (60 mg). This seemed to be the "ceiling" effect since additional doses up to 90 mg did not result in greater pain relief. In the oxycodone group, only two patients (12%) needed maximal dosage (6 x 4 mg), one of them requiring 32 mg of oxycodone. In the nefopam group, 12 patients (75%) needed further pain relief after the maximal dosage (6 x 15 mg). In these patients, oxycodone (maximally 16 mg) gave satisfactory analgesia. Drowsiness and a decrease in the respiratory rate were the principal side-effects of oxycodone, whereas tachycardia, restlessness, sweating and nausea were more frequent after nefopam.


Plasma renin activity and mineralocorticoid replacement therapy in congenital adrenal hyperplasia. Plasma renin activity and serum concentrations of sodium and potassium were repeatedly measured in seven children with congenital adrenal hyperplasia due to steroid-21-hydroxylase deficiency, to monitor the sodium balance during treatment. Infants with the salt-losing form had high plasma renin activity levels 5--11 months after subcutaneous implantation of a pellet containing 100 mg deoxycorticosterone acetate. These elevated plasma renin activity levels were suppressed to the normal range by repeated implantation of DOCA pellet. Moderately elevated values of plasma renin activity in older salt-losers normalized after increasing the dietary sodium intake. Plasma renin activity level has superiority over serum electrolyte concentrations as an index of mineralocorticoid deficiency.


Donor-specific cell-mediated cytotoxicity in renal allograft recipients. The immunological in vitro responses of cadaver kidney transplanted patients against donor specific target cells were investigated with the test systems for antibody-dependent cell-mediated cytotoxicity (ADCC) and direct cell-mediated cytotoxicity (DCMC). The test systems were used in 58 recipients just before the transplantation. Nine recipients (17%) had positive donor directed ADCC reactivity and of these seven had early rejection episodes, but this outcome was not significantly different from the outcome in the ADCC negative group. Only one recipient showed positive donor directed DCMC reactivity and had early loss of the graft in rejection. The test systems were further used to monitor the donor specific responces after the transplantation in 32 recipients. Positive DCMC reactivities were significantly correlated with clinical rejections but most often positive reactions occurred too late to be of predictive value. The donor specific ADCC reactivity after transplantation was not clearly correlated with rejections. It is concluded that the predictive and diagnostic values of the two test systems were too weak to justify their use as routine methods in the clinical management of the kidney transplanted patient.


In vitro influence of endotoxin on human mononuclear phagocyte structure and function. 1. Depression of protein synthesis, phagocytosis of Candida albicans and induction of cytostatic activity. The effect of E. coli endotoxin (LPS) on human monocytes and peritoneal macrophages (PEC) during in vitro differentiation was studied. Short-term (less than 24 hours) exposure to LPS in concentrations up to 50 microgram/ml did not affect monocyte survival or 51Cr-release, but concentrations of 10 microgram/ml or more reduced monocyte survival when LPS exposure was prolonged to 72 h. Undifferentiated monocytes seemed to be sensitive to this effect. Monocyte and PEC protein synthesis was reduced by nontoxic LPS concentrations in both undifferentiated and differentiated cells. LPS exposure reduced monocyte ingestion and degradation of 125I-labelled Candida albicans, dependent on time and dosage. The induction of monocyte- and PEC-mediated cytoststic activity to tumour cells induced by prolonged in vitro culture was also impaired by LPS. The morphological alterations induced in mononuclear phagocytes by LPS included a changes distribution of cells in the monolayer, changes in membrane structure and apparent reduction of lysosomes. LPS thus interferes adversely with several aspects of human mononuclear phagocyte in vitro differentiation.


In vitro influence of endotoxin on human mononuclear phagocyte structure and function. 2. Enhancement of the expression of cytoststic and cytolytic activity of normal and lymphokine-activated monocytes. The presence of non-toxic concentrations of E. coli endotoxin (LPS) during the in vitro interaction of normal human monocytes and a human tumour cell line (NHIK 3025) enhanced monocyte-mediated target cell cytostasis and cytolysis. Monocyte responsiveness to LPS was greatest at an intermediate stage of in vitro differentiation. The expression of cytostatic and cytolytic activity by human monocytes activated with mediators from Corynebacterium parvum-stimulated human lymphocytes was also enhanced by LPS. Lymphokine activation did not induce additional LPS responsiveness in the monocytes. Monocytes activated with lymphokines and subsequently deactivated by in vitro culture did not show any increase in LPS responsiveness. A soluble cytostatic factor, which is probably not cold thymidine, was released from monocytes exposed first to lymphokines and then to LPS. While LPS is ineffective as an induction signal of monocyte cytotoxicity to tumour cells in this system, it enhances the expression of cytotoxicity induced by prolonged in vitro culture or lymphokine activation.


Endotoxin fever in capsaicin treated rats. The fever elicited by 10 micrograms/kg intravenous E. coli endotoxin was significantly higher in capsaicin desensitized rats than in controls, but there was an upper limit to the rise in body temperature in both groups. Capsaicin desensitization permitted the participation of various heat producing mechanisms even if the initial body temperature was high. The fever course was characteristically biphasic, similar as in control rats, thus desensitization did not alter the factors mediating the various phases of the endotoxin response.


Possibility of long-lasting amplification of insulin receptors by a single treatment at newborn age. Administration of insulin to newborn rats was shown to amplify the hormone receptors. Blood sugar values in animals thus treated were lower in the adult age, which could be explained by increased sensitivity to endogenous insulin; the decrease of blood sugar in response to exogenous insulin was similar in magnitude, however, it occurred at a lower level compared to the controls. These changes were more marked in female than in male rats.


Comparison of the effector mechanisms during endotoxin fever in the adult rabbit. In unanaesthetized adult rabbits an intravenous dose of E. coli endotoxin evoked a febrile rise in colonic temperature at ambient temperatures of 9 to 31 degrees C. The rise in colonic temperature and oxygen consumption did not depend on the ambient temperature, while, among the heat loss effectors, in warmer environments only the depression of respiratory heat loss and in cooler environments only ear skin vasoconstriction contributed to the febrile rise in colonic temperature. In moderately warm environments the endotoxin first induced a maximum inhibition of respiratory frequency and this was followed by vasoconstriction. Later, a transient rise in oxygen consumption occurred. During defervescence the timing of the effectors was reversed. The results showed that a febrile response is not necessarily characterized by simultaneous changes in the thermoregulatory effector mechanisms.


Cross-protection aginst Salmonella enteritidis infection in mice. I. Immunization trials. Mice were immunized subcutaneously with live and killed vaccines, with and without complete adjuvant incorporating Salmonella typhi-murium M206, Salmonella gallinarum 9R, Salmonella pullorum Sp223 as well as homologous Salmonella enteritidis Se795. The animals were challenged 21 days post-vaccination with 100 LD50 of virulent S. enteritidis 5694 SMR subcutaneously along with unvaccinated control mice. To assess the immunity against acute and chronic infections, the percentage of absolute survivors i.e. survivors without lesions and without the challenge organism, was taken as the criterion. Live vaccines proved better than killed vaccines. Live vaccines with complete adjuvant induced a good protection. Cross-protection could be induced with the live vaccine with complete adjuvant against S. enteritidis infection in mice.


Cross-protection against Salmonella enteritidis infection in mice. Mice were immunized subcutaneously with live vaccines and live vaccines with complete adjuvant incorporating Salmonella enteritidis Se 795, Salmonella typhi-murium M206, Salmonella gallinarum 9R or Salmonella pullorum Sp223. They were challenged along with unvaccinated controls with 100 LD50 of virulent S. enteritidis 5694 SMR subcutaneously on the 21st day post-vaccination. The humoral immune response was studied by assessing the sequential level of agglutinins, complete and incomplete somatic antibodies, opsonophagocytic antibodies, cytophilic antibodies and bactericidal antibodies before and after challenge. The level of these antibodies and the protection afforded by the particular vaccine is correlated and the possible involvement of a humoral mechanism is discussed.


Cross-protection against Salmonella enteritidis infection in mice. III. Delayed hypersensitivity reaction and clearance of the challenge organism. Mice were immunized with live vaccines and with live vaccines with complete adjuvant incorporating Salmonella enteritidis, Salmonella typhi-murium, Salmonella gallinarum or Salmonella pullorum. On the 21st day after vacination, the hypersensitivity reactions elicited by the mice to extracts of the challenge organism (S. enteritidis 5694 SMR) were assessed. The degree of delayed hypersensitivity reaction was compared with the level of protection induced by the vaccine. The role in protection of delayed hypersensitivity is discussed. Clearance of the challenge organism from the liver of previously vaccinated and unvaccinated mice was assessed quantitatively.


Differentiation of rapidly growing scotochromogenic mycobacteria employing the ZYM API system as substratum. Nineteen enzyme activities were investigated in 15 species of rapidly growing scotochromogenic mycobacteria, employing the ZIM API system is substrate. With this system, the time of identificaiion is reduced from two weeks to four hours.


Elimination of F'lac plasmid by different psychotropic drugs and some related compounds. Desipramine, trimipramine, protriptyline, noxiptyline, promazine, trimeprazine, triflupromazine and chlorprothixene methoiodide eliminated the F'lac plasmid of Escherichia coli, while thiazinanum, toluidine blue, lidocaine and procaine were ineffective in this respect. The plasmid eliminating action of the drug ceased in the presence of 0.05 M magnesium sulphate. Methylene blue did not inhibit plasmid elimination by the psychotropic drugs, and in presence of the dye even lidocaine and procaine became effective. Based on plasmid elimination in the presence of methylene blue and on the selective effects of the lon- mutant, the plasmid eliminating mechanism of psychotropic drugs seems to differ from that of acridine orange.


Effect of immune sera upon enhanced in vitro antibody responses. Immunization of rabbits with S marcescens bacteria in Freund's incomplete adjuvant resulted in development of anti-Serratia sera with bacterial agglutinating properties as well as LPS modulating properties. The antisera reacted with the LPS in counterimmunoelectrophoretic assays. Such antisera also stimulated the LPS induced enhancement of specific anti-SRBC responses from normal spleen cell cultures but did not further enhance the stimulated responses of similar cultures incubated with the smaller molecular weight PS-rich derivative. The antisera had no effect on LPS or PS enhanced nonspecific background anti-SRBC response as compared to normal rabbit serum-treated controls. These results point to a possible role for immune complexes as an enhancer of the immunostimulating activities of LPS antibody-treated cultures and also indicate a difference between LPS and PS as immunomodulators.


Phagocyte functions in familial Mediterranean fever. Monocytes derived from peripheral blood of patients with familial Mediterranean fever (F.M.F.) demonstrated lower phagocytic capacity for Shigella flexneri and depressed bactericidal activity against S. albus when compared to monocytes from healthy individuals. Treatment of patients with colchicine did not alter these functions. On the other hand, chemokinesis of PMN of F.M.F. patients was enhanced especially during attacks. Colchicine treatment decreased significantly the PMN chemotactic migration.


The treatment of established micrometastases with syngeneic macrophages. We demonstrated that macrophages injected systemically can profoundly inhibit the incidence of experimentally induced metasis. In our system mice bearing established micro-metastases were treated with one, two, or three i.v. injections of activated macrophages. Specificially activated (immune) macrophages were most efficient in reducing the number of metastases, but non-specifically activated macrophages were also effective in reducing the metastatic incidence. Macrophage play a major role in host defense against neoplasia (9,22) and have been shown to influence the outcome of spontaneous metastasis (9). Rat sarcomas whose macrophage content was found to be high were also shown to be non-metastatic. Conversly, rat sarcomas with low macrophage content were found to be metastatic (9). Our current data demonstrate that the systemic injection of syngeneic activated (exogenous) macrophages can bring about a significant reduction of lethal cancer metastases. Apparently, treatment with activated macrophages can increase the rate of tumor cell destruction as compared to the rate of tumor cell proliferation which ultimately leads to inhibition of clinical metastasis.


Studies on the endotoxin induced tumor resistance. In summary, this report has discussed the immunologic mechanisms involved in the enhancement of nonspecific resistance to tumor by endotoxin. The optimal conditions for tumor protection involved pretreatment with approximately 25 mug LPS administered at the siteof subsequent tumor challenge. In an attempt to relate endotoxin structural components to the ability to enhance TUR, a variety of whole LPS's, endotoxic glycolipids and PS preparations were compared. While all of the intact LPS's and several of the glycolipids were effective in enhancing TUR, some endotoxic glycolipids were totally inactive although they were equally toxic. Some lipid-free PS preparations were also active although less than whole LPS. Evidence was presented to suggest that mechanism for enhancement of TUR involves B cells and macrophages but not T cells. The mechanism also involves the production of soluble factors which are released into the serum of mice in response to LPS or PS. These factors can transfer and mediate the antitumor effects of LPS. The preinfection of mice with BCG enhanced the activity of LPS and PS in the production of antitumor activity.


Effects of bacterial products on granulopoiesis. Methylated endotoxin and Freeman-type polysaccharide each stimulate granulopoiesis and the production of CSF in mice. These same preparations also protect pretreated mice from lethal X-irradiation. The role of CSF in stimulating granulopoiesis in vivo was shown by the ability of anti-CSF to reduce the number of CFUc in endotoxin-treated mice. C3H/HeJ low responder mice cannot be protected against lethal X-irradiation by pretreatment with endotoxin and they fail to produce CSF in response to phenol water extracted endotoxin and the Freeman-type polysaccharide, but do respond to trichloroacetic acid endotoxin with elevated serum CF levels.


Opsonization of antitumor reactive lymphocyte in SJL/J mice bearing spontaneous or transplanted reticulum cell sarcomas (RCS). Radiolabelled antitumor reactive T lymphocytes (ARC) were prepared in vivo by immunization of SJL/J mice with mitomycin C inactivated syngeneic LA-6 tumor cells followed by injection of 125IUdR to label dividing cells. These ARC were specifically diverted to the liver when injected in LA-6 tumor-bearer serum and injected i.v. into normal SJL/J mice. Likewise, SJL/J anti-Balb/c ARC were diverted to the liver of SJL/J mice bearing spontaneous reticulum cell sarcomas (RCS) carrying Balb/c cross-reactive antigens but not in mice with Balb/c negative neoplasms. Mice with Balb/c positive tumors also had circulating ARC opsonizing factors. These results suggest a mechanism for the survival of antigenic tumors involving macrophages and ARC opsonizing (ARCO) factors. A novel approach to immunotherapy is discussed.


Automated retrieval of purine literature. The scientific papers of the revised literature are not a unit when considered terminologically for automated retrieval. A 60-80% of the total valid references obtained through each data base was stored in the computer memory in virtually closed compartments although they belonged to the same material complex. The retrieval of these papers requires independent profiles series which although they give rise 14-28% duplicate references, the final yield can be increased by 100-200% of the yield obtained through the basic profile of the central subject considered.


Thromboxane A2 biosynthesis during endotoxin-induced aggregation of platelets from normal and sensitized guinea-pigs. Endotoxin lipopolysaccharides Escherichia coli O26:B6 and E. coli O127:B8 were weak inducers of aggregation in normal guinea-pig platelet-rich plasma (PRP), even in the presence of Ca2+. Indomethacin hardly inhibited endotoxin-induced aggregation, indicating that biosynthesis of thromboxane A2 (TXA2) was of little importance. In accordance with this conclusion TXA2 was not detectable by means of bioassay during endotoxin-induced aggregation in normal guinea-pig PRP. Pretreatment of the guinea-pigs with endotoxin sensitized their PRP to endotoxin. This was due to a humoral factor with a selectively directed towards the polysaccharide moiety of endotoxin. The combination of this factor with endotoxin indued a marked biosynthesis of TXA2 and concomitant platelet aggregation.


Acute promyelocytic leukemia.

Acute promyelocytic leukemia. Acute promyelocytic leukemia (APL) is characterized by proliferation of morphologically abnormal promyelocytes and a severe bleeding diathesis. The abnormal promyelocyte is characterized by abundant, large granules, many of which are spindle-shaped. Electron microscopic appearance of the granules closely resembles that of Auer rods. The granules appear to possess tissue thromboplastin activity by both immunologic and clotting assays. Coagulation studies in APL are generally consistent with disseminated intravascular coagulation. Prolongation of the prothrombin time and elevation of fibrinogen degradation products are the tests that are most commonly abnormal. Although occasional reports indicate a favorable response of the coagulopathy to drugs that inhibit fibrinolysis, the use of prophylactic heparin appears to be the treatment of choice. The response rate of APL to chemotherapy regimens that contain an anthracycline is comparable to that of acute myelogenous leukemia. The recent description of the 15;17 chromosomal translocation which may be pathognomonic for APL is only the second example of a chromosomal marker of human neoplasia. Marked elevation of serum vitamin B12 and B12 binding proteins appears to be another characteristic feature of APL. An in vitro cell line of APL cells has been demonstrated to have the capacity to differentiate to functional polymorphonuclear leukocytes, but the cause for the maturation arrest is unknown.


Structural physiology of the human spleen. The structural physiology of the human spleen is discussed in depth here, with particular emphasis on the interrelationships between blood cells and the spleen. The unique microvasculature and structural relationships of the spleen form the basis for a number of functions important in both health and disease. Utilizing scanning electron microscopy one can visualize the interactions between blood elements and the spleen---the passage of deformable erythrocytes through narrow slits in the endothelium separating cord and sinus, the trapping of less deformable cells in the cords, the culling and pitting of abnormal or inclusion-bearing erythrocytes by splenic macrophages, as well as the sites of interaction between antigenic stimuli such as pneumococcal organisms and the T and B cells of the spleen.


Functions of the spleen in host defense against infection. In humans the spleen functions in host defense as a filter and site for phagocytic clearance of the bloodstream. The spleen serves an essential role in this phagocytic clearance if the host has deficient concentrations of opsonizing antibodies. The spleen also produces antibody, and splenic function is required for the host to mount an early IgM response. There is evidence from experiments using animals that the spleen is important in regulating secondary antibody response and in certain aspects of cell-mediated immunity. However, the role of the spleen in these events in the human remains to be defined.


Scrotal reconstruction in Fournier syndrome. The extent of the scrotal defect following debridement of Fournier gangrene ranges from relatively small areas of scrotal loss to complete denudation of the testes and cords. In our experience, denudation of the testis alone is best treated by split-thickness mesh grafts and total denudation of the testis and cord by burial of the testicle in a subcutaneous medial thigh pocket. Three cases are presented illustrating the spectrum of methods that can be used either singly or in combination to repair scrotal defects in Fournier gangrene.


Platysma muscle in rhytidoplasty.

Platysma muscle in rhytidoplasty. Surgical alteration of the platysma muscle improves the results of cervicofacial rhytidoplasty. The operative technique indicated for an individual patient is determined, in part, by the anatomy of the platysma deformity. Many questions regarding the late results of platysma muscle surgery can only be answered by long-term follow-up. This paper presents the results in 75 patients who had platysma muscle flap cervicofacial rhytidoplasty. The 8 most common platysma deformities are discussed. Undesirable results and pitfalls in technique are noted.


Experience with the Fasanella-Servat operation for ptosis of the upper eyelid. A quick, simple, and reliable operation for the correction of mild to moderate ptosis in the presence of fair to good levator function was described by Fasanella and Servat nearly two decades ago. This operation consists of resection of the conjunctiva, tarsus, and müller's muscle using a conjunctival approach. We have performed this operation in 39 patients with good to excellent results in 38. Our criteria and experience are described.


Numerical evaluation of cytologic data. I. Description of profiles. Results of cytologic studies are often presented as graphs, distribution curves or profiles. Further analysis of such data requires description of the profiles in numerical form. This article describes the use of moments about the mean, decomposition into Gaussian components and calculation of Fourier coefficients for the characterization of cytologic data profiles. Fully worked numerical examples suitable for execution on a pocket calculator are given.


Treatment of small external cancers of the nose. There are various ways to remove and repair defects on the nose. When dealing with small basal cell or squamous cell carcinomas, the authors have been utilizing either skin grafts alone or composite skin-cartilage grafts from the ear. We believe that these procedures are simpler for the doctor and easier on the patient, with aesthetically pleasing results.


Use of a craniotome for obtaining cancellous bone and marrow from the ilium. The ilium is a rich source of cancellous bone and marrow for grafting. Grafts can be harvested very rapidly with a standard craniotome. The clutch mechanism prevents inadvertent soft tissue injury if both cortical plates are perforated. The surgical approach is similar to that used in other techniques. No complications have been encountered.


A pattern classification system for automated cervical cytologic screening based on flow microfluorometric analysis. A data analytic technique is described for use in automated cervical cytology. The method entails the application of a two-dimensional Fourier transform to histogram data obtained by flow microfluorometry and the subsequent use of the Fourier coefficients as parameters for pattern classification. Analyses were performed on 186 samples including material from 62 positive and 124 negative cases. Cell suspensions were stained with propidium iodide and fluorescein isothiocyanate, and red and green cytofluoresence were measured simultaneously. The two-dimensional histogram data were normalized, the Fourier transform was applied, and a multivariate classifier based on 30 coefficients was assembled using a training set of half the original series. Performance was then assessed on the remaining cases. Overall accuracy was 79.6%, with a false-positive rate of 14.8% and a false-negative rate of 31.2%. The potential applicability of this approach as the basis of a practical screening system is discussed.


Insulin test after selective gastric and truncal vagotomy. Test response and acid secretion in the early and late postoperative phase. Altogether 540 succesful insulin tests were performed on 377 patients after vagotomy, on 316 patients less than three months after the operation (early phase) and on 182 patients between three months and nine years after (late phase). The proportion of positive insulin test responses after vagotomy and antral resection was similar in the selective gastric (SV) and truncal vagotomy (TV) groups (10.7% and 11.8% respectively in the early phase) and remained the same during follow-up (12.5% and 9.3% in the late phase). In the vagotomy and drainage group there were significantly fewer positive test responses in the early phase after SV (15.6%) than after TV (36.4%), but in the late phase the incidence was similar (56.7% and 55.6%). There was a significant rise in the number of positive responses after SV and drainage during follow-up (from 15.6% to 56.7%). Insulin-stimulated peak acid output (I-PAO) was about the same in the vagotomy and drainage group after SV and TV (3.52 and 5.03 mmol/h in the early phase and 4.20 and 4.93 mmol/h in the late phase). Although the number of Hollander positive insulin tests after vagotomy and drainage increased during follow-up, no corresponding changes were seen in I-PAO. There was no evidence of vagal reinnervation.


Erythromycin levels in serum during treatment with erythromycin stearate and base. The serum concentrations of erythromycin during treatment with erythromycin stearate and erythromycin base were compared in a randomised cross-over study with 21 hospital patients. No statistically significant differences between the brands were found in the serum erythromycin levels at any time or in the areas under the serum level-time curve.


[Fasciola hepatica distomatosis in Maghreb. 2 new Algerian cases]. A bibliographic survey is made of the cases of fasciolasis in Maghreb, and it can be concluded that: The notion of "epidemy", or better, of simultaneous cases, brought to the diagnosis evocation, to explorations by I.D.R. and to early treatment, before the excretion of eggs. Due to drug-efficiency, the coprological proof of the disease was generally missing in the old "epidemies" of the Maghreb. Isolated cases, in contrast, where the fasciolasic etiology was not evocated, could follow natural evolution and the proof by egg or adult discovery was possible in more than half the cases. Progress in immunology of fasciolasis made possible the diagnosis of less than 10 nw cases in Tunisia and Marocco. The authors report 2 new cases from the Constantine region (Algeria). The repartition of the ascertained cases and the possible ones is shown on a map.


Anterior crowns and gingival health.

Anterior crowns and gingival health. Clinical examination was made of 101 aluminous porcelain jacket crowns and 88 porcelain bonded to metal crowns. Overcontouring of the crowns appeared to be less important in causing gingivitis than the location of margins, marginal defects, and unglazed surfaces. Laboratory studies showed a marginal gap of 154 +/- 90 micron in the fit of porcelain jacket crowns on brass dies. Retention of plaque on well-glazed surfaces could not be detected and polished gold showed no plaque formation except along some marginal defects.


Cicatricial pemphigoid: a review of eleven cases. Eleven cases of cicatricial pemphigoid are presented. The clinical, histopathological and immunopathological features of the disease as well as present methods of treatment and dental management are also discussed.


A supplemental test system to measure competitive exclusion of Salmonellae by native microflora in the chicken gut. An improved individual challenge test system is described for evaluation of competititve exclusion of salmonellae in day-old chicks by native gut microflora. Evaluation of salmonella protection is based on culture of cloacal and fecal samples by enrichment methods plus enumeration of salmonellae in fresh droppings collected from test groups. The use of a nalidixic-acid-resistant strain of salmonella allowed for ease of measurement. Comparative data are included that were developed by parallel tests by the seeder bird and this individual challenge test system on salmonella protection provided by microflora from a specific-pathogen-free population and from intestinal microflora propagated anaerobically in several media. The individual-bird challenge test system appeared to yield a more precise measurement of protection than the seeder-bird system and indicated that trypticase soy broth is as effective as VL broth for anaerobic culture of the protective microflora. Fresh fecal suspensions were somewhat more dependable than anaerobic cultures in providing a high level of protection against subsequent salmonella infection.


Estimation of state and amount of phenylalanine residues in proteins by second derivative spectrophotometry. The second derivative absorption spectra of serum albumin, insulin, ribonuclease and lysozyme were measured under various conditions to determine the state and amount of their phenylalanine residues. The second derivative spectra of these proteins were very similar to that of phenylalanine in the region between 245 and 270 nm where tryptophan and tyrosine residues caused no appreciable interference. Denaturation of proteins with urea or guanidine hydrochloride caused decrease in the intensity of the second derivative spectra, but scarcely affected the positions of peaks and troughs. The amounts of phenylalanine residues in proteins calculated from a second derivative spectra of denatured proteins coincided well with those reported in the literature. The states of the phenylalanine residues in the proteins could be deduced from the change in optical intensity on denaturation.


[Mechanisms of aliphatic alcohols oxidation by enzymatic systems of the liver]. The main pathways of aliphatic alcohols oxidation in human and mammalian liver, i.e. dehydration of alcohols by cytosolic alcohol dehydrogenases and oxidation in the presence of microsomal enzymatic system, catalase and hydrogen peroxide are described. A special emphasis is laid upon the interaction of alcohols with terminal oxidase of the microsomal hydroxylating system, i.e. cytochrome P-450. The relative role of these three oxidative pathways in alcohol conversions is evaluated.


[Synthesis of globin mRNA in cultured murine erythroleukemic cells, transformed by Rauscher leukemia virus]. In contrast to cultured erythroleukemic cells transformed by Friend leukemia virus, in the cultured erythroleukemic murine cells transformed by Rauscher leukemia virus, the synthesis of haemoglobin cannot be induced after treatment with 1--2% dimethylsulfoxide, actinomycin D and proteolytic enzymes. Study of disturbances in the haemoglobin synthesis in this cell culture revealed that globin 9S-mRNA is either absent or present in negligible amounts in the culture. The data obtained suggest that the disturbances in haemoglobin synthesis occur at the level of transcription or processing of globin mRNA, rather than at the level of translation.


Heart rate and finger pulse amplitude during muscular relaxation with frontalis versus forearm EMG feedback. Twenty-nine volunteers participated in a one-session experiment consisting of 10 min rest followed by a 30 min treatment period. Brief relaxation instructions were given at the beginning of the rest period. The treatment was either frontalis EMG feedback, forearm EMG feedback, or non-contingent stimulation. The two feedback groups showed EMG decreases in their respective target muscles during the no-feedback rest period, with no further decrease during feedback training, indicating that feedback was no more effective than relaxation instructions. Heart rate decreased significantly in both feedback groups. Finger pulse amplitude decreased significantly in the forearm feedback group. It is pointed out that the latter change does not necessarily indicate peripheral vasoconstriction, but may be due to a fall in pulse pressure as a consequence of increased blood flow to the relaxing muscles. The results are unsupportive of the assumption that frontalis relaxation is particularly effective in inducing a generalized relaxation.


An alternative method for isolating homozygotes of autosomal translocations in the mosquito Culex tarsalis. An alternative pseudolinkage procedure for isolating homozygotes of autosomal translocations has been developed with the mosquito Culex tarsalis (Coquillet). The first step was to induce a translocation heterozygote in a population that was marked with recessive mutants. Interbred translocation heterozygotes produced translocation homozygotes that were phenotypically different from their translocation heterozygote and normal siblings. Thus, a translocation homozygote line of this species was selected and established in shorter time and with less effort than by prior pseudolinkage procedure.


[Postoperative hypergastrinemia].

[Postoperative hypergastrinemia]. After reviewing the more recent acquisitions on the physiology and pathophysiology of gastrin, the authors concentrate on situations of hypergastrinemia, which they divide into a hyperhydrochloric and a hypohydrochloric variety. Among the former, which they subdivide into preoperative and postoperative, the authors discuss problems of differential diagnosis versus peptic ulcers in patients so afflicted. To that end they propose diagnostic policies comprising among other instrumental and laboratory tests the study of gastric secretion, blood gastrin levels in basal conditions and after stimulation by a protein meal, BBS, secretin, and calcium. From analysis of the results of such tests they were able to find a precise nosographic placement for postoperative hypergastrinemia, and from there they arrived at surgical programs aiming to correct postoperative peptic ulcers on the basis of their etiology and pathogenesis.


[Chemotaxis of blood monocytes and polymorphonuclear leukocytes from patients with diabetes mellitus]. The chemotaxis of blood monocytes and polymorphonuclear leukocytes was measured in 20 adult patients with diabetes mellitus and 11 normal control subjects. In experiments dealing with monocytes, the diabetics had a chemotaxis value (125+/-10) significantly lower than that of controls (368+/-22); the polymorphonuclear leukocytes chemotaxis value of diabetics (468+/-31) was also lower than normal (1256+/-62). Adding insulin (10 unit/1000 cc) to the diabetes leukocytes suspension significantly increased the value of chemotaxis.


Prevalence of intestinal parasitic infections among inhabitants of Tan-nan village, Nantou County, Taiwan. The pork infected with cysticerci was sent to our laboratory in June 1971. Microscopic examination revealed the infection of Cysticercus cellulosae. Subsequently, the source of the pork was traced, and the survey of intestinal parasitism was carried out among inhabitants at Tan-nan village, Hsin-I District, Nantou County, Taiwan, in August 1973. Results obtained only indicated the presence rather than endemic of taeniasis solium in this village. The parasites and infection rates found in the present study from 417 individuals by means of direct smear and formalin-ether sedimentation technic of stool specimens are as follows: Ascaris lumbricoides (81.3%), hookworm (30.9%), Trichuris trichiura (73.6%), Strongyloides stercoralis (0.5%), Clonorchis sinensis (2.9%), Hymenolepis diminuta (0.7%), Taenia solium (0.2%), Taenia saginata (0.2%), Entamoeba histolytica (3.1%), Entamoeba coli (8.4%), Endolimax nana (2.6%), and Giardia lamblia (4.3%).


Mutagenicity studies on urine concentrates from female users of dark hair color products. Urines from women, collected before and after hair dyeing, were evaluated for mutagenic activity in the Ames Salmonella-Microsome Test. Thirty (30) sets of samples were tested as concentrates following removal of histidine on an XAD-2 resin column. None of the samples taken following the use of various Clairol products containing high levels of dyes gave any indication of increased mutagenic activity when compared to samples taken before hair dyeing. These results indicate that the use of hair dyes does not result in exposure of the urinary system to mutagens detectable in a sensitive microbial system, and thus suggest the absence of significant biological effects among users of hair dyes and persons occupationally exposed.


[Endocrine and exocrine functional disorders in pancreatic diabetes]. In diabetic diseases of pancreatic origin we find three typical patterns of insulin secretion. The different insulin secretion allows a clear distinction of a diabetes of the maturity onset type and of the juvenile onset type type on the one hand and of a diabetes caused by a pancreatitis on the other hand. In a pancreatitis we see the expected reduction of the exocrine function. In the so called maturity onset diabetes a slight reduction of excretory functions could be seen. These results suggest that in maturity onset diabetes only a selective defect of the beta-cells exists, while in juvenile onset diabetes a destruction or reduction of beta-cells but an intact excretory function may be assumed.


[Changes in the metallic phase at the metal-ceramic margin of baked alloys of nonprecious metals]. Five base metal alloys were investigated to determine if phase changes in the alloy microstructure occurred as a result of the porcelain baking procedure. It was found that during the oxidation treatments concentration changes in the alloy surface led to a depletion of certain elements in four of the alloys investigated. It was also found that phase changes could occur in a region 20 micrometers wide next to the alloy surface. Phase changes and alloying element depletion occurs as a result of the oxidation treatments prior to the fusion of porcelain and not as a result of or during porcelain fusion.


Unresponsiveness to hypoglycemia of centers controlling epinephrine release in cerebral infarct patients. Urinary excretion of catecholamines under insulin hypoglycemia was studied in cerebral infarct patients as well as in patients with Parkinson's disease and subjects with lumbar discopathy (control group). While in the last two categories of subjects a normal response to hypoglycemia, i.e., an increase in urinary excretion of epinephrine was noticed, no such increase was found in patients with cerebral infarction. The disorder is attributed to the unresponsiveness to hypoglycemia of the brain stem centers controlling epinephrine secretion.


[Goethe's personal testimony on his work with "organic creatures". II. Letters (1776-1817)]. Once more following the Sophien-Ausgabe of Weimar, Author gives an extract from GOETHE's Letters to literati, scientists, and princes of his time, concerning notices on his employment about sciences without botany. The GOETHE's own words reflect his engagement better than any description from a second hand. Anatomists may take an especial interest in the letters No 1903 to HERDER and No 1904 to CHARLOTTE v. STEIN (both dated the March 27, 1784) which demonstrate the discoverer's mirth in finding out the human os intermaxillare.


[The structure of the gastric mucosa of the llamas (Lama guanocoe and Lama lamae). I. Forestomach]. The mucous membrane of the first and second compartments (ventral regions) as well as of the third compartment of Lama guanacoe and Lama lamae stomach shows tubular glands opening into pits. Below the surface epithelium blood capillaries of the fenestrated type form a regular network, each mesh of which surrounds a gastric pit. From a morphological point of view (thin section and freeze-fracture replicas) the columnar cells of the surface epithelium and those of the pits closest to the capillaries are largely similar to the epithelial cells of the rabbit gallbladder. This similarity suggests that at the level of the columnar cells sodium-dependent water reabsorption occurs. This reabsorption has already been demonstrated in the abovementioned compartments by physiological methods. The surface and foveolae epithelial cells as well as some cells of the tubular glands have a secretory function. Their secretory granules contain mucosubstances, as indicated by light-(PAS- and Alcian blue reactions) and electron microscopic (PA-TCH-Ag-reaction) histochemistry. The secretory granules originate from the Golgi complex which shows a positive histochemical reaction in its innermost sacculi at the electron microscope level. Endocrine cells (s. second part of this investigation) are rare. The mucosal membrane of each muscular lip separating the glandular sacs in the first compartment shows a stratified, not keratinized, squamous epithelium.


A suppressor of mating-type locus mutations in Saccharomyces cerevisiae: evidence for and identification of cryptic mating-type loci. A mutation has been identified that suppresses the mating and sporulation defects of all mutations in the mating-type loci of S. cerevisiae. This suppressor, sir1-1, restores mating ability to mat alpha 1 and mat alpha 2 mutants and restores sporulation ability to mat alpha 2 and mata1 mutants. MATa sir1-1 strains exhibit a polar budding pattern and have reduced sensitivity to alpha-factor, both properties of a/alpha diploids. Furthermore, sir1-1 allows MATa/MATa, mat alpha 1/mat alpha/, and MAT alpha/MAT alpha strains to sporulate efficiently. All actions of sir1-1 are recessive to SIR1. The ability of sir1-1 to supply all functions necessary for mating and sporulation and its effects in a cells are explained by proposing that sir1-1 allows expression of mating type loci which are ordinarily not expressed. The ability of sir1-1 to suppress the mat alpha 1-5 mutation is dependent on the HMa gene, previously identified as required for switching of mating types from a to alpha. Thus, as predicted by the cassette model, HMa is functionally equivalent to MAT alpha since it supplies functions of MAT alpha. We propose that sir1-1 is defective in a function. Sir ("Silent-information regulator"), whose role may be to regulate expression of HMa and HM alpha.


The incidence, significance and prognosis of arrhythmias in acute myocardial infarction. Concepts of the incidence, significance and prognosis of almost all cardiac arrhythmias during acute myocardial infarction have changed greatly in the last 15 years. In some cities facilities are available to reach patients in the very earliest phases of ischaemia or infarction. As previously suspected but now confirmed, ventricular fibrillation occurs commonly at this time and depending on whether ischaemia or infarction is the basis of its occurrence, has a variable long-term prognosis. In the coronary care unit ventricular arrhythmias are more frequent than was originally believed and current research suggests that they have little if any predictive value in defining individuals who would develop ventricular fibrillation. Such events, however, appear related to the severity of myocardial or coronary artery disease. Similarly, asystole and heart block in acute myocardial infarction are important causes of mortality through their association with severe underlying disease. Other cardiac arrhythmias are not infrequent in acute myocardial infarction. They may carry an immediate prognostic implication for the patient but rarely have long-term implications. Autonomic nervous system disturbances may underlie many arrhythmias occurring particularly in the earliest phases of infarction.


Prostaglandin regulation of colony-stimulating factor production by lipopolysaccharide-stimulated murine leukocytes. The production of colony-stimulating factor by lipopolysaccharide-stimulated murine peritoneal leukocytes and their adherent subpopulations (greater than 80% macrophages) was markedly enhanced by indomethacin at concentrations sufficient to block prostaglandin E synthesis. Addition of physiological concentrations of E-series prostaglandins reversed this enhancing effect of indomethacin in a dose-dependent manner. These results indicate that colony-stimulating factor production by stimulated leukocytes is regulated by E-series prostaglandins and suggest that prostaglandins function to limit myelopoiesis by inhibiting colony-stimulating factor production and concomitantly the induction of cell proliferation.


Chemotaxigenesis and activation of the alternative complement pathway by encapsulated and non-encapsulated Cryptococcus neoformans. In the presence of serum, whole cells of encapsulated and non-encapsulated Cryptococcus neoformans generated a chemotactic response by neutrophils. Heat inactivation of serum ablated all chemotactic activity. Cryptococcal polysaccharide was not chemotaxigenic. Assays for alternative complement pathway activation such as depletion of alternative complement pathway factor B or electrophoretic conversion of factor B closely paralleled chemotaxis assays. Cells of encapsulated and non-encapsulated C. neoformans activated the alternative complement pathway, whereas cryptococcal polysaccharide was inactive. Failure of the capsular material to activate the alternative pathway was not due to serotype specificity because polysaccharide of several serotypes failed to achieve activation. The results suggest that chemotaxigenesis and alternative complement pathway activation are functions of the yeast cell wall. The results support our proposal that the cryptococcal capsul does not prevent potential opsonins from reaching binding and activation sites at the yeast cell wall or the release of biologically active soluble cleavage products into the surrounding medium; however, cell wall-bound cleavage products remain bound to the cell wall beneath the capsule. Therefore, they are unable to participate as opsonins in phagocytosis.


Immune response modulation by colonization of germfree rats with Propionibacterium acnes. Propionibacterium acnes (oral and/or parenteral administration) had a modulating effect on antibody-and cell-mediated immune responses of germfree (GF) and monoassociated (MA) rats. In conventionally reared rodents, parenteral injection of killed P. acnes stimulated the splenic plaque-forming cell response to sheep erythrocytes. However, in GF rats and in rats monoassociated with viable P. acnes, parenteral injection of killed P. acnes antigen inhibited the plaque-forming cell response to sheep erythrocytes. When compared with the responses of GF control rats, splenocytes from GF rats parenterally injected with P. acnes antigen had a decreased in vitro blastogenic response to phytohemagglutinin and concanavalin A and  an increased blastogenic response to homologous bacterial antigens. Conversely, a parenteral injection of P. acnes antigen into P. acnes MA rats resulted in an increased splenocyte blastogenic response to phytohemagglutinin and concanavalin A but not to homologous (P. acnes) antigens. Thus the presence or absence of intestinal antigenic stimuli (in MA and GF rats) had a modulating effect on the immune response to a parenteral injection of P. acnes antigen.


Longitudinal investigation of the role of Streptococcus mutans in human fissure decay. A prospective study was initiated in order to detect changes in the levels and proportions of Streptococcus mutans, S. sanguis, and lactobacilli before and at the time of caries development on occlusal fissures. The bacteriological analysis was performed on 195 teeth that received four examinations at approximately 6-month intervals. The data obtained from 42 carious fissures and 153 caries-free fissures strongly indicated an etiological role for S. mutans in most of the diagnosed fissure lesions. This was demonstrated by the longitudinal analysis, which showed the proportions of S. mutans to increase significantly at the time of caries diagnosis, and by cross-sectional comparisons, which showed that the proportions of S. mutans in the carious fissures were significantly higher than in caries-free fissures. Three subjects who had a low caries expereince developed five new carious lesions. Lactobacilli were prominent members of the caries-associated flora in these subjects greatly outnumbering S. mutans. The levels and proportions of S. sanguis tended to be higher in the caries-free fissures. Altho1gh the results are striking in that they implicate S. mutans in fissure decay, they show that clinical decay can occur in a few instances in the absence of detectable S. mutans, as was observed in the fissures high in lactobacilli.


Comparison of techniques for primary isolation of respiratory Mycoplasma pulmonis from rats. Studies were performed to determine the optimal sites for primary isolation of Mycoplasma pulmonis from the respiratory system of laboratory rats. In a preliminary study, a group of 42 rats was cultured for respiratory M. pulmonis at several sites. Tracheal washes yielded the highest number of positive cultures (61.9%) and ground lung tissue yielded the lowest (19.0%), with the nasopharyngeal culture in the middle (52.38%). In a subsequent study, the tracheal wash was again the optimal method since 76.7% of 103 rats were positive for M. pulmonis, whereas culture of the nasopharyngeal area resulted in 53.9% positive cultures. In a third study, all 45 rats were positive for M. pulmonis when the tracheal wash method was used, whereas only 51% were positive when the nasopharyngeal area was cultured, indicating that the tracheal wash was the most reliable of the commonly used procedures. Other aspects of these experiments demonstrated the tympanic cavity of animals with otitis media to be an excellent source for obtaining material to culture for M. pulmonis.


Experimental vaginal colonization and mother-infant transmission of group B streptococci in rats. An animal model for group B streptococcal vaginal colonization and neonatal acquisition was developed with albino rats. Intravaginal inoculation of genital isolates of group B streptococci of serotypes Ia, II, and III either once or on 3 successive days resulted in carriage of the organisms for 7 days or longer in 26% of the virgin animals and 43% of the pregnant animals. Throat and perianal cultures of the offspring of pregnant rats revealed that 51% of the rat pups acquired the organisms at some time. Litter exchange studies were done to explore the contributions of environmental and intralitter spread. Significantly more infants born to mothers with positive vaginal cultures acquired the organisms than infants of culture-negative mothers who were suckled by positive adoptive mothers. However, 13% of the offsprinital cultures acquired group B streptococci. This model may be valuable in understanding the dynamics of vaginal carriage and mother-infant transmission of group B streptococci.


Pathogenesis of K virus infection in newborn mice. Newborn mice were inoculated with a murine papovavirus, K virus, by intracranial, intraperitoneal, oral, and intranasal routes, and the pathogenesis of infection was studied with immunofluorescence, virus assay, and histopathology. Inoculation by each route produced a fatal interstitial pneumonia. Pulmonary vascular endothelium and, to a lesser extent, cells lining hepatic sinusoids were the major sites of viral replication, but intranuclear antigen or inclusions or both were also found in extrapulmonary vascular endothelia, spleens, lymph nodes, and brains. Although K virus produced a predominantly respiratory illness, the virus was less infectious by intranasal than by oral inoculation and did not replicate in respiratory epithelial tissues. The earliest site of K virus replication was the jejunal submucosa, suggesting that in nature K virus may be transmitted by the oral route. Viral antigen was present in brains of animals inoculated by each route and correlated with the duration of viremia. Despite the presence of abundant viral antigen, however, the nervous system remained morphologically normal. The present study indicates that a member of the papovavirus group may produce clinically silent, noninflammatory involvement of the central nervous system during the initial infection of its natural host.