The suppression of defective translation by ppGpp and its role in the stringent response. Amino acid starvation is shown to decrease the fidelity of translation in E. coli. When proteins are analyzed by two-dimensional gel electrophoresis, missense errors are detected as an unusual heterogeneity in their isoelectric points, while premature termination of protein synthesis can be recognized by a decreased relative rate of synthesis of higher molecular weight proteins and by the the accumulation of a complex group of new small polypeptides. The types of translational errors observed are amino acid-specific. For example, starvation of a rel- strain for histidine produces severe isoelectric point heterogeneity with little evidence of premature termination, while starvation for leucine has little effect on the isoelectric points, but produces a drastic decrease in the average molecular weight of the newly synthesized protein. These differences suggest codon-specific errors in reading the genetic code. In these rel- cells, the effect of amino acid starvation on the rates of synthesis of complete individual proteins is both protein- and amino acid-specific. For example, ribosomal protein L7/12, which lacks histidine, is made at a higher level during histidine starvation than during isoleucine or leucine starvation. This suggests that in rel- cells, the modulation of gene expression caused by the lack of a particular amino acid is, at least in part, a function of the abundance of that amino acid in particular proteins-that is, the response of rel- cells to starvation is consistent with the theory that the inhibition of protein synthesis and the accompanying increase in error frequency both result from low levels of the correct substrate. In marked contrast, virtually no starvation-induced translational errors are detected in a rel+ strain, and the response is not amino acid-specific. Varoius data strongly imply that in this rel+ strain, essentially all the changes caused by starvation are due to the accumulation of ppGpp, which independently reduces protein synthesis, thereby suppressing all the direct effects of amino acid limitation seen in rel- strains (where ppGpp does not accumulate upon starvation). A model is presented which describes how ppGpp might suppress the direct effects of starvation and avoid the loss of translational fidelity. In addition, the direct and specific effects of ppGpp on gene expression are examined independently of amino acid starvation.


[Use of the modified Gustafson technic for the determination of age by teeth from paleoanthropological material of Czech ruling princes at the turn of the 9th and 10th centuries]. 1. A modification of Gustafson's method is described with a view to estimating individual age according to the state of teeth in prehistoric bone material. Age estimation is made on he basis of a hisological investigation of the hard dental tissue and of the changes that affect teeth as the individual grows old. 4 markers are ascertained on thick sagittal sections of singleroot teeth in prehistorical material: degree of dental abrasion, secondary dentin desposition, cement aposition, and dental apex resorption [Fig. 1.], with scores ranging from 0--3 points. Using the marker system described by Gustafson the corresponding average age values were estimated for the total scores of the 4 markers ascertained [Fig. 2, Tab. 1] and the standard error of estimation was calculated [Tab. 2]. 2. The above method helped to estimated the age of Czech Princes ruling at the turn of the 9th and 10th centruies, whose remains were discovereed at Prague Castle. The age of Prince K 1 was thus estimated at 30--35 years, that of St. Wenceslaus at 40--45 years, and that of he Prince of Zizi at +/- 60 years. 3. The modification makes it possible for anthropologists and forensic experts to use the histological method of Gustafson's section in estimating the age both in prehistorical and in recent bone material.


Vinyl chloride and vinyl benzene (styrene)--metabolism, mutagenicity and carcinogenicity. Vinyl chloride and vinyl benzene (styrene) are mutagenic in microbial tests, in Drosophila, in yeast, and in mammalian cells. Reports from various countries have shown an excess of chromosomal aberrations in the lymphocytes of workers exposed to vinyl chloride monomer when the workers were compared with controls. Workers occupationally exposed to styrene also revealed a clear increase in the rate of chromosome aberrations in their lymphocytes. Both chloroethylene oxide and styrene oxide, the primary biotransformation products of vinyl chloirde and styrene respectively, bind covalently to cellular macromolecules. Vinyl chloride is a carcinogen in both animals and man. Styrene is currently being tested in animals. These findings, the demonstration of mutagenic response via microbial and other test systems and with observations of significant excesses of chromosomal aberrations among workers exposed to these agents, raise scientific and health oriented concern about the possible genetic risks of vinyl chloride and styrene to man.


Radioimmunoassay for urinary albumin.

Radioimmunoassay for urinary albumin. We describe a rapid, sensitive, and precise radioimmunoassay for urinary albumin (Ualb). Aliquots of diluted urine were incubated at room temperature for 1 h with 125I-labeled albumin and a rabbit antiserum monospecific for human albumin. Phase separation was effected by the double-antibody technique. The dose-response curve as linear in the range of 15.6-10000 ng, equivalent to 4 to 3000 mg/liter of urine. The limit of sensitivity was 16 ng of albumin. The coefficient of assay variation was 4.8%, both at 44 mg/liter and at 1304 mg/liter. A displacement curve obtained with a serially diluted urine sample of high albumin concentration was completely superimposable with the curve for which human albumin was used as a standard. In 26 normal individuals the range for Ualb was 2.2--12.6 mg/24h, and for albumin clearance (Calb, 1.8 x 10(-5)-19.6 x 10(-5) ml/min. After renal homografts in 25 patients, Ualb ranged from 16.9 to 9928 mg/24 h, and Calb from 2.7 x 10(-4) to 1.7 x 10(-1) ml/min. Both increased Ualb and Calb correlated well with the severity of renal homograft rejection.


Washington University Case Conference: Theophylline toxicity. This case demonstrates the importance of monitoring theophylline concentrations in serum during therapy with this drug. The commonly used body-weight-derived guidelines for therapeutic dose are not adequate and do not preclude the necessity for such monitoring. The ultraviolet spectrophotometric methods available for serum theophylline analysis are generally suitable; however, the more specific liquid-chromatographic techniques have certain advantages in that they require only small amounts of serum (25--50 microliter) and are relatively free of interferences from other commonly used drugs. The enzyme immunoassay procedure also appears well suited for the routine measurement of theophylline. The therapeutic range for serum theophylline is well established (10--20 mg/liter) and theophylline values correlate well with therapeutic response and toxicity. We therefore recommend that theophylline in the serum be monitored regularly and dosages adjusted accordingly.


Enzyme-coupled ultraviolet determination of alpha-amylase activity with the GEMSAEC centrifugal analyzer. We evaluated the Harleco alpha-glucosidase/hexokinase/glucose-6-phosphate dehydrogenase-coupled alpha-amylase method, bu use of the GEMSAEC centrifugal analyzer. Performance evaluation included kinetic studies of substrate and maltose hydrolysis as well as effects of endogenous glucose and fructose. The reagent was found to give a linear response with alpha-amylase activity to greater than 1200 U/liter. Within-run precision resulted in coefficients of variation (CV) of 0.9 to 3.2% over the range studied. Day-to-day precision corresponded to CV's of 2.4 to 4.4% over the same range of alpha-amylase procedure was found to be good (r = 0.997) for patients' sera examined.


Spurious brain creatine kinase in serum from patients with renal disease. Creatine kinase isoenzyme I(BB) is generally not detectable in normal serum, and its occurrence in serum has been documented in only a few disease states. In particular, increased activity of this isoenzyme has been reported in association with chronic renal failure, hemodialysis, and renal transplantation. The present study demonstrates that the apparent creatine kinase observed in the serum of such renal patients is an artifact, observed as a result of measuring creatine kinase isoenzymes by fluorescence. Our observations resemble those of McKenzie et al. [Clin. Chim. Acta 70, 333(1976)] concerning an artifact in the fluorometric determination of lactate dehydrogenase isoenzymes in the sera of patients with end-stage renal failure. The artifact binds to albumin, is not a protein, and occurs in some normal sera at very low concentrations. This artifact can be mistakenly identified as isoenzyme I in renal-disease patients if CK isoenzymes are determined fluorometrically.


An improved technique for immunofixation of electrophoretograms. Immunofixation coupled with electrophoresis is winning favor as an easy, sensitive, and versatile method for detecting specific protein fractions. Here, we discuss problems which appear when antisera are applied onto the electrophoretic medium (Cellogel or cellulose acetate). Longitudinal slits can be made in the electrophoretic medium without worsening resolution. Such longitudinally slitted electrophoretic membranes can be used in electrophoresis and specific antisera applied simply by pipetting them onto the electrophoretograms. The method has been used successfully in typing immunoglobulins.


Induction of cleft palates by triamcinolone acetonide: re-examination of the problem. We have examined the uptake of 3H-triamcinolone acetonide (3H-TAC) into various maternal and embryonic tissues of A/J mice. We report that the fetal tissues were able to retain TAC for long periods, although the concentrations of TAC in the maternal tissues were significantly lower. We have also examined the binding of 3H-TAC both to nuclei and cytosols from maxillary processes. We report that 3H-TAC can bind to chromatin both at low and high affinity. This leads to the isolation of two chromosmal protein fractions containing bound 3H-TAC. Therefore, triamcinolone acetonide is favorably retained in fetal tissues by its ability to bind tightly to chromatin.


Effect of niridazole in cellular immunity in vivo and in vitro. The influence of niridazole, an anti-helminthic drug, on cell-mediated immune responses was investigated. Allograft rejection in mice as well as the in vitro induction of cytotoxic T lymphocytes (CTL) against murine alloantigen were used as the test system. Repeated daily oral treatment of host mice with niridazole (100 mg/kg) prior to and during allotransplantation resulte in the postponement of graft rejection, inducing a transitory functional state of allograft tolerance. The time interval between the termination of niridazole administration and onset of graft rejection was estimated to be 5-7 days. In order to test the effect of niridazole or its derivatives on the in vitro induction of alloreactive CTL, the serum or urine of mice which were treated with niridazole were added to the cultures, instead of adding niridazole directly to the cultures. Such serum and urine were found to be inhibitory for in vitro induction of CTL. The serum and urine had no effect on the effector phase of CTL.


The effects on polymorphonuclear leucocyte function of prednisolone and azathioprine in vivo and prednisolone, azathioprine and 6-mercaptopurine in vitro. The effects of prednisolone azathioprine and 6-mercaptopurine on polymorphonuclear neutrophil chemotaxis, phagocytosis, and killing of Staphylococcus aureus and Candida albicans have been studied. In twenty patients with a functioning kidney graft, taking both azathioprine 2.5 mg/kg/day and prednisolone (mean dose 0.59 mg/kg/day; range 0.30-1.0 mg/kg/day), the polymorphonuclear function did not significantly differ from that in either twenty-two normal or eighteen uraemic controls. Addition of prednisolone, 1.2 X 10(-5) M, azathioprine, 2.1 X 10(-5) M, and 6-mercaptopurine, 2.1 X 10(-5) M, using each drug alone, to normal human polymorphonuclear cells in vitro did not significantly alter their function. It is concluded that prednisolone and azathioprine together in vivo and that both these drugs and 6-mercaptopurine singly in vitro have no significant deleterious effect on polymorphonuclear function and do not contribute, in this way, to the increased susceptibility of patients receiving these drugs to infection.


In vitro suppression of lymphocyte blastogenic response to mitogen and antigen by Leishmania tropica. Cell-mediated immune (CMI) responses are important in the immunity against Leishmania spp. infection in man. However, an infection continues to persist for a limited or indefinite period of time in spite of demonstrable CMI. The factors which allow the infection to persist in the presence of the CMI are hitherto unknown. Evidence is presented here that Leishmania tropica or their products suppress the in vitro proliferative response of normal human lymphocytes to mitogen and specific antigens. The suppressive effect of L. tropica is neither due to a direct toxic action on lymphocytes nor to competition for nutrients or antigens. In vivo such an immunosuppressive effect could both facilitate macrophage parasitization and the intracellular survival of L. tropica, even after the CMI develops to processed L. tropica antigen. Persistence of infection is seen in many other bacterial, viral and fungal infections. The in vitro suppressive effect of L. tropica on the immune response observed in our study therefore becomes relevant to the understanding of the host-parasite interaction, which may determine the eventual outcome of infection in many other intracellular infections.


Nephrotoxic potency of antisera to three rat glomerular basement membrane glycoproteins. In a previous article, we cited studies which have allowed us to isolate diverse glycoproteins of the rat glomerular basement membrane (GMB) and to study their biochemical structures and antigenicity. This present study attempts to examine, using the heterologous nephrotoxic nephritis model (Masugi's nephritis) the nephrotoxicity of immune sera prepared from three of these glycoproteins: one fairly rich in collagen-like structures (A3), another lacking collagen-like structures (A1), and a third of intermediate composition (A2). The results obtained are discussed in relation to those already published concerning the nature of the GBM antigen(s) responsible for the nephrotoxicity of the sera.


Inhibition of polyclonal B-cell activation by suppressor monocytes in patients with sarcoidosis. The present study employed a direct plaque-forming cell (PGC) assay following pokeweed mitogen (PWM) induced polyclonal activation of B lymphocytes in sarcoidosis to evaluate the in vitro humoral immune response in this disease and to delineate the immunoregulation of this response. Sarcoidosis lymphocytes had a suppressed PFC response to polyclonal activation, but were unable to suppress normal B-cell PFC responses in allogeneic co-cultures. Removal of a cell type, which was corticosteroid-resistant, radio-resistant, adherent and a non-T cell, from sarcoidosis mononuclear cell suspensions reversed the suppressed PFC response, indicating the presence of a suppressor monocyte. Thus in vitro suppressor cell activity has now been demonstrated in this disease, which is characterized by multiple immunological aberrancies.


Free flaps: an overview.

Free flaps: an overview. The free flap represents a dramatic one-stage procedure for distant transfer of skin flaps. The operative technique consists of: identification of healthy recipient vessels; isolation of viable island skin flap; distant transfer followed by revascularization via microvascular anastomoses. New techniques warrant classification of free tissue transfers into single tissue transfers (skin, muscle, bone, nerve) and compound tissue transfers (osteocutaneous, musculocutaneous). When compared to conventional techniques, free flap transfers offer shorter hospitalization and immobilization as well as a greater reconstructive potential. However, their utilization mandates extensive experience in multiple microvascular techniques and clinical microsurgery.


Clinical experiences in free flap transfer. In this series of 62 free flap transfers, 48 (80%) have been successful. There have been a significant number of vascular complications, 39% of which the majority were arterial thrombosis. Fifty per cent of those which thrombosed were salvaged on exploration and revision of the vessels. The frequency of complications has diminished with experience but they remain significantly high. Free flap surgery demands considerable expertise in both donor site dissection and microvascular technique. Two surgeons with microvascular experience, each with adequate assistance, are preferred and ready availability of operating room is essential. Close postoperative observation and readiness to revise anastomoses are equally important. About 50% of failed free flap sites have been repaired by application of split skin grafts.


Vascularized free flap transfers.

Vascularized free flap transfers. The success of a free flap transfer depends entirely on the suture of a paired artery and vein between the donor and recipient sites. The interrupted suturing method with biangulation or successive interrupted suturing is the method of choice. The size of the site, small or large, does not effect either the resulting patency or the process of intimal healing. When occlusion of the anastomosed site is encountered, the transferred free flap can be saved by exploration within 6 hours after surgery. Reapplication of the clamp proximally or distally to the anastomosed site does not change the patency rate. Free groin flaps can be successfully transferred in 2 orthopedic cases.


Management of bone in digital replantation: free vascularized and composite bone grafts. Microvascular surgical techniques have been applied to the problem of digital amputation, persistent nonunion and complicated extremity injuries with segmental bone and soft tissue loss. In replantations, adequate bone shortening and fixation with intramedullary pins or rods is mandatory. Proper patient selection, preoperative management of the amputated parts, application of microsurgical disciplines, employment of an organized surgical sequence, and rigid postoperative monitoring has resulted in an 80% viability rate in 121 replantations. Recent advances in the management of skeletal injuries using microvascular techniques include free vascularized bone grafting and salvage of the preamputation limb using free composite grafts of skin, subcutaneous tissue and bone. These free composite grafts techniques are exacting and time consuming. Meticulous planning, preoperative rehearsal and careful coordination between the operating teams make the functional restoration of a severely injured limb possible.


Artificial shoulder joint by Péan (1893): the facts of an exceptional intervention and the prosthetic method. In 1893, the famous French surgeon E. J. Péan substituted the proximal end of a humerus with a total shoulder arthroplasty made of platinum and rubber. After 2 years, the prosthesis was removed and nothing more was heard about it. After more than 80 years from that historic operation, the author has found Péan's original prosthesis in the Smithsonian Institution of Washington, D.C. This exceptional medical document was designed by a Parisian dentist, J. Porter Michaels and was brought to the United States by Edward A. Bogue, an American dentist who worked in Paris. Bogue donated it in 1916 to the Armed Forces Institute of Pathology in Washington. At the present time the prosthesis is being kept in the Smithsonian Institution. The intervention was not a complete success since Péan had to remove the artificial joint due to a persistent tubercular infection. Nevertheless this prosthesis represents a milestone in the history of medicine, an event justly deserving of our note.


Microsurgery of the peripheral nerve: a physiological approach. Results with peripheral nerve injuries, which today still fall short of our goals, should intensify our efforts in this specialized field of microsurgery. We are living in an exciting era of functional reconstitution. Long gone are the times when a pink replanted digit or a successful free flap comprised the end-point of our surgical efforts. The direction from now on is toward achieving functional restoration by utilizing basic principles while armed with the unlimited potentials of reconstructive microsurgery. To this end we need the assistance and cooperation of other sciences since the enigma of the peripheral nerve can be deciphered only by a multidisciplinary approach.


A comparison of epineurial, perineurial and epiperineurial methods of nerve suture. An experimental study was designed to compare the effectiveness of epineurial, perineurial, and combined epineurial and perineurial suture after laceration of the sciatic nerve in rabbits by measuring biochemical determinations in the distal stump of the nerve after both immediate and delayed repairs. Relatively more myelin was found in the immediate epineurial group, which suggests that nerve regeneration was most rapid in this group. Additional experiments are needed to evaluate end-organ reinnervation which is another criterion for evaluating the best method of nerve suture in clinical situations.


Microvascular surgery and its clinical applications. Experience with a surgical technique of microvascular anastomosis for free tissue transfers and digital replantations has been applied in 184 cases, and demonstrates that complications such as total flap necrosis are avoidable by experience and technical skill.


Steady-state kinetics of valproic acid in epileptic patients. Pharmacokinetic evaluation and prediction were carried out in 20 epileptic patients. Using conventional pharmacokinetic techniques and a one-compartment model, predicted and observed valproic acid plasma concentrations were compared. Valproic acid assay was performed by gas-liquid chromatography. There was good agreement between predicted and observed plasma concentrations. Most patients had predicted half-lives (t1/2s) of 6 to 8 hr, independent of the plasma concentration of valproic acid. Five patients had predicted t1/2s of 12 hr. The correlation between dose and plasma level was poor. Most patients had valproic acid plasma levels between 55 and 100 microgram/ml. Administration of valproic acid three times a day with determination of individual plasma concentrations offers a reliable method of monitoring. Constant levels are maintained in individual patients, but there is substantial intersubject variation.


Combined effects of fenmetozole and ethanol. Eight male subjects took none or 200 mg fenmetozole 1 hr before drinking a beverage containing none or 50 ml/70 kg ethanol. Tests designed to measure mental and motor performance were administered 2 hr after fenmetozole ingestion. Fenmetozole alone impaired standing steadiness but improved mental performance in one test. Fenmetozole did not antagonize the decrement in performance induced by this amount of ethanol. In combination, the subjective symptoms caused by fenmetozole were additive with those of ethanol.


Short intensive topical APF applications and dental caries in a fluoridated area. Three groups of approximately 200 children, consuming fluoridated water since birth, were given either 5, 10 or 25 consecutive topical applications with an APF gel (1.2% F, pH 3.2) in mouthpieces. After 1 year, mean DMFS increments were 7.2%, 30.4% and 35.3% less respectively for the three groups as compared with untreated control groups. Although enamel fluoride levels remained high after the 1st year, differences in dental caries increments between treated and control groups were too small to show group differences. The results suggest that in a fluoridated area, when caries activity is low, it would be difficult to show a long-term anticaries effect by increasing the fluoride concentration in sound enamel by a short series of self-applied topical fluoride applications.


Supply and demand for prosthetic treatment in Victoria, Australia. Surveys were conducted in Victoria, Australia, to estimate the demand for prosthetic treatment by examining the needs of a randomly selected group of the population. Similar surveys were conducted in relation to the contribution made by the dentists in Victoria and also that of a recently introduced group of workers, the Advanced Dental Technicians. It was found that approximately 19% of the population required prosthetic treatment in the full denture field and that the existing dentists were not meeting this need. When the Advanced Dental Technicians are more fully engaged in clinical work, the need may well be met.


Allotypes of IgM and IgD receptors in the mouse: a probe for lymphocyte differentiation. Antibodies to IgD and IgM are present in many mouse alloantisera made against lymphocytes. Antibodies to IgM are also present in a small minority of conventional antiallotype sera made against pertussis/anti-pertussis complexes. These antibodies reflect different allelic forms of IgD and IgM in different mouse strains, and allowed the mapping of the delta- and mu-chain genes (Ig-5 and Ig-6, respectively) to the heavy-chain complex. The variable portions of IgM and IgD receptors on individual cells bearing both chains are similar or identical. Both receptors show allelic exclusion and come from the same chromosome on individual cells (haplotype exclusion). It is suggested that very early in B lymphocyte differentiation there is a commitment to a given chromosome, and translocation of one copy of a given variable region gene to each heavy-chain gene. Subsequent switches of immunoglobulin class then involve differential gene activation. Immature B cells possess IgM receptors only and mature into cells bearing both IgM and IgD receptors. After activation with antigen, IgD is probably lost. These findings are discussed within the framework of the clonal abortion theory of B-lymphocyte tolerance.


The effects of asbestos on macrophages.

The effects of asbestos on macrophages. The exact role of the alveolar macrophage in the pathogenesis of asbestosis is not known. Most studies of the effect of asbestos on macrophages have been concerned with the in vitro biochemical or cytotoxic properties of the dust and have made use of peritoneal macrophages. In general, chrysotile had a toxic effect on the macrophages, whereas amphibole varieties did not. Most forms of absetos, however, are actively fibrogenic in man and animals, and there is no clear correlation between in vitro cytotoxicity of various forms of asbestos and their fibrogenicity. Recent experiments in which animals are exposed to asbestos in vivo provide evidence of alteration of macrophage activity, as demonstrated by changes in surface morphology and IgG receptor sites, as well as released of various secretory products. Deposition of complement components found on the surface of alveolar marcophages from animals exposed to asbestos could be a manifestation of a humoral immune response directed against an altered cell. The capacity of macrophages to participate in inflammation, tissue repair, and immunity suggests an immunopathogenic concept for the development of asbestosis.


The toxicity of salt.

The toxicity of salt. The subject of sodium toxicity has been controversial for a long time. There is no question that the element can be noxious when consumed acutely in large quantities and there is little doubt as to cause and effect Conversely the consequences of mederate chronic sodium consumption are much harder to document. The effects are insidious and are subject to modification by a variety of environmental influences such as dietary potassium. In addition most studies of chronic sodium excess have dealt with elusive subject of "essential" hypertension. Interpretations of data have been very difficult, and conflicting reports have occurred. Nevertheless epidemiological, clinical, and animal studies show that chronic excess sodium ingestion acting upon a substrate of genetic susceptibility, is an important etiologic factor in essential hypertension and the expression of its sequelae. Positive correlations have also have been obtained between dietary salt and the incidence of stroke and gastric cancer. Dietary potassium appears to confer some degree of protection from the toxic properties of sodium through some unknown mechanism. Available evidence indicates that a  suitable intake of salt for man might be approximately 3.5 g/day and probably less. Salt consumption in most developed countries ranges between 8 to 40 g/day, and modern methods of food processing and preparation deplete the protective potassium. The incidences of hypertension in these countries range between 15 to 40% of their populations, and it exacts a dreadful toll. Recognition of the toxic properties of sodium and knowledge of the mechanisms involved in its toxicity offer great possibilities in the area of preventive medicine It may be possible by the sorting out of hypertension-prone subjects and dietary intervention to prevent or minimize the development of hypertension in susceptible individuals. This says nothing of other aspects of sodium toxicity, of which we are largely ignorant.


Management of recurrent aphthous stomatitis. A review. The management of recurrent aphthous ulceration is discussed. It appears that the treatment of choice in mild to moderately severe aphthous stomatitis is repeated application of topical tetracycline hydrochloride. Viscous lidocaine (2 percent) provides symptomatic relief and is therefore a useful adjunct to therapy. Cyclical estrogens appear to be helpful in recurrent premenstrual aphthosis. Immune-regulating agents such as levamisole hold promise for the future.


The role of calcium in renal gluconeogenesis: studies using ionophore A23187. The divalent cation ionophore A23187 was found to increase glucose production from alpha-ketoglutarate, glutamine, succinate, and lactate but not from glycerol in isolated rat renal cortical tubules at external Ca++ concentrations of 0.1 mM. At an external Ca++ concentration of 1.0 mM or in the absence of external Ca++, the ionophore did not increase glucose production from alpha-ketoglutarate. Ionophore A 23187 did not increase cyclic AMP levels in renal cortical tubules or slices. The increase in glucose production produced by ionophore A23187 was completely prevented by pre-incubation of the tubules with 10(-5) M pentobarbital, a known inhibitor of calcium transport in biological systems. The experiments suggest that ionophore A23187 increases gluconeogenesis from a variety of substrates by altering the levels of cytosolic calcium without affecting the concentrations of cyclic AMP.


Cardiac and pulmonary effects of therapy with albuterol and isoproterenol. This study evaluated the cardiac and pulmonary effects of administering multiple inhaled doses of albuterol, isoproterenol sulfate, and placebo in ten patients with reversible obstructive disease of the airways. The pulmonary effects of therapy with albuterol were similar in magnitude to those of isoproterenol but lasted longer. The inotropic and chronotropic effects of therapy with isoproterenol were greater than those of albuterol. It appears that albuterol has beta2-adrenergic selectivity over a wide range of dosages and is an effective bronchodilator drug.


Echocardiographic manifestation of flail right and noncoronary aortic valve leaflets. Echocardiographic studies provide information useful in determining the etiology and location of aortic valvular lesions, but assessment of their severity remains difficult. We report the findings in two patients with surgically confirmed right (case 1) and noncoronary (case 2) flail aortic leaflets in whom dense echoes filled the aortic root in systole, only to move from this position into the left ventricular outflow tract during diastole. This echocardiographic finding is a clinically useful noninvasive indicator of rupture of the right or noncoronary aortic cusp and dictates a need for early surgery.


Children of depressed and schizophrenic mothers. A sample of psychotic mothers and their children who were five years or younger when first recruited for our study of high risk children was followed up five years later. The current sample, obtained from our previous work, consisted of 18 schizophrenic, 12 depressed and psychotic, and 22 well mothers and their six to 12 year old children. The mothers were equated for education and age, and the children for sex and age. Cognitive style tests and interviews measuring social adjustment and functioning were given to both the parents and the children.


Fluorescent antibody study of diseased, end-stage human kidneys. Forty cases of diseased kidneys at end-stage were studied by fluorescent antibody technique in search for viral etiology of glomerulonephritis and other renal diseases. Among these 40 cases, 12 (30%) were ascribed to immune complex disease because of detection of immunoglobulins and complement in glomeruli of the same kidney specimen. In 8 cases (20%) only complement was detected in glomeruli. In the remaining 50% neither complement nor immunoglobulin deposit was found in glomeruli. The etiologies of the latter cases remain unknown. Of 12 cases of kidney disease of immune complex origin, hepatitis virus type B surface antigen was detected in 2 cases. In these 2 cases the magnitude of immune complex deposits with complement was greater than that of other cases. Other than hepatitis B virus antigen, no other viruses including Coxsackieviruses, ECHO viruses, and HSV-1 could be detected by indirect fluorescent antibody techniques. The proportion of complement deposit to the deposition of complement with immune complex in the diseased kidneys at end-stage was calculated and statistically analyzed.


Evaluation of microscopic examination for bacteriuria. In order to find an easily available, simple, reliable and inexpensive method for demonstrating significant bacteriuria in routine urine examination, microscopic observation and bacteriological cultures have been made in parallel on total of 206 urine samples. Microscopic examinations of centrifuged deposit for both pus cells and bacteria were found to be more satisfactory in urine specimens with significant bacteriuria than the examinations for either of these elements alone. The criteria of more than five pus cells per high power field and organisms visible in methylene blue stain had sensitivity of 79% and a false positive rate of 13%.


[Hepato-biliary sequential scintigraphy. A diagnostic possibility for monitoring bile secretion following orthotopic liver transplantation]. One often finds complicating diagnostic uncertainties, when evaluating cholestasis in the early postoperative phase as well as in the follow-up of orthotopic liver transplants. One potential complication is the obstruction of the biliary tract caused by various conditions. The diagnostic value of hepatobiliary sequential imaging is demonstrated in there patients. This method is a noninvasive, simple way of investigating the bile flow after orthotopic liver transplantation, and therefore proves a valueable tool among the diagnostic procedures used for differentiation of the cholestasis syndrome.


The characterization of high-resolution G-banded chromosomes of man. The detailed characterization of G-banding patterns of high resolution human chromosomes has been possible with the utilization of a refined cell synchronization technique which routinely yields a large number of excellent quality cells in late prophase, prometaphase, early metaphase, and mid-metaphase. The mitotic cells exhibit up to a 400% increase in the number of bands previously visualized by standard methods. From studies of the banding patterns, it has become evident that the G-positive and, to some extent, the G-negative bands of mid-metaphase results from a coalescence of finer subbands of earlier stages and that each band and its corresponding subbands maintain a constant location throughout the process of chromosome condensation. A precise schematic representation of the number, position, height and staining intensity of bands is presented for the five largest chromosomes of the complement at the four mitotic stages.


Effect of salt-treatment on manually isolated polytene chromosomes from Chironomus tentans. A method for the rapid manual isolation of polytene chromosomes and nuclear membranes from salivary glands of Chironomus tentans is presented and the analysis of some of their RNA and protein components before and after treatment with 2 M salt solutions is summarized.--After salt-incubation the chromosomes still display a considerable number of bands which stain with ethidium bromide and which are sensitive to treatment with DNase, RNase, trypsin, and proteinase K, to a lesser extent with pronase and papain. Analysis of the iodinated residual proteins on SDS gels yield three major and two minor bands (MW between 50,000 and 70,000 dalton) which were also shown to be present in interphase chromosomes of Ehrlich ascites cells which had been treated similarly and are also tightly bound constituents of DNA prepared according to Gross-Bellard et al. (1973). This result indicates the existence of a general class of non-histone proteins involved in keeping the DNA in a supercoiled state. Furthermore their presence in salt-treated nuclear membranes of Chironomus salivary gland cells (and Xenopus oocytes, unpubl.) will be of interest with respect to functional aspects of the nuclear matrix.


Production and characterization of antisera against three individual NHC proteins; a case of a generally distributed NHC protein. In order to assess the selectivity of the distribution patterns of individual nonhistone chromosomal proteins (NHC proteins), immunofluorescent staining experiments were performed on Drosophila polytene chromosomes. Antisera have been prepared against three individual NHC proteins which were isolated by sequential preparative slab gel isoelectric focusing and SDS polyacrylamide gel electrophoresis. In two cases, immunofluorescent staining of the chromosomes indicated a specific limited distribution pattern; apparently the antigen in each case is present at a reproducible and distinct subset of chromomeres. This type of pattern has also been obtained with antisera prepared against molecular weight subfractions of NHC proteins (Silver and Elgin, 1977). Each selective fluorescence distribution pattern obtained so far is reproducible and unique to the antiserum under study. In a third case, an antiserum caused prominant staining at dense chromomeres and the chromocenter in a pattern mimicking DNA (and presumably histone) distribution. Indirect radioimmunostaining of SDS and isoelectric focusing gels on which total NHC proteins had been separated confirmed that this antiserum reacted specifically with a protein(s) of molecular weight 21,000 D and pI 5.2. The data in conjunction with absorption experiments indicates that the chromosomal staining is due to an interaction of antibodies with NHC protein(s) and not with histones. This finding suggests that at least one major acidic NHC protein plays a very general role (comparable to that of the histones) in maintaining chromatin structure.


The search for circadian rhythm pacemakers in the light of lesion experiments. Considering the huge phylogenetic tree of evolution of the animal kingdom, only very limited observations have been made on the pacemaker mechanism of the circadian rhythms of various biological phenomena. If there is a master clock controlling the circadian rhythmicity in the animal body, lesions in it should certainly produce arrhythmic activity. On the basis of very scattered data available at present, it can be presumed that in the central nervous system there is a group of cells which functions as a master clock. Its location is close enough to the primary photoreceptors to be entrained by the environmental light-dark cycle. The clock unidirectionally controls all body activities and also other secondary pacemakers, if they exist. The influence of a secondary pacemaker is seen in pathological conditions or after destruction of the master clock. Lesions in the coupling site between the clock and overt activity may result in arrhythmia without damaging clock activity. Hence, care must be taken in assessing the data recorded. Up to now, the optic lobes in several insect species and the suprachiasmatic nucleus in several rodent species are the most likely sites of a master clock, and lesions in these instantaneously induce arrhythmia. Increasing study of the retinohypothalamic projection in other mammals and birds will throw more and more light on this nucleus. A search for the circadian master clock in the body should, therefore, be extended to all species of animals and this will clarify the circadian clock mechanism, no matter whether it functions as a result of membrane activity, genetic influence or a very specific biochemical mechanism resistant to environmental changes.


The biological importance of organophosphorus compounds containing a carbon-phosphorus bond. Organophosphorus anticholinesterase compounds may be derivatives of phosphoric acid or of a phosphonic acid. The phosphonic acid derivatives are usually more reactive and more toxic than the phosphoric acid derivatives. Examples are given to show that differences in the chemical and biological reactivity of phosphates and phosphonates reflect many different aspects of their chemical structure. Some recently discovered naturally-occurring phosphonates are described, together with some synthetic phosphonate analogues of naturally-occurring phosphates. The utility of these synthetic phosphonates as tools for probing enzymic reaction sequences is discussed.


Metabolic factors and the utilization of phosphorus by plants. The overall process of entry and transport of phosphate by plants has been separated into its component parts. Rapid esterification is involved but a small proportion of the total transport may occur by a non-metabolic route. Mannose alters the metabolism of phosphate in roots of cereals and thereby reduces the transport to the shoot by as much as 99% whereas dicotyledonous species are much less sensitive. The sequestration of phosphate as mannose 6-phosphate is reversible in some species depending on the extent of its conversion into fructose 6-phosphate and it is possible that in vivo controls of this type operate in whole plants. The factors involved in the control of distribution of inorganic phosphate between cellular organelles and throughout the plant are discussed. Enzymic hydrolysis of organic forms by roots and associated microorganisms may also be important in soils where available orthophosphate is limiting. Other inorganic nutrients, particularly boron, play an important role during the transport of phosphate across membranes. Major differences have been found in the capacities of different species to transport absorbed phosphate to the shoot. Peas and field beans absorb efficiently in the early weeks of growth but the rate of transport is about one thirtieth that of oats, barley, mung bean or sunflower. The relevance of the experimental findings to the wider problem of efficiency of fertilizer use and the possible selection of genotypes with high capacities for absorption and transport are discussed.


Phosphorus cycles of forest and upland grassland ecosystems and some effects of land management practices. The distribution of phosphorus capital and net annual transfers of phosphorus between the major components of two unfertilized phosphorus-deficient UK ecosystems, an oak--ash woodland in the Lake District and an Agrostis-Festuca grassland in Snowdonia (both on acid brown-earth soils), have been estimted in terms of kg P ha--1. In both ecosystems less than 3% of the phosphorus, totalling 1890 kg P ha--1 and 3040 kg P ha--1 for the woodland and grassland, respectively, is contained in the living biomass and half that is below ground level. Nearly all the phosphorus is in the soil matrix. Although the biomass phosphorus is mostly in the vegetation, the soil fauna and vegetation is slower (25%) than in the grassland vegetatation (208%). More than 85% of the net annual vegetation uptake of phosphorus from the soil is returned to the soil, mainly in organic debris, which in the grassland ecosystem is more than twice as rich in phosphorus (0.125% P) as in the woodland ecosystem (0.053% P). These concentrations are related to the rates of turnover (input/P content) of phosphorus in the litter layer on the soil surface; it is faster in the grassland (460%) than in the woodland (144%). In both cycles plant uptake of phosphorus largely depends on the release of phosphorus through decomposition of the organic matter returned to soil. In both the woodland and the grassland, the amount of cycling phosphorus is potentially reduced by its immobilization in tree and sheep production and in undecomposed organic matter accumulating in soil. It is assumed that the reductions are counterbalanced by the replenishment of cycling phosphorus by (i) some mineralization of organically bound phosphorus in the mineral soil, (ii) the income in rainfall and aerosols not being effectively lost in soil drainage waters and (iii) rock weathering. The effects of the growth of conifers and sheep grazing on the balance between decomposition and accumulation of organic matter returned to soil are considered in relation to the rate of phosphorus cycling and the pedogenetic changes in soil phosphorus condition leading to reduced fertility. Although controlled sheep grazing speeds up phosphorus cycling and may reverse the pedogenetic trend in favour of soil improvement, conifers may slow down phosphorus cycling and promote the pedogenetic trend towards infertility.


Phosphorus and the eutrophication of lakes--a personal view. The availability and abundance of biologically-active forms of phosphorus in natural waters are briefly reviewed in relation to the requirements, growth and development of algal populations. The consequences of artificial enrichment of lakes with agricultural, domestic and industrial effluents ('eutrophication') attributed to increased phosphorus loading are compared with evidence from a selection of natural lakes and experimental systems in the UK. The suggestion is made that increased loadings on richer lakes make relatively less impact than does mild eutrophication of unproductive waters. Within limits the effects of eutrophication are reversible.


The dissipation of phosphorus in sewage and sewage effluents. Of the 41 kt of phosphorus reaching the sewage works in England and Wales 15 kt is removed in sewage sludge and the remainder is disposed of to rivers. 60% of the sewage sludge is now used as fertilizer and this proportion will no doubt increase in the future. The total use of sewage sludge, however, represents only about 5% of the current annual usage of artificial phosphorus fertilizer. At present there is no general economic incentive to make better use of the phosphorus in effluents. Phosphorus removal is expensive--about 2--3 pence/m3. If all the sewage effluents in England and Wales were to be so treated the cost would be about 100--150 million pounds annually, that is about 50% of the present costs of sewage treatment. In certain cases, but rarely in the UK, phosphate is removed, not to conserve phosphorus but to minimize the problems it creates in the environment. The phosphorus removed has little value as fertilizer. Alternative methods of using the phosphorus in effluents by the production and harvesting of crops of algae or aquatic plants have so far proved uneconomic. However, these methods need to be reviewed periodically as they may in the future become economically more attractive, especially in warmer climates where plant growth can be maintained throughout the year.


World resources of phosphorus.

World resources of phosphorus. The geochemistry of phosphorus and the global distribution of its resources are reviewed. The concept of reserves and resources is discussed in view of recent price developments in the phosphate mining industry. A description is given on the application of a model called MIMIC (Mining Industry Model for Inventorization and Cost evaluation of mineral resources) for estimating the inferred global reserves and resources in different cost categories. Based on the size and growth rate of annual production, the inferred reserves can be estimated at +/- 20 000 Mt of phosphorus. This figure is in reasonable agreement with conventionally estimated demonstrated resources. Estimates of exploitable resources with the MIMIC model vary between 40 000 and 500 000 Mt with about 20 000 Mt in deposits containing about 14% P (70% BPL). The inferred reserves alone would satisfy current consumption for many hundreds of years. In this context, the historical growth rate of slightly less than 7% per annum appears neither exceptional nor particularly alarming with respect to the next doubling of the world population.


Some economic and technical factors affecting use of phosphate raw materials. In comparison with phosphate resources most of the other industrial minerals essential to man have much higher unit values. Furthermore, they generally have more narrowly defined geochemical origins, concentration requirements, and end-use markets. Consequently, an economic assessment of their mined production cost in relation to market value is more easily and reliably defined. Thus, the mere knowledge of existing or newly discovered ore bodies provides economic incentives for exploitation plans--even in the most remote geographical location (as is well illustrated by iron, copper, tin, lead, and similar mineral commodities). Unfortunately, this is not the case for phosphate resources. Much of the known vast reserves of more than 1 X 10(11) tons, which are favourably dispersed among the worldwide markets, remains uneconomical to recover, despite the growing need for phosphate in world food production. A complex set of interrelated technical and economic factors decide the economic potential of any particular phosphate reserve. Although technical similarities may exist among deposits, economic analogies are rare. The economic evaluation of the mineability of the ore and the mill preparation of the concentrates must also take into account the geological setting and character of the ore deposit as well as the eventual end-use markets and their locations.


Effects of apomorphine and apomorphine-L-dopa-carbidopa on alcohol post-intoxication symptoms. In a randomised double-blind clinical trial on 58 gamma-alcoholics, the effect of apomorphine given orally in individual subemetic doses was compared with apomorphine-L-dopa-carbidopa and with placebo. No positive effects of treatment with apomorphine, or with the combination apomorphine-L-dopa-carbidopa, on alcohol consumption or post-intoxication symptoms could be demonstrated. In the group which received the combination apomorphine-L-dopa-carbidopa, the post-intoxication symptoms lasted significantly longer than in the other two groups.


Phosphorus and mankind's problems today. The unprecedented increase in the worldwide population of humans--a growth which has been underway for two centuries and has been continuously accelerating--seems to be a root cause of many of the problems of today, including including those treated in this symposium. Current events once more arouse fears that the probable conclusion of our present growth era will unfortunately consist of widespread death from famine, pestilence, and social disruption of various kinds (perhaps involving nuclear devices). Non-local efforts to avoid famine induced by rapid population growth seem only to delay an eventuality that will thereby finally lead to many more people starving. In this paper, phosphate pollution and soil erosion are treated as indirect results of the population boom; and some radical changes in soil and water management are suggested for lessening these problems for large populations.


[Herpes virus hominis diseases (author's transl)]. In a 14-year-old girl treated with cytostatics because of leukaemia a severe and chronic atypical herpes virus hominis infection occurred. The same disease also occurred in a 30-year-old man under immunosuppression after a renal transplant. The skin reactions posed diagnostic and therapeutic problems. In both cases withdrawal of the cytostatic agent or drastic reduction of the immunosuppressive drug were successful therapeutically.


Modern mankind's influence on the natural cycles of phosphorus. When the molten surface of the earth solidified over 4 X 10(9) years ago the quantity of phosphorus to be contained in the storehouse of the new planet had already been resolved. The phosphorus was locked in an igneous lithosphere as orthophosphate. With the advent of the first primitive rainstorms the slow endless process of liberating the phosphorus from the igneous rock strata had begun. It required about 3 X 10(9) years for this process to supply enough soluble phosphates for the seas of the earth to become saturated with respect to apatites. Today slightly more than half of the phosphate is contained in sedimentary deposits. The established phosphorus cycles of the earth were almost independent of the activities of mankind for more than 4 X 10(9) years. Only in the past 200 years has the influence been worthy of consideration and as late as the 1960s too few reliable data were available for us to assess the status of our activities on the natural cycles. Today a reasonably clear picture is emerging.


Phosphorus biochemistry.

Phosphorus biochemistry. The biochemistry of phosphorus is outlined. As this element appears to have no redox reactions in biological systems phosphorus is always handled as phosphate and, as all phosphate compounds are thermodynamically unstable in water, phosphate uptake and incorporation are associated with energy consumption. The subsequent use of phosphate in metabolism and synthesis is illustrated by metabolic pathways and DNA (RNA) polymerizations, respectively. The importance and unique chemical significance of phosphorus in biology cannot be overestimated.


[Mechanic-technological and metallographical studies on soldering of dental alloys]. It can be proved that the reliability of soldering is in practice not very high, as properties of solidity and the quality of compounds very greatly. This is unavoidable in spite of the most careful execution of the welding and observation of the corresponding soldering directions. Low sigmaB-values are attributable to: 1. the insufficient filling of the soldering space (ca. 80%); 2. many lacunae in the solder commissures, which partly communicate with one another; 3. small diffusion zones and poor wettability in case of the pairing of the materials Co-Cr-Mo/Au-solder.


Age difference in the response to synthetic luteinizing hormone-releasing hormone (LHRH) in androgenized rats with special reference to the dose of testosterone propionate for androgenization. Five-day-old female rats were androgenized with 1,000 or 100 microgram testosterone propionate and were examined regarding the response to LHRH at 4, 7 and 12 weeks of age by measuring peripheral LH concentrations. The order of magnitude in LH release was 7 greater than 4 greater than 12 weeks old, whereas in normal rats, 4 greater than 12 greater than 7 weeks old. LH release in 4- and 7-week-old rats was higher than that in normal controls at the respective age, but was much lower than that in normal controls 12 weeks old. The LH release by Des-Gly10-(D-Ala6)-LHRH-ethylamide (TAP127) was greater than that by natural LHRH both in normal and androgenized rats at 7 or 12 weeks old. The results indicate that the pituitary gland in androgenized rats responds to LHRH to a much larger extent during the premature period and its responsiveness declines during the course of maturation. A marked hypersensitivity was observed in 7-week-old rats androgenized with 100 microgram testosterone propionate. The process of androgenization may include the induction of alterations in the sensitivity of the pituitary to LHRH and probably in the LH synthesizing ability of the pituitary.


Conditions for establishment of reflex ovulation in light estrous rats. Continual anovulatory state associating with persistent vaginal cornification (light estrus) was induced by placing 4-day cycling rats under continuous lighting (LL). Uterine cervical stimulation was applied at arbitrary solar hours to light estrous rats showing continual vaginal estrus for more than 2 weeks. The ovulation was induced between 14 and 16 hr after the stimulation dissociating entirely with solar hours. Injection of anti-LHRH serum 5 min after the stimulation but not later than 20 min blocked this ovulation. Ovulation thus induced was always followed by pseudopregnancy with continual leucocytic vaginal smear lasting 10.70 days. The change in concentrations of peripheral serum progesterone during this period was almost similar to that of normal pseudopregnancy except extremely low levels observed at the start and end. Effectiveness of the cervical stimulation for induction of ovulation in light estrous rats was related to not only the duration of light estrus but also the time after transfer to LL, suggesting that the neural mechanism of ovulation in light estrous rats shifted from that of the spontaneous to reflex ovulators due to the extinction of environmental photic cue.


Bombesin inhibits insulin release from isolated pancreatic islets of rats in vitro. The effect of bombesin on insulin release from isolated pancreatic islets of rats was examined in vitro. Bombesin, at the doses ranging from 10 ng/ml to 1 microgram/ml, significantly inhibited 16.7 mM glucose-induced insulin release, while bombesin had no inhibitory effect on insulin release at 8.3 mM and 3.3 mM glucose. Moreover, bombesin also suppressed insulin release elicited by 10 mM arginine at the doses of 100 ng/ml and 1 microgram/ml. These results indicate that bombesin has a direct inhibitory action on insulin release.


Influence of hormonal contraceptives on the pituitary response to LH/FSH-releasing hormone. In the pre-ovulatory phase the absolute and relative LH increase was much greater than during the luteal phase and less pronounced in the early follicular phase of the normal cycle. FSH release was affected only during the pre-ovulatory period, where a retarded, 3- or 4-fold increase compared to basal levels was recorded. In the women taking oral contraceptives of the conventional type the first LH-RH test showed gonadotropin responses similar to those obtained during the luteal phase of the controls. The second test brought a significantly lower LH response, suggesting an increasing exogenous steroid inhibition at the pituitary level in the course of the therapeutic cycle. This inhibition seems to be reversed during the monthly tablet-free interval. A particularly small and retarded gonadotropin response was observed in patients taking Deposiston. These results are discussed as to their clinical significance.


Study of actin and its interactions with heavy meromyosin and the regulatory proteins by the pulse fluorimetry in polarized light of a fluorescent probe attached to an actin cysteine. The decay of anisotropy of the N-iodoacetyl-N'-(5-sulfo-1-naphthyl)-ethylenediamine fluorescence attached to cysteine-373 of actin can be characterized by two correlation times theta1 and theta2. theta1 has a value of several nanoseconds and is thought to represent some local protein motion. theta2 is of the order of several hundreds of nanoseconds. Its value increases with actin concentration. It represents an average of the G and F actin correlation times. When actin interacts with heavy meromyosin, theta2 increases and becomes infinite at a molar ratio of one heavy meromyosin molecule per four actin protomers. It is concluded that a definite complex is then formed between F actin and heavy meromyosin. In the same time, G actin concentration becomes equal to zero. Finally, when F actin forms a complex with the regulatory proteins tropomyosin and troponin, the value of theta2 is greater in the absence than in the presence of Ca2+. This result indicates that micromolar concentrations of Ca2+ induces a conformation change of the complex of F actin with the regulatory proteins.


Sulfite binding to a flavodehydrogenase, cytochrome b2 from baker's yeast. Baker's yeast L-lactate dehydrogenase (flavocytochrome b2) is a typical flavodehydrogenase, in that it accepts two electrons from the substrate but has a monoelectronic acceptor. Yet it forms a red semiquinone [Capeillère Blandin et al. Eur. J. Biochem. 54, 549--566 (1975)] and it is shown in this paper that it forms a reversible covalent complex with sulfite (Kd = 1.4 muM). This complex can be observed by difference spectroscopy and provides a convenient tool for visualizing the flavin chromophore, usually hidden behind the intense heme absorbance. A number of anions (D-lactate, oxalate and pyruvate) are inhibitors of the enzymatic reaction and induce spectral perturbations of the flavin spectrum. It is concluded that probably two positive charges exist at the active site: one which stabilizes the red semiquinone and one which attracts organic anions and sulfite. It is also concluded that the correlation between reactivity with sulfite and reactivity with oxygen among flavo-proteins may not be as general as previously proposed [Massey et al. J. Biol. Chem. 244, 3999--4006 (1969)].


Paracrystalline arrays of protein-synthesis elongation factor Tu. Comparison with polymerized actin. Homogeneous protein synthesis elongation factor Tu from Escherichia coli forms aggregates at high concentrations of ammonium sulfate which have a filamentous appearance in the light microscope. Electron microscopy of negatively stained preparations shows that these aggregates are paracrystalline, including three different forms. On the basis of analyses by optical diffraction, this polymorphism can be explained in terms of three different tubular foldings of the same basic two-dimensional surface lattice. This can be compared with that underlying the structure of actin filaments, thus providing a crucial test of the putative relationship between the elongation factor and actin [Rosenbusch, J. P. et al. (1976) J. Supramol. Struct. 5, 391-396]. The differences between the surface lattices, in conjunction with the negative results of sensitive immunochemical tests for possible cross-reactivities between the two proteins, suggest that any such relationship is very remote.


Acid maltase deficiency in adults. Clinical, morphological and biochemical study of three patients. 3 adult women with distinct clinical pictures of progressive myopathy were studied. The morphological findings of biopsied skeletal muscle suggested the diagnosis of type II glycogenosis. Biochemical analysis confirmed a profound deficiency of alpha-1,4-glucosidase activity. Electrophoresis of muscle acid maltase showed the presence of one band in normal individuals. A very faint band with normal electrophoretic mobility was present in the patients' muscles. Muscle neutral maltase is composed of four bands in normal adult individuals: two of the four bands were clearly reduced in the muscles of the patients. The acid and neutral maltases were not significantly reduced in the patients' leukocytes. Acid maltase determination in urine made it possible to identify the homozygous, but not to completely segregate the heterozygous, from unaffected adult subjects.


Transcutaneous PO2 measurement for evaluating the oxygen supply of skin allo- and autografts. Theory and practical application. The condition of skin autografts and allografts in rats and rabbits was checked by transcutaneous PO2 measurement according to R. HUCH, D. W. LUBBERS and A. HUCH. The tcPO2 values obtained with standardized maximal hyperemia allow conclusions concerning the oxygen supply and thus the vascularization of a transplant. This method seems suitable to monitor the healing of autografts and to register quantitatively the progress of rejection in allografts.


Splenic transposition with ligation of the vascular pedicle in rodents. Immunological consequences. By splenic subcutaneous transposition and ligation of the vascular pedicle, the direct relation spleen-liver was interrupted in rodents infected with malaria. It was demonstrated that in this situation detoxification of the liver and recovery from malaria was evidently hampered by the lack of a direct splenic cell supply, due to retardation of the homing and differentiation in the spleen of precursors of immunologically competent cells. In the presence of blood-borne antigens and/or hepatotoxins, this simple 'shunt' operation appears to constitute a serious immunological handicap. However, it may be a useful model for the study of cellular and microenvironmental interrelationships of the immune response versus blood-borne antigens.


Ontogeny of B lymphocyte function. VI. Ontogeny of thymus cell capacity to facilitate the functional maturation of B lymphocytes. The differentiation of the B cell population from fetal mice to produce a normal, adult-like, heterogeneous reponse, with respect to antibody affinity, has been shown to require (or to be facilitated by) thymus cells. The maturation of the thymus cell population to be capable of facilitating this differentiation of the B cell population was studied. It was found that the thymus cell population acquires the capacity fo facilitate (or induce) this maturation of the B cell population between seven and ten days after birth. Thus, the normal maturation of the B cell population to give a response which is heterogeneous with respect to affinity, appears to be controlled by the maturation of thymus function.


The use of a right atrial catheter in bone marrow transplantation for acute leukemia. A right atrial catheter was implanted into 15 patients undergoing bone marrow transplantation as a treatment for acute leukemia. The catheter remained in position for 79 +/- 34 days. No catheter-related septicemia was observed. It appears that this catheter is helpful in supporting bone marrow transplant recipients.


Image processing in pathology. V. Interpretation of feature distributions of liver cell nuclei in histological sections. A new method is applied for calculating the volume and extinction of liver cell nuclei from area and extinction of their sections in histological slices. With a special classificator for the automatical processing of microscopical pictures 96 per cent of morphologically controlled aequatorial sections of liver cell nuclei are correctly recognized. Using a mathematical model (additive fitting of three normal distributions to the given feature distribution) ploidie classes and volume classes can be recorded more exactly.


Nephrotoxic and pneumotoxic antibodies and their acute action on lungs. III. Organ localization of antibodies after experimental administration of lethal doses. Experimental intravenous administration of large doses of heterologous anti-glomerular and anti-lung antibodies induces acute exsudative haemorrhagic changes in the lungs resulting in death of the experimental animals. The specific localization of these antibodies labelled with radioactive isotopes of iodine and administered using the paired-isotope technique with radioiodinated normal IgG, displayed high values in the lungs, liver and kidneys. Pulmonary changes developing after administration of the same dose of anti-glomerular antibodies into the left heart ventricle are of lesser extent and the animals survive. On this mode of administration, the specific localization of antibodies presents lower values in the lungs, whereas the values in the kidneys and liver are approximately the same as seen after intravenous administration. Antibody localization in the kidneys and liver is facilitated by the morphologic structure of the capillaries, whereas in the lungs a direct transendothelial transfer must be considered, since in this organ capillary endothelium forms a coherent layer. Attention is being drawn to the high specific localization of antibodies in the liver and to the potential effect of these antibodies on the liver.


Morphologic aspects of alveolar microcirculation. Direct observations of the flow direction and connections between arteries and veins in the mammal lung are difficult. When we divide the lung into smaller units like acini or segments we can observe a central supply of the unit with arterial blood that has venous drainage at different points of the periphery. Consideration of the situation prevailing at birth strongly suggests a preferential flow direction through paths located in primary septa at the bottom of alveoli. Capillaries of the secondary septa placed between alveoli open to the same duct represent collaterals of the mainstream flow filled only if pressure conditions permit. Another significant feature is the presence of pleated alveolar septa. While capillaries inside the interalveolar wall mostly appear flat or collapsed, the capillaries of the pleated alveolar corners are always wide open. Often they show openings into a small venule placed inside the pleated area, which strongly suggests that the pleated areas contain the venous side of the capillaries.


Pharmacological factors influencing permeability of the bronchial microcirculation. The bronchial microcirculation is organized as a network of interconnected superficial and deep small blood vessels that extend throughout the bronchial tree. The close proximity of the bronchial venules to the origin of the pulmonary lymphatics suggests a role in fluid balance in the lung. The responsiveness of the venous segment of this network to agents influencing permeability clearly indicates a role in the genesis of certain types of noncardiogenic interstitial edema. The responsiveness of the venous segment of the bronchial circulation to neural and humoral stimuli raises the possibility of a significant role in the distribution of blood flow between the mucosa and peribronchial space. Such control may play a significant role in heat and water exchange between blood and air. Thus, these observations indicate that the bronchial microcirculation is involved with aspects of pulmonary function other than the nutrition of the bronchi, nerves, pleura, and large pulmonary blood vessels.


Structural basis for some permeability properties of the air--blood barrier. The structural basis for the permeability of the alveolar-capillary membrane to water-soluble solutes rests in part on the structure and function of its intercellular junctions and the pinocytotic vesicles within its cells. Intercellular junctions between endothelial cells of the pulmonary capillary bed differ both in permeability to enzyme tracers and in their structure. As determined by freeze fracture, the junctions in the arteriolar, capillary, and venular portion of the capillary network vary in complexity, and in the number of rows of particles constituting the junction. Because there are few particles associated with the junctions in the venular end of the capillary bed, these are considered to be the most permeable of the three types of vascular junctions. Epithelial junctions, in contrast, are impermeable to all enzyme tracers studied, and they are composed of a continuous, complex network of junctional fibrils. While intercellular junctions form seals of varying 'tightness,' pinocytotic vesicles provide a means for the transport of water-soluble macromolecules across the alveolar-capillary membrane.


Pulmonary metabolism of epoxides.

Pulmonary metabolism of epoxides. Activities of epoxide hydrase (EH) and glutathione S-transferase (GST) have been measured in pulmonary tissue from several species. On the basis of total organ activity, pulmonary tissue has less capacity than liver tissue to metabolize epoxides. Pulmonary EH and GST appear to be refractory to induction by typical agents. Rat pulmonary GST will conjugate a variety of epoxides, but K-region epoxides are metabolized at lower rates than alkene oxides. In the isolated perfused rabbit lung, benzo (a) pyrene-4,5-oxide (BPO) is metabolized by EH and GST at similar initial rates, but EH activity is lost after a few minutes, apparently owing to inadequate local substrate levels. GST from rabbit lung cytosol has been separated by chromatographic methods into six peaks of enzymic activity (toward 1-chloro-2,4-denitrobenzene). Of these peaks, all six metabolized BPO and two metabolized styrene oxide. Although EH and GST are less active in lung than in liver, pulmonary metabolism of epoxides is important because this tissue must be able to protect itself from arene oxides generated by pulmonary oxidative metabolism of polycyclic aromatic hydrocarbons.


Pleural reactions to environmental agents. In the past, pleural disease has been uncommon, generally limited to infection derived from underlying pulmonary involvement or the result of local neoplastic invasion or hematogenous metastases. The deep, protected location of the lung's mesothelial surface provides insufficient defense against environmentally derived very fine biologically active inorganic particles, and a new set of abnormalities--pleural plaques, fibrosis, unique calcification, malignancy (mesothelioma), benign asbestotic effusion--have introduced problems of pathogenesis, diagnosis, management, and therapy. These changes are becoming frequent among individuals who were exposed to asbestos more than 20 years ago. Occupational exposure (direct and indirect), and in some cases environmental exposure (household contacts of asbestos-exposed workers and factory neighborhood residents), have been associated with higher prevalence of radiographically evident pleural abnormalities. What effects such changes will have on morbidity and mortality rates is incompletely understood.


Inhalation anesthetics.

Inhalation anesthetics. The inhalation anesthetics affect operating room personnel as well as the patient. This occupational exposure is similar in all respects to industrial solvent exposures. Although the extent of the hazard is not yet established, it is clear that only quite low levels of these active chemical should be allowed in the operating room air.


Environmental injury of the lung: role of humoral mediators. Environmental lung injury may take the form of acute tracheobronchitis, asthma, pulmonary edema, chronic bronchitis, emphysema, allergic pneumonitis, fibrosing alveolitis, pleurisy, and neoplastic disease. Environmental factors eliciting these responses include irritant gases and fumes, oxidants, organic allergens, inorganic dust, bacterial enzymes, and high partial pressures of oxygen. The basic pulmonary reactions to these toxic agents--bronchoconstriction, vasoconstriction, increased vascular permeability, inflammation, carcinogenesis--may be mediated, aggravated, or modulated by biologically active substances. These humoral agents include biogenic amines (e.g. histamine): peptides (e.g., bradykinin, vasoactive intestinal peptide, and spasmogenic lung peptide); enzymes (e.g., proteases, superoxide dismutase, and mixed function oxidases); and acidic lipids (e.g., prostaglandins, prostaglandin endoperoxides, and thromboxanes).


RNA transcription and chromatin structure during meiotic and postmeiotic stages of spermatogenesis. Autoradiographic procedures for the study of RNA and protein synthesis during spermatogenesis have been complemented with electron microscope techniques for visualization of gene activity. These procedures have enabled us to determine that RNA transcription is highly selective with respect to RNA species, timing of synthesis, types  of chromosomes (autosomes and sex chromosomes), segments of chromosomes (i.e., the lampbrush segment), and chromatin structure. In mouse and human spermatocytes, a peak production of ribosomal RNA (rRNA) occurs during leptotene-zygotene, preceding nonnucleolar RNA synthesis, which is at a peak in middle pachytene. Transcription in late spermatids decreases in coincidence with changes in chromatin structure and high incorporation rates of [3H]arginine. In these cells, a particulate repeating pattern of chromatin is replaced by chromatin fibers of uniform diameter as highly arginine-rich proteins replace somatic histones. In spermatogonia, spermatocytes and Sertoli cells, the products of transcription are mainly heterogeneous nuclear RNA (hnRNA) and rRNA, whereas spermatids transcribe predominantly hnRNA during early spermiogenesis. Persistent long-lived [3H]-uridine-labeled RNA species in pachytene spermatocyte nuclei contrast with a fast turnover of [3H]uridine-labeled RNA in Sertoli cells as detected at the same pulse labeling time (8--12 days). From these results one can postulate a still undefined control mechanism of gene expression during spermatogenesis for modulating a cascade of events required for male gamete formation.


t-Alleles and the possibility of post-meiotic gene expression during mammalian spermatogenesis. Although there is strong evidence for post-meiotic RNA synthesis during spermatogenesis, definitive proof of haploid gene transcription is lacking. Segregation distortion in t-allele-bearing males provides evidence for post-meiotic gene expression since delayed mating experiments argue strongly that there are similar numbers of qualitatively different spermatozoa in ejaculates of males carrying moderately distorting t-alleles. Such post-meiotic transcription may not be infrequent but the intercellular bridges connecting spermatids would usually maintain gametic equivalence.


Severe psoriasis--oral therapy with a new retinoid. Ro 10-9359 is a retinoic acid derivative, selected for study because of a better tolerance than retinoic acid, shown in animal experiments. Doses of 25 mg b.i.d., 25 mg t.i.d. and 50 mg b.i.d. were administered orally to 27 patients suffering from severe chronic generalized psoriasis. The clinical efficacy was evaluated by means of a new index, psoriasis area and severity index (PASI) based on severity and area of psoriatic lesions. At doses of 25 mg t.i.d. or 50 mg b.i.d. Ro 10--9359 proved to be an extremely potent antipsoriatic drug. A more than 90% reduction of psoriatic lesions could be seen in 10 patients out of 20 after 4-8 weeks of treatment. This good effect lasted about 5 weeks after treatment. Side effects were frequent, but mostly mild and completely reversible after termination of treatment.


Treatment of urogenital/rectal gonorrhoea in males and females with epicillin in combination with probenecid. This paper describes the results of treatment of 124 patients (78 male and 46 female) with urogenital/rectal gonorrhoea with epicillin (3.5 g orally) in combination with 1 g of probenecid (instant therapy). High cure rates were found for both the male (98.6%) and female patients (100%). Serious drawbacks of this treatment are a high frequency of postgonococcal urethritis (45.6%) and a short-lived increase in the frequency and looseness of faecal discharge in a considerable amount of patients (6.8% in the male and 22.7% in the female patients).


Immunological milestones in ontogeny.

Immunological milestones in ontogeny. Age-equivalence shows that certain differentiative events and the onset of various types of immunocompetence follow the same sequence in all species as lymphocytes emerge during development.


Effect of temperature on transplantation immunity in Ambystoma mexicanum. Juvenile and mature neotenous Ambystoma mexicanum received allogeneic and xenogeneic skin transplants. Rejection times for 1st-set, and 3rd-set grafts were noted at 21 degrees C, and for axolotls placed in a cold-room at 7 degrees C 7 h post-grafting, 1 week post-grafting and 2 weeks post-grafting respectively. In all cases graft-rejection was chronic; 2nd and 3rd-set grafts were rejected progressively more rapidly than 1st-set grafts. An important temperature-sensitive event occurs during the 1st week post-grafting.


Specific visualization of the distribution of the calcium dependent regulatory protein of cyclic nucleotide phosphodiesterase (modulator protein) in tissue culture cells by immunofluorescence microscopy: mitosis and intercellular bridge. Monospecific antibodies against the homogeneous Ca++ dependent regulatory protein of cyclic nucleotide phosphodiesterase (CDR protein) from bovine brain were used in indirect immunofluorescence microscopy to visualize the cytoplasmic organization of this key regulatory protein in growing tissue culture cells. Although cells during interphase reveal only a weak general cytoplasmic fluorescence, a dramatic reorganization of CDR protein occurs with the onset of mitosis. Throughout the different mitotic stages CDR protein is strongly concentrated in the two polar parts of each half spindle. After completion of telophase (CDR protein appears at both cytoplasmic ends of the intercellular bridge which still connects the two daughter cells. Parallel use of monospecific antibodies against CDR protein and tubulin emphasizes the spatial restriction in the localization of CDR protein during mitosis and early G1 phase of the cell cycle.


The intermediate-sized filaments in rat kangaroo PtK2 cells. I. Morphology in situ. The system of the intermediate-sized filaments (IF) of rat kangaroo PtK2 cells which can be specifically demonstrated by immunofluorescence microscopy using certain rabbit autoantibodies and guinea pig antibodies against bovine hoof prekeratin has been studied by electron microscopy. The characteristic ornamental, curved arrays of this system are shown after fixation in situ in both thin sections and whole-cell-preparations to represent bundles of 6 to 11 nm thick filaments extending through the whole cytoplasm, although in some cells they appear to be enriched in the perinuclear region. While many individual IF are recognized in the cytoplasm the tendency of such filaments to aggregate laterally into bundles is one of their prominent features. Among such bundle formations one form that consists of tightly packed IF cemented together in a dense osmiophilic matrix is especially conspicious. The appearance and mode of arrangement of the IF is not significantly altered in cells treated with colcemid and/or cytochalasin B. Spatial relationships of IF with microfilament-containing cables and microtubules as well as with membranous structures are also described. IF are heterogeneous in width and reveal an unstained, apparently hollow core, indicative of a tubular organization. Many IF show small, sometimes periodically arranged lateral projections which seem to be involved in IF cross-linking. Associations with polyribosomes are common. The changes in the IF system during mitosis have also been examined. The structural details of the IF as well as their possible role as cytoskeletal elements involved in the control of cell shape and cytoplasmic architecture are discussed in relation to data on various intermediate-sized filaments from other cell types. The close similarity of the IF of PtK2 cells to aggregates of prekeratin filaments is emphasized. It is suggested that PtK2 cells represent an epithelial cell line growing in a state of balanced semi-keratinization.


The intermediate-sized filaments in rat kangaroo PtK2 cells. II. Structure and composition of isolated filaments. When cultured cells of the rat kangaroo cell line PtK2 grown on plastic or glass surfaces are lysed and extracted with combinations of low and high salt buffers and the non-ionic detergent Triton X-100 cytoskeletal preparations are obtained that show an enrichment of 6 to 11 nm thick filaments. The arrays of these filaments have been examined by various light and electron microscopic techniques, including ultrathin sectioning, whole mount transmission electron microscopy, negative staining, and indirect immunofluorescence microscopy. In addition, 6 to 11 nm filaments isolated from these cells with similar extraction procedures and with centrifugation techniques have been examined by electron microscopy. The arrays of these isolated intermediate-sized filaments, their ultrastructure and their specific decoration by certain antibodies present in normal rabbit sera as well as by guinea pig antibodies against purified bovine prekeratin is demonstrated. When preparations enriched in these intermediate-sized filaments are examined by SDS-polyacrylamide gel electrophoresis a corresponding enrichment of three polypeptide bands with apparent molecular weights of about 45 000, 52 000 and 58 000 (the latter component sometimes appears split into two bands) is observed, besides some residual actin and a few high molecular weight bands. The morphology of the isolated filaments, their immunological reaction with antibodies decorating prekeratin-containing structures, and the sizes of their constitutive polypeptides suggest that these filaments are closely related to prekeratin-containing filaments observed in a variety of epithelial cells.


Amikacin in gram-negative paediatric infections. Amikacin was used in the treatment of various Gram-negative infections in sixty-six children ranging in age from two days to thirteen years. Over 72% of the infections treated were classified as severe and the remainder were moderate. Among infections in which the site of origin was the urinary or gastro-intestinal tract, amikacin achieved thirty-eight (95%) complete or partial cures in forty patients. In respiratory tract infections, amikacin completely or partially cured six (75%) out of eight patients. The remaining eighteen infections involved skin, soft tissue and other miscellaneous categories in which amikacin therapy resulted in seventeen (94%) complete or partial cures. Overall, amikacin achieved fifty-four  complete cures and seven clinical or bacteriological cures in sixty-six patients, which represents an 82% complete cure rate and 10% partial cure rate for all the patients in the study.


Amikacin in the treatment of genito-urinary tract infections in cancer patients. Amikacin was used in the treatment of severe urinary tract infections in twenty-five seriously ill patients. In twenty-four of the patients, cystitis or pyelonephritis complicated carcinoma of the bladder. Structural changes in the urinary tract, resulting from schistosomiasis, presented additional obstacles to treatment in many of the patients. The most commonly isolated pathogens were Escherichia coli and Pseudomonas. Most patients received 500 mg of amikacin every twelve hours. Three patients experienced adverse renal reactions which showed subsequent improvement. Amikacin effected twenty-one (84%) complete cures and four (16%) clinical cures in the twenty-five patients. This represents 100% clinical success in this study.


Clinical experience with cefadroxil in upper and lower respiratory tract infections. Cefadroxil is a new semisynthetic oral cephalosporin with a broad spectrum of activity against both Gram-positive and Gram-negative organisms. Absorption of cefadroxil is unaffected by food, its serum levels are prolonged and it is excreted in the urine at a relatively slow rate compared to cephalexin. In the treatment of 108 patient with upper or lower respiratory tract infections, cefadroxil effected 93% complete cures. Fifty-five of the patients had upper respiratory tract infections and fifty-three had lower respiratory tract infections; among them cefadroxil acheived clinical success rates of 100% and 96%, respectively. Cefadroxil was clinically successful in eight (89%) out of nine patients whose infections were caused by mixed aetiologies. The principal causative agents were Staphylococcus aureus, beta-haemolytic streptococci, Streptococcus pneumoniae and Klebsiella pneumoniae. Overall bacterial eradication produced by cefadroxil was 112 (91%) of 123 organisms isolated from 108 patients. Reports of mild and transient side-effects in only 3.7% of the patients showed that the drug was well tolerated.


Netilmicin: a review of toxicity in laboratory animals. The data on the toxicity of netilmicin in laboratory animals as well as preliminary data in man are reviewed. Netilmicin is less toxic to the VIIIth nerve than is gentamicin in all species tested. The data suggest that it probably is less ototoxic than tobramycin, although confirmatory studies should be performed. Netilmicin is also nephrotoxic than gentamicin in all species tested. It is less nephrotoxic than tobramycin in the rat and dog. Comparisons in the rat suggest that netilmicin has a flat dose--response curve that resembles the curve produced by streptomycin. In animals, netilmicin produces more neuromuscular blockade than gentamicin; however, neuromuscular blockade with aminoglycosides in man is rare and thus far no episodes have been associated with netilmicin during clinical investigation. Initial clinical studies in man indicate that netilmicin is efficacious and well tolerated. Presently available data suggest that netilmicin offers distinct advantages over older aminoglycosides. Final conclusions must await prospective randomized double-blind trials in man.


A double-blind crossover evaluation of ketoprofen (Orudis) and placebo in rheumatoid arthritis with assessment of long-term tolerance. A two-week double-blind crossover study of ketoprofen, a non-steroidal antiinflammatory agent, and placebo was done in ten patients with active rheumatoid arthritis in order to obtain a preliminary efficacy estimate of this new drug. Even after only one week of treatment, joint activity was significantly reduced while other parameters of disease activity showed strong clinical trends in favour of the drug. Only one adverse reaction (mild nausea) was reported during ketoprofen therapy. At the conclusion of the double-blind study, seven patients volunteered to continue on ketoprofen to evaluate the tolerance of the drug during proptracted administration. All patients completed over twelve months of treatment. Overall, ketoprofen gave good control of pain and inflammation, gastro-intestinal disturbance was reported in a single instance and laboratory values were not adversely affected by the drug.


Kinetics of analgesic response in man; an example with two non-steroidal anti-inflammatory analgesic drugs. A double-blind, controlled trial is described in which a total of forty hospital in-patients suffering from severe post-operative pain were randomly allocated to treatment with one of two non-steroidal anti-inflammatory drugs, namely, either indoprofen which has a short half-life (two-hours) or naproxen which has a long half-life (thirteen hours). The drugs were administered orally on a single-dose basis. The doses used in this way were 300 mg of indoprofen or 250 mg of naproxen. Patients scored the severity of their pain on a five-point scale and these scores were recorded prior to and at fixed time intervals up to eight hours following administration of medication. No significant differences emerged between the two test drugs and the duration of the response was also found to be similar for the two compounds despite their very different plasma half-life values.


Effect of anticancer therapy of lymphocyte cytotoxicity in lung cancer patients. Cytotoxicity of lymphocytes against allogeneic target cells of a bronchogenic squamous cell carcinoma was examined by a microcytotoxicity test in lung cancer patients after the various kinds of anticancer treatment. Cytotoxicity in untreated cases at stages I, II, and III was higher than the range of controls, but cytotoxicity in those at stage IV decreased to the range of controls. Tumor resection augmented cytotoxicity in patients at stages II and III, when the assays were carried out 3 weeks after the operation. Local irradiation of tumors augmented cytotoxicity in patients at stages II, III, and IV, when the assays were carried out 1 week after the last irradiation. Immunotherapy with BCG cell-wall skeleton augmented cytotoxicity  to a marked degree in patients at stages I, II, III, and IV, when the assays were carried out after 4 months of a continuous treatment. The microcytotoxicity test may be useful for estimating the reactivity of lymphocytes in lung cancer patients in various situations.


Effect of intravenous infusion of somatostatin on gastric, pancreatic and biliary secretion in the rat. The effect of somatostatin (GH-RIH) on gastric, pancreatic and biliary secretion was examined in the anesthetized rats. Intravenous infusion of the hormone, in graded doses ranging from 1 to 16 microgram/kg/hr, produced a dose dependent inhibition of pentagastrin, 1.5 microgram/kg/hr, induced acid secretion, reaching about 54% of control level at the dose of 16 microgram/kg/hr. Somatostatin, 4, 16 and 64 microgram/kg/hr, inhibited the pancreatic juice volume stimulated by intravenous injection of secretin, 1 u/kg, as a bolus. Somatostastin, 2, 8, 32 and 128 microgram/kg/30 min, did not change the bile flow rate in control period. Somatostatin may play a physiological role in the regulation of the secretory process of the stomach and pancreas.


[Goethe's morphology definition and the problem of relationship of the Cro-magnons to the primitive Germans (Carl Gegenbaur)]. The problem of the Teutons' origin has been considered to be open up to this day though some scientists have worked on this field since 1912. Anthropologists and linguists as BRAUN, FEIST, GUNTERT, KOPPELMANN, PAUDLER and V.D. VELDEN produced many evidences in favour of the hypothesis the Teutons to be a mixture of the Old European Cro-Magnons speaking an archaic ural-altaic idiom with the Indo-Europeans immigrating into Europe from Asia. The Kelts may have a similar origin but they might include the Berbers of ancient Iberia as a third component. The hypothesis mentioned above was able to be ignored as far as an archaic language of the postulated type was unknown in the extremely western Euro-Saharanian territory. By means of a aerohydrodynamic model a hint was received to the probable existence of such a language in western Atlas or in one of the Mauretanian oases. This is not the case. But an archaic not-Berberized language preserved until the Spanish Conquest is found on the central isles of the Canary Islands. This language is handed down by some Spanish, Portuguese, and French chroniclers but mostly by the Italian engineer TORRIANI. His autograph found out and published by WOLFEL (1940) contains two poems (endechas), some sentences, and many separate words. Other clauses and single words are held in the manuscripts of the other writers. The oldest layer of Canary language (i.e. the Altaic stratum) passed for unintelligible until the summer of 1977. The earliest colonization of the Canary Islands by Crô-Magnons is doubtless on the strength of many anthropological examinations. The analysis of the two endechas and of 12 clauses tolerably handed down shows an Altaic language of an early type which still consists of words and formatives surviving only in one or two of the today's Altaic daughter-languages as Turkish, Mongolian, and Tunguso-Manchu, only seldom in all of them. The conicidence of surviving both of Crô-Magnon-typical men and of the archaic Altaic language on the Canary Islands as a reservation of megalithic civilization up to the Middle Ages (XVIth century) approves the hypothesis mentioned above.


[The nasal cavity and paranasal sinuses of the red deer (Cervus elaphus)--anatomical corrosion studies]. By means of thirty skulls of dominating female animals the formation and topography of the Cavum nasi and its Sinus paranasales of the red-deer are described. The main results are on the one hand the total absence of a Sinus frontalis and a Sinus sphenoidalis and on the other hand the characteristic formation of the Sinus ethmoidales. Amongst critical discussion with the available literature concerning the pneumatisation of skulls of red-deer a comparison with the well-known findings about the Cavum nasi and its Sinus paranasalis at the sheep, goat, roe-deer and cattle is following.