Loss of suppressor T-lymphocyte function in patients with systemic lupus erythematosus (SLE).

Immunological reactivity in patients with SLE was studied in vitro trinitrobenzene sulphonate (TNP) specific antibody formation by peripheral blood lymphocytes. Lymphocytes from patients with SLE could produce an increased number of TNP-specific plaque-forming cells (PFC), while no such response could be seen in normal controls. Co-culture of lymphocytes from active SLE patients and normal controls was performed with TNP-Horse red blood cells (TNP-HRBC). The number of PFC by B lymphocytes from active SLE patients was suppressed by T lymphocytes from normal controls. On the other hand, the number of PFC by B lymphocytes from normal controls was increased by T lymphocytes from active SLE patients. Co-culture of lymphocytes from identical twins discordant for SLE was also performed, and the same results were obtained. We further examined the effects of Con A on antibody formation. Con A-treated T lymphocytes from a normal control markedly suppressed TNP-specific PFC by peripheral lymphocytes from active SLE patients. However, Con A-treated T lymphocytes from an active SLE patient did not suppress TNP-specific PFC by lymphocytes from another active SLE patient. These results suggest that active SLE patients showed a loss of suppressor T-lymphocyte function.


Polyclonal B-cell activation during rodent malarial infections.

The numbers of 'background' plaque-forming cells (PFC) secreting IgM specific for either sheep erythrocytes or horse erythrocytes were found to be elevated in the spleens of BALB/c mice during Plasmodium berghei and P. yoelii infection. 'Background' PFC numbers were similarly elevated in the spleens of uninfected mice injected with high speed supernatants of lysates of parasitized red blood cells. The active factor (or factors) in the supernatants was (were) non-dialysable and stable at 56 degrees C, but was (were) destroyed by heating to 100 degrees C.


Delayed removal of renal-bound antigen in decomplemented rabbits with acute serum sickness.

We have examined the effects of complement depletion, brought about by cobra venom factor (CVF), on the clearance of radiolabelled BSA from the kidney in acute serum sickness in rabbits. The decomplemented group showed a significant decrease in the rate of clearance of renal-bound antigen with a mean half-clearance time of 19.5 days (range 9.3--60) vs 11.3 (range 8.7--15) for the control group. C3 was rapidly cleared from the glomerulus (as assessed by immunofluorescence) when further deposition was prevented by treatment with CVF. Glomerular immune complexes apparently activated the alternative pathway in vitro. These findings suggest that in immune complex nephritis, the clearance of deposited complexes from the kidney is complement-dependent.


The influence of phagocyte function on glomerular localization of aggregated IgM in rats.

The blood clearance and hepatic localization of aggregated human IgM (AIgM) were studied in relation to the glomerular localization patterns in rats. AIgM was cleared rapidly from the circulation by sinusoidal cells in the liver, monomeric IgM (MIgM) was cleared less rapidly. Localization of AIgM within the glomerulus was dependent on the level in the blood. Low doses led only to a mesangial localization, whereas high doeses resulted in a localization along the capillary walls. Immunoelectron microscopy showed that in the glomerular capillaries the AIgM was localized within endothelial cells or subendothelially, and did not occur within the glomerular basement membrane. Inhibition of the hepatic uptake of AIgM by colloidal carbon resulted in increased levels of circulating AIgM and prolonged the deposition of AIgM in the glomerular capillaries.


Immunofluorescent antibodies in patients with bird-fancier's lung.

To assess its value as a screen for avian antibodies, indirect immunofluorescence against avian intestinal tissue has been to test sera from thirty-nine patients with documented bird-fancier's lung disease, thirty-eight asymptomatic bird-fanciers and 257 controls without known avian contact. Immunofluorescent antibodies occurred more frequently than precipitins among patients with BFL and asymptomatic bird-fanicers. Globular fluorescence within the mucus occurred only in patients with avian contact, although other fluorescent antibodies were seen with control patients. No particular pattern was confined to patients with the lung disease. When included in an autoantibody profile, indirect immunofluorescence provides a sensitive and convenient alternative to precipitin methods in screening for avian antibodies.


Differentiation between antibodies to protamines and somatic nuclear antigens by means of a comparative fluorescence study on swollen nuclei of spermatozoa and somatic cells.

The indirect immunofluorescence test on swollen nuclei of rat thymocytes, chicken red blood cells and human and salmon spermatozoa was found to be an easy and satisfactory method for the discrimination between antibodies to sperm-specific nuclear antigens and somatic nuclear antigens. This study shows that nuclear antibodies present in the sera of vasectomized men and in rabbit antisera to human protamines are directed against the human sperm-specific nuclear antigens (protamines), and that they may cross-react with salmon protamine. These sera do not react with somatic nuclear antigens. This comparative fluorescence study and a complement fixation study, performed with sera from diabetic patients, proved that the administration of insulin retard (protamine-zinc-insulin) may lead to the formation of antibodies to the fish protamine. These antibodies may reveal a weak cross reaction with human protamines. The results obtained in this study also prove that the nuclei of chicken red blood cells and human sperm do not contain, or contain very small amounts of, histone fraction H1, and that salmon sperm nuclei do not contain any of the histone fractions, and suggest that the nuclei of mature human spermatozoa contain smaller amounts of histones in comparison to somatic cell nuclei.


Immunofluorescence titres of sperm centrifuged at different speeds.

Two washing procedures were used on spermatozoa to test the effect of centrifugation on immunofluorescent staining. The rapidly centrifuged spermatozoa often exhibited a loss of acrosomal but an increase in tail antigenicity. A standard technique of sperm preparation for immunofluorescence is recommended in order to have reliable and comparable results.


Vitamin C and immunity: an assessment of the evidence.

The high concentration of ascorbate in leucocytes and its rapid expenditure during infection and phagocytosis suggests a role for the vitamin in the immune process. Evidence published to date shows an involvement in the migration and phagocytosis by macrophages and leucocytes, as well as the induction and expression of delayed hypersensitivity. Its effect on antibody production and complement levels is controversial but probably minimal. This study suggests there is room for further investigation into the effect of ascorbate on immunity, particularly with defined populations, but cautions the use of megadose therapy.


Changes in the collagen of synovial membrane in rheumatoid arthritis and effect of D-penicillamine.

1. Normal synovial membrane contains approximately equal proportions of two genetically distinct forms of collagen, types I and III. The proportion of these two collagens is unchanged in rheumatoid synovium but in addition a small amount of basement membrane collagen is present. Tissue culture of rheumatoid synovium confirms the synthesis of both type I and III collagens. 2. In young normal synovium both type I and type III collagens are stabilized by a reducible keto cross-link, which is replaced in adult tissue by an as yet unknown non-reducible cross-link. During the proliferation of the collagen in adult rheumatoid synovium a high proportion of the keto cross-link is present. This cross-link is not susceptible to cleavage by D-penicillamine, nor does the drug have any effect on the rate of synthesis in vitro. The mode of action of D-penicillamine in rheumatoid arthritis does not appear to involve a direct effect on the synovial membrane collagen.


Potentially lethal complications of diabetes mellitus.

A case can be made that life expectancy has been prolonged in the diabetic, and some disabling symptoms have been ameliorated by the more recent procedures employed in the management of coronary artery disease and nephropathy. At the same time, the procedures described admittedly present problems and may not be generally available to the vast majority of diabetics. The definitive answer lies in attempting to control diabetes to prevent the development of these and other complications. A number of laboratories are attempting to develop an artificial pancreas or islet transplantation to substitute for the insulin secretory capacity that has been lost or impaired. This is an area of research that demands the highest priority. One cannot be confident that present therapeutic programs can be altered to provide the type of diabetic control necessary for the prevention of complications.


Inhibition of ovulation in women by chronic treatment with a stimulatory LRH analogue--a new approach to birth control?

A stimulatory luteinizing hormone-releasing hormone (LRH) analogue D-Ser(TBU)6-EA10-LRH was administered subcutaneously once daily in a dose of 5 microgram to four regularly menstruating women. Treatment was instituted within the first three days of the menstrual bleeding and continued for 22--30 days. Ovulation was inhibited in all the women during the treatment cycle. The treatment resulted in disturbances in the pituitary gonadotropin secretion which presumably led to disordered follicular menuration and anovulation. The maximum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses to the LRH analogue were obtained during the first few days of treatment. The gonadotropin responses then rapidly decreased during the prolonged treatment. This change in the pituitary responsiveness probably prevented the release of a normal preovulatory LH surge. After the treatment, all the women resumed normal ovulatory menstrual cycles. The results suggest that it might be possible to use stimulatory LRH analogues for birth control.


Immunohistological diagnosis of drug-induced hypersensitivity nephritis.

The immunohistological findings in 10 cases of DIHN and in 6 cases of R-ARF were compared with the patterns of experimental models and human examples of immunological nephritis. In most cases the simultaneous involvement of glomerular and extraglomerular structures was observed. A linear pattern on tubules together with a granular pattern on glomeruli and other structures was more frequently seen in Rifampicin adverse reactions. Direct and indirect immunofluorescence techniques performed in these last cases gave no evidence of the presence of the antigen and specific antibodies in the kidneys.


Dipyridamole therapy in the nephrotic syndrome.

Dipyridamole was used in 30 cases of nephrotic syndrome, mostly of intractable type. The results indicate that the drug therapy proved to be effective in decreasing urinary protein and controlling nephrotic condition in 40% of the cases after an initial period of treatment. Long-term results of the drug on urinary protein and on nephrotic condition were rated as good in 36.7 and 53.3%, respectively, of the cases treated. The exact mechanism of action of dipyridamole in the nephrotic syndrome is still obscure in many respects. However, the fact that the drug shares its anti-platelet action with the non-steroid anti-inflammatory drugs, e.g. aspirin and indomethacin, and the rapidity with which it produces its urinary protein-decreasing effect, strongly suggests that it inhibits the release of vasoactive amines and other chemical mediators from blood platelets. As far as the present study is concerned, adverse side effects of dipyridamole were few or minimal, even when the drug used in large doses over a prolonged period of time. From these results it is considered that dipyridamole provides a new remedy which is worthy of trying in nephrotic syndrome as a means of reducing the requirement of steroids and immunosuppressive drugs.


Double-blind paired comparison clinical trial of halcinonide and hydrocortisone.

Fifty patients with a diagnosis of psoriasis, eczematous dermatitis, atopic dermatitis, or neurodermatitis and with bilateral symmetric lesions of equal severity participated in this study. A double-blind paired comparison technique was used in which halcinonide-neomycin-amphotericin ointment was applied to the lesions on one side of the body and hydrocortisone ointment to similar lesions on the other side according to a randomized schedule. The halcinonide-containing combination was statistically superior (p less than 0.05) to hydrocortisone ointment in the treatment of psoriasis patients. No statistically significant difference between the two drugs was obtained for the three other indications studied. No side effects with either ointment were observed. Halcinonide as formulated in this combination is an effective and safe corticosteroid.


Oxygen-related intrapulmonary shunting in obstructive pulmonary disease.

A simple and previously validated double-indicator technique was used to quantitate shunt in patients with obstructive pulmonary disease at rest, during exercise, and during breathing of 100 percent oxygen. The method avoids several inherent difficulties encountered in previous double-indicator techniques and is independent of the fraction of oxygen in the inspired gas. Sixteen  resting patients with mild obstructive pulmonary disease were found to have intrapulmonary shunting less than or equal to 0.7 percent of the cardiac output (mean, 0-3 +/- 0.2 percent [SD]). During submaximal exercise, shunting was also low (mean, 0.3 +/- 0.1 percent of cardiac output). After breathing pure oxygen for 30 minutes, 11 patients had similar results; however, in four patients, breathing 100 percent oxygen caused an increase intrapulmonary shunting to 1 to 6 percent of the cardiac output. It is concluded that some patients with obstructive pulmonary disease develop intrapulmonary shunting in response to breathing oxygen.


The effect of lidoflazine on exercise tolerance in patients with angina pectoris.

The effect of therapy with lidoflazine on maximal exercise in the upright position was evaluated in 21 patients with angina pectoris. The study consisted of the following three consecutive periods: (1) a three-month period of receving placebo; (2) six months of therapy with lidoflazine; and (3) a six-month period in which patients were randomized to either therapy with lidoflazine or placebo. Functional status was monitored by multistage tests of exercise capacity and the amount of nitroglycerin consumed. From period 1 to period 2, the mean maxial exercise time increased from 4.4 to 6.5 minutes (48 percent; P less than 0.001), and the external workload increased by 68 percent (P less than 0.001). the mean heart rate at two minutes of exercise decreased from 114 to 101 beats per minute (P less than 0.001) but was unchanged at symptom-tolerated maximal exercise. During period 3, the patients receiving therapy with liodflazine maintained their improved exercise tolerance, and the reduction in mean heart rate at two minutes of exercise persisted. Patients receiving placebo during period 3 had a decrease in exercise tolerance, and the mean heart rate at two minutes of exercise increased to control values. Lidoflazine in effective as an antianginal medication, in part due to suppression of the heart rate during exercise.


Absorption, distribution and elimination of cefazolin in patients with normal renal function.

Cefazolin was given intramuscularly in a dosage of 1.0 g to 13 bed-ridden patients during treatment for various infections, and the pharmacokinetics evaluated in each subject. In 9 patients the mean serum half-life was 2.7 h, whereas in 4 patients--all over 60 years of age--it was significantly above this value. Impaired renal fuction could not explain the prolonged excretion time in the last group.


[Drug-induced oesophageal ulcers (author's transl)].

Within a one-year period seven patients were observed who had developed ulcers of the upper and mid oesophagus after treatment with doxycycline hydrochloride (n = 3), emepronium bromide (n = 3) or Pantogar (n = 1). In each instance the drug had apparently been swallowed dry. The typical symptoms were a sudden onset of retrosternal chest pain and odynophagia during bed rest. Once the drug had been discontinued and treatment with antacid combined with topical anaesthetics and/or alginic acid instituted the symptoms disappeared within a few days. The authors stress that drugs should be swallowed only with good amounts of fluid and generally not immediately before bed rest.


[Treatment of severe haemolytic-uraemic syndrome by dialysis (author's transl)].

Since 1973 haemodialysis was performed on 30 children with severe haemolytic-uraemic syndrome. Serial measurements were made of blood pressure, blood picture, renal function, complement values, excretion of fibrinogen split-products and beta2-microglobulin in urine. Of 22 children in the acute severe stage two died, in one case treatment having been started too late, in the other as a result of fulminating pneumococcal pneumonia. Twenty children survived without residual symptoms and with normal renal function. Of six children with severe progressive haemolytic-uraemic syndrome two developed terminal renal failure. In one child a renal transplantation has since been performed. One child requires chronic dialysis after nephrectomy. Three children died as a result of arterial hypertension, one of yeast septicaemia. Of two children with recurrent haemolytic-uraemic syndrome one developed terminal renal failure which was successfully treated by renal transplantation. One child died in a hypertensive crisis. The overall death rate of the group was 23%, in the group with the acute severe haemolytic-uraemic syndrome it was 9%. The results suggest that haemodialysis significantly improves the prognosis of severe haemolytic-uraemic syndrome.


Tamoxifen: a review of its pharmacological properties and therapeutic use in the treatment of breast cancer.

Tamoxifen 1 is a triphenylethlene oestrogen antagonist which has partial oestrogen agonist activity in some species. Most therapeutic trials with tamoxifen have involved postmenopausal women with advanced brease cancer, about 25 to 60% of patients showing same improvement while receiving treatment (usually 20 or 40mg daily); however- poorly defined assessment criteria in some studies make it difficult to compare the results of different authors. 7 to 18% of patients have had complete clinical remissions lasting for a few months to several years. Although few comparative studies with other treatments have been done, it nevertheless appears that tamoxifen is at least as effective as standard oestrogen or androgen therapy in postmenopausal women, while producing a lower incidence of troublesome adverse effects. In the only comparison with a cytotoxic treatment regimen, the response rates with tamoxifen and cytotoxic therapy were similar (41% versus 50%) in patients who were more than 5 years postmenopausal and had primarily soft-tissue involvement; but in patients who were within 2 to 5 years of their last menstrual period cytotoxic treatment was more effective. Similarly, most authors have reported a higher response rate with tamoxifen in women several years postmenopausal than in those more recently postmenopausal. Tumours which contain receptors respond more often to tamoxifen than those which do not. Administering tamoxifen concomitantly with other chemotherapeutic agents such as cytotoxic drugs appears to increase the response rate, but as might be expected also increases the incidence of adverse reactions. When used alone tamoxifen has been relatively well tolerated in all studies, the overall withdrawal rate due to side-effects being less than 3%.


Drug-induced liver disease.

The large number of chemical agents administered for therapeutic or diagnostic purposes can produce various types of hepatic injury by several mechanism. Acute injury may be cytotoxic, cholestatic or mixed. Cytotoxic injury may consist of necrosis or steatosis. Cholestatic injury may be cholangiolitic (hepatocanalicular) or bland (canalicular). Chronic hepatic lesions caused by medicinal agents include chronic active hepatitis, steatosis, cirrhosis, fibrosis, hepatoportal sclerosis (non-cirrhotic portal hypertension), hepatic vein thrombosis, peliosis hepatis, adenoma, carcinoma, and angiosarcoma. There is a useful relationship between the type of hepatic injury and the chemical setting in which the drugs are employed. Some agents produce the liver damage because they are intrinsic (true, predictable) hepatotoxins. Other (non-predictable "hepatotoxins"), produce hepatic injury only in the rare and unusually susceptible individual (idiosyncratic injury). Hepatotoxic agents can be recognised by their dose-dependent and experimental reproducibility, properties which are not shared by agents which produce hepatic injury only in idiosyncratic hosts. Intrinsic hepatotoxins may be categorised as direct or indirect. Direct hepatotoxins injure the hepatocyte by direct physiochemical alteration and as a consequence produce metabolic defects. Indirect hepatotoxins selectively block metabolic pathways and, by producing a precise biochemical lesion, lead to structural changes. They may lead to hepatic steatosis or necrosis (cytotoxic indirect hepatotoxins) or block bile flow (cholestatic indirect hepatotoxins). Direct hepatotoxins are rarely encountered as drugs. Overdoses of some drugs and antineoplastic agents appear to be indirect cytotoxic hepatotoxins, and the C-17 alkylated anabolic and contraceptive steroids are indirect, cholestatic hepatotoxins. Idiosyncracy of the host is the mechanism for most types of drug-induced hepatic injury. It may reflect allergy to the drug or a metabolic aberration of the host permitting the production of hepatotoxic metabolites.


[Statistical considerations on the evaluation of the Krogh-Poulsen clinical functional analysis].

361 patients, who five years previously were supplied with removable partial protheses, were submitted to Krogh-Poulson clinical function analyses. The test showed no suggestion of functional disturbances in only 12% of patients. Investigations showed that the test should be improved as to reliability, objectivity and validity before being used as a screening procedure in practice.


[Casting faults and structural studies on bonded alloys comparing centrifugal castings and vacuum pressure castings].

The casting processes in use today such as centrifugal casting and vacuum pressure casting were compared with one another. An effort was made to answer the question whether the occurrence of shrink cavities and the mean diameter of the grain of the alloy is dependent on the method of casting. 80 crowns were made by both processes from the baked alloys Degudent Universal, Degudent N and the trial alloy 4437 of the firm Degusa. Slice sections were examined for macro and micro-porosity and the structural appearance was evaluated by linear analysis. Statistical analysis showed that casting faults and casting structure is independent of the method used and their causes must be found in the conditions of casting and the composition of the alloy.


[VMK conus crowns in a prolonged-use study].

The adhesability and behaviour of ceramic facings of telescoping adhesive elements from baked alloys were tested in prolonged experiments. It was shown that these materials stand up to all requirements if their preparation was properly carried out.


[Orientation studies on the stability of metal-ceramic crowns made from new materials].

Materials for metal-ceramic crowns have been developed further in the last few years and the use of this type of crown increases steadily. Numerous investigations concern themselves with binding and other properties of this material as well as with its favourable moulding capacity. The present investigation is oriented towards establishing the order of magnitude and limits of confidence of fracture resistance which has to be reckoned with when using a metal-ceramic crown in the mouth.


[Repairs on metal-ceramic bonded dentures].

It was shown that the adhesion to metal was always less than to ceramic. The mean value of adhesiveness of Enamelite 500 surpasses with 1.2 daN/cm2 that of Den Mat with 0.8 daN/cm2. The bonding agent which is added to the package was replaced by the adhesive agent Fusion in a further experiment. Here the values for Den Mat increased to 1.65 daN/cm2 whilst those of Enamelite 500 decreased to 0.88 daN/cm2. In clinical trials the repairs held which were not under stress through occlusion or articulation contacts. The colour formation as well as transparency or smoothness of the material were not always satisfactory, the preparation however was quick and simple.


[Experimental studies on the hardness and adhesiveness of repair materials for metal ceramics].

This is a report of tests on the hardness and ability to adhere of materials which are recommended for the correction of cracked ceramic facings. The test for adhesiveness was carried out on three typical baked alloys and on a ceramic mass. Further tests were carried out to determine the influence of three Cyanoacrylate glues and a special adhesive agent. Results showed that all materials, especially the cyanoacrylate glues (excepting the adhesive agent) suffer from lowering of their adhesive capacity through the influence of moisture.


[Prosthetic principles in endosseous implantation (I) and implantation-based dentures (II)].

The prosthetic principles in intraosseous implantation and of the implanted replacement are surveyed and an indication is given of the important prosthetic indications. The significance of proper positioning of the implant and shaping of the implanted replacement are specially dealt with.


[Effect of separation of wax models from the matrix at room temperature on the precision of cast crowns].

Protracting the separation of wax model and work stump in order to overcome the inner tension in the wax at room temperature is not a dependable measure for preventing shrinkage of the cast.


[Aspects of orthodontic-prosthetic planning in adults].

The introduction of firm fitting orthodontic appliances has increased considerably the treatment potential of adults. Many aesthetic and functional problems allow a more satisfactory solution through preparatory orthodontic treatment than was possible up to now by prosthetic means. Surgical measures can facilitate and complement this therapy. In addition dental orthopaedic measures must be stabilised by prosthesis for reasons of retention.


[Prosthetic treatment of cleft patients after orthodontic treatment].

The relationship between the therapeutic effort of orthodontic and prosthetic measures was described ana analysed by means of net-plan technique. At the end of surgical treatment three treatment situations were found. Analysis showed that orthodontic and prosthetic therapeutic effort stood in a reciprocal relationship.


[Kinetics of supporting teeth in patients with partial dentures].

In 2 female patients with partial prostheses in the lower jaw, a pilot study was undertaken by means of inductive distance measures into the kinetics of supporting teeth during blank mastication over a period of 10 weeks. 1. Already at the beginning the end supports show unphysiological characteristics of movement during pressing and rubbing. 2. The existing canine guidance shows no abnormal kinetics of the supporting teeth during the excursions. 3. The direction of the kinetics of the supporting teeth changes in embedded part prostheses. 4. The abutment teeth show higher kinetic values after 10 weeks (without embedded partial prosthesis) than in the beginning. 5. In embedded partial prostheses all kinetic values closely approach the physiological norm. The directions on the other hand do not correspond with the physiological norm. The partial prosthesis acts as a splint for the abutment teeth.


[Precision in fixation and remounting of cast parts].

The exactitude of transferring castings was tested in two currently used methods of casting. Results showed that alginate casting from a remontage matrix and simple casting with IMPREGUM are sufficiently exact for clinical purposes. When the mixing relations between the casting substances is exactly maintained a transfer exactitude of +/- 0.11 is achieved by the methods tested. When there is a change in the relationship of the mixtures deviations of up to 0.20 mm occur.


[Critical considerations on the retention of individually cut attachments based on follow-up studies].

10 prostheses with individually cut attachments and 50 prosthetic appliances with parallel walled telescopic crowns were tested for their retention after a wear of between 2 and 7 1/2 years. Of the attachments only 3 cases showed good retention; in 4 it was minimal and no rentention was seen in 3 cases. Good retention was maintained in 10 telescoping prostheses, 24 had minimal and 16 no retention. Severe grades of loosening was only seen in telescoping supporting teeth where the anchor had good friction.


Distribution of LH-RH nerve endings in the median eminence of proestrus female rats: fluorescence and peroxidase anti-peroxidase (PAP) immunohistochemistry.

The morphological distribution of the nerve terminals containing LH-RH in the hypothalamus especially in the median eminence of the proestrus female rat was demonstrated by immunohistochemistry, using FITC and peroxidase antibody. The terminals containing LH-RH were classified into four groups on the topographic relationship. LH-RH nerve processes terminated mainly in the infurdibular radix within an elliptical zone surrounding the bases of the infundibular recessus. The heaviest concentration of LH-RH terminals immunohistochemically demonstrated lay on each side of the region extending from the dorsal part of tuberoinfundibular sulcus  to the lateral part of the external layer of the superior labium of the infundibulum. We were unable to detect any neuronal soma with the immunoreactivity to LH-RH in the hypothalamic gray matter. The distributional patterns of LH-RH, GH-RIH and monoamine in the median eminence as well as their relationships were briefly discussed.


Enzyme-linked immunoassay of somatostatin.

An enzyme-linked immunoassay for somatostatin using somatostatin-alkaline phosphatase conjugate as "labeled" antigen was developed. Minimal detectable dose at present was 40 pg per tube. Serial dilutions of rat hypothalamic extract gave a gradual change of antibody-bound alkaline phosphatase activity which was parallel to that with standard somatostatin. Precision and accuracy of the method were comparable to those in radioimmunoassay reported by others. This method will be a useful tool for the determination of somatostatin, especially in tissues.


Influence of pilocarpine pretreatment on (pro)insulin biosynthesis of isolated islets of rats.

3[H]-Leucine incorporation into (pro)insulin and insulin secretion was investigated using islets prepared by collagenase digestion from pancreata of rats pretreated with the cholimimetic agent pilocarpine or with saline (controls). Under the influence of pilocarpine pretreatment the [3H]-leucine incorporation into islet proteins with insulin immunoreactivity is enhanced at 6 mM glucose in the incubation medium of the islets but the incorporated radioactivity at 18 mM glucose is independent of the pretreatment of the animals. Only small or no changes were found regarding insulin secretion. It is concluded that an influence of pilocarpine pretreatment should be taken into consideration using such islets for studies on the regulation of (pro)insulin biosynthesis.


The stimulus-secretion coupling of glucose-induced insulin release. Cationic and secretory effects of menadione in the endocrine pancreas.

1. Menadione (2-methyl-1,4-naphthoquinone) inhibits insulin release evoked in the rat endocrine pancreas by glucose or glyceraldehyde, but fails to affect the secretory response to Ca2+, Ba2+, theophylline or gliclazide. The inhibitory effect of menadione upon glucose-induced insulin release is a dose-related, rapid and reversible phenomenon, menadione and glucose acting apparently as competitive antagonists. Menadione affects both the early and late phase of the secretory response to glucose. Menadione also antagonizes in a dose-related fashion the ability of glucose to reduce 86Rb efflux, to provoke 86Rb accumulation, to cause biphasic changes in 45 Ca efflux and to stimulate 45 Ca net uptake in pancreatic islets. 2. It is concluded that menadione impairs the insulinotropic action of glucose and other nutrients by impeding the remodelling of cationic fluxes normally provoked by these secretagogues in islet cells. Menadione, however, does not affect the capacity of divalent cations to activate the effector system which controls the release of secretory granules. Menadione may therefore represent a valuable  tool to elucidate the mechanism by which glucose normally modifies the movement of cations in the pancreatic B-cell.


Consequences of a specific cleavage in situ of 16-S ribosomal RNA for polypeptide chain initiation.

The effect of bacteriocin (cloacin DF13) treatment of Escherichia coli ribosomes on initiation of protein synthesis has been studied in detail. In agreement with our previous findings [Baan et al. (1976) Proc. Natl Acad. Sci. U.S.A. 73, 702--706] it is shown that 70-S initiation complexes can be formed with cloacin-treated ribosomes, but that the initiation factor IF-1 does not function properly. The following pleiotropic effects of this factor have been studied: (a) the acceleration of ribosomal subunit exchange with 70-S couples; (b) the stimulation of the IF-3-mediated dissociation of 70-S ribosomes; (c) the stimulation of 30-S initiation complex formation; (d) the enhancement of the rate of release of IF-2 from 70-S initiation complexes. The effects (a) and (b) are virtually abolished after cleavage of 16-S rRNA. The effect (d) is only partially reduced whereas effect (c) seems to be unimpaired. It is concluded that 70-S initiation complex formation with cloacin-treated ribosomes suffers from improper functioning of IF-1 in the generation of active subunits from 70-S tight couples. This is the only effect on initiation. It can be compensated for by adding more IF-3. The data provide functional evidence that 16-S rRNA is involved in ribosomal subunit interaction.


The synthesis of cytochrome b on mitochondrial ribosomes in baker's yeast.

Antiserum against a major cytochrome b peptide isolated from yeast mitochondria as described previously (Lin, L.-F.H., and Beattie, D.S., J. Biol. Chem. 1978, 253, 2412--2418) was raised in rabbits and shown to be monospecific against the pure antigen. Mitochondria were isolated from yeast cells grown in [3H]leucine, extracted with Lubrol and treated with antiserum to cytochrome b. Analysis of the immunoprecipitates by sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed the presence of a single major band of molecular weight 31 000 corresponding to cytochrome b. In order to determine the intracellular site of translation of cytochrome b, yeast cells were labeled in vivo under non-growing conditions with [3H]leucine in the absence or presence of inhibitors of cytoplasmic and mitochondrial protein synthesis. The incorporation of radioactive leucine into the apoprotein of cytochrome b isolated by immunoprecipitation followed by gel electrophoresis was insensitive to cycloheximide (an inhibitor of cytoplasmic protein synthesis) and sensitive to acriflavin, erythromycin, and chloramphenicol (inhibitors of mitochondrial protein synthesis). Furthermore, no cytochrome b apoprotein was present in a cytoplasmic petite mutant which lacked mitochondrial protein synthesis. Cytochrome b is thus a product of protein synthesis on mitochondrial ribosomes.


Metabolism of 2-deoxy-2-fluoro-D-[3H]glucose and 2-deoxy-2-fluoro-D-[3H]mannose in yeast and chick-embryo cells.

2-Deoxy-2-fluoro-D-[3H]glucose and 2-deoxy-2-fluoro-D-[3H]mannose have been prepared by tritiation of the corresponding unlabeled 2-fluoro sugars. The tritiated 2-fluoro sugars are phosphorylated and activated by UTP and by GTP to yield UDP-2-deoxy-2-fluoro-D-[3H]glucose, UDP-2-deoxy-2-fluoro-D-[3H]mannose, GDP-2-deoxy-2-fluoro-D-[3H]glucose and GDP-2-deoxy-2-fluoro-D-[3H]mannose in both cell types. The nucleotide derivatives could also be labeled in the nucleotide moiety by feeding the cells with [14C]uridine or [14C]guanosine in the presence of unlabeled 2-fluoro sugar. No evidence was obtained for metabolic steps in which the six-carbon chain of 2-fluoro sugars was not preserved. No epimerisation of the label to 2-deoxy-2-fluoro-D-[3H]galactose could be observed by radioactive gas-liquid chromatography of the enzymatic cleavage products of the different 2-fluoro sugar metabolites isolated from either cell type. Yeast and chick embryo cells both incorporate 2-deoxy-2-fluoro-D-[3H]glucose and 2-deoxy-2-fluoro-D-[3H]mannose specifically into glycoproteins, although this incorporation is very low when compared to the incorporation of 2-deoxy-D-[3H]glucose.


Small-angle X-ray scattering on malate synthase from baker's yeast. The native substrate-free enzyme and enzyme-substrate complexes.

Malate synthase from baker's yeast has been investigated in solution by the small-angle X-ray scattering technique. Size, shape and structure of the native substrate-free enzyme and of various enzyme-substrate complexes have been determined. As the enzyme was found to be rather unstable against X-rays, several precautions as well as sophisticated evaluation procedures had to be adopted to make sure that the results were not influenced by radiation damage. These included use of low primary intensity, short time of measurement, the presence of high concentrations of dithiothreitol, combined use of the conventional slit-collimation system and the new cone-collimation system. 1. For the native substrate-free enzyme the following molecular parameters could be established: radius of gyration R = 3.96 +/- 0.02 nm, maximum particle diameter D = 11.2 +/- 0.6 nm, radius of gyration of the thickness Rt = 1.04 +/- 0.04 nm, molecular weight Mr = 187000 +/- 3000, correlation volume Vc = 338 +/- 5 nm3, hydration x = 0.35 +/- 0.02 g/g, mean intersection length - l = 5.0 +/- 0.2 nm. Comparison of the experimental scattering curve with theoretical curves for various models showed that the enzyme is equivalent in scattering to an oblate ellipsoid of revolution rather than to a circular cylinder. The semiaxes of this ellipsoid are a = b = 6.06 nm and c = 2.21 nm. Thus with an axial ratio of about 1:0.36 the enzyme is of very anisometric shape. 2. Binding of the substrates (acetyl-CoA, glyoxylate) or the substrate analogue pyruvate causes slight structural changes of the enzyme. These changes are reflected mainly by a slight decrease of the radius of gyration (0.3--1.3%, as established both with the slit-smeared and the desmeared curves). Concomitantly there occurs a decrease of the maximum particle diameter and an increase of the radius of gyration of the thickness. These changes imply an increase of the axial ratio by 2.2--6.9%, i.e. substrate binding induces a decrease of anisometry. While the particle volume appears to be unchanged on binding glyoxylate or its analogue pyruvate, binding of acetyl-CoA causes slight changes of this parameter. In a similar manner the binding of acetyl-CoA leads to a slight enhancement of the molecular weight; this increase corresponds to the binding of 2.7 +/- 1 molecules of acetyl-CoA.


The purification and properties of the aspartate aminotransferase and aromatic-amino-acid aminotransferase from Escherichia coli.

A simple and convenient procedure is described for the isolation in good yield of two amino-transferases from various strains of Escherichia coli. On the basis of their substrate specificities one of the enzymes has been classified as an aromatic amino acid aminotransferase and the other as an aspartate aminotransferase, but both act on a wide range of substrates. Pyridoxal phosphate is bound more strongly to the aspartate aminotransferase than to the aromatic amino transferase which cannot be fully re-activated after removal of the prosthetic group. Both enzymes are composed of two subunits which appear to be identical.


Identification of the amino acid functional groups responsible for 30-S ribosome recognition of messenger RNA.

About 30 protein-selective chemical reagents have been tested for their ability to inhibit the mRNA binding activity of the 30-S ribosome. A number of reagents were investigated which have been shown by other workers to be capable of modifying free epsilon-amino groups of lysine and all were found to inactivate 30-S ribosomes completely for natural mRNA binding activity. Several reagents selective for histidine, tyrosine, and tryptophan were also found to inactivate. We suggest that the epsilon-amino groups of lysine play an important role in mRNA binding to the 30-S ribosome.


Optimisation of conditions for the affinity chromatography of human enterokinase on immobilised p-aminobenzamidine. Improvement of the preparative procedure by inclusion of negative affinity chromatography with glycylglycyl-aniline.

The affinity chromatography of human enterokinase using p-aminobenzamidine as the ligand [Grant, D.A.W. & Hermon-Taylor, J. (1976) Biochem. J. 155, 243-254] has been reassessed and the optimal conditions for the synthesis and operation of the derivatised gel defined. Satisfactory adsorbants were only produced using high concentrations of both CNBr and spacer-arm in the initial coupling slurry. Under these conditions it seemed likely that the majority of the ligand in a sterically favourable position to bind enterokinase was on the external surface of the bead. Trypsin binding to the adsorbant was not so critically dependent on the synthetic conditions and correlated closely with the degree of substitution. Dilution of the adsorbant with unlabelled Sepharose 4B indicated that there was more than one binding site per enterokinase molecule. The highest affinity was presumably for the active site, with adsorption supported by secondary interactions with spacer-arm or gel matrix not necessarily on the same bead. Maximal resolution was obtained by prolonged washing of the gel after loading; two populations of intestinal aminopeptidase were identified. Substitution of aniline for p-aminobenzamidine abolished specific enterokinase adsorption and improved the purification procedure by further removal of onon-specifically adsorbed contaminants.


Structural studies on the immunogenic form of the enterobacterial common antigen.

It has been shown that enterobacterial common antigen is chemically linked to the hexose region of the R1-type lipopolysaccharide fo the Escherichia coli strain F470 which is immunogenic for this antigen. The number of R core stubs substituted is very small but it is a-parently sufficient to induce antibody formation to the enterobacterial common antigen in the rabbit.


Structure of the hexose region of Shigella sonnei phase II lipopolysaccharide with 3-deoxy-D-manno-octulosonic acid as possible immunodeterminant and its relation to Escherichia coli R1 core.

Comparative chemical analysis (methylation, gas chromatography/mass spectrometry, periodate oxidation, etc.) of the lipopolysaccharides and degraded polysaccharides derived from Shigella sonnei phase I, phase II and galactose-deficient R mutants revealed a structure as shown: (formula: see text) 3-Deoxy-D-manno-octulosonic acid (dOclA) as an immunodeterminant was observed in the passive hemolysis inhibition test by (a) selective inhibition of the phase II system by dOclA; (b) the kinetics of the change of serological activity during mild acid treatment: 1% acetic acid abolished serological activity; (c) a lack of activity in galactose-less R mutants and reactivity with Re mutants including Salmonella minnesota Re. An enhanced sensitivity of phase II lipopolysaccharide to galactose oxidase after prolonged treatment with 1% acetic acid suggests that dOclA is linked to C-6 of the terminal or subterminal galactose. dOclA as immunodeterminant could explain some different polysaccharide structures described for Escherichia coli R1 core.


Maximal exercise test in patients with essential hypertension treated with propranolol.

Maximal exercise test was performed in 15 patients with essential hypertension before and after 10 days of treatment with oral propranolol in daily doses of 320 mg. After the treatment, heart rate, and systolic and diastolic blood pressure significantly fell both at rest and after the test; a greater, though not significantly, workload was tolerated; a significant decrease was observed in the product of heart rate and systolic blood pressure, together with a marked reduction in electrocardiographic ischemic changes. Propranolol treatment, besides being an effective antihypertensive agent, improved ischemic changes induced by exercise and cardiac performance in hypertensive patients, also in the presence of left ventricular hypertrophy.


Control of heart rate during movement in acute myocardial infarction.

Among patients with acute myocardial infarction and a normal heart rate and blood pressure, a high incidence of sympathetic overactivity was recorded during transport. The combined administration of atropine and sotalol had no significant effect on the mean maximum heart rate on movement. However, this drug combination prevented excessive slowing of the heart rate. Sotalol caused a significant reduction in the mean maximum heart rate on movement. The side-effects were minimal. 10% of patients who received sotalol required atropine for the correction of bradyarrhythmia.


Efficacy of oral mexiletine in the prevention of exercise-induced ventricular ectopic activity.

The anti-arrhythmic effect of oral mexiletine on exercise-induced ventricular arrhythmia was studied in a double blind trial of 10 patients suffering from ventricular ectopic beats of different origins. There was a good reproducibility of the amount of ectopic ventricular activity between consecutive exercise tests when no active drug was given. Treatment for 1 week with mexiletine 600 mg daily resulted in a statistically significant reduction in ventricular ectopic beats, particularly during and after exercise; there were virtually no side-effects. The results suggest that mexiletine has considerable potential in the treatment of ventricular arrhythmias.


Ventricular arrhythmias after an acute myocardial infarction. Prognostic weight and natural history.

160 consecutive CCU-treated AMI patients below 66 yr were investigated for ventricular ectopic beats (VEB) by 6-h telemetry prior to discharge and after 1 yr. During the follow-up year 11 patients died suddenly and 20 suffered reinfarction. By stepwise discriminant analysis three independent prognostic parameters were found: (1) radiologic cardiomegaly; (2) severe VEBs prior to discharge; (3) diabetes mellitus. Previous infarct, angina, functional class II to IV, smoking, higher age and radiologic cardiomegaly were significantly more frequent in patients with VEBs prior to discharge. History of heart failure, functional class deterioration, higher age, male sex, large first infarct, VT or VF in CCU, transmural infarction, radiologic cardiomegaly were more frequent in patients with severe VEBs prior to discharge. VEB severity increased significantly during the follow-up year in survivors without reinfarction. This increase occurred in patients with previous infarction, angina pectoris, higher age and heart failure.


Acute double blind trial of a new anti-anginal drug: molsidomine.

The antianginal activity of Molsidomine, a recently developed compound, was studied in 6 patients with stable angina pectoris who attended 3 trial sessions. On different days the patients received single doses of Molsidomine (M; 2 mg), isosorbide dinitrate (ISDN; 5 mg) or placebo (P), in a double blind cross-over manner. All patients performed exercise tests at time 0 (before medication) and 30, 60, 120, 240 and 360 min after drug intake. Tests were performed on a treadmill using the Bruce protocol; the ECG were recorded on 3 channel equipment and was stored on 2 channel magnetic tape (Holter system). No difference between basal values before treatment and on exercise during placebo were observed. At a similar submaximal workload after M and ISDN there was no significant change in heart rate or pressure-rate product, a decrease in systolic blood pressure, a reduction of ST ischemic response between 30 to 120 min after drug intake, and after M alone, a significant decrease in diastolic blood pressure during the 6 hour period. Molsidomine produced clear inhibition of exercise-evoked ischemic ST changes and a long-lasting effect on diastolic blood pressure.


Treatment of chronic heart failure with slow release phentolamine.

Oral medication with phentolamine SR produced subjective and objective improvement in all 45 patients with refractory chronic heart failure of various aetiologies, who were already receiving digitalis and diuretics. This was shown by an increase in pulse-pressure amplitude and urine volume, a decrease in bodyweight and marked reduction in cardiac size and pulmonary congestion, the latter changes being more pronounced in patients with arteriosclerotic heart disease (ASHD). Exercise tolerance tests in a further 34 patients with less severe chronic heart failure demonstrated that phentolamine SR markedly increased physical capacity. This effect was more pronounced in patients with slightly compromised cardiac status (functional Class 2, NYHA) than in those with moderately compromised cardiac status (Class 3). The improvement in clinical condition was attributed mainly to arterial and venous dilatation, as well as to the positive inotropic effect of the drug. The most important side-effects were diarrhoea and, in the patients with ASHD, increased attacks of angina pectoris; The side-effects were well controlled by the anticholinergic agent oxyphenonium bromide (Antrenyl) and a slight increase in the dose of nitrates. It is concluded that oral phentolamine SR may be a valuable therapeutic adjunct in the management of patients with refractory chronic heart failure.


Effect of diazepam and chlorpromazine on memory functions in man.

The effect of a single oral dose of diazepam 10 mg or chlorpromazine 25 mg on memory in man was examined in a double-blind study, each drug being crossed-over against placebo, with 20 subjects for each drug. Kahn's Test for Symbol Arrangement and a paired association-learning task were used for assessment of acquisition, storage and retrieval, and state-dependency effects. A flicker-fusion test, two coordination tests, and a choice reaction task were used to evaluate alertness in the subjects. Diazepam significantly impaired acquisition, but slightly facilitated recall. Reaction time was shortened after acute diazepam treatment and coordination was impaired after two weeks treatment with diazepam. Acute treatment with chlorpromazine did not change memory or psychomotor performance.


Effect of active metabolites of chlordiazepoxide and diazepam, alone or in combination with alcohol, on psychomotor skills related to driving.

Interaction of the main metabolites of diazepam and chlordiazepoxide with alcohol was measured in two subacute double-blind cross-over experiments on 40 healthy, young volunteers. The drugs were administered for two week periods. The variables measured were choice reaction time and accuracy, eye-hand co-ordination, divided attention, flicker fusion, proprioception and nystagmus. Chlordiazepoxide lactam, methyloxazepam and oxazepam significantly enhanced the alcohol-induced impairment of psychomotor skills, whereas N-desmethyl-diazepam did so only exceptionally in certain subjects in the choice reaction test. It is concluded that diazepam-alcohol interaction on psychomotor skills is mainly due to the parent compound. No correlation between the serum level of the agents and the changes in performance were found.


Antibodies to ganglioside GM1 induce mitogenic stimulation and cap formation in rat thymocytes.

Antibodies towards the ganglioside GM1 [galactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosyglucosyl ceramide] stimulated DNA synthesis in rat thymocytes. No mitogenic stimulation was observed  with the monomeric Fab fragment of anti-GM1, suggesting that cross-linking of the gangliosides or associated components was required for activation by these antibodies. Incubation of thymocytes with anti-GM1 and fluorescein-labeled anti-rabbit IgG at 0 degree C resulted in uniform ring-like or patchy staining that developed into a pronounced cap upon elevation of temperature. The cap had a characteristic uropod form, enriched with intracellular organelles. Sodium azide and cytochalasin B completely inhibited cap formation, while colchicine was without effect. These results imply a possible direct or indirect association between surface gangliosides and submembraneous cytoskeletal assemblies that control modulation of these surface components and may transmit stimuli to the interior of the cell.


Generation and release of eosinophil chemotactic factor from human polymorphonuclear neutrophils by arachidonic acid.

This study describes the generation and release of an eosinophil chemotactic factor from human polymorphonuclear neutrophils, rat basophilic leukemia cells, and from a lymphocyte monocyte basophil suspension by arachidonic acid (AA). The eosinophil chemotactic factor (ECF) is highly specific for eosinophils and resembles the ECF activity obtained from human polymorphonuclear neutrophils after stimulation with the Ca ionophore or during phagocytosis. In this regard, AA-induced ECF represents a biological activity distinct from oxidized AA and its conversion products. AA may therefore have a dual function: it represents an important mechanism of cell activation; as AA is converted into prostaglandins, it appears likely that they exert a modulatory and a suppressive role on biological functions, such as chemotaxis and phagocytosis.


Gabaminergic and serotonergic modulation of the antidyskinetic effects of tiapride and oxiperomide in the model using 2-(N,N-dipropyl)animo-5,6-dihydroxytetralin.

The activities of oxiperomide and tiapride were compared with those of control "neuroleptic" agents in the dyskinesia model using 2-(N,N-dipropyl)amino-5,6-dihydroxytetralin to induce peri-oral movements, in order to determine whether the differential activities (oxiperomide and tiapride being comparatively more effective as antagonists) may involve striatal gabaminergic and serotonergic mechanisms. The peri-oral movements induced by the 2-aminotetralin compound (0.05 mg/kg s.c.) were antagonised by intrastriatal GABA (2.5--10 microgram bilateral) and serotonin (25--100 microgram bilateral). Sodium valproate (i.p.) had little effect but 1.25 mg/kg s.c. quipazine abolished the peri-oral dyskinesia. Subthreshold doses (i.p.) of oxiperomide and tiapride synergised with subthreshold intrastriatal doses of both GABA and serotonin, and with s.c. quipazine, to antagonise the peri-oral movements induced by the 2-aminotetralin compound. Subthreshold doses of haloperidol, sultopride, metoclopramide and pimozide failed to consistently antagonise peri-oral movements when similarly combined with GABA, serotonin or quipazine. It is suggested that, in addition to their known action on cerebral dopamine mechanisms, oxiperomide and tiapride may modify abnormal peri-oral movements by modulation of striatal gabaminergic and serotonergic mechanisms.


Localization of luteinizing hormone-releasing factor in the human placenta.

Luteinizing hormone-releasing factor (LRF) has been found to be produced by the placenta. In the present study, the localization of this releasing factor was delineated by the use of an immunofluorescnece technique. Intense fluorescence was localized in the cytotrophoblast, along the outer surface layer of the syncytiotrophoblast, and in the villous stroma. The cytoplasm of the syncytiotrophoblast did not exhibit any fluorescence. It may be speculated that placental LRF plays a role in regulating the production of human chorionic gonadotropin.


Evidence of suppresssor cell-mechanism of allograft tolerance induced by spleen extract and hydrocortisone.

The mechanism of allograft tolerance in mice induced by cell-free spleen extract in combination with hydrocortisone was investigated. HC potentiated tolerance induction when given after the spleen extract. When HC was given before, or during the first 2 weeks of antigenic treatment, it counteracted rather than potentiated the tolerance-inducing effect. Spleen or lymph node cells transferred from tolerant donors to untreated or sublethally irradiated syngeneic recipients suppressed the recipients' response to the particular alloantigens. The suppressive activity of lymphoid cells from tolerant donors was abolished when before their transfer the subpopulation of T cells was eliminated by means of anti Thy-1.2 serum and complement. This finding suggests that suppressor T cells may be involved in tolerance induced by spleen extract and hydrocortisone.


Effects of cytochalasin B on endocytosis and exocytosis.

The complex effects of cytochalasin B on endocytosis and exocytosis are reviewed. Cytochalasin B inhibits phagocytosis by both mononulcear phagocytes and polymorphonuclear leukocytes but it does not affect the micropinocytic activity of mononulear phagocytes and other cell types. Cytochalasin B causes increased selective release of acid hydrolase from phagocytic cells but its effect on other secretory cells is more variable, stimulating secretion by some cell types, inhibiting secretion in others and having no effect at all in some instances. The possible mechanisms of action of cytochalsin B are discussed with particular emphasis being placed on its effect on the activity of various protein components of cellular contractile systems. We suggest that many of the biolgoical effects of cytochalasin B may be accounted for by such effects.


The use of cytochalasins to probe the immunobiolgoy of lymphocytes.

No attempt will be made to summarize in any formal way the "pot-pourri" of experiments we have considered in this chapter. It may occur to some that immunologists as a group have been somewhat removed from the advances made in cellular biology during the last decade. Specifically, they may appear to lack an appreciation of the many ways in which durgs like the cytochalasins can affect cell function. Perhaps because of this naivety however, the immunologists have used the cytochalasins to probe systems so complex that they would never have been comtemplated by more conservative investigaors. In doing so they have revealed insight into many systems that will hopefully be of broad biolgical interest. To date the insights have been mostly of a rather superficial nature and clearly demand more thorough investigation. If they are to be done, such studies will have to be performed by non-immunologists bringing new tools and new perspectives to bear on the immunologists' problems.


[Studies on the effect of the therapeutic dosage of indomethacin on human gonadotropin secretion (author's transl)].

To investigate the effect of the therapeutic dosage (50 approximately 100 mg/day) of indomethacin (IDM), which is well-known to inhibit the synthesis of prostaglandins, on the human pituitary-gonadal axis, five experiments were performed. Exp. I and Exp. II: Six healthy male subjects pretreated with IDM for two days (Exp. I), and 12 male patients receiving IDM for 1 to 19 months (Exp. II) were examined. In these two IDM treated groups, resting levels of plasma LH did not change, and LH response to LH-RH (100 microgram i.v.) slightly increased as compared with nontreated control males (N=11). Resting levels of plasma FSH, and FSH response to LH-RH statistically and significantly suppressed in both IDM treated groups, except for FSH response to LH-RH in the IDM pretreated healthy male group. Exp. III: Two healthy women with regular menstrual cycles were treated with IDM for several days just before ovulation. These women's preovulatory LH surges were not blocked by IDM and were followed by a normal luteal pattern of basal body temperature. Exp. IV: Ten female patients receiving IDM for 1 to 10 months were examined. In 9 patients, normal preovulatory LH surges were observed. It was interesting that the duration of the luteal phase was shortened (less than 10 days) in 5 of the 10 patients, and mid-luteal plasma progesterone levels were less than 500 ng/dl even if some of those patients had a normal duration of the luteal phase. Exp. V: In five female patients treated with IDM for 1 to 9 months, mid-follicular gonadotropin secretions were estimated. Resting levels of plasma gonadotropins and their responses to LH-RH did not differ from the control female group (N=4). From these results, it was indicated that (1) the therapeutic dosage of IDM acted on the central nervous system and the anterior pituitary, and then suppressed FSH secretion in male subjects. There was sexual difference in the IDM effect on FSH secretion, that is, mid-follicular FSH secretion was not affected by IDM in female subjects. (2) LH secretion was not suppressed by IDM in either male or female subjects in the mid-follicular phase. (3) The therapeutic dosage of IDM did not block the preovulatory LH surge and ovulation in female subjects, but IDM might act on corpus luteum and cause luteal dysfunction.


Effectiveness of topically applied antibiotics on anaerobic bacteria in the pilo-sebaceous duct.

An unspecific cream vehicle containing 1% erythromycin base was applied once a day for 10 days to one side of the forehead of 16 healthy subjects and the same vehicle without the active agent to the other side. Using the same procedure a solution containing 1.19% clindamycin phosphate (corresponding to 1% clindamycin base) and the corresponding unspecific vehicle was administered to another group of 17 healthy males. Prior to the treatment and after the end bacteria were obtained from the pilosebaceous ducts by means of a special sampling technique. Both ointments containing the antibiotics lead to a significant reduction of the bacterial growth in the pilosebaceous ducts regardless of whether evaluation is made of the total bacterial count or of Propionibacteria. Thus, it could be demonstrated that topical application enables some antibiotics to penetrate into the pilosebaceous duct in an adequate concentration to ensure antibacterial effectiveness if a suitable vehicle is used.


Protective effect of rabbit immune serum administered orally to rats infected by a human pathogenic strain of E. coli.

1-week-old rats were inoculated orally with a strain of E. coli (serotype 078) isolated from the blood of a newborn baby who had died of septicemia. During the 3 weeks following inoculation, approximately 50% of the animals died of septicemia and 60% of the surviving rats had pathogenic bacteria in their rectum. Some of the surviving rats were severely impaired in their development. Autopsy showed evidence of active intestinal infection localized mainly in the ileum and cecum. A rabbit anti-E. coli (strain 23) serum (agglutinating titer: 1/2,500) afforded 100% protection when as little as 0.03 mg of serum protein per gram of rat body weight was orally administered in a single dose. The immune serum had an effect both on the mortality rate and on the growth of the rats. However, it never affected the survival of pathogenic bacteria in the rectum, even when administered at a daily dose of 1.5 mg of serum protein per gram of rat body weight on 4 consecutive days. The immune rabbit serum had only a weak bactericidal effect in vitro. The hemagglutination test showed the presence in the immune serum of antibodies against the fimbriae of the pathogenic E. coli strain (titer: 1/1,000). The role of antibody in inhibiting the adherence of bacteria to epithelial cells and/or their progression across the mucous layer are discussed as possible immune mechanisms in the intestinal lumen.


Proteus mirabilis brain abscess in a neonate.

Occasionally a brain abscess has been observed in a neonate. This report presents a unique case of a septic infant who developed a proteus mirabilis brain abscess shortly after birth, which persisted undetected until 21/2 months of age.


Isolated mouse pancreatic islets in culture: effects of serum and different culture media on the insulin production of the islets.

Various conditions for tissue culture of collangenase-isolated mouse pancreatic islets were studied in an attempt to optimize the maintenance of glucose stimulated insulin biosynthesis and release in the cultured specimens. Islets which had been cultured at a physiological glucose concentration (5.5 mmol/1) in the absence of serum had an impaired glucose-stimulated insulin biosynthesis and release as well as a reduced insulin content. Thus, insulin biosynthesis was three times higher after culture in a serum supplemented medium. Further, the insulin secretion of islets cultured in the presence of serum was markedly enhanced in acute incubations with high concentrations of glucose. This response was most pronounced in islets which had been cultured free-floating. A comparison between different culture media showed that islets cultured in RPMI 1640 had the highest insulin production. The present data suggest that the most favourable conditions for long-term storage of isolated islets in culture may be obtained when the islets are maintained as free-floating explants in a culture medium consisting of RPMI 1640 supplemented with serum.


The quantitative distribution of certain enzymes along the small intestine of the rat and its correlation with the villous area and the Paneth cells.

The distribution of lysozyme, alkaline phosphatase, aminopeptidase, maltase and amylase was studied throughout the small intestine of the adult rat. Lysozyme activity increases along the length of the small intestine and the behaviour of this enzyme slightly differs from the mucosal enzymes reported in this investigation. A positive correlation is found between the percentage of crypts with granulated Paneth cells and the lysozyme activity. This corroborates with the secretory origin of this enzyme from these intestinal cells.


Intrahepatic metabolism and secretion of biliary lipids.

The purpose of this work is to review the arguments which support the role of mixed micelle formation in the biliary secretion of lipids. These arguments are derived from in vitro physicochemical studies and from results obtained in vivo during biliary drainage in animals and in man. They show that, for the essential, mixed micelle formation between lecithins, cholesterol and bile salts can explain the biliary lipid secretion. The amount of lipids transported into the bile depends on the intrahepatic metabolism of cholesterol and lecithins. Different bile salts have opposite effects on the saturation of bile with cholesterol. During chronic administration of bile salts, the differences may be explained by specific actions on cholesterol metabolism and particularly on cholesterol absorption. On the contrary, during acute injection of bile salts, in most animal species, those bile salts which have the greatest ability of dissolving cholesterol in vitro (dihydroxy being more efficient than trihydroxy) are those which determine the greatest biliary secretion of cholesterol.


Effect of BCG cell-wall skeleton on metastasis of syngeneic tumor in rats, with special reference to lymphocyte trapping.

Oil-attached BCG cell-wall skeleton (BCG-CWS) was demonstrated to have an activity inducing lymphocyte trapping in the draining node in rats. It acts also as a potent adjuvant for the lymphocyte trapping when injected into the growing syngeneic transplantable tumor. Treatment with repeated intratumor injections into the primary tumor resulted in suppression of tumor growth in both primary and metastatic sites. Even when the primary tumor escaped regression, inhibitory effect on metastatic spread was attained by the therapy. The contribution of BCG-CWS to suppression of metastasis especially in the draining node was discussed from the point of lymphocyte trapping in the draining node.


Immune response of mice in immunotherapy of tumors with syngeneic antitumor serum plus lipopolysaccharide.

Humoral and cellular immune responses were investigated after combination therapy with syngeneic antitumor serum and bacterial lipopolysaccharide (LPS). The titer of antitumor antibody determined by using a macrophage-mediated system was very high in mice cured by the combination therapy, and this high titer lasted for a long time. In contrast, no significant titer was detected using an antibody-dependent lymphocyte-mediated system. Thus, antibody-dependent macrophage-mediated cytolysis was a more sensitive method for detecting antitumor antibody. The cellular immune response was measured as the delayed hypersensitivity reaction to tumor cells. In mice that had been cured by combination therapy, this reaction appeared at an early stage, before any antitumor antibody was detectable, but it soon decreased. On the other hand, tumor-bearing mice showed a low level of antibody and no significant delayed hypersensitivity reaction.


Lymphoma of the colon: the spectrum of radiologic changes.

Primary lymphoma of the colon is rare and comprises less than 1% of large bowel malignancies. Secondary colonic involvement in patients with advanced lymphoma is not uncommon and is frequently undetected. The radiographic findings of 34 patients with colonic lymphoma were reviewed. Thirteen patients had primary tumors, while the remaining 21 had colonic involvement secondary to systemic disease. The radiologic features were classified as mucosal nodularity, endo-exoenteric mass, intraluminal mass, mural infiltration, and mesenteric invasion. One patient with diffuse mucosal nodularity developed acute colonic dilatation, while two other patients had pneumatosis coli secondary to local tumor depositions. Lymphoma is now a well-described complication of chronic ulcerative colitis, and a further case is described here. Although colonic lymphoma is a relatively rare tumor, the spectrum of radiologic changes reviewed here may enable a more accurate radiologic diagnosis.


Corticosteroid therapy of alcoholic hepatitis.

Fifty-five patients with alcoholic hepatitis were studied in a 28- to 32-day randomized double blind treatment trial comparing prednisolone (40 mg per day) with placebo therapy. Of 31 placebo-treated patients, 4 died during the study interval and 2 more died within 5 days of study completion. Only 1 of 24 prednisolone-treated patients died during the same interval (Fisher exact test; P = 0.10). Stepwise discriminant analysis of laboratory factors associated with death revealed independently significant associations with prolongation of prothrombin time and height of serum bilirubin at the initiation of the study. When treatment was included as a variable in this discriminant analysis, it was found that corticosteroid therapy significantly decreased mortality (P less than 0.05). The corrected wedged hepatic venous presure decreased to a similar extent in the two groups. These studies suggest that corticosteroid therapy does decrease early mortality in patients with severe alcoholic hepatitis, but has no short term effect on the development of portal hypertension.


Reversal of jejunal water secretion by glucose in rats exposed to coliform enterotoxins.

Glucose absorption and glucose-facilitated water transport were assessed in rats exposed to semipurified preparations of the heat-labile (LT) and heat-stable (ST) enterotoxins of Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae by in vivo jejunal perfusion of these toxins alone and with varying amounts of glucose. Progressive increases in the glucose concentration of from 12 to 56 mM resulted in incremental rises in water absorption from perfusates containing each of these toxins, with similar delta water values to those for the electrolyte perfusion solution without toxins. Water secretion was reversed to absorption by the addition of 12 mM glucose when secretion was mild, but 24 mM was required to achieve this in the presence of severe secretion; absolute values for water transport did not return to normal in any instance. Glucose absorption from solutions containing 24 and 56 mM glucose was severely reduced by all of the ST toxins and marginally reduced by some of the LT toxins; the effect of LT was not attributable to the toxin itself, however, but to another unidentified factor present in LT, but not ST, preparations from both toxigenic and nontoxigenic strains. These observations indicate that glucose-facilitated water transport remains intact in intestinal tissue exposed to various coliform enterotoxins and that this occurs despite the presence of impaired glucose absorption in some instances. They provide a rational basis for treatment with oral glucose-electrolyte solutions of persons whose diarrhea is caused by toxigenic coliform bacteria.


Erythromycin resistance and the chloroplast ribosome in Chlamydomonas reinhardi.

Five classes of erythromycin-resistant mutants of Chlamydomonas reinhardi have been identified. Each class corresponds to a different genetic locus, three nuclear and two chloroplast. The three nuclear loci appear to be unlinked, while Conde et al. (1975) have shown that the two chloroplast loci are linked, but not allelic. Mutants in each class have a unique pattern of cross-resistance in vivo to other antibiotics (lincomycin, carbomycin, and cleocin) that affect chloroplast protein synthesis. The chloroplast ribosomes from each class have a distinctive erythromycin-binding reaction in vitro.--Haploid and diploid strains containing combinations of different genes affecting the chloroplast ribosome were constructed to probe ribosome structure. New phenotypes were obtained by such combinations, demonstrating interactions between the gene products of a number of loci specifying ribosome components.


Genetic instability in auxotrophs of Salmonella typhimurium requiring cysteine or methionine and resistant to inhibition by 1,2,4-triazole.

Triazole-resistant (Trz(r)) derivatives of six cysteine- or methionine-requiring (Cym(-)) mutants of Salmonella typhimurium were isolated. Some of the derivatives of each mutant (CTS) were prototrophic, i.e., Cym(-) was suppressed. In every case suppression was initially unstable, Cym(-) auxotrophs being segregated at high frequency, although Trz(r) was stable. After several subcultures on selective medium, CTS strains were classified as either persistently unstable or stabilized. The unstable strains segregated Cym( -) auxotrophs at frequencies of 50-70%, whereas the stabilized strains segregated at frequencies of less than 1%. All suppressed strains had a stable Trz(r) marker co-transducible with cysA. However, there was a correlation between the class of CTS strain and Cym(- ) phenotype. The stabilized strains were Cym(+), whereas the unstable strains were Cym(-). Acriflavin and ethidium bromide increased segregation in the unstable strains, suggesting the involvement of a plasmid. The stabilized strains were refractory to the curing agents. There was no detectable change in the quantity or quality of the S. typhimurium cryptic plasmid. The Trz(r) phenotype of the CTS strains suggested that Trz(r) mutations were of the stable TrzA type. It is suggested that correction of the Cym(-) lesions in CTS strains results from an insertion within the cysCDHIJ gene cluster of a DNA species originating in the cysALKptsHI region of the S. typhimurium chromosome.


The nature of genetic instability in auxotrophs of Salmonella typhimurium requiring cysteine or methionine and resistant to inhibition by 1,2,4-triazole.

We tested the hypothesis that unstable suppression of auxotrophy in triazole-resistant derivatives of Cym- mutants of Salmonella typhimurium is due to reversible insertion at the Cym- site of genetic material originating in the cysALKptsHI region. We have shown that the unstable phenotype was co-transducible with markers in the cysCDHIJ region. The suppression of the Cym phenotype was recA dependent and frequencies of segregation were affected by UV irradiation. Restored enzyme activity in suppressed strains was determined by wild-type enzyme, suggesting that the unstable regions are located in cys gene regulatory regions. These results support the hypothesis. In contradiction, we found no evidence for a deletion in the cysALKptsHI region.


[Genetic control of the sensitivity of Aspergillus nidulans to mutagenic factors. VII. Inheritance of cross-sensitivity to different mutagenic factors by uvs-mutants].

To study the inheritance of the sensitivity to UV, X-rays, methylmethanesulphonate (MMS), nitrosoguanidine (NG) and nitrous acid (NA) in five uvs mutants of Aspergillus nidulans, having multiple sensitivity to these factors, the sensitivity of recombinants obtained from crossing uvs mutants with uvs+ strain, resistant to all the factors analysed, and uvs leads to uvs+ revertants is investigated. Four uvs mutants (15, 17, 19 and 26) are found to have a nomogenic control of sensitivity to different mutagens. In one mutant (uvs11) the sensitivity to five factors is controlled by two non-linked mutations, one of them determining the sensitivity to UV, NG, NA, and the other--to X-rays and MMC. Phenotypic manifestations of uvs mutations is modified by cell genotype, both chromosomal and cytoplasmic factors being responsible for the modification. Phenotypic modification of uvs mutation results in the change to some (but not to all) mutagenic factors. It suggests, that not the product of uvs gene, but some other components of the reparation complex are modified. Otherwise, reparation of different DNA damages can be carried out by a single enzyme acting in different reparation complexes.


[Role of the product of recB-gene in the thymine-less death and characteristics of this phenomenon in a thy-recB--mutant of Escherichia coli K-12].

Thymine requiring mutants of rec+ and recB- Escherichia coli strains have been tested for their response to thymine deprivation. Exonuclease V-deficient mutant is less sensitive to thymine deprivation than the wild type strain, because there is no lag period at thymineless death of recB- thy- cells. However, the mechanism of thymineless death of thy- rec+ and thy- recB- cells may be different. Two types of thymineless death are proposed to exist. The first type is due to DNA primary structure damages (single-strand breaks or gaps), accompanied by DNA degradation. The restoration of the balance disturbed by the thymine deprivation between DNA and protein synthesis rates by their balanced inhibition promotes a complete repair of structural damages in DNA and prevents the death of rec+ cells. The second type of thymineless death is not linked with the formation of DNA damages, and this is observed in recB- thy- mutant, defective in exonuclease V.


[Intergeneric conjugational hybridization of Escherichia coli and Salmonella typhimurium. 1. Obtaining a salmonella hybrid possessing greater recipient activity in crosses with Escherichia coli].

Intergeneric hybrids were selected from mating HfrH Escherichia coli with F- Salmonella typhimurium. The hybrid obtained from E. coli leu+ and pro+ genes possessed the increased recipient ability in the mating with E. coli HfrR1 (O--ilv--metE--ara). This hybrid lacked the ability to restrict the phage P1 DNA propagated on E. coli K-12. The replacement of mutated uvrA gene of Salmonella for uvrA+ gene of E. coli restore uvr+ phenotype of Salmonella mutant.


[Genetic and heteroduplex analysis of deletion mutants of plasmid pAS8].

Heteroduplex analysis of deletion mutants of plasmid pAS8 permitted to construct a physical map and to elaborate in greater detail the genetic map of RP4 plasmid. The correlation between the ability of mutants to replicate in cells lacking functional DNA-polymerase I and the length of the deleted segment permitted to map rep genes of RP4 on DNA region with coordinates 9.8-17.3 kb. A relationship between the manifestation of incompatibility of mutants with IncP-1 plasmids and the length of deletions indicates that inc genes(s) are located on DNA region with coordinates 2.1-9.8 kb. The analysis of replication of deletion mutants and the manifestation of incompatibility just as of the data about the size of appropriate deletions permitted to make the conclusion about the functional and genetic non-identity of the replication control and incompatibility control in RP4 plasmid. Different degrees of incompatibility manifested by different plasmids suggest a possible polygenic control of the incompatibility.


[Induction of direct mutations of intracellular phage cd exposed to O-methylhydroxylamine].

Intracellular development of DNA-containing cd phage in the presence of O-methylhydroxylamine (in vivo mutagenesis) results in 50-fold increase of mutants in the phage progeny. The main effect is due to the mutagen presence during replication of phage DNA (within 10-20 min after the infection). The presence of the mutagen both before and after DNA replication does not produce any considerable mutagenic effect. Comparison of the data obtained with kinetic reaction of O-methylhydroxylamine with nucleic acid components is due to enzymatic formation of modified precursors, N4-metoxycytidine and/or N6-metoxyadenosine derivatives, which have dual functional specificity, and to their incorporation into genome under DNA replication. The presence of O-methylhydroxylamine increases not only the number of mixed clones with a high content of mutants, but also the number of pure mutant clones. Recombinogenic activity of O-methylhydroxylamine is considered to be a possible cause of this effect.


[Partial suppression of the effect of gene re1A in Fusr-mutant Escherichia coli K-12 cells].

Mutants of Escherichia coli K-12 re1A+-strain CP 78 resistant to fusidic acid (Fusr) were isolated and forms sensitive to high concentration of leucine (500 g/ml) were selected. When shifted down from nutrient broth to minimal medium M9 with supplemented glucose and required amino acids, these leucine-sensitive mutants continued RNA synthesis and demonstrated the prolonged lag-phase in contrast to the parent strain CP 78. Both properties are known to be characteristic of the Rel- strains. At the same time withdrawal of the required amino acids results in cessation of RNA synthesis in Fusr mutants, in the parent Rel+ strain. Thus, leucine-sensitive Fusr mutants show Rel- phenotype only upon amino acid starvation caused by shift down from nutrient broth to minimal medium.


[Mutagenic activity of dioxydine].

A previous evaluation of mutagenic activity of some drugs and perspective substances is carried out using indicator microorganisms. The mutagenicity of dioxydine, a drag with discovered antibacterial activity, is investigated. Dioxydine is shown to induce reversions in mutant of Salmonella typhimurium TA-1950, the indicator strain which demonstrates mutagenic activity of agents, producing mutations of base pair substitution type. Dioxydine proved to affect logariphmiically growing bacterial culture with great activity. Mutageni effect of dioxydine is not modified itself in microsomal oxidation system in vitro. Some data concerning participation of excision reparation enzyme (uvr-B+ gene product) in repair of lethal damages induced by dioxydine, have been obtained. The dioxydine ability to cause bacterial gene mutations in host mediated assay as well as dominant and recessive sex-linked lethal mutations in Drosophila is demonstrated. Dioxydine is capable of inducing chromosome aberrations in bone marrow cells and dominant lethal mutations in mouse germ cells.


[Problem of chromosome formation in T-even phages].

Three basic versions for the formation of circularly permuted and terminally redundant chromosomes with rings, concatemers, or fragments as replicative intermediates were considered. Experimental results show that the chromosome of T-even phage can turn into 4-6 large fragments soon after it penetrates inside the Escherichia coli cell. The fragments are capable for autonomous replication and contribute their material to progeny phage chromosomes. These results confirm the suggestion that circularly permuted and terminally redundant chromosomes of T-even phages are made of fragments. A theoretical analysis of different modes of parental chromosome fragments formation, autonomous replication and ordered association was carried out. In particular, it was emphasized that at a low multiplicity of infection the reassociation of fragments by means of recombination can be accomplished only if breaks in complementary strands of the parental chromosome were made with a shift for about 3000 nucleotides. Complexity is a feature of linear chromosomes that ensures their reproduction without defects at the ends.


[Construction and study of a new type of phage lambda DNA vector molecule].

A group of lambda mutants (mutants lambda 0) harbouring lesser number of EcoRI restriction sites on DNA molecules was selected. lambda3-1 recombinant (genotype lambdab221amgamma210Sr1lambda3+c-Px) was created by crosses of lambda02 phage with other lambda mutants. This phage DNA may be used as a vector molecule which makes it possible to select easily phages harbouring insertions of EcoRI DNA fragments. The maximal size of DNA fragment, the insertion of which would not decrease lambda3-1 viability, is 7.7 megadaltone. Lambda3-1 DNA has three regions heterological to lambda DNA, two of which probably include sites SRIlambda4 and SRIlambda5 and some juxtaposed genes. For example, Ptgene of lambda phage in juxtaposition with site SRIlambda4 is substituted by Px gene on the lambda3-1 DNA molecule.


[Localization of Rsf- mutation in Escherichia coli HfrC7].

The contransduction frequency of MAAs, UVs phenotype of Escherichia coli HfrC7 and its 7-51F- derivative with purE markers is found to be 1-2% which indicates that the mutation N 7 is located close to the F integration site in HfrC strain. E. coli strains K-12 7-51F+ and 7-51ColV2+ transfer chromosome markers in the same direction as does HfrC strain. The results suggest the presence of an integrated F fragment (sfa locus) into K-12 7-51F- chromosome.


[Spinocellular carcinoma of the hand].

The proper treatment of squamous cell carcinoma of the hand is surgical only. Radical cure and preservation of function need not exclude one another if the following points are considered: praeoperative biopsy and intraoperative pathological examination, consideration of the degree of malignancy and the possibilities of surgical reconstruction.


The treatment of infections in granulocytopenic patients with granulocyte transfusions.

Twenty-three severely neutropenic patients were given 31 courses of ABO and HL-A compatible granulocyte-rich plasma transfusions between 1974--76 at the National Institute of Haematology and Blood Transfusion. The criteria for the effectiveness of therapy were disappearance of fever and survival for over 3 weeks after granulocyte transfusion. Of the 28 evaluated cases granulocyte transfusions were effective in 16 and ineffective in 12 cases. The effectiveness of granulocyte transfusion was favourably influenced by early introduction of therapy, and continuation for several days.


Bone marrow cell separation on Ficoll gradient.

Cell fraction from rat and murine bone marrow were obtained by sedimentation at unit gravity. A linear gradient of polymerized sucrose (Ficoll) was used and some properties of individual cell fractions were studied. The 3rd cell fraction containing the lymphoblasts and lymphocytes contained also stem cells.


Chromosomes in malignant lymphomas (study on short-term lymph node cultures).

In 15 cases, chromosome studies were performed in short-term lymph node cultures, using the banding technique. Clonal aberrations were found in two cases of Hodgkin's disease and in two of lymphosarcoma. In agreement with earlier observations, the cases of lymphosarcoma with abnormal karyotypes proved hyperdiploid. No chromosomal aberrations were found in three cases of reactive lymphoreticular hyperplasia.


A simple allogeneic test system for the study of antibody-dependent cellular cytotoxicity (ADCC) in man.

A simple allogeneic test system for the study of ADCC activity of human mononuclear peripheral blood leucocytes (MPBL) is presented. The test uses human Rh-positive erythrocytes as target cells coated with specific human IgG antibody. The effector function of human MPBL is demonstrated after depletion of most of the monocytes and B lymphocytes on nylon wool column. The test system seems to be useful in the clinical study of ADCC activity in man.


The effect of ultrasound and its combination with radiation on the genetic material of Saccharomyces cerevisiae.

Ultrasonication at 20 kHz, intensity 35 W/cm2 and amplitude 15--25 micron of a diploid strain of Saccharomyces cerevisiae was found to act as a weak mutagen with maximum efficiency at the 20% survival of the cells. Under these conditions, the frequency of reversion of the suppressible allel ilv1-92 increased ten times, the frequency of mitotic gene conversion four times. Doses leading to survivals lower than 20% led to a slight increase in the frequency of cytoplasmic respiration-deficient mutants. Submutagenic doses applied immediately after gammaradiation or UV light did not substantially increase the effect of these physical agents on the genetic material of the yeast strain investigated. Application of ultrasound prior to UV radiation did not considerably influence the effect of the radiation either.


[Cruciate ligament injuries. Results of a follow-up study].

The paper describes the long term results of 48 patients treated operatively or conservatively because of injury to the cruciate ligaments. The first part deals with the main problems in treating these damages. The second part draws up the extent, age and cause of the injury in these 48 patients. 21 patients (with 22 damages to the cruciate ligaments) underwent clinical and radiological follow-up examination. There were 1 very good, 4 good, 11 fair, and 6 bad results. The results felt subjectively by the patients were: 5 very good, 6 good, 8 fair, and 3 bad.


[Problems of male contraception. 2. Male hormonal contraception, post-testicular points of attack, immunization and enzyme inhibition].

In principle control of male fertility is possible by mechanical, surgical and pharmacological methods. However, up to now only the following mechanical and surgical procedures are practicable: coitus interruptus, coitus condomatus and vasectomy. Since the safety of the latter is comparable to the pill, vasectomy is a major alternative to the contraceptive methods used by the female partner. Practical aspects of vasectomy and possible complications are reviewed. Finally, pharmacological approaches and problems involved in the control of male fertility are discussed with special reference to antispermatogenic substances, steroid hormones, immunization and enzyme inhibitors. The concept of antienzymatic contraception is based on the inhibition of penetration of enzymes (acrosin) localized within the acrosomal cap. Unfortunately, penetration of most of the acrosin inhibitors into the acrosome to inactivate acrosin is prevented by the high selectivity of the acrosomal membranes. Thus, pharmacological control of male fertility is still far from being practicable.


[Juvenile reticulosarcoma].

The prognosis of malignant lymphoma of bone in childhood has been improved. This is due to the modern chemotherapy. Pain in the bones is one of the early symptoms. If these early symptoms are not recognized, diagnosis and therapy may be delayed. The problems of classification, diagnosis and therapy are discussed, 2 case-reports with so-called reticulum cell sarcoma are given.


[Reticulum cell sarcoma of the pelvis. Diagnostic and therapeutic problems].

Diagnostic and operative problems of malignant bone tumors of the pelvis are discussed. Especially mentioned is resection therapy of pelvis tumor including large parts of the pelvis and the hip joint. A case-report is given. In this case replacement of the entire hip joint was successfully performed with a special prosthesis. Stabile fixation of the prosthesis is one of the major problems to be dealth with. Follow-up examination of our patient one year after the operation showed no loosening of the prosthesis and free movement of the hip joint iwth partial loack capacity of the leg.


[Debrisorb in the treatment of decubital ulcers. An empirical study].

During first 6 months of 1978 skin lesions of 22 patients suffering from paraplegia were treated with Debrisorb at the Dept. of spinal cord injuries of Bergmannsheil, Bochum. Contrary to the earlier used treatment (wet dressings, necrectomy and fibrinolytic ointments) it appeared that under Debrisorb treatment edema around expanded lesions was quickly reduced. Thereby this infections no longer had a sufficient nutrient. The necessary plastic surgery could be performed earlier than in the past. Debrisorb represent an essential help in the treatment of pressure sores. The common methods of treating pressure sores especially in paraplegic patients may not be changed. The load capacity of the scar is attained faster through Debrisorb. However, Debrisorb cannot replace plastic surgery.


[Valproic acid in the treatment of epilepsy with special emphasis on serum level determination (author's transl)].

Valproic acid has become a regular component of antiepileptic therapy. Generally it is used against genetically caused, primary generalized epilepsies with bilateral hypersynchronous neuronal discharges in the EEG. An improvement can also be observed by Valproic acid-treatment for secondary generalized and partial epilepsies. Therapeutic results could possibly be improved through a consideration of the serum concentration of valproic acid. Some of the commercial preparations contain the sodium salt of Valproic acid. The free acid which is quickly absorbed, is released in the stomach (tablet) or in the intestine (dragee). The half life is about 15 to 17 hours (one finds a range of 6 to 20 hours in the literature). In view of the half life, it is recommended that the daily dose should be divided into three single doses. About 84 to 95% of the substance is protein bound. Up to now, clinically relevant observations concerning the displacement of valproic acid from its protein binding are unknown. Recently in in vitro studies a decreased protein binding of valproic acid due to phenylbutazone, salicylic acid, and sulfadimethoxine and vice versa, a displacement of phenobarbital and phenytoin caused by valproic acid could be demonstrated. The therapeutic range of the serum level was between 50 and 120 mcg/ml. Individual patients showed that the dispensed dose did not reliably yield the expected serum levels. The necessary daily dose lies for adults between 600 and 2400 mg, in children between 15 and 150 mg/kg. The wide range of allowable dosis is dependent on whether or not valproic acid is to be given in conjunction with other antiepileptic drugs. When phenobarbital and valproic acid are given in conjunction one should be alert for a rise in the phenobarbital serum level. Results of studies in which valproic acid was combined with several other antiepileptic and psychotropic drugs are reported. The majority of the researchers determine a clear parallelism between clinical improvement and a normalization of the EEG in primary generalized epilepsies with bilateral synchronous 3/sec. spikes and waves. The background activity, determined by visual inspection, is not affected. Few workers discuss the correlation of the side effects of valproic acid and its serum level. Tiredness and impaired function of thrombocytes has been observed to be dependent on the valproic acid plasma level.


[Social psychiatry of migrant workers (author's transl)].

A review of literature about psychic illness in migrant workers (with special reference to the situation in Europe) is presented, including the problems of incidence and prevalence, course of the illness, typical syndromes and treatment. Results concerning incidence and prevalence of psychic disease in migrant workers are contradictory and partly--for methodological reasons--of questionable quality. It cannot be take for granted, that migrant workers suffer more often from psychiatric disturbances than either of the two possible control groups: the populations of the emigration or immigration countries respectively. There are two high risk periods for migrants: shortly after the migration and after a longer period in the guest country. Differences between the migrant's culture and that of the immigration context (language, mythical beliefs, illness behavior) influence the manifestations of psychiatric syndromes. The following syndromes are typical for migrant workers: paranoid reactions, hypochondric-depressive syndromes, psychosomatic conditions and sexual neurosis. Special attention requests the treatment of migrant workers with psychiatric problems; the aspects of psychotherapy, accompanying social measures and the return as therapeutic measure are discussed. In the second part, a general frame of reference for the sociological analysis of the problem of migrant workers is presented. Reasons for the mass immigration of foreign workers to the industrialized countries of central Europe were the demand of labor force and the large gap in socio-economic development between the countries. In the immigration context, the foreign workers find themselves in the lowest social strata and numerous problems accumulate there. Empirical evidence for different sociological explanations of mental illnes of migrant workers ist presented: hypotheses of social selection vs. social causation (low socio-economic status, goal-striving-stress, culture-shock theory, theory of culture change and isolation hypothesis).