[Modification of arginine residues in pyruvate kinase (author's transl)]. Pyruvate kinase from pig heart is inactivated by the specific arginyl reagent phenylglyoxal. The loss of activity is caused by the reaction of a single molecule of phenylglyoxal per subunit of enzyme. During inactivation 3 - 6 arginyl residues are modified dependent on the concentration of phenylglyoxal used for modification. The solubility of the protein is reduced by the modification. ATP or phosphoenolpyruvate protect against inactivation. A single arginine is less subject to chemical modification in their presence. Therefore we assume that an arginine is essential at the substrate binding site. The activating ion K does not affectinactivation, where as Mg2 diminishes inactivation. Pyruvate kinase from rabbit muscle is modified by phenylglyoxal in a similar manner.


Structure and activity of insulin, XV[1-5]. Further evidence for the importance of arginine residue B22 in the activity of insulin. Semisyntheses of despentapeptide-(B23 - 30)-insulins varied in B22 using desnonapeptide-(B22 - 30)-insulin and tetrapeptides. Insulin hexamethyl ester was digested by trypsin. The resulting desoctapeptide-(B23 - 30)-insulin pentamethyl ester was purified. This compound was digested by carboxypeptidase B to remove the arginine residue B22 at the end of the B chain. Then the N-terminal amino groups of the remaining desnonapeptide-(B22 - 30)-insulin pentamethyl ester were protected with the Boc residue. The free carboxyl group of the glutamic acid residue B21 of this product was coupled to the following synthetic tetrapeptide esters: Arg-Gly-Phe-Phe-OMe, Lys(Boc)-Gly-Phe-Phe-OMe, Orn(Boc)-Gly-Phe-Phe-OMe, Cit-Gly-Phe-Phe-OMe, Ala-Gly-Phe-Phe-OMe and Gly-Gly-Phe-Phe-OMe. The syntheses of these peptide esters are described. After removal of all protecting groups, despentapeptide-insulin (B22-Arg) and analogues of this product with variation in position B22 could be obtained. They were purified by column chromatography. The biological activities of these components were determined by the mouse fall test. In the case of despentapeptide insulin (C-terminus Arg-Gly-Phe-Phe), the activity rose to the expected value of 34%. The insulin variants with amino acid residues other than arginine in position B22 had much lower activities: with lysine 13%, with ornithine 12%, with citrulline 9%, with alanine 8% and with glycine 6%. Desnonapeptide-insulin by itself posses an activity of 3%. These results demonstrate once more the essential nature of arginine residue B22 for insulin activity.


Kinetics of the appearance of nuclear estrogen binding sites in chicken liver. A single injection of estradiol to immature male chickens results in a very rapid increase in the number of both soluble and tightly bound nuclear estrogen binding sites. After an intermediate levelling off, a second longer lasting increase in binding sites is observed. Whereas the first rapid increase seems to be independent of RNA and protein synthesis, the second one obviously requires intact RNA and protein synthesis. From these results we conclude that there is a pool of cytoplasmic estrogen binding sites, which supplies the precursor for the nuclear binding sites. After this pool is exhausted, it is replenished by new synthesis of binding sites. However, although several laboratories have attempted to demonstrate directly the existence of such a cytoplasmic estrogen receptor in the chicken liver, all have so far been unsuccessful.


Purification and characterization of the DNA-dependent RNA polymerase and its subunit sigma from Micrococcus luteus. DNA-dependent RNA polymerase from Micrococcus luteus can be isolated from cell extracts after removal of an excess of nucleic acids by fractionation with ammonium sulfate, followed by two consecutive gel filtrations through agarose and chromatography on cellulose phospate. Either homogeneous holoenzyme or a mixture of core and holoenzyme is obtained in this way, as is indicated by electrophoresis in polyacrylamide gels in the absence of detergent, where core enzyme migrates ahead of holoenzyme. Homogeneous core enzyme can be isolated from holoenzyme by chromatography on DEAE-cellulose. Core enzyme contains the subunits alpha, beta and beta' previously described [U.I. Lill et al., (1975) Eur. J. Biochem. 52, 411-420] in a molar ratio of 2:1:1. Holoenzyme contains an additional subunit sigma of 80 000 molecular weight (molar subunit composition alpha2 betabeta' sigma) and two relatively small polypeptides (molecular weight 14 000 and 25 000, respectively). Subunit sigma may be isolated from holoenzyme by chromatography on DEAE-cellulose at pH 6.9 in the presence of low concentrations of glycerol. The behaviour of holoenzyme during sedimentation in a glycerol gradient at low ionic strength indicates its occurrence as a dimer of the alpha2betabeta'sigma-protomer, whereas the monomeric form is preferred by core enzyme. Holoenzyme is much more active than core enzyme in RNA synthesis on bacteriophage T4DNA as template. The activity of the latter is stimulated by isolated sigma. M. luteus sigma as well as holoenzyme enhances also the activity of core enzyme fro- Escherichia coli. The formation of a hybrid between micrococcal sigma and E. coli core polymerase is also suggested by the influence of sigma on the oligomerisation of the enzyme from E. coli.


Demonstration of 9-O-acetyl-N-acetylneuraminic acid in brain gangliosides from various vertebrates including man. Ganglioside fractions were isolated from brains of man, cow, horse, pig, sheep, cat, rabbit, rat, chicken and codfish. The acylneuraminic acid residues, liberated from these gangliosides by treatment with dilute aqueous acid or neuraminidase, were analysed by the thin-layer chromatography and combined gas-liquid chromatography/mass spectrometry. Small amounts (up to 20%) of 9-O-acetyl-N-acetylneuraminic acid, and in bovine and porcine brain gangliosides also traces of N-glycoloylneuraminic acid, were found in addition to N-acetylneuraminic acid.


Bovine fetal fluid cells in vitro: fate and fetal sex prediction accuracy. The in vitro fate of bovine fetal fluid cells and the efficiency of fetal sex predication from cultures of these cells are studied using aspirates from live animals and pregnant uteri collected from the  slaughterhouse. Over 70 percent of bovine amniotic fluid samples aspirated from pregnant uteri at the time of slaughter yielded cultures adequate for chromosome analysis whereas only 10 percent of allantoic fluid samples produced growth of cells satisfactory for chromosome analysis. Fetal sexing accuracy was 100 percent in all samples studied. Seven readily recognizable cell types were noted in cultures of fetal fluid cells obtained at various stages of gestation. In a majority of cases, the in vitro morphology of cells from both fetal cavities was similar to that observed in primary human amniotic fluid cell cultures.


Effect of CO2 on short-term human lymphocyte culture in vitro. There was no significant difference in the mitotic indices of the cultures maintained at different CO2 concentrations, i.e. 0 percent, 5 percent and 10 percent. However, considerable variation was recorded among different individuals.


[Viral haemorrhagic fever].

[Viral haemorrhagic fever]. Two outbreaks of haemorrhagic fever caused by a Marburg-like virus occurred in the Sudan and Zaire from August to November 1976. The inital epidemiological investigations and emergency control measures were carried out by Sudanese and Zairian health personnel and several of them unfortunately died in the course of their duties. In view of the unusual gravity of the outbreaks and the unknown nature of the agent, assistance was provided by a WHO team in the Sudan and a multinational team in Zaire. A consultation arranged by WHO was held at the London School of Hygiene and Tropical Medicine in January 1977 to review the experience acquired during these outbreaks and to make recommendations which, to a large extent, may be applicable to other outbreaks of suspected viral haemorrhagic fever. Because it is felt that this information would be of value to many health administrations, large abstracts of the report of this consultation are given here.


Morphology of the spleen and lymph nodes in fatal visceral leishmaniasis. Histological appearances of the spleen and lymph nodes were analysed in twenty fatal cases of human visceral leishmaniasis from Sudan. Marked atrophy of the splenic white pulp was associated with necrosis and fibrosis of thymus-dependent area, accumulation of parasite-containing histiocytes and plasma cell hyperplasia. Depletion of small lymphocytes in the paracortical areas of the lymph nodes was accomplained by proliferation of plasma cells and histiocytes in the paracortex. Depletion of small lymphocytes in thymus-dependent regions of lymph nodes and spleen is viewed as arising from immune suppression associated with antigen overloading or other factors, which may impair those aspects of lymphocyte-macrophage cooperation that are presumably necessary to kill the invading parasites.


Effect of X irradiation on homocytotropic and agglutinating antibody production in mice. The effect of X irradiation on homocytotropic and agglutinating antibody production was studied in mice exposed to 400 rad either before or after immunization with dinitrophenylated  Ascaris plus aluminium hydroxide as adjuvant. The adjuvant effect of irradiation was also determined in animals receiving antigen alone. Irradiation 1 day before immunization with adjuvant enhanced IgE and slightly enhanced IgM-antibody formation, although the onset was delayed, but partially suppressed IgG-antibody formation. When the same treatment followed antigen priming, there was a similar enhancement of IgE production which varied with the time between the two procedures. IgG AND IgM production, however, were fairly resistant under the same conditions. Irradiation preceding immunization with soluble antigen had no significant adjuvant effect on IgE-, IgG- or IgM-antibody production. On the contrary, it suppressed production of the latter two classes. The results may indicate that production of IgE and IgG and IgM antibodies in the mouse is regulated by separate mechanisms.


Effect of early bursectomy on germinal centre and immunoglobulin production in chickens. Chickens were bursectomized in ovo on days 18, 19 or 20 of incubation or within 6 h of hatch and immunized at day 28 after hatch by an intravenous injection of sheep red blood cells (SRBC). The immune response in the blood was measured by haemagglutination tests on the serum and by immunocyto-adherence tests for enumeration of rosette-forming cells with SRBC. Total serum 19S and 7S immunoglobulins were determined by radial immunodiffusion and the number of germinal centres per mm2 of fixed and stained spleen tissue sections was determined. In ovo bursectomy produced undetectably low serum levels of haemagglutinins, a reduction in SRBC rosette-forming cells with normal or increased 19S and reduced 7S immunoglobulins together with a complete disappearance (absence) of germinal centres in the spleen. The role of 19S antibody in the generation of germinal centres is discussed. The finding that birds which are equipped with serum 19S but no 7S Ig lack splenic germinal centres casts doubt on the hypothesis that the switch 19S leads to 7S Ig is necessarily an intrabursal event.


Effect of cyclophosphamide on delayed hypersensitivity to Staphylococcus aureus in mice. Mice given cyclophosphamide 2-3 days before a single subcutaneous infection with Staphylococcus aures on cotton dust develop much more delayed type hypersensitivity (DTH) than normal. The enhancement is due to removal of rapidly dividing cells from the spleen. Passive transfer experiments before infection or before challenge show that immune serum suppresses the induction but not the expression but do not prevent induction. There may therefore be 2 suppressor or regulating systems involved. Cell commitment to suppressor function may be self-limiting. The results explain why DTH to staphylococci is only fully established after repeated infections and support the view that the suppressor system may function as a check on the excessive and potentially harmful development of DTH.


Neutralization of tetanus toxin by human and rabbit immunoglobulin classes and subunits. This investigation found that the human antibody class of importance in neutralizing tetanus toxin in mice was IgG, and that toxin neutralization was retained by the F(ab')2 and Fab' subunits of the human IgG class. Although human IgM and IgA classes appeared to neutralize tetanus toxin at very low levels, evidence was obtained that this neutralization was probably due to IgG contamination. Human Fabmu isolated from the IgM class did not neutralize tetanus toxin. Human antibodies of the IgG, IgM and IgA classes reacted with tetanus toxoid in the indirect haemagglutination (HA) test with IgG giving the highest HA titre. Rabbit antibodies of the IgG class also neutralized tetanus toxin, with neutralization being retained by the F(ab')2 and Fab' subunits of the rabbit IgG class. Absorption of several rabbit antisera to tetanus toxoid with goat-antirabbit Fc which is specific for absorption of IgG from antiserum, rendered them incapable of neutralizing tetanus toxin.


Relationships between different functional properties of human monocytes. Various methods for measuring monocyte numbers and function in human blood are compared. The assays used were: phagocytosis of antibody-sensitized sheep red cells; staining for diffuse non-specific esterase activity; capacity to adhere to polystyrene and ability to lyse human A1 red cells sensitized with allogeneic anti-A1 antibody. The following conclusions are drawn from the results: (1) Previous observations showing that sensitized A1 red cells are lysed by phagocytic cells and not K cells are confirmed. (2) Granulocytes lyse sensitized A1 red cells more rapidly than monocytes and this assay is only useful for assessing monocyte function if granulocytes are first removed from preparations. (3) Phagocytosis is important in the lysis of sensitized A1 red cells by monocytes. (4) Esterase positive cells correlate significantly with the number of cells phagocytosing sensitized sheep red blood cells, r = 0.83 (P less than 0.001) and with the number of cells adhering to polystyrene, r = 0.53 (P less than 0.05). (5) The lysis of sensitized A1 red cells correlated significantly with esterase positive cell numbers, r = 0.57 (P less than 0.001) and phagocytosis of sensitized sheep red cells, r = 0.50 (P less than 0.01 but not with the numbers of adherent cells, r = 0.34 (P greater than 0.05).


Transfer of anaphylactic antibodies from mother to young in the rat. The transfer of anaphylactic antibodies of classes IgE and IgGa from immunized female rats to babies was examined during primary and secondary immunization by injection, and also in rats infested with Trichinella spiralis. IgE antibodies were never detected in the blood of the babies, although they were sometimes detected in the milk in their stomachs. Similarly, no IgE antibodies were found in the serum of babies from mothers infested with Trichinella spiralis during pregnancy. IgGa antibodies were present in the serum and milk of the mothers following secondary immunization, and were readily absorbed through the intestine of the babies.


Dimethyl diotadecyl ammonium bromide as adjuvant for delayed hypersensitivity in mice. Immunization of mice with antigen mixed with cationic surface active lipid dimethyl dioctadecyl ammonium bromide (DDA) produced delayed type hypersensitivity (DH), measured as a footpad swelling. The DH to sheep red blood cells or dinitrophenyl conjugated with bovine serum albumin (DNP28-BSA) in DDA exceeded the response of the same antigens in Freund's Complete Adjuvant (FCA) significantly. Treatment of mice with CY 8 hr prior to the injection of antigen in FCA or DDA resulted in delay of the onset of footpad swelling past day 5 and in elimination of the differences in the response due to the adjuvants. Immunization with carrier or hapten-carrier complexes with different epitope density in DDA and elicitation with the homologous and heterologous antigens revealed that the DH was DNP-specific. In vivo priming with DNP28-BSA in DDA and in vitro stimulation with the same antigen resulted in peak responses which were twice as high and were reached almost twice as fast as the earlier found response following immunization in FCA. The advantages of DDA as adjuvant over covalently linked fatty acid chains and over FCA are discussed.


Chemotaxis for polymorphonuclear leucocytes induced by soluble antigen- antibody complexes. Guinea-pig soluble immune complexes formed either by simply mixing antibody and antigen in excess or by redissolving a washed immune precipitate with antigen, after incubation with fresh serum, could induce a migration of polymorphonuclear leucocytes in vitro. This chemotactic effect of soluble complexes, although less than that of insoluble complexes, persisted despite experimental changes in the specificity, the dose and the class of antibodies. Soluble complexes of various molecular compositions induced chemotaxis but the most efficient complex was of Ab 1 Ag 1 formula. Unlike larger complexes, the Ab 1 Ag 1 complexes induced little or no complement fixation. Another source of chemotactic mediators was needed, apparently related to the esterases of the contact system of coagulation.


A comparison of internal fixation and prosthetic replacement in the treatment of displaced subcapital fractures. This paper presents a retrospective review of 348 operations performed for subcapital fractures of the neck of the femur. A similar proportion of satisfactory results was obtained with internal fixation and prosthetic replacement. The mortality was higher in those treated by prosthetic replacement and careful selection of patients for this treatment is required.


A new external fixation device for treatment of complicated fractures of the leg. An external fixation device has been designed for rigid fixation of fragments of bone. It can be used in operations to lengthen the tibia and can be adapted to the compression fixation of fractures. This paper describes the apparatus and its use in the treatment of 10 complicated fractures.


Mechanical stability and post-traumatic osteitis: an experimental evaluation of the relation between infection of bone and internal fixation. Stable and unstable internal fixation of fractures was performed in rabbits. After inoculation with Staphylococcus aureus, clinically manifest osteitis occurred only in the very unstable fractures. Abscesses, sinuses and sequestra developed in 45 per cent of the unstable fractures, whereas clinically manifest osteitis did not occur after rigid fixation. With rigid fixation there was no significant difference in the time to bony union between the infected and uninfected fractures. It seems that the development of osteitis and the healing of a fracture are both related to the degree of rigidity, but remain independent of each other. The significance of these findings in the management of posttraumatic osteitis is discussed.


The operative management of the difficult supracondylar fracture of the humerus in the child. A series of supracondylar fractures of the humerus in children is presented. The majority was reduced by closed manipulation. The difficult fractures were defined as those in which adequate reduction either could not be achieved by manipulation or was not maintained, or those in which neurological or vascular complications occurred. Such cases were treated by open reduction and internal fixation. The results were assessed with regard to loss of elbow movement, deformity and symptoms. The results of the operative series were comparable with those achieved by closed manipulation in the easier cases. No secondary corrective procedures were necessary. It is concluded that closed manipulation should be used routinely as the method of treatment for supracondylar fractures of the humerus in children, except in the difficult case, for which operative treatment should be undertaken. Stiffness or deformity does not follow open reduction and internal fixation.


A comparison of the treatment of trochanteric fractures of the femur by internal fixation with a nail plate and the Ender technique. In our experience, trochanteric fractures fixed with Ender nails achieved a degree of success similar to those treated by nail plating, but the risk of wound infection was much less with the former method. The results of 78 trochanteric fractures of the femur internally fixed with Ender nails have been analysed and compared with the results in 100 similar patients treated by nail plate fixation. The Ender method has advantages over existing operative methods, in that in our series the infection rate was zero and we found that the operation produced less shock. We consider that this method, although technically more difficult, can be used for most intertrochanteric fractures and merits further trial.


Fracture-dislocation of the ankylosed thoracic spine. A patient with a fracture of an ankylosed thoracic spine was treated initially along conservative lines. Subsequently the fracture displaced, causing paraplegia. Internal fixation proved difficult but stability was obtained by wiring two Sherman plates to the posterior elements. This succeeded in holding the fracture until the death of the patient 13 days postoperatively. The difficulties in the management of these fractures are discussed.


A case of gastrojejunal rupture.

A case of gastrojejunal rupture. Rupture of the stomach, duodenum and jejunum are well-recognized complications of non-penetrating abdominal trauma. This case is thought to be the first recorded injury of its kind.


An unusual cause of blocked reduction of the Galeazzi injury. Two cases of the Galeazzi lesion are described, in which a mechanical block to closed reduction of the dislocated inferior radio-ulnar joint was encountered. This does not seem to have been described before.


Angiography after paint-gun injury of the hand: a case report. Because the severity and extent of vascular damage may determine the surgical treatment, angiography may be an important preoperative investigation of injection injuries. An example of a paint-gun injury to the hand, in which serious vascular damage was confirmed by angiography, is described.


Dislocation of both interphalangeal joints of one finger. A rare type of dislocation involving both interphalangeal joints of one finger is described. The mechanism of injury is discussed, and the importance of immobilizing the finger in the correct position is stressed.


Accuracy of reduction of femoral subcapital fractures. Fifty-four patients with recent subcapital fractures of the femur underwent a Flynn reduction manoeuvre and are compared with 68 patients who were treated by a different method of reduction. Analysis of the postoperative radiographs showed no significant difference in the accuracy of reduction (0.1 greater than P greater than 0.05). The Flynn reduction manoeuvre is recommended as a method which compares favourably with other manoeuvres.


Abdominal injuries due to blank cartridges. Blank cartridges may produce serious injury and the recognition of this hazard must be borne in mind when treating these wounds. This paper reports two cases of complicated abdominal injury inflicted by a blank cartridge.


The infra-isthmal fracture of the shaft of the femur. The common infra-isthmal fracture of the shaft of the femur is defined. The difficulties in its management are discussed and various methods of treatment are critically reviewed. The operative treatment of 21 such fractures with a single plate by the AO method is described. Strict adherence to every detail of the operative and postoperative technique and a cooperative patient are essential for a successful result.


Multiple intramedullary nailing of pertrochanteric fractures with elastic nails: operative procedure and results. Two hundred and sixty-six pertrochanteric fractures were operated on using intramedullary fixation according to the method of Ender and Simon-Weidner. Evaluation of both early and late results prove it to be a method with a low complication rate and a high incidence of functional recovery.


Displaced radial neck fractures in children. Forty-eight children with displaced fractures of the radial neck were studied. Five types of injury were seen, that associated with a valgus strain being the most common. Good results were obtained in just over one-half of the cases. It is concluded that treatment of these fractures should be by closed means whenever possible. It is generally unwise to attempt operative correction unless the radial head remains displaced or the residual angulation approaches 45 degrees. Open reduction should be checked by intraoperative radiographs. Internal fixation is seldom necessary and has its complications. Late manipulation of the fracture causes additonal trauma and the results are bad. Avascular necrosis and radio-ulnar synostosis were the two most disabling complication encountered.


Fractures in previously abnormal parts.

Fractures in previously abnormal parts. This paper discussed fractures in defective or deformed bones, in stiff, wasted or anaesthetic limbs and at the ends of metal implants. Suggestions are made as to how treatment should be modified in these situations.


Lumbosacral fracture-dislocation: a case managed conservatively, with return to heavy work. A 41-year-old agricultural sustained a lumbosacral fracture-dislocation when a tree fell across his back. The initial anterior displacement of half the depth of the body of L5 progressed to three-quarters of the body over a 2-year period. Neurological deficit was minimal and the management was conservative. Spontaneous arrest of the displacement occurred by anterior sacral buttressing and the patient has returned to his previous heavy work.


The jammed Küntscher nail: a method of releasing the nail and report of a case. A case of jamming of a Küntscher nail is presented and the technique of longitudinal splitting of the femur by which the nail was released is described. The possible causes of jamming are summarized and some precautions are suggested to avoid this dilemma. Other methods of dealing with a jammed nail are reviewed.


Unstable dorsal fractrue-dislocation of the fifth carpometacarpal jont. Four cases of unstable fracture-dislocation of the fifth carpometacarpal joint are reproted, including 3 isolated dorsal fracture-dislocation and 1 dorsal fracture-dislocation associated with a fracture of the fourth metacarpal bone. All cases required open reduction and Kirschner wire fixation which resulted in good function. Attention is drawn to the frequent delay in diagnosis. The applied anatomy is discussed.


Spontaneous rupture of the gastrocnemius muscle. Nineteen ruptures of the medial head of the gastrocnemius muslce are described. These were caused by sudden overstretching of the muscle though concomitant ankle dorsiflexion and knee extension. Surgical exploration in 12 patients verified rupture of the musculotendinous junction. A 2-year follow-up showed that the surgical approach with suture of the muscle gave better results than conservative treatment, especially in the younger and athletic patients.


The effect of haemorrhage on renal blood flow and intrarenal flow distribution. Bleeding of dogs to constant arterial pressure of 90 mm/g and 60 mmHg respectively decreased renal blood flow in proportion to pressure reduction. There was no evidence of autoregulation of renal blood flow or of selective renal vasoconstriction. With the radioactive microsphere technique a moderate shift of blood flow from the outer to the inner cortex was observed. In the renal 133Xe wash-out curves exponent 1(attributed to the elimination of the indicator from the cortex) was more reduced than exponents 2 and 3 (medulla). These findings may not indicate a redistribution of renal blood flow through resistance changes in specific parts of the renal vasculature but may represent the consequences of focal cortical ischaemia, most prominent in the outer cortex.


Spinal injuries in belt-wearing car occupants killed by head-on collisions. In 34 post-mortem examinations of car occupants wearing seat belts and killed in straight or oblique head-on collisions, a thorough investigation of the spine was performed. The autopsy results were correlated with the findings in the cars in order to reconstruct the events when the occupant's body struck the interior of the car. In 2 cases the victims had worn lap belts, in 15 cases shoulder belts and in 17 cases combined shoulder-lap belts (three-point belts). In victims involved in head-on collisions while wearing lap belts, fractures of the neural arch of the axis were found which were probably due to flexion of the neck pivoting round the lower part of the impacting face and simultaneous stretching of the neck. Severe injuries to the cervical spine in those victims wearing shoulder belts were mainly due to the occupant sliding under the belt which then caught the neck and mandible. Such injuries were also caused by the impact of the head against forward parts of the car. In those wearing shoulder-lap belts injuries to the upper part of the cervical spine resulted from the impact of the head against internal parts of the car. When a slight impact of the head occurred minor injuries to the lower cervical spine were seen. Injuries to the thoracolumbar spine in the cases examined were the consequence of a violent extension between the upper part of the trunk held back by the shoulder belt and the pelvis restrained by the lap belt or by the knees striking the fascia panel. In front seat occupants this extension can be increased if either rear seat occupants without belts or heavy objects on the rear seat are projected forwards against their backs.


Fractures of the humerus from arm wrestling. Two cases of humeral shaft fracture following 'arm wrestling' are described. Only one has previously been reported from Great Britain. The literature is reviewed and the mechanism of the injury discussed.


Bull horn injury: a clinical study.

Bull horn injury: a clinical study. Seventy-three cases of bull horn injury from a predominantly rural population around Allahabad were admitted to our unit between 1966 and 1975. Injury to the deep viscera is uncommon and the possible explanations of this pattern of injury are discussed. The abdomen was the commonest site of injury with prolapse of loops of small intestine in 60 per cent of cases. Management differs from other penetrating abdominal wounds and simple cleansing and careful examination of the bowel is sufficient in those injuries with prolapse of the intestine.


Rectal tear causing prolapsed ileum after closed abdominal injury. A case of prolapsed ileum through a tear in the rectal wall, passing through a tear in the rectal wall, passing through the anal canal, after a blunt injury to the abdomen in a child is presented. The cause and management of the condition are discussed.


Early protected weight bearing in African patients with fractures of the femur. Among 100 cases of closed fracture of the femur admitted to a Nigerian hospital during the years 1954--71, and treated by skin or skeletal traction, the mean time to clinical union was 6 weeks and to discharge on protected weight bearing 7 weeks. There were no cases on non-union. It is suggested that the traditional recommendation of 12-14 weeks in traction to ensure clinical union of a fracture of the femur should be revised, at least in African patients.


Fractures of the tibial shaft: is medical audit possible? Eight reports dealing with fractures of the tibial shaft have been examined to ascertain whether an audit of the results could be made. This was possible in only two instances owing to wide variations in the systems of classification of fractures, in definitions of certain terms and in presentation of results. Histograms in the form of frequency distribution curves of healing time were not helpful for making comparisons but the presentation of the results in the form of cumulative percentage curves appears to have advantages as a simple visual means of comparison. Statistical analysis is then still necessary. Little useful information is gained by attempting to compare reports which incorporate different systems of classification and definition as well as different methods of presenting results. A medical audit of different methods of treatment will only be made possible by standardization in these matters. A system of classification is required which will subclassify serious fractures so that specific problem fracture types can be studies on a multicentre basis.


Demonstration of cross-protection between Pasteurella multocida type A and Pasteurella haemolytica, serotype 1. Mice immunized with the potassium thiocyanate extract of Pasteurella haemolytica, serotype 1, were found to resist a challenge infection of P. multocida type A, thus demonstrating cross-protection. This finding was further supported by the finding that an antiserum directed against the potassium thiocyanate extract of P. haemolytica was bactericidal to P. multocida and vice versa.


Effect of serum from various animal species on erythrocyte attachment of endotoxins and other bacterial antigens. Lipopolysaccharide O antigens (endotoxins) and other bacterial antigens readily attach to erythrocytes in vitro. This attachment is prevented by certain mammalian and avian sera. In this study, the inhibitory capacity of sera from lower animals was compared with that of higher animals for a total of 30 species. Antigens and the corresponding antisera included both crude O antigens and purified lipopolysaccharide preparations, the common enterobacterial antigen from Escherichia coli O14, the Vi antigen from Citrobacter ballerup, the polyribose-phosphate antigen from Haemophilus influenzae type b, and the crude teichoic acid antigen from Staphylococcus aureus. Antigen and serum mixtures were incubated at 37 degrees C for 30 min and used for erythrocyte modification; failure of hemagglutination by homologous bacterial antiserum provided evidence of inhibitory capacity. Sera from the classes Mammalia and Aves were very strong inhibitors; those of Reptilia and Osteichthyes were moderate in activity, displaying variation within the classes; those of Amphibia and Chondrichthyes were minimal inhibitors; and those of Merostomata, Crustacea, and Lamellibranchiata displayed questionable or no inhibitory capacity. Inhibitory sera were active with all antigens tested. The findings suggest evolution of inhibitory factors consistent with the theory of two diverging lines of animal phylogeny based on embryological criteria and closely parallel the observations of an endotoxin-altering capacity in vertebrate sera that is not found in invertebrate sera or hemolymph.


Distribution of dextransucrase in Streptococcus mutans and observations on the effect of soluble dextran on dextransucrase activities. Total and insoluble dextransucrase activities were measured in cell-associated and supernatant fractions of Streptococcus mutans GS-5 grown in several media. Although the amount of cell-associated and supernatant activity varied greatly as a function of medium, the total activity appeared constant. The distribution of dextransucrase could be altered without changing the total dextransucrase activity. This indicates that the distribution of the enzyme can be regulated independently of its synthesis. Strain GS-5 had significant cell-associated activity in media devoid of sucrose. In all cases, the ratio of insoluble to total dextransucrase activity was higher in the cell-associated fractions than in the cell-free supernatants. It is also demonstrated that exogenous soluble dextran caused a decrease in insoluble dextransucrase activity and an increase in soluble dextransucrase activity in both the cell-associated fraction and the culture supernatant. The stimulation of soluble dextran-synthesizing activity was not due to de novo synthesis. The inhibition of insoluble dextran-synthesizing activity is shown to be noncompetitive. These results support a physical rather than metabolic mechanism for the effect of soluble dextran on dextransucrase activities.


Induction and expression of immunity after BCG immunization. The induction and expression of immunity to Mycobacterium tuberculosis after BCG immunization by intravenous, subcutaneous, and pulmonary routes has been investigated in mice. The speed with which protective immunity was engendered was a function of inoculum size; the immunization route was a less influential factor. Tuberculin hypersensitivity varied both with the inoculim size and immunization route, being least after pulmonary immunization. Once immunity was established, a steady state ensued in which the number of sensitized lymphocytes in the spleen was similar, regardless of the route or dose of vaccination. Actively immunized animals controlled intravenous and subcutaneous challenge infections, regardless of the method of vaccination. However, pulmonary challenge was resisted most efficiently by mice immunized by the pulmonary route. Adoptive immunity was well expressed in the spleen only, but the lungs were no more deficient in this regard than the footpad. It is suggested that enhanced immunity in the lungs depends on a population of resident sensitized lymphocytes.


Effects of streptolysin O on transport of amino acids, nucleosides, and glucose analogs in mammalian cells. The transport of several amino acids, nucleosides, and glucose analogs was studies in HeLa cells treated with sublethal concentrations of streptolysin O. A differential effect of toxin on the various solutes tested was observed. The uptake of the neutral amino acids alanine, alpha-aminoisobutyric acid, leucine, and phenylalanine was reduced by 60 about to 70%. Less inhibition of transport was observed with acidic and basic amino acids, and the uptake of nucleosides and glucose analogs was reduced by 20% or less. The decreased uptake of alpha-aminoisobutyric acid could be explained by the inability of toxin-treated cells to retain this amino acid. The altered transport of phenylalanine and lysine, however, appeared to be due to decreased initial rates of uptake rather than to the loss of these amino acids from intracellular pools in toxin-treated cells. After treatment with sublethal concentrations of streptolysin O, the cells recovered their ability to transport and accumulate alpha-aminoisobutyric acid in about 4 h. The data suggest that the alterations in membrane transport observed in toxin-treated cells are due to an effect of streptolysin O on specific transport systems, rather than to the production of holes or pores in the membrane.


Defective neutrophil chemotaxis in juvenile periodontitis. Neutrophil chemotaxis was evaluated in nine patients with juvenile periodontitis, with normal subjects and patients with the adult form of periodontitis as controls. Defective chemotactic responses were observed in neutrophils from seven of nine juvenile patients, and a reduced level of complement-derived chemotactic activity was demonstrated in serum from four patients. These determinations were normal in all the patients with adult periodontitis. Serum from five of the juvenile patients contained a heat-stable, non-dialyzable factor that markedly inhibited the chemotaxis of normal neutrophils. Thus the characteristic tissue destruction seen in juvenile periodontitis may be, at least in part, a consequence of a failure of host defense mechanisms.


Adherence of Veillonella species mediated by extracellular glucosyltransferase from Streptococcus salivarius. The effect of extracellular products from Streptococcus salivarius on sucrose-dependent adherence to smooth surfaces by other oral bacteria was studied in vitro. Strains of Streptococcus mitis, Streptococcus pyogenes, and Veillonella parvula without innate ability to adhere to a steel wire were able to do so when incubated with sucrose and cell-free culture fluid from S. salivarius strains 9759, 25975, CNII, and MEPI. These culture fluids synthesized more adherent material and water-insoluble glucan than those from Streptococcus mutans C67-1 and seven other S. salivarius strains. Among the S. salivarius strains, glucosyltransferase (GT; dextransucrase, EC 2.4.1.5) activity varied more than 100-fold. Cells of Veillonella and S. mitis S3 that had been incubated in culture fluids from S. salivarius 25975 and 9759, respectively, and then washed adhered upon subsequent incubation with sucrose. This was due to adsorbed GT because (i) the adherence was sensitive to dextranase; (ii) it was observed only with the high-GT culture fluids; (iii) it was dependent on sucrose; and (iv) the washed Veillonella cells synthesized glucan, but not fructan, from sucrose. These results suggest that sucrose-dependent adherence of bacteria without such innate ability can be mediated by (i) entrapment in insoluble glucan synthesized by S. salivarius culture fluids, and (ii) prior adsorption of GT from S. salivarius culture fluids. The possibility that GT formed by high-yield strains of S. salivarius is distributed through the mouth by the action of salivary flow and contributes to sucrose-dependent adherence and plaque formation is considered.


Effect of alveolar macrophages on Toxoplasma gondii. As pulmonary involvement can occur in disseminated toxoplasmosis in immunosuppressed patients, studies were initiated to define local mechanisms of resistance of the lung to Toxoplasma gondii. Alveolar macrophages were obtained from normal mice and mice chronically infected with T. gondii by bronchopulmonary lavage and cultured in vitro. Although normal alveolar macrophages were difficult to infect with Toxoplasma, they supported intracellular multiplication of this organism. When exposed to Toxoplasma that had been pretreated with heat-inactivated serum containing specific antibody, the number of intracellular organisms increased remarkably, and the macrophages destroyed the coated parasites. After development of chronic infections with Toxoplasma, there was a transient period during which a striking increase in numbers of alveolar macrophages was observed in lavage specimens. These macrophages differed from those of normal alveolar macrophages. There was a greater percentage of large cells, a greater tendency to spread on glass, and an increased number of intracellular Toxoplasma, and the cells were activated to kill or inhibit multiplication of the parasite. During the period when activated macrophages were demonstrable in bronchopulmonary washings, histological changes in the lungs revealed a marked mononuclear cell infiltrate. These studies support a role for the activated alveolar macrophage as an effector in resistance of the lung to infection with Toxoplasma.


Epidemic caprine keratoconjunctivitis: recovery of Mycoplasma conjunctivae and its possible role in pathogenesis. Clinical, microbiological, serological, histological, and therapeutic aspects of two separate outbreaks of caprine keratoconjunctivitis are described. The disease was characterized by a high rate of contagion, rapid onset, intense lacrimation, conjunctival hyperemia, and corneal opacity with neovascularization. In addition, many of the animals developed respiratory illness during the second epidemic. The only organism consistentlyisolated was Mycoplasma conjunctivae. A total of 23 strains were isolated from 18 inflamed conjunctivae, one normal conjunctiva, and the nasal secretions of four goats with concomitant respiratory illness. The convalescent sera of goats in the first outbreak had neutralizing antibody titers to M. conjunctivae that ranged from 1:32 to 1:256. In the milder second outbreak the antibody titers ranged from 1:4 to 1:32 in animals with only ocular disease and from 1:4 to 1:64 in animals with only respiratory disease. Whereas little change was noted in antibody titers of goats with only localized eye disease, 43% of the goats with respiratory disease showed significant fourfold rises. The histological picture was consistent with acute corneal infection. Animals requiring antibiotic treatment appeared to respond favorably to a combination of oxytetracycline and polymyxin B, but not to penicillin. These findings suggest that M. conjunctivae is one cause of epidemic caprine keratoconjunctivitis.


Epidemic caprine keratoconjunctivitis: experimentally induced disease with a pure culture of Mycoplasma conjunctivae. The induction of caprine keratoconjunctivitis by the subconjunctival inoculation of a cloned culture of Mycoplasma conjunctivae is described. The clinical course of the experimental disease was similar to that noted in naturally occurring outbreaks of "pink-eye" among goats, and biopsies of inflamed conjunctivae showed similar histological response. M. conjunctivae was consistently recovered from the inflamed conjunctival tissues of inoculated animals that developed ocular disease, thus fulfilling Koch's postulates and establishing this organism as an etiological agent of caprine keratoconjunctivitis. Immunological studies suggested that cellular immune mechanisms may play a role in protecting animals from disease produced by this mycoplasma.


Experimental Rat model for Corynebacterium renale-induced pyelonephritis. The laboratory rat was able to serve as a model for ascending pyelonephritis after implantation of a zinc disk coated with Corynebacterium renale into the urinary bladder because it satisfied three different criteria for infection. The production of an alkaline urine and the presence of significant numbers of C. renale in the kidneys, as well as distinct pyelonephritic lesions as revealed by histological examination, were observed in all rats infected with C. renale. Control rats that harbored sterile disks in their urinary bladders exhibited none of the above effects.


Serum and tissue lysozyme in leprosy.

Serum and tissue lysozyme in leprosy. Mean serum lysozyme values were found to be elevated in untreated leprosy patients. Statistically significant elevations were present in each of the three major categories of leprosy, tuberculoid, borderline, and lepromatous. Values were particularly high in patients with severe reversal reactions or Lucio's phenomenon. Prolonged sulfone therapy was associated with a fall in serum lysozyme values. With an immunoperoxidase method to localize lysozyme in leprous tissues, two distinct staining patterns were found, granular and saccular. The grandular pattern of lysozymal staining was found in epithelioid cells and in giant cells, and the intensity of staining showed a positive correlation with serum lysozyme levels. Conversely, a saccular pattern of lysozymal staining was found in lepromatous histiocytes, buth the intensity of staining was unrelated to serum lysozyme levels; the saccular structures contained dense aggregates of Mycobacterium leprae. These two patterns of staining probably represent different functional responses of monocyte-derived granuloma cells, whereas the serum levels reflect, to a varying degree, both the absolute number of such cells and the rate of secretory activity of this cell population as a whole.


The in vitro effects of calcium and potassium in resensitization of tracheal smooth muscles of the allergized guinea pig. Tracheal smooth muscle obtained from allergized guinea pigs gives rise in vitro to two-phase cycles of responsiveness to antigen administration desensitization produced immediately after a conditioning antigen dose, followed by resensitization within 4 h. As in the case of resensitization to a drug, resensitization to an antigen is a Ca++- and K+-dependent phenomenon. A comprehensive receptor model of the chemical excitatory action of antigen in cells is consistent with a Ca++-dependent resensitization phenomenon in the allergized systems. On the other hand, the results bear weight against both a 'pharmacological mediator-depletion theory' and an 'antibody saturation-desaturation theory', which have been invoked to explain desensitization and resensitization to antigen in allergized systems.


Suppression of the IgE antibody response in mice to kentucky blue grass pollen allergens. Reagins in murine strains A/HeJ, RF/J C3H/HeJ and B6D2F1 were induced by immunization, in the presence of A1(OH)3, with the retentate (R) obtained by dialysis from the aqueous extract of Kentucky blue grass pollen (KBG-Aq. ext.). Administration of doses of R ranging from 50-200 microgram resulted in IgE antibody responses which were sustained for periods of the order of 6 months. The possibility of suppressing the anti-R IgE antibody response in sensitized A/HeJ mice was tested by the administration into these animals for a period of 14 weeks, biweekly injections of a skin-active, immunogenic fraction (DI) isolated from the dialysate of KBG-Aq. ext. This treatment effectively suppressed the secondary IgE antibody response to R and markedly increased levels of hemagglutinating antibodies. On the basis of the fact that DI comprised only 1.5% of the parent fraction KBG-Aq. ext. and since it was capable of modulating the immune response to R as described, it is suggested that DI may prove to be a useful agent for the immunotherapy of allergies to KBG pollen.


A new well-characterized, purified allergen preparation from timothy pollen. I. Chemical properties. A purified allergen preparation, Timothy N, from timothy pollen (Phleum pratense) was characterized with respect to chemical properties in comparison with a commercially available crude extract, Timothy O, from the same pollen material. In Timothy N about 94% of the protein and 99% of both hexoses and pentoses were removed during the purification. Timothy N contains a limited number of proteins with molecular weights of about 15,000 and 30,000. A Timothy N solution of 0.010 mg/ml will have an allergenic activity of 1 HEP.


Decreased antibody response following immunization with enantiomorphic synthetic polypeptides. The ability to decrease the antibody response to poly(Glu52Lys33Tyr15) in the DA and PVG strains of rats by prior immunization with its D-amino acid enantiomorph poly(DGlu48DLys38DTyr14) was tested as part of a continuing investigation into the role of optical isomerism in the ability of an antigen to induce an antibody response. The results showed that prior immunization with the D-amino acid polymer decreased the immune response to the isomeric L-polypeptide in both strains.


Serum complement changes in W/Fu rats inoculated with syngeneic (C58NT) D lymphoma cells. Weanling W/Fu rats were inoculated intraperitoneally with 1 X 10(6) to 1 X 10(7) (C58NT)D Gross virus-induced lymphoma cells. Sera obtained 7 days later showed moderate to marked depressions of overall hemolytic activity, C1, C3 and properdin. These changes were not observed in uninjected W/Fu rats or in animals inoculated with syngeneic normal spleen cells. In the latter group and in the tumor-bearing animals, factor B levels were also depressed. Evidence of complement utilization was also observed in the ascitic fluids of the tumor-bearing W/Fu rats.


Significance of Hageman factor (coagulation factor XII) for neutrophil locomotion and chemotaxis. Neutrophils separated from Hageman factor-deficient blood exhibit normal random and directional locomotion. No defect in cytotaxin formation could be demonstrated in Hageman factor-deficient plasma, nor did kallikrein inhibitor interfere with the chemotactic activity of normal immune complex-activated human plasma. The results suggest that the chemotactic activity which is detectable in unfractionated human plasma is not derived from Hageman factor-dependent pathways.


The role of hyperemia in cellular hypersensitivity reactions. The three physiological processes vascular permeability, blood flow and lymphocyte migration were all enhanced in tuberculin reactions induced in guinea pigs and sheep and also in normal lymphocyte transfer reactions in sheep. Microspheres labelled with 85Sr were used to measure blood flow to dermal sites and it was found that cellular hypersensitivity  reactions had blood flows 7-25 times that of normal skin at the reaction peak. Vascular permeability was measured as an increase in the flow rate of afferent lymph or, in guinea pigs, as the enhanced leakage of intravascular 125I-albumin. When the permeability-inducing peptide bradykinin was injected directly into tuberculin reaction, the resulting permeability was greater than the sum of the tuberculin and bradykinin permeability taken individually and it was concluded that the hyperemia enhanced the permeability-inducing capacity of bradykinin. When the traffic of lymphocytes through hypersensitivity lesions was measured in sheep by cannulating the regional afferent lymph vessels and continuously collecting the lymph, the increase in lymphocyte traffic was of the same order of magnitude as the increase in blood flow. It is suggested than the antigen-induced enhancement of blood flow caused the increase in lymphocyte traffic and that the mechanism was similar to that occurring within lymph nodes during the immune response to all antigens.


A new well-characterized, purified allergen preparation from timothy pollen. II. Allergenic in vivo and vitro properties. A purified allergen preparation, Timothy N, from timothy pollen and a crude commercial extract, Timothy O, prepared from the same pollen material, were tested in tenfold dilutions on 59 adults with allergic rhinitis and on 29 children with bronchial asthma. All patients were allergic to grass pollen. Using the prick and intracutaneous methods, dose-response tablets were established for the two preparations showing a good correlation. Nasal provocation tests on the adult patients and bronchial provocation tests on the children gave positive reactions in all cases when using Timothy N. No irritant effect resulting in non specific reactions were elicited. The availability of stable, freeze-dried and purified allergen preparations supplied in different vials with defined allergenic activities fulfils the clinical demands for a modern diagnostic allergen preparation.


Increase in the severity of allergic-type bronchospasm in sensitized and challenged cats treated with cortisone. The feline model of immediate hypersensitivity to intraperitoneal ovalbumin sensitization, followed 65 days later by intravenous challenge, was used in this study to determine the effect of cortisone acetate administration on the severity of allergic bronchospasm. Cortisone acetate given intramuscularly prior to, during and immediately after sensitization increased the severity of the allergic response. Comparison of the respiratory, blood pressure and heart rate responses in cortisone-treated animals with nontreated controls indicated a significantly increased challenge reaction among the treated group. Of 7 cats receiving cortisone treatment, 5 died during the 30-min challenge monitoring period. None of the nontreated control group died. It is hypothesized that cortisone treatment impaired the activity of the cortisone-sensitive thymus-derived (T) cells.


A new well-characterized, purified allergen preparation from timothy pollen. III. Immunological properties in the human immunoglobulin E system. The following methods were used in vitro to characterize and quantitate the allergenic activity of a purified allergen preparation, Timothy N, from timothy pollen: radioallergosorbent test (RAST), direct-titration RAST and RAST inhibition. Vials containing freeze-dried and standardized quantities of this preparation showed good uniformity and accuracy with regard to the allergenic activity. The stability of the preparation in solution and in the freeze-dried state was tested by RAST inhibition and was found to be acceptable. Using the same method, the allergenic activity of Timothy N was compared to the allergenic activity of a crude extract, Timothy O, indicating a discrepancy which was not observed in vivo.


Autoallergic states. Tumor immunology. Impaired function of peripheral lymphocytes in systemic lupus erythematosus. DNA synthesis by peripheral lymphocytes from active non-treated SLE patients and matched normal donors was assessed at various times after stimulation with high and low doses of PHA, PWM and ConA and in non-stimulated control cultures. The time response curve of SLE lymphocytes stimulated with a suboptimal dose of PHA, and with both optimal and suboptimal doses of PWM and ConA was markedly depressed, while their spontaneous DNA synthesis was significantly increased. Preincubation of the cells to remove putative coating antibodies did not revert the response of patients' lymphocytes to normal values. The antibody-induced cell-mediated lysis of 51Cr-labelled chicken results demonstrate that cellular factors contribute to the depressed in vitro responses in active SLE, suggesting a wide defect of lymphocyte populations in this disease.


Relationship of serum total IgE and cell-mediated immunity in patients with Hodgkin's disease. Thymus-derived lymphocytes have been shown to play a role in the regulation of IgE synthesis in the rat. Both anergy and elevated serum IgE levels may be present in patients with Hodgkin's disease. Cell-mediated immunity (CMI) was investigated by measurement of delayed skin test reactions with five common antigens. Serum IgE levels were determined at the same time. Impaired CMI was more prevalent in patients in stage III (13 of 15) and IV (15 of 19), as compared to patients in stage I and II (9 of 17). All 12 patients with elevated serum IgE levels (greater than 300 U/ml) had impaired CMI. These findings strongly suggest a relationship between impaired CMI and serum IgE in Hodgkin's disease patients.


Antineoplastic effects of long-term Trichinella spiralis infection on B-16 melanoma. Oral infection of mice with Trichinella spiralis has been shown to induce a potentiation of the delayed hypersensitive (DTH) response to BCG. The present investigation was initiated to determine whether nematode-induced potentiation of DTH influenced the induction and progression of a transplantable mouse tumor. B6D2F1/J mice were orally infected with 200 T. spiralis larvae 176 days preceding subcutaneous administration of 5 X 10(5) viable B-16 melanoma cells. The antineoplastic effects of long-term nematode infection were assessed by daily observation of the animals monitoring development and progression of neoplastic nodules. Control mice developed tumors by day 28 following tumor challenge, while none of the corresponding T. spiralis-infected animals demonstrated any signs of neoplasia. All control mice died within 60 days, while none of the nematode-infected animals developed detectable neoplasms. This phenomenon suggested that the presence of well-established larval cysts was capable of stimulating host antineoplastic activity.


In vitro responses of spleen cells from Trichinella spiralis-infected mice. The in vitro cellular immune responses of spleen cells from mice infected with Trichinella spiralis and immunized with BCG have been investigated. ICR/CD-1 mice were originally infected with 200 T. spiralis larvae 22 days prior to infection with 4 X 10(6) viable or heat-killed mycobacteria. Analysis of the splenic cell populations indicated that significant increases in adherent cells (macrophages) were noted only in groups previously infected with the nematode; the concentration of non-adherent cells (lymphocytes) did not vary insignificantly among any of the experimental groups. Assay of blast cell transformation and 3H-thymidine incorporation demonstrated the ability of T. spiralis infection to potentiate in vitro cellular immune reactions. These findings support earlier in vivo studies concerning nematode-induced immunopotentiation of delayed-type hypersensitivity reactions, and provide additional evidence that infection with this nematode enhances the immune capabilities of both stimulated lymphocytes and nonspecific phagocytic cells.


Host response to Treponema pallidum infection. I. Quantitative changes of lipids in rabbit organs. Levels of phospholipids, glycolipids and cardiolipin were determined in various organs of Treponema pallidum-infected rabbits. The phospholipid levels on the second week of infection decreased significantly in the spleen but remained unchanged in other organs. During the same time, glycolipids decreased significantly in both kidney and heart. 3 days after infection, a brief but significant increase of cardiolipin in the spleen was observed. Heat-killed T. pallidum but not Treponema reiteri caused a similar effect. The possible implication of these changes in the immunopathology of syphilis is discussed.


In vitro infection of murine macrophage by Leishmania brasiliensis. Mechanism of penetration. The in vitro infection of peritoneal murine macrophages by a cultured pathogenic strain of Leishmania brasiliensis was studied. By phase contrast and light microscopy it could be observed that L. brasiliensis is rapidly endocytosed by the macrophages and localized in the cytoplasm in a vacuole inside which it multiplies. By phase contrast and electron microscopy it was observed that L. brasiliensis enters the macrophage by the anterior end through which it first attaches to the cell membrane. This penetration involves invagination of the cell membrane around the entering flagellum and parasite body. A mechanism of entry involving and active participation of the parasite membrane through receptor sites and membrane activity by the microfilament system is presented.


Specific antibody levels in the intestinal perfusates of Heligosomoides polygyrus-infected mice. Radial immunodiffusion analysis was performed on intestinal perfusates from ICR/CD1 mice following oral infection and challenge with viable Heligosomoides polygyrus larvae. Infection of these mice resulted in an alteration in the amount and class of immunoglobulins, as well as anti-parasitic antibody. Specific IgA peaked at 3 days post-infection and then showed a gradual decline until day 21. This rapid elevation in IgA levels was temporally associated with early events in the parasite life cycle, and the increase in IgA was significantly higher in mice infected twice with H. polygyrus prior to challenge. Differences in both the concentrations and kinetics of specific IgA and IgG1 were also observed in the perfusates from these mice when compared to those noted for animals infected only once.


Inhibition of specific immune responses by feeding protein antigens. A profound and long-lasting state of specific immune unresponsiveness may be induced in adult inbred mice given a single dose of protein immunogens--such as ovalbumin or hemocyanin--by the digestive route. The degree of unresponsiveness induced by intragastric exposure to ovalbumin could not be achieved by intravenous injection of deaggregated ovalbumin solutions across a wide range of doses. Unresponsiveness induced by intragastric exposure to hapten-protein conjugates is specific to the carrier protein.


Reaginic immune response to tree pollen antigen in LBN rats. The immunogenicity and cross-antigenicity of ten common tree pollen allergens were studied in LBN rats. The rats produced IgE antibodies to each of the allergens used (maple, willow, poplar, ash, oak, sycamore, hickory, walnut, birch, and elm), yet the allergens had extremely limited cross-reactivity. The possible explanation for the limited cross-antigenicity is discussed.


Multiple myeloma, IgA cryoglobulinemia and serum hyperviscosity in a dog. Clinical signs of hyperviscosity syndrome in a 6-year-old dog included listlessness, polydipsia, anorexia, vomiting, and recurrent bleeding from the gums. Fundoscopy showed the typical retinal changes associated with this syndrome. A polymeric IgA cryoglobulin characterized in the dog's serum was later isolated and structurally studied. It was found to contain J chain but no secretory component. The heavy and light chains were covalently bound.


Anaphylactoid responses in rats.

Anaphylactoid responses in rats. The relative activities of dextran, mannan and ovomucoid as agents inducing anaphylactoid responses in rats vary with the route of injection, mannan being the most active especially by the intradermal route. All of these responses are potentiated by pretreatment with insulin and inhibited by glucose. Carrageenan and concanavalin A are also active but only by the subcutaneous route. Whereas the concanavalin A response is potentiated by insulin, that of carrageenan is reduced. There are therefore at least three classes of agents capable of inducing anaphylactoid responses in rats.


HLA in primary open-angle glaucoma.

HLA in primary open-angle glaucoma. Histocompatibility antigen typing was carried out in 50 Caucasian patients with primary open-angle glaucoma (POAG) and 50 Caucasian ocular-normotensive subjects. HLA-A 3 was present in 46%, B7 in 52%, B12 in 50%, and either B7 or B12 in 88% of p,tients with POAG. These prevalences in POAG patients were significantly greater than in ocular-normotensive subjects (p less than 0.01, p less than 0.0005, p less than 0.001, and p less than less than 0.0005, respectively). The prevalences of A 3-B 7, A 3-B 12 and either combination were also significantly greater in POAG patients than in the ocular normotensives (p less than 0.005, p less than 0.005, and p less than 0.0005, respectively). HLA-BW 35 was noted to be in deficit in Caucasian POAG patients (8%) as compared to Caucasian ocular normotensives (32%; p less than 0.01).


Effect of thymectomy on lymphocyte subpopulations in the pig. Demonstration of a thymus-dependent 'null' cell. Thymectomy in neonatal pigs results in marked lymphopenia. Surface Ig immunofluorescence, Fc rosettes and SRBC rosettes have been used to identify blood lymphocyte subpopulations. There was no marked reduction in numbers of cells in these subpopulations after thymectomy, although their proportion increased. This change was explained by a 90% reduction in 'null' lymphocytes, defined as those lacking sIg and Dextran SRBC receptor, which comprised 30-45% of blood lymphocytes.


A method of fitting non-symmetric Gompertz functions for characterising malignant growth. A basic symmetrically asymptotic Gompertz equation was extended to account for more complex growth and life-table data. This extended Gompertz or non-symmetric asymptotic regression equation was found to be suitable for fitting a large variety of data exhibiting growth and experimentally-induced regression effects expressed in the same curve. The statistical and computational properties of this fitting function are discussed in theory and example.


Hospital activity analysis: a source of information about serial hospital admissions. This paper describes a method for linking serial hospital admissions for the same patient on the basis of existing Hospital Activity Analysis data. Details are given of a linkage procedure suitable for use with a computer, which takes account of possible errors in the recording of items of personal information. Applications of the procedure to give the clinician better access to information about previous hospital admissions and as a basis for monitoring the effectiveness of particular hospital-based procedures are described.


Application of Kendall's partial tau to a problem in accident analysis. Kendall's partial rank correlation coefficient is suggested as a method of nonparametric analysis of covariance when the independent variable of interest is dichotomous.


On the visualisation of nonstationarities in point processes. A method is described for graphically presenting interval data, such as neural interspike intervals or electrocardiographic R-R intervals, in a form that facilitates the identification of nonstationaries. The method is essentially a plot of isoprobability contours of the cumulative interval histogram, as functions of time. A sequential algorithm is used for updating the contour-line positions. This display is used in an interactive system for visually identifying nonstationarities, and for subsequently comparing selected segments of the data quantitatively using the Kolmogorov-Smirnov test.


Automatisation of a localising technique in aphasia based upon averaged evoked potentials. Averaged evoked potentials were utilised as a localising technique in aphasia. Based on a set of measurements extracted from various evoked potentials, subjects from four diagnostic categories were correctly classified in more than 70% of the cases. The measurements were derived from amplitudes and latencies of significant peaks which were selected by human judgement from plots of the recorded evoked potentials. An algorithm has been developed which simulates the manual procedure and reduces the processing time per patient by several magnitudes. The automated method yields results which are more consistent with expected results than those from the manual method. The percentage of correct classification is in both cases essentially the same.


Increase in immunogenicity of a pulmonary squamous-cell carcinoma, propagated in vitro. The chemically induced, non-immunogenic lung squamous-cell carcinoma (MSC-10) propagated in vitro gradually loses tumorigenicity in immunocompetent hosts with increasing in vitro passage. This was found to be related to an increase in antigenicity, since immunosuppressed hosts (thymectomy plus 600 rads whole body X-irradiation) supported the growth of tumor cells, whereas immunocompetent recipients did not. The antigens involved in rejection are not heterologous serum proteins present in culture media since the cell line grown in isologous serum is also rejected. Immunization with the in vitro tumor line partially protected against the parental in vivo line, therefore the antigens involved must be present on both tumor lines. Inoculation of the cultured cell line into normal or immunosuppressed hosts produced tumors with the same histological characteristics as those of the in vivo tumor line. We concluded that by in vitro culture the weakly antigenic carcinoma becomes more immunogenic and thereby capable of inducing transplantation resistance. The cultured tumor cells retain their antigenic specificity and histologic characteristics while increasing their antigenic potency.


Risk factors for lung cancer in Singapore Chinese, a population with high female incidence rates. The high incidence of lung cancer in Chinese females in Singapore, especially among those belonging to the Cantonese dialect group, and the relatively high rates in Chinese males have been studied by means of interviews of cases and controls. A significant dose-response effect of cigarette smoking was found for all male and female groups, but neither smoking nor any other exposure explains the high incidence of lung cancer observed in Cantonese females who exhibit high rates of adenocarcinoma appraently unrelated to smoking. In general, persons with a low consumption of green vegetables were at higher risk for lung cancer. This finding might be due to an increased susceptibility in the presence of a relative deficiency of vitamin A.


In vitro assessment of immunocompetence in patients with malignant melanoma. Ninety-four patients with malignant melanoma and 96 healthy controls were tested for lymphocyte proliferative capacity in a microblastogenesis assay. Each lymphocyte sample was assayed for incorporation of (3H)thymidine after stimulation with PHA, PWM, Con A (two doses), PPD, and allogeneic lymphocytes (MLC). MLC was the only assay that revealed a substantial and significant difference between the melanoma patients and controls. Almost all assays showed lower values in patients with more advanced disease. However, it was not possible to accurately predict clinical outcome from data obtained from in vitro immunocompetence tests. These results indicate the relatively limited clinical usefulness of assays of lymphocyte proliferative capacity in melanoma patients.


Human tumour--lymphocyte interaction in vitro. V. Comparison of the reactivity of tumour-infiltrating, blood and lymph-node lymphocytes with autologous tumour cells. Lymphocytes prepared from the blood, tumour-draining lymph node and tumour were tested for immune reactivity with freshly isolated autologous tumour cells from biopsies. Reactivity was assessed by the autologous tumour stimulation assay and by lymphocytotoxicity. Activity was found in 6/11 blood preparations, 7/10 lymph nodes and 1/7 tumour-infiltrating lymphocytes in tumour stimulation assays and in 6/19 blood, 8/18 lymph-node and 5/20 tumour-infiltrating lymphocytes in cytotoxicity assays. Tests with material from patients with nasopharyngeal carcinoma showed a higher frequency of cytotoxicity in the tumour-infiltrating lymphocytes than in other solid tumours. There was a correlation between results of the two assays when performed on the same preparations and between the levels of reactivity in lymph node and blood from the same patient. Cytotoxicity in the lymph nodes showed specificity in that cells from a long-term culture (K562) known to be sensitive to natural killer activity and from allogeneic tumour biopsies were only rarely damaged. Cytotoxicity against K562 was more frequently determined in blood lymphocytes. Tumour-infiltrating lymphocytes were non-reactive in patients when the blood and lymph-node lymphocytes were active.


C. parvum immuntherapy of transplanted rat tumours. C.parvum (Wellcome CN 6134) has been tested for tumour suppression against a range of syngeneically transplanted rat tumours, both carcinogen-induced and of spontaneous origin. Subcutaneous growth was not prevented by distant subcutaneous or intravenous injection of the preparation, although growth rates were sometimes depressed or accelerated. In contrast, C. parvum injected in admixture with tumour cells consistently suppressed their growth and with highly immunogenic tumours induced systemic tumour immunity, C. parvum injected intravenously retarded development of pulmonary tumour deposits, and intrapleural injection suppressed growth of pleural tumours and malignant effusions. Host immunosuppression failed to abrogate the tumour-suppressive effect of locally applied C. parvum, but host macrophage depletion with silica totally abolished the response. These studies indicate that in the rat, tumour suppression is most consistently achieved by regional application of C. parvum, and that this response is more dependent upon local macrophage stimulation than generation of systemic immune responses.


The effect of chronic protozoan infection by Babesia rodhaini on leukemogenesis in mice. The effect of chronic infection with the protozoan parasite Babesia rodhaini on the subsequent development of mouse leukemia was investigated in three different murine leukemia-lymphoma model systems: congenital lymphoma (in AKR mice), irradiation-induced lymphoma (in C57BL mice), and Rauscher-virus-induced leukemia in NMRI mice. Leukemia incidence was significantly greater than in controls in Babesia-infected (NMRI strain) mice that had been infected with an adjusted dose of Rauscher leukemia virus.


Is on-site urine testing of therapeutic value in a methadone treatment program? Patients in a methadone maintenance clinic were randomly assigned to two groups: one to have urine tests on-site (by the EMIT system) with immediate feedback of results to patients and staff; the other to have urine specimens sent away to an offsite laboratory for testing by thin-layer chromatography. Although other advantages might justify the adoption of on-site testing in methadone programs, the method appeared to have little or no therapeutic advantage over customary off-site testing. There were negligibly small differences between the groups with respect to illicit drug use.


An investigation of the feasibility of predicting outcome indices in the treatment of heroid addiction. An exploratory study employing multiple linear regression techniques was conducted to investigate the feasibility of predicting outcome indices in the treatment of heroin addiction. Demographic and biographic intake variables were obtained for heroin addicts prior to treatment in one of two different types of residential treatment programs. Length of treatment, further categorized into "split-stay" categories, was chosen as the criterion because of its importance from the standpoint of program management. Subsequent stepwise regression procedures resulted in 11 variables of sufficient predictability to account for approximately 30% of the variability in the split-stay criterion. The employment of the derived equation resulted in correct classification in approximately 75% of the cases. This was beyond what could have been predicted by chance alone or from the knowledge of the observed split-stay ratio. A clear demonstration of the feasibility of the model was obtained; however, as to its utility, implementation in the actual treatment setting would be required. Implications for the use of this type of prediction model were discussed.


Behavior therapy: a promising drug abuse treatment and research approach of choice. Behavior therapy appears a promising drug abuse treatment and research approach of choice, reporting effective pilot studies utilizing such techniques as token economy, aversive conditioning, relaxation training, contract writing, covert conditioning, and combinative approaches. Behavior therapy appears to merit considerable investment of funds, time, and facilities to design and to execute carefully controlled research studies with systematic follow-up. Behavioral research and treatment is also consistent with presently available diagnostic techniques--the highly structured interview and the Synanon Game--and seems eminently applicable in specific work sites, to problems of staff selection and training, and to patient screening problems.


Construction of outcome scales measuring addicts' community functioning. The current status of research in chemical abuse has depended heavily on unreliable cure rate as a criterion measure. This study was designed to construct reliable and valid quantitative outcome scales. One hundred and eighteen true-false items, all indicating changeable criterion behaviors, were written and administered to 154 hospitalized chemical abusers and 93 staff members. Clinical and factorial manipulation were employed to delete unwanted items. Tentatively, three scales of 41 items were derived, namely, Personal/Economic Independence, Chemical Use, and Job Satisfaction.


Problems of methadone diversion and implications for control. With the expansion of methadone maintenance there has been an increase in accidental ingestion and related deaths. This is at least partially due to programs involving take-home methadone. The use of 1-alpha-acetylmethadol (LAAM), a congener of methadone that suppresses withdrawal for up to 72 hours, may reduce diversion and accidental overdose.


Detoxification from methadone maintenance: the state of the art. The reasons for successful withdrawal from methadone maintenance remain to be clarified. The theories, methods, and outcome of methadone maintenance withdrawal are reviewed, and it is concluded that successful withdrawal is possible for at least a sizable minority.


Evaluation methodology.

Evaluation methodology. The results of several large methadone maintenance programs are reviewed and the outcome measures used are analyzed. Criteria measures were often vague and sometimes not defined. Many studies base their findings on unverified patient self-reports because costs for more reliable and systematic data collection are prohibitive. Available data does not allow for resolution of the pro- or antimethadone maintenance views for treatment of heroin addiction.


Clinical aspects of the use of narcotic antagonists: the state of the art. The clinical application of narcotic antagonists would theoretically be of value to several major groups of users. However, while it is clear that supportive services are needed, these services have not been defined by controlled studies.


Prospects, problems, side effects, and safety of narcotic antagonists. The use of the narcotic antagonists naltrexone, naloxone, and cyclazocine is reviewed with attention being given to their prospects, problems, side effects, and safety.


Heroin detoxification with acupuncture and electrical stimulation. Acupuncture with electrical stimulation is a feasible nonchemical method for detoxification of heroin addicts, with particular limitations as regards to heavy users. Short-term follow-up seems to indicate reversion to heroin is comparable to other detoxification methods. It could be of great interest to study the effect of easily available postdetoxification maintenance acupuncture as an alternative to heroin. Withdrawal symptoms are relieved in a hierarchial manner with apparent parasympathetically mediated symptoms subsiding first, and frequently with incomplete resolution of bone and joint pain.


Evaluation of the 21-day outpatient heroin detoxification. There is a paucity of studies in the literature documenting failure rates of outpatient detoxification from heroin. This study reports on the results of the 21-day ambulatory treatment program at the Miami Veterans Administration Hospital. Heroin users with less than a 2-year history of opiate use must complete the detoxification process within 21 days according to federal regulations. The results of this study indicate 100% "unsuccessful drug rehabilitation" utilizing the 21-day outpatient detoxification treatment modality, a finding similar to studies conducted to evaluate results of inpatient methadone treatment programs.


The causes of heroin addiction-- a review of the literature. Part II. Theories on the causes of heroin addiction are reviewed in this two part article. Part II reviews the literature that considers the family of the addict and the stepping stone theory.


Treatment experiences of alcoholic patients: an analysis of five residential alcoholism programs. Five different residential alcoholism programs were studied to determine the influence of patient attributes on the treatment process. The relationship between patient characteristics and treatment experiences was analyzed separately for each of the five programs. There was no systematic relationship between patient characteristics and the kind or extent of treatment patients received or length of patient stay in treatment. The authors recommend more attention be paid to the type and intensity of treatment in relation to patient characteristics and a routine evaluation of program effectiveness.


The believability of the media as sources of information on drugs. Based on an analysis of data gathered by a school drug survey given to junior and senior high school students in a middle-class community in the spring 1974, important differences were found to exist in the believability of various sources of drug information. Overall, comparisons indicate that friend, expert (e.g., doctor, staff member of a drug program), and ex-user drug information sources are perceived to be more credible than pamphlets, newspapers/magazines, radio, and television. Among the media, pamphlets were felt to be most believable. Examination of the believability in the media as sources of drug information by youngsters with varying substance use behavior found that the more students are involved with substances, the less credible they percieve the media to be.


Dimensions of marijuana use in a midwest Catholic university: subcultural considerations. Theorists and researchers for over two decades have indicated repeatedly that marijuana use by college students has a subculture base. Crucial here is the impact that the subculture has on its members' identities, values, attitudes, and belief patterns. While it may be true that not all members of a subculture evidence the same commitment to a subculture's attitudinal and normative patterns, nonetheless they share common patterns and the more an individual becomes involved, the more he manifests these subcultural patterns. Explorations of this subculture rationale are conducted utilizing a trichotomy of marijuana type users. The findings lend support more to the theoretical notion of subculture intervention as a threshold variable than a continuum variable.


Computerized EEG analysis for studying the effect of drugs on the central nervous system. Samples of our experience in quantitative pharmaco-EEG are reviewed to discuss and define its applicability and limits. Simple processing systems, such as the computation of Hjorth's descriptors, are useful for on-line monitoring of drug-induced EEG modifications which are evident also at the visual visual analysis. Power spectral analysis is suitable to identify and quantify EEG effects not evident at the visual inspection. It demonstrated how the EEG effects of compounds in a long-acting formulation vary according to the sampling time and the explored cerebral area. EEG modifications not detected by power spectral analysis can be defined by comparing statistically (F test) the spectral values of the EEG from a single lead at the different samples (longitudinal comparison), or the spectral values from different leads at any sample (intrahemispheric comparison). The presently available procedures of quantitative pharmaco-EEG are effective when applied to the study of mutltilead EEG recordings in a statistically significant sample of population. They do not seem reliable in the monitoring of directing of neuropyschiatric therapies in single patients, due to individual variability of drug effects.


[Effect of chlortetracycline on the peptide spectrum of rat serum]. Application of chlortetracycline in rats resulted in the occurence of certain peptides in the blood-serum, which could not be detected in the serum of an untreated control group. These results were obtained by means of high voltage electrophoresis and paper electrophoresis of the serum of rats which was analyzed 1,3, and 13 hours respectively after a single dose of 50 mg chlortetracycline per 100 g body weight in comparison to an untreated control group. The new peptides could be found in the slight alkaline range 1 and 3 hours after application of chlortetracycline and in the strong acidic area of the electrochromatogram 13 hours thereafter. A more detailed investigation of the new peptides could demonstrate that the number of the following amino acids was reduced in the peptide chains after chlortetracycline: leucine, valine, serine, arginine, and lysine. On the other hand, amino acids, such as citrulline, sarcosine, alpha-aminobutyric acid, and ornithine, could be found which are normally not present in proteins.


The structure of urban mortality. A methodological study of Hannover, Germany. Part II. An extension is made of a prior analysis of the relation of density to cause-specific mortality in small areas of Hannover, Germany. The analysis was designed to impose statistical controls for certain socio-demographic characteristics of these small areas under a model where all of the effects of density were assumed to operate on mortality only indrectly by affecting the residential decisions of select socio-demographic groups. It was found that, despite the sizeable effects of socio-demographic factors on cause-specific mortality, density retained a direct effect on five of 14 cause-specific rates. Implications of these results for modelling density-mortality relations are discussed.


Lead Absorption in a community of potters in Barbados. In a community of potters in Barbados where lead glazes traditionally have been used, a survey of 12 potters, 19 of their family members, and 24 controls revealed elevated blood lead levels in the potters, their family members, and the neighbours who used pottery for culinary purposes. Dust from the potters' homes and work areas contained lead in concentrations up to 320,000 ppm. Pottery was found to have lead release levels up to 3,125 microgram/ml. Six people had upper extremity tremor associated with elevated blood lead levels. This survey demonstrates the risk of using lead glazes in pottery production to family members of potters as well as the potters themselves and emphasizes the need for surveillance of occupational hazards in developing countries.


Age and sex distribution of infections with Entamoeba histolytica and Giardia intestinalis in the Lagos population. Stool samples were collected from 2,099 persons and examined for parasites: 9.5 percent were infected with Entamoeba histolytica, 7.9 percent were infected with Giardia intestinalis and 15.5 percent were infected with Iodamoeba butschlii. The infections with E. histolytica and I. butschlii occurred more frequently in females than in males and adults were also more frequently infected than children. Infection with G. intestinalis, on the other hand, was more prevalent in males than in females and children were more frequently infected than adults with the highest incidence of infection (13.8 percent) in the age-group 1-5 years.


A household study of illness prevalence and health care preferences in a rural district of Cameroon. This report gives the results of a health interview survey using a recall interval of one month, in Rural Cameroon carried out between 5 November 1973 and 7 March 1974 on a random selection of 1886 families with 9362 individuals. The disease prevalence in the study area (a positive illness rate of 27.8 percent for a four-week recall period) is analysed by age, sex and treatment preference. People under the age of 15 years suffered predominantly from respiratory (20 percent), digestive (29 percent) and parasitic (12.5 percent) diseases for which Western treatment was preferred (average of 65 percent). In adults musculoskeletal, digestive diseases and generalized body pains were responsible for 63.0 percent of diseases in the age-group 45 and over. The treatment choice was partly Western (50 percent) and partly traditional (20 percent). Traditional treatment was generally preferred for seizures (65 percent) and mental illnesses (87 percent) except for children under four years who received 50.6 percent treatment for seizures from traditional sources and 49.4 percent from Western sources.


A retrospective study of physical activity and coronary deaths. For a series of 568 married white men aged 30-70 years who died from coronary heart diseases, (CHD), and a matched sample of living neighbourhood controls, information was collected on a large number of variables, including physical activity, (PA), classified according to the Health Insurance Plan Study criteria. Increased leisure PA was associated with a decreased risk of coronary death (p less than .001) but there was no association between job activity and coronary deaths. Step-up multiple regression, based on within-pair differences, was used to control for the possible confounding effects of all variables studied. Even when these variables were controlled for there was still a significant association between increased leisure PA and decreased risk of death due to CHD (P less than .001). These data are consistent with the hypothesis that increased leisure PA can contribute to the prevention of death from CHD.


Mortality of male members of the Danish Semi-skilled Unskilled Workers' Union in 1973. The purpose of this cross-sectional study is to evaluate contemporary age and cause specific mortalities of a large group of employed men. The population is the 228,612 male members, aged 20-64, of Denmark's largest trade union, the Semi-skilled and Unskilled Workers' Union (SID). A Standard Mortality Ratio (SMR) of 93.9 compared to all men in Denmark is found. However, the distribution of mortality by age does not resemble that found in many other studies, and is usually said to result from the 'healthy worker effect'. Excess mortality is found in the younger age groups, while the opposite is the case in the older groups, mainly because of a deficit of deaths from chronic illness. Notably higher age and cause specific SMRs are found for violent and unnatural deaths, and higher SMRs for cancer of the lungs and of lymphatic and haemopoietic tissues. Regional variations are found, but no correlation found between mortality and size of union 'local'. However, cancer mortality is higher among members of specialized locals, which are situated in larger urban area. The excess mortality of members of the largest locals in the Copenhagen area is due to deaths by cancer and by violent and unnatural causes. Findings and problems will be examined further in an ongoing cohort study and in other specialized studies under preparation.


Disease and mobility: a neglected factor in epidemiology. There is much historical evidence of the spread of disease through human mobility. Today in spite of medical advances and international health measures there is still much cause for concern. There is now more mobility, facilitated by modern transport and sometimes precipitated by major natural and man-made disasters. Redistribution of population is occuring in the developing world, particularly massive rural-urban movements. Population mobility has contributed to the transmission of malaria and prejudiced programmes for control and eradication; but mobility and other human factors have not been adequately studied. Parasites and vectors receive more attention than do people. Epidemiological studies need to pay greater attention to the nature and variety of population movements and to their differing impacts upon disease and health. It is essential to distinguish between migration (involving change of residence) and circulation (movement away from residence with sebsequent return). In tropical Africa various spatial and temporal dimensions can be applied to differentiate within these two major categories of mobility. In turn there are various associated physical and psychological health hazards.


A study on the stability of diphenylindenonesulphonyl derivatives of amino acids to acid hydrolyses. The stability of the diphenylindenonesulphonyl (disyl) derivatives of tryptophan, proline, hydroxyproline, histidine, serine, threonine and aspartic acid, as well as of glycine, alanine, alpha-amino butyric acid, phenylalanine, valine, leucine and isoleucine to acid hydrolysis is studied. The results indicate that the disyl derivatives are much more stable in comparison with the corresponding DNP- and DNS-derivatives. Hence, the dysil-chloride method possesses definite advantages over these widely used methods for determination of N-terminal groups, not only because of its higher sensitivity, but also because of the higher stability of the disyl derivatives of amino acids to acid hydrolysis.


Physical properties of Tamm-Horsfall glycoprotein and its glycopolypeptide. The molecular weight of the constituent glycopolypeptide chain of T-H glycoprotein was determined by sedimentation equilibrium under two entirely different sets of denaturing conditions. For both sets of denaturing conditions, the average molecular weight estimated for T-H glycopolypeptide was 74,000. The gel chromatographic behavior in 6M guanidium chloride of T-H glycopolypeptide with disulfide bonds intact as compared with its gel chromatographic behavior with disulfide bonds broken indicated that the glycopolypeptide is highly constrained by intrachain disulfide bonds.


Conformational stability of a snake cardiotoxin. A snake cardiotoxin from the venom of the Formosan cobra, Naja naja atra, is a basic polypeptide. The protein can be denatured in 6.0 M guanidine hydrochloride or at elevated temperatures. Its conformation remains virtually the same in solvents of lower polarity than water such as 1, 2-ethanediol or 1-propanol and 1, 2-ethanediol (1:1 v/v). The circular dichroism spectrum is atypical in water in that the peptide chromophores show a small negative CD band at 214 nm and a large positive one at 195 nm. To some extent the CD pattern resembles that of the beta-form but differs in specific positions and magnitudes. Considering that the theoretical CD of the reverse beta-bend and the characteristics of model polypeptides in beta-form manifest a similar pattern, we suggest that cobra cardiotoxin is rich in beta structure including beta pleated-sheets and beta reverse-turns.


Conformations of proline-containing cyclic peptides. 1H and 13C n.m.r. evidence for a solvent stabilized All-Cis X-Pro conformer of Cyclo-(Pro-Gly-Gly-Pro)2. As inferred from 13C, 1H n.m.r. data, CD measurements and ion-binding experiments, the title molecule can assume two major C2 symmetric conformations. One of these has an all-trans X-Pro peptide backbone and two 1 comes from 4 intramolecular H-bonds and represents the predominant (greater than or equal to 95%) form in D2O and nonpolar (CD3CN) solvents. Stabilized by specific solvent-solute interactions, the other conformer becomes competitive (45%) in DMSO solution. It is shown to possess a four-cis X-Pro skeleton and no intramolecular H-bonds. The Mg++ complex of the cyclic peptide in CD3CN is again C2 symmetric and its formation proceeds via a slow trans leads to cis isomerization of two X-Pro peptide bonds.


Synthesis, biological activity, and tritiation of L-3, 4-dehydroproline-containing peptides. A series of analogs of thyroliberin (TRH) ([L-delta3Pro3]-TRH, [D-delta3Pro3]-TRH, [L-3-MeHis2, L-delta3Pro3]-TRH) in which proline was replaced by L- or D-3, 4-dehydroproline was synthesized. The analogs exhibited approximately the same biological activity as the corresponding proline-containing peptides. These analogs and others in which 3, 4-dehydroproline is present at the NH2-terminal, COOH-terminal or internal positions in the peptide were successfully reduced with deuterium or tritium to provide the 3, 4-2H2-proline or 3,4-3H2-proline analogs, respectively, with near theoretical values of substitution. A novel procedure for the chemical resolution of DL-3, 4-dehydroproline is also described.