Quinton-Scribner arteriovenous shunts for hemodialysis. A review of 6.5 years' experience. Quinton-Scribner shunts have been used as a reliable access to the blood-stream in 56 patients treated with intermittent hemodialysis in the years 1965-71. The mean age of 29 men and 27 women was 39 years. Two hundred and thirty-two cannulae showed a mean survival time of 11.2 months for 103 arterial cannulae and 9.0 months for 129 venous cannulae. 700 shunt clotting episodes occurred during 1157 patient months, i.e. 0.6 clotting episode/month. In 350 episodes where saline flushing could not remove the clot, the effect of treatment with streptokinase was considered evident in 79.7%. Shunt cannula infection was a common complication while aseptic cutaneous necrosis and bleeding from the cannulated vessel were seen less frequently. Both severe and less harmful bleeding episodes were seen as a complication of dicumarol therapy. The number of complications to streptokinase treatments was low. The advantages and disadvantages of the Quinton-Scribner shunt for hemodialysis are discussed.


Increased association of diabetes mellitus with capsulitis of the shoulder and shoulder-hand syndrome. Sixty consecutive patients with capsulitis of the shoulder (including those with shoulder-hand syndrome) seen in our clinic since 1971 underwent an oral glucose tolerance test (5 with previously recognized diabetes were excluded from this test). Capsulitis was primary in 35, secondary to other factors in 25 subjects. Females (34) out-numbered males (26). Their ages ranged from 40 to 72 years (mean age: 54 years). Sixty control subjects matched for age and sex with the 60 "capsulitis" patients underwent the same OGTT (except one with previously recognized diabetes). We have found diabetes in 17 out of 60 patients with capsulitis according to Hayner's criteria (12 according to Jackson's criteria) versus 7 (2 according to Jackson's criteria) in the 60 control subjects. The difference is statistically significant by both methods, with a p value of less than 0.02).


[Vitelline components in teratomas and serum alpha-1 fetoprotein]. Serum alpha1-fetoprotein (AFP) had been determined in 31 patient with (mostly malignant) teratomas before or immediately after operation, and later in the evolution of 3 other cases with clinical evidence of recurrence or metastases. Without knowledge of these serum AFP levels, histological slides of the same 34 teratomas were reexamined, especially for the presence of yolk sac components. Two pure yolk sac tumors and 6 teratomas containing yolk sac structures were associated with serum AFP levels above 500 ng/ml. Teratomas without yolk sac structures were associated with normal serum AFP levels (i.e. 10-500 ng/ml) in 14 cases, and high serum levels (i.e. above 500 ng/ml) in one case. Histologic analysis of the 14 cases with slightly elevated AFP levels did not reveal tissue possibly responsible for the low but nevertheless abnormal AFP synthesis. High AFP levels, which are easily detectable by counter-current immunoelectrophoresis, are, however, highly specific for the yolk sac tumor or the yolk sac component of teratomas, and hence suggest that this extra-embryonic structure should be distinguished from other teratoma components.


[Drug therapy of Basedow's disease. Long term functional results (302 cases)]. 302 cases of Graves' disease were treated with a single course of antithyroid drugs and followed during 2 to 15 years. 71% of the patients showed a prolonged remission, 27,1% recurred and 1.9% were hypothyroid. Considering the yearly incidence of the recurrencies, the risk of a recurrency estimated 14 years after the treatment was 35% (cumulative incidence). Among the factors studied, hyperthyroidism of short duration seemed to correlate with a prolonged remission.


Niemann-Pick disease experimental model: sphingomyelinase reduction induced by AY-9944. Organs of rats treated with the drug A Y-9944 for 5 days showed a significant reduction in sphingomyelinase activity. Evidence is presented which suggests that the reduction is due to impaired enzyme synthesis.


Radiation therapy in cancer of the rectum and rectosigmoid. Carcinoma of the rectum and rectosigmoid is one of the major causes of death in adults. Despite marked advances in surgical skills, anesthesia, and antibiotics, the results remain poor. Although papers in the medical literature have stressed the importance of adjunctive radiation therapy, most general surgeons do not refer patients with this disease for radiation therapy. Irradiation is important adjunctive therapy which should not be ignored. We have reviewed the medical literature and summarized the basic concepts on this subject.


Fell tube insertion after orthograde dilatation of malignant esophageal obstruction: palliation and morbidity. Twenty-eight patients with malignant esophageal obstruction had palliative treatment using the Fell endoesophageal tube. The usual plan for these patients, irradiation followed by resection, was not followed because of the presence of tracheoesophageal fistula, celiac or hepatic metastases, or marked debilitation which precluded major operation. Palliation was obtained in ten patients who were discharged in a mean of 16.5 days with the ability to swallow liquids or pureed or ground foods and had a mean survival of 116 days. There was a high incidence of tube-related symptoms in all patients, and increased dysphagia, tube regurgitation, and difficulties in initiating swallowing were noted in patients with lesions above 24 cm from the incisors. The high incidence of postoperative ocmplications was responsible for the poor palliation and low survival in the remaining 18 patients who had a mean survival of 41 days. It was concluded that orthograde dilatation or forced seating of the prosthesis through a malignant esophageal obstruction carries a significant risk of perforation of the esophagus which, if it occurs, negates the palliative aspects of the procedure, increases hospitalization, and decreases survival. It is recommended that this procedure be used selectively in patients not otherwise amenable to resectional therapy with lesions beyond 24 cm from the incisors.


[2 new cases of Refsum's disease. Course during diet]. The authors report two cases of Refsum's disease treated with a low phytanic acid and low phytol diet for more than 5 years. The clinical, neurological improvement was undoubted in both cases but it was very gradual, appearing after 10 1/2 and 6 months treatment respectively. During these 5 years, no neurological aggravation occurred in the first patient ; but her sister presented in september 1972, 18 months after she started the diet, a mild attack from which she recovered. On the other hand, the sight and hearing disorders remained unchanged in spite of the considerable fall in phytanemia. In spite of the demanding and unagreeable character of the diet, almost constant moderate diarrhoea, the diet was worth following.


[Refsum's disease].

[Refsum's disease]. Refsum's disease although rare is of great interest for it may benefit at least partially from treatment. Its clinical diagnosis depends on the association of pigmented retinitis, polyneuritis and cerebellar syndrome. It is confirmed beyond doubt by the increased C.S.F. protein and phytanemia. A full family history is necessary for it is possible to detect heterozygous carriers of the defect by enzyme studies on fibroblast cultures.


Some characteristics of Mozambican Shangaans with primary hepatocellular cancer. Certain characteristics of 328 Mozambican male Shangaans with primary hepatocellular cancer (PHC) have been compared with those of 163 Shangaan men with hepatomegaly from causes other than PHC and with those of 122 Black Southern African men with the same tumour but who belonged to tribes other than the Shangaan. Shangaans with PHC were significantly younger than non-Shangaans with the tumour (mean age 33,4 cf. 40,0 years; Pless than 0,001). They also had a significantly higher positivity rate of alpha-fetoprotein by immunodiffusion (71,4%) than the non-Shangaans (16%), although in other respects the tumours appeared to be similar. Cirrhosis of the non-tumorous part of the liver was present at necropsy in 62% of the Shangaans and in 66% of the non-Shangaans. The hepatitis B (surface) antigen (HBsAg) was detected in the serum of 60% of the Shangaans with PHC compared with only 9% of the controls. The antigen was present in 53,4% of the non-Shangaans with PHC (the difference between this fifure and that in the Shangaans was not significant). HBsAg was detected in the serum of 64% of the Shangaans with PHC and cirrhosis, but also in 74% of those with the tumour without associated cirrhosis. The possible role of the hepatitis B verus in the aetiology of PHC is considered in the light both of these findings and of the possibility that the frequency with which the tumour is associated with cirrhosis may be decreasing in Shangaans. Some of the dietary habits of the Shangaans with PHC were compared with those of the controls. Virtually all the patients with PHC, but also almost all the controls, ate groundnuts in large quantities from an early age, as well as cashew nuts in smaller amounts. Cycad pips, mopani leaves and pods, mopani worms and locusts were not eaten by significantly more of the Shangaans with PHC than the controls. The limitations of this type of dietary analysis are discussed.


Alpha1-fetorprotein concentrations in maternal serum during normal pregnancy. Measurement of amniotic fluid concentrations of alpha1-fetoprotein has been proposed as a potentially important screening test of fetal well-being. Because maternal serum is more easily obtainable, the present study was performed to determine if there is a definable normal pattern of maternal serum alpha1-fetoprotein levels during gestation. Sequential alpha1-fetoprotein determinations were performed throughout gestation on the serums of 151 women having apparently normal pregnancies. Before 13 weeks, all samples contained less than 20 nanograms of alpha1-fetoprotein per milliliter of serum, and in 12.5 per cent of normal pregnancies, alpha1-fetoprotein was still undetectable as late as 21 weeks of gestation. One normal term delivery followed a negative alpha1-fetoprotein determination at the 24th week of pregnancy. Beyond the 21st week of pregnancy, there was a wide range of normal absolute values noted between women at the same stage of pregnancy. Moreover, wide fluctuations in maternal serum concentrations of alpha1-fetoprotein were observed from point to point in specimens from individual women studied longitudinally throughout gestation. The distribution of alpha1-fetoprotein concentrations at each stage of pregnancy was skewed. We conclude that studies of maternal serum alpha1-fetoprotein concentrations are likely to be more meaningful from a diagnostic point of view prior to 21 weeks of gestation, when the range of circulating maternal alpha1-fetroportein values is relatively small. Undetectable maternal serum alpha1-fetoprotein as late as the 24th week of pregnancy is compatible witha viable conceptus. Because unexplained and marked elevations of maternal alpha1-fetoprotein may occur, particularly in the third trimester, it would appear inappropriate to base clinical decision on maternal serum alpha1-fetoprotein measurements alone, and such decisions certainly should not be taken after only single maternal serum alpha1-fetoprotein measurements. Finally, no correlation was found between maternal alpha1-fetoprotein concentrations near term and the birth weight of the infant.


Plasma fibrinolytic inhibitors after operation. The response of the fibrinolytic system to the stress of a surgical operation has been studied in a group of 39 patients. Fibrinolytic activity was stimulated during the operation but depressed during the early postoperative period. This was accompanied by an increase in the level of fibrinolytic inhibitors in the plasma after operation. This increase in fibrinolytic inhibitors was a result of a significant rise in alpha1 antitrypsin; the level of alpha2 macroglobulin fell both during and after the operation.


Proper management of hepatic adenoma associated with oral contraceptives. Four patients with oral contraceptive associated hepatic adenoma have been studied and the literature reviewed. Clinically, these patients can be divided into ruptured and nonruptured hepatoma groups. In instances of ruptured hepatomas, resection only sufficient to control hemorrhage definitely is recommended. In instances of nonruptured hepatomas, major resection should only be attempted by skilled surgeons, and small multiple lesions should be observed. These management principles will deserve re-evaluation as more experience with these tumors accumulates. Until then, a conservative approach is indicated. This includes the avoidance of oral contraception until the biochemistry of these tumors is better clarified.


Identification of the presence and type of biliary microflora by immediate gram stains. Immediate gram stains were performed on gallbladder bile aspirated at the start of an operation for biliary disease in 191 consecutive patients undergoing elective biliary surgery. The results of the gram stains were telephoned to the operating theater within 20 minutes of collection. The over-all accuracy rate of the telephone gram stain reports compared with the subsequent bile cultures was 77 percent. The incidence of false-positive results was 12 percent, and false-negative results were recorded in 7 percent. The organism was identified wrongly by the gram stain in 4 percent of patients. These results have improved with experience and the over-all accuracy rate of gram stains on bile over the last 6 months have been 87 percent.


Selecting patients requiring antibiotics in biliary surgery by immediate gram stains of bile at operation. The value of selecting patients for antibiotic cover during biliary surgery by the use of immediate gram stains of bile was determined in a nonrandomized prospective study which compared two groups of patients. Group A consisted of 119 consecutive patients in whom antibiotics were administered during operation according to the results of immediate gram stains on bile. Group B included 101 patients, none of whom received antibiotics. In Group A gentamicin was given for gram-negative bacteria, ampicillin for gram-positive organisms, and no antibiotics were given if no bacteria were seen on the gram stain. In Group A the incidence of wound sepsis was 7 percent, compared with 22 percent in Group B (p less than 0.005). Septicemia occured in 2 percent of Group A, compared with 8 percent in Group B. It is concluded that immediate gram stains of bile will provide a means of selecting patients requiring antibiotic cover during biliary surgery; furthermore, this procedure is a practical way of reducing postoperative sepsis while avoiding unnecessary antibiotic administration.


HLA determinants in chronic active liver disease: possible relation of HLA-Dw3 to prognosis. Thirty-eight patients with severe chronic active liver disease (CALD) were found to have a significantly higher frequency of HLA-Dw3 (68%) than 91 healthy controls (24%) (P less than 0;0001). The association of CALD was statistically significantly stronger with the D locus than with the B locus of HLA. The response to treatment was significantly worse in patients with HLA-Dw3 than in patients who lacked this antigen.


An HLA-D specificity found in the Japanese population. A new HLA-D specificity was found in the Japanese population in two different laboratories. Japanese cell YT, found at Stanford, California, was A9,BW22J,CW1 and cell Wa, found at Sapporo, Japan, was A9,BW22J homozygous. They were shown to be HLA-D identical to the homozygous Japanese cell AH which submitted to the VIth International Histocompatibility Testing Workshop (Workshop number 2-001). This specificity was common in the Japanese (gf = 0.089) but completely absent from 62 Caucasians tested. Strong association of this specificity with HLA-BW22J was demonstrated.


Further evidence for the involvement of base and base sequence in the antigenic determination of thermally denatured DNA. The antigenic determinant of thermally denatured salmon sperm (ss) DNA was extensively investigated with a radioimmunoassay technique using the ssDNA immune system. It was demonstrated that mixed sequences of purines and pyrimidines play a key role in the antigenic determination of DNA. On the other hand, the importance of the bases in the manifestation of DNA antigenicity was demonstrated by using brominated, methylated and/or ultraviolet irradiated ssDNA preparations.


Hydroxyethyl starch and prednisone as adjuncts to granulocyte collection. A total of 232 leukaphereses were performed with a continuous flow (CFC) of 89 donors related to recipients to obtain granulocytes for infected granulocytopenic recipients. One hundred fifteen runs were done without pretreatment of the donors and were used as controls. Pharmacological pretreatment of the remaining one hundred seventeen donors included Prednisone, given in an oral dose (50 mg) the evening prior to the run, and/or 250ml of 6 per cent hydroxyethyl starch added to the input line of the CFC throughout the run. A median of 9.2 liters of donor blood was processed with each run. The pretreatment of the donors with Prednisone plus the addition of HES to the input line significantly increased the number of granulocytes collected. Donors tolerated the leukapheresis procedure well, and no significant side effects were associated with Prednisone or HES administration. Early and frequent use of such granulocytes was effective in the short-term control of fever in the granulocytopenic recipients who failed to respond to 48 hours of broad spectrum antibiotic coverage.


Use of dextran 75 as a macromolecular agent in centrifugal leukapheresis. Twenty-five leukaphereses were done by the Haemonetics system using citrated Dextran 75 in normal saline as anticoagulant, and were compared with a much larger series using hydroxyethyl starch (HES) with and without steroid premedication. The granulocyte and platelet yields were only minimally different between the two agents. Both were inferior in granulocyte collection to the group that was premedicated with a steroid. Dextran is thus a satisfactory substitute for HES in leukapheresis with this system.


RNA tumor viruses as causative agents of chronic neurological disease. These studies were designed to determine if RIDP was present in a particulate fraction of brains from patients with ALS and PD. Evidence that we have detected RIDP is as follows: (a) DNA polymerase activity persists in the presence of concentrations of actinomycin D and distamycin that inhibit most DNA-directed DNA synthesis (25); (b) the majority of endogenous DNA polymerase activity is sensitive to prior treatment with RNase; (c) the early reaction product is a 4-5 S DNA heteropolymer joined by hydrogen bonds to an RNA molecule; and (d) the purified [3H]DNA product anneals to RNA extracted from the enzyme-containing pellet more extensively than to normal brain RNA or poly(rA). The enzyme activity is in a cytoplasmic particle that can be sedimented at high speed and has the buoyant density of RNA tumor viruses (1.16-1.18 gm/ml). This particulate fraction is not disrupted by physical manipulation and maintains its characteristic density with repeated centrifugations. Treatment with the nonionic surfactant Sterox changes the buoyant density of the enzyme-containing particle to 1.24 gm/ml, the density of the onconavirus virion core. Synthesis of RNA-DNA hybrids by an endogenous reverse transcriptase reaction was found only in normal and diseased Chamorro brains. Examination of a limited number of normal and diseased brains from individuals who lived in the United States produced negative results (39). Definitive characterization of this polymerase activity and identification as a true viral polymerase will depend on purification of biochemically active quantities of this polymerase to determine its template specificities, its cation preference, the fidelity of its transcription product, as well as its antigenic relationship to animal virus and human leukemic RIDP. Of critical importance in these studies will be differentiation of this activity from normal brain DNA polymerase  gamma and terminal deoxynucleotidyltransferase.


[Concentration of estrone, estradiol and estriol in the blood of pregnant sheep after induction of estrus with chlormadinone acetate and medroxyprogesterone acetate]. The radioisotopic method of 131J-labelled albumin was employed to determine the distribution of acidic proteinase activity in some organs and tissues of chickens. The highest enzymatic activities were found in intestine wall, in pancreas, and in liver. Considerably lower activities were ascertained in kidneys, brain, lungs, and heart. The different proportions of these enzymes in homogenates and supernatant fractions (106 000 g) testify to a lack of uniformity in the solubility of cathepsins in the organs tested. The tested organs, with the exception of pancreas, did not show any enzymatic activity of neutral proteinases.


[Heterogeneity of neurospecific protein S-100]. Protein S-100 specific for the nervous system was isolated from the bull cerebral hemispheres by the Steward method and antiserum monospecific to it was obtained. In immunoelectrophoretical study of the initial brain extract with antiserum detected the paired line of precipitation consisting of two arcs in the zone of prealbumins and alpha2-globulins of the the serum, and that with purified protein fraction showed only one arc corresponding to the prealbumin component. The purified protein S-100 fraction in agar gel is divided into a series of prealbumin electrophoretic zones, with a pre-protein locating chiefly in the most mobile zone. It is established that heterogeneity of protein S-100 with electrophoresis in agar gel and immunophoresis is due to the presence of calcium ions in the systems. In the presence of 1 mM EDTA solution the one or two closely located prealbumin zones of purified protein S-100 migrates. The obtained monospecific antiserum made it possible to establish that two-fractional antigen A detected previously by the heterogenic antisera is protein S-100.


Physical methods for the analysis of molecular interactions in dyes utilizable in viral biology studies. The possibilities of the main physical methods for the analysis of molecular interactions in solution are discussed on the ground of recent data of the literature. Spectrophotometry, (micro)cryoscopy and the isopiestic method are presented in more detail. These methods were applied to several dyes of common use in viral biology studies and to some new chromophore structures. The results obtained demonstrate the occurrence of molecular aggregation in solution in several of the above mentioned systems, both upon concentration rises and in the presence of inorganic ions.


[Antibodies in gamma-globulin preparations (author's transl)]. A commerical preparation of gamma-globulin with 16% protein content for i. m. administration, as well as two commercial preparations of 5% protein content for i.v. administration, were tested for their antibodies to different viruses. The highest antibody titres were found in the 16% gamma-globulin. Sufficient levels of antibodies to justify prophylactic use were demonstrated in the case of rubella, measles, polio and EBV, whilst antibodies to mumps, coxsackie A9, B1-5 and herpes simplex type I and II were present to a moderate degree. Only low concentrations of antibodies or none at all were found with respect to influence A and B, para-influenza 1--3, vaccinia, adeno 3 and 7, and echo 4, 6, 9, 18 and HBs-antigen. This study shows that normal gamma-globulin can be used prohylactically against many different viral diseases.


[Global review of tuberculosis morbidity and mortality in the world (1961-1971)]. The main objective of gathering available world-wide information on tuberculosis is to present an overall picture of how tuberculosis infection, morbidity and mortality, can be reflected today and to suggest the necessity to improve international epidemiological statistical intelligence. The highest levels of tuberculosis infection in the world (i.e. 60-80% in children 14 years old) may be found in eastern Asia, Oceania and in several areas in Africa. Considerable differences still do exist between the highest and lowest prevalence level within each continent. The ratio between the highest and lowest prevalence level of infection is varying from 1 to 2 in the Americas, to 1 to 10 in Europe. While, in general, in developed countries the annual infection rate reached 0.5% (1969-1972), in developing countries, annual infection rates of 2% or more were reported. The decrease of the annual infection rate in developed countries is, in general, 10% each year, whereas in the developing part of the world the fall in the rates has been slower or the level even remained constant for the last ten years. The information concerning tuberculosis morbidity is sometimes incomplete or inconsistent because of the lack of standard criteria for diagnosing and reporting tuberculosis. Although the bacteriological confirmation of tuberculosis cases has an important bearing on the recording system, official reports are particularly deficient in this respect. Estimating the total number of newly registered tuberculosis cases, one may say that more than 3.8 million, and approximately 4 million cases could have occurred 1967 and 1971 respectively. The prevalence of tuberculosis cases can be estimated to be around 6-8 in 1967 and 8 million cases in 1971. The highest incidence rates reported in 1971 were in Asia, Oceania and in some African countries (i.e. 250-523 per 100000 population). In Europe and America, tuberculosis incidence did not exceed a level of 200 per 100000 population. The average tuberculosis incidence rate for 1971 in the world may be estimated to be 111.5 per 100000 population (111.4 in 1967).


[Trends in tuberculosis hospital and sanatorium beds throughout the world (1960-1975)]. The most important problem facing phthisiologists in the past was how to ensure a sufficient number of sanatorium beds for the management of tuberculosis patients, their rehabilitation and the prevention of transmission of infection by isolating them. There is considerable evidence today, however, that the results obtained with ambulatory treatment are as good as those following in-patient treatment. The latter is now considered unnecessary as it serves merely to prolong duration of the patient's incapacity and to increase the cost of treatment. The presentation of the available information on the trend of beds designated for tuberculosis aims at stimulating the new approach to efficient control of the disease so as to prevent the misuse of available resources. During the period 1960-1965 there were more than 870000 tuberculosis beds reported in the world. Between 1970 and 1975, the number of tuberculosis beds was reduced to 609000. The average percentage of tuberculosis beds to the existing total bed complement was 8.4 in 1960-1uberculosis bed density"--was 3.9 and 3.1 respectively, for the two periods. Owing to the very large variety of reporting systems and sometimes to their defective patterns, international comparisons are hazardous. In general, there is a considerable declining trend in the tuberculosis bed density, in countries with a high initial level, whereas in other countries an upwards trend is sometimes to be found. The analysis of the particular patterns of tuberculosis bed density is difficult, as in many countries the still existing high bed density is actually a combined tuberculosis and respiratory diseases bed density. In countries with a well developed network of institutional units, treatment costs account for approximately half the total cost of the tuberculosis control programme. In a broad public health sense bed strategy is becoming increasingly important since apart from the substantial capital cost of institutional facilities, it also influences both the pattern of service rendered and the use of resources available.


Formation of infectious proviruses.

Formation of infectious proviruses. Formation of DNA proviruses was studied in chronic and acute cellular infections caused by RNA viruses. Some general considerations on the nature of reverse syntheses in eukaryotic cells are discussed.


[Effect of the gamma-isomer of HCCH on the functional state of the sex glands of rats]. The effect of the HCCH gamma-isomer on the function of sexual glands in rats was studied. Administration of the HCCH gamma-isomer in a dose of 5mg/kg body weight was found to bring down the pregnancy index in the group where test females were mated with test males. This indicator, as well as the mating index were down in the group where control males were mated with test females. Moreover, the offspring of animals, where test females were mated with test males and also in the group of control males and test females sacrificed before and during gestation a significant lagging of the weight gain at the end of the nursing period was recorded. Animals receiving the HCCH gamma-isomer in a dose of 0.05 mg/kg body weight did not differ from the control rats in all of the indicators under study.


[Echinococcus alveolaris and cysticus of the liver]. From 1964-1976 34 patients were treated for Echinococcus of the liver at the Mainz University department of surgery. There were 25 cases of E. cysticus and 9 cases of E. alveolaris. Decisive for the diagnosis are Casoni's intracutaneous test, scout film of the abdomen, liver scan and arteriography. In all cases a surgical therapy is indicated. A central localization of the parasite cysts makes problems to the surgical management. In these cases we prefere the cystectomy. All other echinococcal cysts were removed totally, either by pericystectomy or hepatic lobectomy. Such a radicality is the exception in E. alveolaris. Twice we performed right hepatic lobectomy. In the other cases operative treatment was carried out to confirm diagnosis and ensure bile passage by a hepato-enterostomy. However, palliative bile draining procedures may prolong survival time to more than 10 years.


Transfer of drug-resistance-plasmids in mixed cultures of Staphylococci. Transfer of pen- and chl-plasmids does not only occur between strains of Staph, aureus but also betwen strains of Staph, aureus and Staph, epidermidis. In Staph, aureus, the frequency of transfer of a tet-plasmid is less frequent than the transfer of pen- and chl-plasmids. Lysogenization of the donor strain by a sero-group-B-phage has no influence on the frequency of transfer. The transfer is not inhibited by gamma-globulin. gamma-globulin inhibits unspecifically phage adsorption and also the transduction by phage 80. The transfer is also possible when an encapsulated recipient strain is used. Phages are inhibited by the capsular material (SCHEER and KOFT, 1975); a transduction to an encapsulated strain is impossible. These results speak against a phage-mediated transfer in mixed cultures. A dilution of the incubation mixture leads to an unproportional decrease of the frequency of transfer. A prerequisite to the transfer is probably a close cell-to-cell contact.


Salmonella gallinarum - Salmonella enteritidis relationship in rabbits. The polysaccharide of S. gallinarum, sharing factors 9.12 with the Salmonellae of group D. cross-reacts with one of two serological determinants, present in the polysaccharide of S. enteritidis, and is different from the determinant responsible for the cross-reaction of S. enteritidis and S. typhy polysaccharides. The absorption of anti S. gallinarum sera with proteins from S. enteritidis removed all the antibodies induced for the homologous antigens; in contrast, the absorption of the anti S. enteritidis sera with proteins from S. gallinarum removed all the antigens common to S. gallinarum and S. enteritidis, leaving for reaction the antibodies induced to specific antigens of S. enteritidis.


Normal values in the adult Zambian. V. Plasma alpha-2 macroglobulin. A study on the normal concentration of alpha-2 macroglobulin in the adult Zambian is presented. The values are time-related but fall within the normal range for Europeans and North Americans. An important difference in concentration between males and females is recorded.


[Use of the indirect hemagglutination test in the study of ornithosis. I. Hemosensitizing activity of ornithosis phosphlipid antigen and a method of performing tests with it]. A possibility was shown of using the phospholipid group-specific antigen of the ornitosis causative agent in the capacity of a hemosensitin for conducting the indirect hemagglutination test (IHAT). There was revealed a direct proportional relationship between the sensitizing activity and the complement fixing properties of the antigens obtained. A method of sorption of this antigen on the tannin-treated erythrocytes and the optimal parameters of conducting the test with it were elaborated. A sufficiently high sensitivity and specificity of the IHAT was revealed as a result of parallel titration of hetero-and homologous sera in the complement fixation test and in the IHAT. The suggested test can be successfully used for the diagnosis of ornithosis.


[Electron microscopic determination of the localization of the group-specific antigen of Halprowise (Chlamydiae) by the direct immunoperoxidase method]. The direct immunoperoxidase technique was applied to the study of the localization of a group-specific antigen of Halprowiae (Chlamydiae) in the causative agents of meningopneumonia (strain MP) and of paratrachoma (strain LB-I) at the individual stages of their developmental cycle in the L-cell (16, 24 and 48 hours after infection of the culture). The product of reaction to peroxidase pointing to the localization of the group-specific antigen was localized not only on the surface, but in the whole thickness of the cell wall of the initial bodies in the form of an even electron dense layer, 200--280 A in thickness. A weak positive reaction was also noted on the outer layer of the sytoplasmic membrane. The periplasmic space remained free of the reaction product. Localization of the reaction product in the intermediate and elementary bodies remained unchanged. At the initial stages of the developmental cycle (16 hours after the infection) the reaction) the reaction product was revealed not in the whole cell wall, butin some of its areas only. There were found no qualitative differences in the localization of the group-specific antigen in the Malprowiae strains under study.


[Protein and antigenic spectrum of different species of yeasts of the genus Candida]. The methods of electrophoresis in polyacrylamide gel, immunoelectrophoresis and immunoprecipitation were applied to the study of the protein and antigenic spectra of different species of Candida yeasts. It was revealed that for the majority of the yeast species the prevalence of proteins of definite fractions was characteristic. C. albincans displayed a marked (in comparison with the nonpathogenic species) content of proteins of proteins of group b. The most pronounced antigenic properties in C. albicans and C. tropicalis were possessed by the proteins of the basic character. C. albicans and C. tropicalis yeasts were characterized by similar antigenic spectra, whereas the C. crusei species showed the least affinity with the C. albicans.


Chemotherapeutic remissions in Wistar Furth rat acute myelogenous leukemia: a model for human AML. Acute myelogenous leukemia (AML) of the inbred Wistar/Furth (W/Fu) rat is pathophysiologically similar to human AML. Subcutaneous transplantation of 1.0 X 10(6) cells of a clonal tissue culture line of W/Fu AML into 6- to 8-week-old rats produced local myeloblastomas in 8--10 days which progressed to infiltration of regional nodes, replacement of greater than 90% of the bone marrow, ascites, and fatal peripheral blood leukemia with concomitant hyperlysozymemia. Single doses of adriamycin, daunomycin, actinomycin, cytosine arabinoside, or Cytoxan in rats with 1.0 cm myeloblastomas produced complete tumor regression while bu-sulfan, vinblastine, vincristine, dexamethasone, and Methotrexate was relatively ineffective. Responses were associated with delay in progression to peripheral blood leukemia and prolonged survival. Similar results were obtained following treatment of rats with already disseminated leukemia. The demonstration of response to drugs known active against human AML indicates that the W/Fu AML should be a valuable model for rapid evaluation of new chemotherapeutic agents for clinical use.


Preparation, purification and in vitro properties of a serum against human lymphoblastic leukemia-associated antigens. A serum against human lymphoblastic leukemia cells was obtained inoculating rabbits. We studied the specificity of the serum before and after particular absorptions in various clinical conditions. The serum was cytotoxic against many cases of acute lymphoblastic leukemia, against continuously cultured Burkitt's lymphoma cells and against chronic myelogenous leukemia in blast crisis. On the contrary, the serum was not cytotoxic against lymphocytes of normal donors, acute lymphoblastic leukemia in remission and other lymphoproliferative disorders.


Imidazole carboxamide (DTIC) in the treatment of advanced lymphomas. Efficacy of DTIC in cases which fail to respond to conventional chemotherupetic combinations. 15 patients with malignant lymphomas (stage III B or IV) who had become resistant to previous combination chemotherapy were treated with DTIC. The drug was administered intravenously as a single agent in doses of 300 mg/m2 on 5 consecutive days, once a month. The results demonstrate good responses in Hodgkin's disease, while in non-Hodgkin's lymphomas only incomplete and short remissions or failures were recorded. The only untoward side effects were nausea, vomiting and pain in the vein during the injection.


Large granules and lysosomal fusion in human Chediak-Higashi white blood cells. The phenomenon of giant anomalous lysosome formation in human Chediak-Higashi syndrome leukocytes was analyzed. Ultrastructure findings combined with cytochemical procedures for visualizing acid phosphatase and peroxidase activity showed giant anomalous granules in addition to normal, small and enlarged granules. Massive granules in lymphocytes had an appearance and structure different from those found in other leukocytes. The giant granules seem to be a product of an active fusion between primary and secondary normal sized or enlarged lysosomes. This fusion occurs in polymorphonuclear neutrophils, eosinophils and in monocytes. No fusion was found in lymphocyte granules.


Diagnostic significance of alpha-fetoproteins in neonatal hyperbilirubinaemias and primary cancer of the liver in adults. The presence in the serum of alpha-1-fetoprotein (AFP) was studied by the following immunological methods: immunoprecipitation electrophoresis after Pesendorfer et al., modified micro Ouchterlony technique as described by Prince, and for quantitative determination of this fraction commercial Partigen plates with sensitivity above 1 mg/100 ml. were used (Behringwerke A.G.). Anti AFP serum produced by the same company was used. In our experiance these three methods were equally sensitive In the newborn (41) with hyperbilirubinemia (cytomegalic inclusion disease, toxoplasmosis, ABO and Rh incompatibility) despite persisting abnormal laboratory tests indicating liver damage AFP disappeared from circulation by the end of the first month. Fetoprotein has been demonstrated in the serum by the end of the third month in nine babies in whom malformation of the biliary ducts was confirmed intraoperatively (7,14). In adults AFP was observed in the serum of only those patients in whom presence of primary hepatocellular liver cancer was proved pathohistologically Out of 15 verified cases of primary liver cancer AFP was positive in 43.7%.


Duplication of the haemoglobin alpha-gene. Gene duplication is one of the basic processes underlying evolutionary changes. The gamma-chains of human foetal haemoglobin is coded by multiple structural genes. The delta-chains of Hb A2 can be regarded as a duplication of the beta-locus. We have presented the first evidence for the presence of two major alpha-chain loci in man. The alpha-gene appears to have duplicated recently, since apart of the single point mutations characterizing Hb J-Buda and Hb G-Pest, the two alpha-gene products seem to be identical. Sensitive immunochemical measurement techniques may reveal structural differences which might escape detection by chemical methods based on differences in charge and/or chromatographic behaviour. Anti-alpha-chain sera recognizing the single amino acid substitution in alphaJ-Buda could be raised in rabbits. The anti-alpha-chain sera were found to be more powerful tools for detecting differences in the primary structure of the chain than the immune sera raised against the whole tetramer. None of the immune sera could reliably differentiate Hb G-Pest from Hb A1. The relative strength of complement fixation of the alpha-chains from haemoglobin A1 F and A2 was compared by hybridizing these human haemoglobins with caninehaemoglobin and measuring the quantitative complement fixation of the different hybrids with anti-Hb A1 and anti-alphaA1 rabbit immune sera. No antigenic difference among the alpha-chains from haemoglobins A1, A2 and F could be detected by this method either with anti-A1 or with anti-alphaA1 sera. These results do not exclude the possibility of conformational differences between the alpha-chains in native Hb A and Hb F. The antigenic activity of the alpha-chains of Hb A from normal subjects (alphaA1) and of the alpha-chains of Hb A from a double heterozygote for alphaJ-Buda and alphaG-Pest (alphaA1) were compared by the complement fixation technique. Definite differences could be detected in the relative strength of complement fixation by alphaA1 and alphaA1 with anti-alphaA1 serum. Final decision as to whether alpha-chain duplication is a universal phenomenon or whether it is restricted to only a part of mankind cannot be drawn until the presence of a silent alpha-thalassaemia gene is not excluded in some debated cases by reliable chemical methods. Measurement of alpha-globin genes in Hb H disease with cDNA enriched in alpha-globin sequences provided direct evidence that a non-thalassaemic subject has to have at least four alpha-globin genes per diploid cell.


[Transferrin in various hematological syndrome]. In 100 patients with various haematological syndromes and in 22 healthy subjects serum transferrin was determined by the method of radial immunodiffusion of Mancini. The results were correlated with total iron-binding capacity, iron concentration, beta1 globulin and albumin levels. A statistically significant rise in serum transferrin concentration was demonstrated only in patients with sideropenic anaemia. In the remaining groups of patients transferrin concentration was decreased without regard to associated disturbances of iron metabolism and iron level. The comparison of the total iron-binding capacity with transferrin level determined by radial immunodiffusion may suggest presence of iron-binding proteins other than transferrin.


[Simultaneous presence of HB-s and anti-HB-s antibody with different specificity in serum]. By means of counterelectrophoresis (CEP) HBs-Ag and anti-HBs were found in the serum of a patient with a third episode of virus hepatitis. Presence of HBs-Ag was confirmed by complement fixation (CF) and immunodiffusion (AGD) but the antibody was not demonstrated by these methods. The subtype of HBsAg in this case was ayw and the antibody was monospecific anti-HBs/d. The presence of HBsAg and anti-HBs differing in specificity was due, probably, to double infection with HB viruses of different subtypes--ayw and adw in this case.


Regeneration of the basal melanocytes of the human skin. The stages of regeneration of the basal melanocyte of human skin after Feulgen reaction were found to be granule, unipolar cell, bipolar cell and bidendritic, tridendritic and quadridendritic melanocyte, in that order. The last mentioned cell either divided by mitosis to form two daughter melanocytes or matured to form a replica of the original basal melanocyte of the human skin.


Development and peripheral innervation of the palatal muscles. Following the observation of 51 embryos and human fetuses of between 9 and 190 mm vertex/coccys length, cut transversally, frontally, or sagittally, depending on the case, and coloured with HE, Azan, or by the Bielschowsky method, we studied the development, and peripheral innervation of the palatal muscles. We reached a series of conclusions which we put forward in this paper. The m. tensor veli palatini is the one which develops earliest. It derives from the sam blastematic mass as the muscles of mastication, and it is innervated by a branch of the n. mandibularis. The m. levator veli palatini and m. pharyngopalatinus coincide chronologically with the appearance of the m. cephalopharyngeus. They derive from the pharyngeal musculature, and are innervated by fibres proceeding from the n. glossopharyngeus, in the case of the first one, and, in the case of the second, by direct branches from the n. glossopharyngeus and n. vagus, which penetrate the muscle directly, without prior contact with any nerve plexus. The m. uvulae is first formed, at the time the palatine processes close. In the first place, two outlines may be seen; but after 50 mm approximately it is formed by one muscle only, on the medial line; it is innervated by branches which proceed from the posterior n. palatinus. The m. glossopalatinus is the last to appear. It is closely linked to the musculature of the tongue and, therefore, we think that it derives from the hypobranchial musculature, and that is innervated in the body of the tongue itself, by means of the n. hypoglossus.


[Changes in the cerebellum of the rat after actinomycin during the postnatal period]. A single dose of actinomycin was applied to young Wistar albino rats in the critical phase of their cerebellar development. The morphological alterations of the cerebellar cortex were studied by means of light and electron microscopy on several postnatal days. The cell types of the cerebellar cortex reacted in different ways toward the noxious substance according to their stage of development. The acute alterations consisted of an edematous reaction of the neuronal and glial perikarya (light degeneration) and a shrinkage of the neurons (dark degeneration). A massive intercellular edema and a rarefaction of glia cells as well as the Purkinje cell fibres proved to be the long-term damage. This pattern of the alteration was discussed regarding the chemodifferentiation of the cells of the cerebellar cortex, the onset of cerebellar function on day 14, and the establishment of a neuroglial functional unit.


Electron-microscopic studies of the innervation of the pulmonary veins of the mouse. The innervation of the pulmonary veins was studied with electron microscopy. The adrenergic and cholinergic nerves were differentiated with potassium permanganate fixation. All three layers of the venous wall, namely, the tunica intima, media and adventitia, contained unmyelinated axons. Adrenergic and cholinergic axons were located near the cardiac muscle in the tunica media and near the smooth muscle in the tunica intima. The morphological relationships may explain the pharmacological and electrophysiological responses of the large pulmonary veins observed by others.


[Ultrastructure of the contact between interstitial cells and myocardial cells in mammalian hearts]. By combination of light, electron-microscopical and histochemical findings in the myocardium of dog and mice, the hypothesis of an intimate contact between a widely branched interstitial cell type, rich in proteoglycans, and myocardial cells could be strengthened. The branches seem to penetrate the transversal tubular system of the myocardial cells. Functionally, this interstitial (mast cell-like) cell type might influence via proteoglycans - delivered into the transversal tubuli - the excitation phenomena of the myocardial cell membrane. One of the earliest pathomorphological changes in the myocardium, as revealed by the light-microscopie, is the disengagement of these interstitial cells and the myocardial cells. From this point of view the genesis of myocardial cell necrosis has been discussed.


Staining of rabbit eosinophil and pseudoeosinophil leukocytes. Air-dried rabbit blood was stained by HE, PAS and a modification of the Undritz II method. Eosin stained granules red in the eosinophil leukocytes. PAS was negative and the modified Undritz method failed to give consistent results. Cells with eosinophilic granules appeared in the corneal stroma 1 h after removing the corneal epithelium. They were stained red consistently by both eosin and the modified Undritz II method. Electron micrographs failed to demonstrate crystalloids in the granules. Because of the staining characteristics and the lack of crystalloids in their granules these cells were classified as pseudoeosinophil leukocytes. The electron micrographs showed some glycogen 12 h after denuding the cornea, however, glycogen was not well stained by PAS until 18 h after denuding.


Different stainability of Purkinje cells. Regarding the different stainability when using the Luxol fast blue methods, two kinds of Purkinje cells of the rat are described: Luxol-positive and Luxol-negative cells. Since, by this method, phospholipids are demonstrated, the author suggests the prospective varying functional conditions of these cells. Different tinction of Purkinje cells has been confirmed also by other methods (gallocyanin-chromalaun, thionine, toluidine blue, lithium-haematoxylin, chromalaun-haematoxylin-phloxine and acid phosphatase) in both animal and human material. After 96 h of immobilization the different stainability of Purkinje cells becomes more marked, which penomenon can be as well explained with regard to the functional point of view. Similar differences, though less marked, were found also in neurosecretory cells of the nucelus supra-opticus of the rat and in the nuclear region of the ganglion semilunare Gasseri cells in man. Finally, the author refers to the relations between the Luxol blue staining method and Baker's method employing acid haematoxylin for demonstration of phospholipids in certain kinds of nervous system cells, taking into consideration Kroon's findings.


Oligoclonal aspect in the CSF of multiple sclerosis patients: a statistical and physiopathological study. Oligoclonal aspect (O.A.) is observed in 51 per cent of 468 MS patients investigated. Elevation of gammaglobulins and lymphocytic pleiocytosis increase significantly its frequency. O.A. is more frequent in presence of an inflammatory transsudate. Clinical aggravation and O.A seem significantly connected. In the first years of the MS, when the course is intermittent, the frequency of O.A. is significantly influenced by the proximity of the last bout. No such differences exist in patients with continuous course. In conclusion O.A. appears as intermittent expression of a local and general immunity reaction, in connection with the progression of the disease and as a very probable manifestation of persistant virus. We proposed 3 years ago in Göteborg a physiopathological hypothesis suggesting multiple sclerosis (MS) is a two-phase disease. In this first paper, we demonstrated the existence of two successive immunological reactions: The first one is an intermittent synthesis of IgG obviously linked to a lymphocytic pleiocytosis which is also intermittent. This firs CSF pattern appears in the same time of a bout and disappears quickly like the clinical symptoms. It may represent the manifestation of a brief and only infectious aggression. After a few years (more than 5 in average) a second mechanism progress slowly: The synthesis of IgG appears continuous, in remission as in aggravation, the lymphocyte count becomes normal and the level of albumin increases progressively. This second pattern suggests, contrary to the first, a continuous auto-immune processus with the intervention of the general (systemic) immunity. The purpose of this second paper is an attempt to elucidate the signification of oligoclonal aspect in relation to this schema.


Demonstration of ochratoxin A in kidneys of pigs and rats by immunofluorescence microscopy. Ochratoxin A was localized in the kidney of pigs and rats by means of immunofluorescence microscopy after short-time exposure. Antibody against ochratoxin A was obtained from rabbits after repeated injections of bovine serum albumin-ochratoxin A conjugate. Ochratoxin A was localized exclusively in the proximal tubule. Light microscopically, necrosis and desquamation of epithelial cells in the pig kidneys were restricted to the proximal tubule where the toxin was found. The investigation had demonstrated conclusively that the proximal tubule is the target part of the nephron in ochratoxin A-induced mycotoxic nephropathy.


Spatial distribution of the EOG in the rat; a variation with odour quality. The spatial distribution of olfactory receptors in the rat has been studied by simultaneous recordings of the electroolfactograms (EOGs) from areas of the olfactory mucosa. The potentials were recorded from the dorsal surface of the cribriform plate, leaving the mucosa and the nasal cavities intact. The ratio between the peak amplitude of the EOG potentials served as a measure of the relative sensitivity of one area against the other. The results obtained by stimulating with 31 substances at 38 positions demonstrate a non-homogeneous distribution of different receptors. Each substance gives a spatial pattern of response efficiency. The response distributions are mapped on the cribriform plate for the different odours.


Decrease in alpha-lipoprotein cholesterol in men after cessation of exposure to chlorinate hydrocarbon pesticides. Eight men who in 1970 had been exposed to chlorinated pesticides and for whom the exposure had ceased in 1976, showed a significant fall in alpha-lipoprotein (HDL) cholesterol between these years. The cholesterol concentration of the other lipoprotein classes showed no significant trend. The data support our previous suggestion that exposure to chlorinated pesticides, mainly lindane, may raise the alpha-lipoprotein levels.


Interspecies interactions of arboviruses. II. Participation of the genomes of two flaviviruses, West Nile and Japanese encephalitis, in formation of a virus clone with dual antigenic determinants. A peculiar clone, 41/WN+JE+, possessing antigenic determinants of a flaviviruses, West Nile (WN) and Japanese encphalitis (JE), is described. The antigenic duality of this clone exceeded the cross reactions between WN and JE viruses; either antiserum neutralized 104--105 PFU/ml of the virus. The property of antigenic duality was inherited in over 340 virus generations and retained upon propagation in selective cell systems and after recloning. The progeny of infectious RNA consisted of 3 types of virus particle: antigenetically distinct WN and JE viruses and particles retaining dual antigenic determinants WN+JE+. The nature of clone 41/WN+JE+ (a stable heterozygote accompanied by phenotypic mixing) and its origin due to inadvertent contamination of attenuated WN virus with JE virus is discussed.


Cardiac pacing and pacemakers II. Serial electrophysiologic-pharmacologic testing for control of recurrent tachyarrhythmias. The place of pacemakers in the treatment of tachyarrhythmias has expanded far beyond the initial role in the brady-tachy syndrome, of providing a "minimum guaranteed rate" while medications suppress the tachycardia. Techniques have been developed for prevention, termination, and duplication of a patient's spontaneous tachycardia under safe catheterization laboratory conditions. Combined with accumulating information about the normal responses to electrophysiologic stresses, these techniques have led to a new dimension in arrhythmia control. Most tachycardias previously felt to be refractory can be controlled after serial electrophysiologic-pharmacologic testing, during which sequential pharmacologic and pacer regimens are tested until a combination is found which prevents induction of tachycardias, and/or a pace mode is found which reliably terminates the tachycardia. Use of such an approach reduces hospital admissions and referral for surgery, and eliminates prolonged hospitalization for assessment of therapy in patients with infrequent but potentially lethal spontaneous tachycardias.


Use of acupuncture anesthesia for normal delivery. In order to evaluate the efficacy of acupuncture anesthesia for normal delivery, 32 parturients were selected and studied. Definite subjective as well as objective relief of labor pain was produced in about 60% of 16 primapara and about 90% of multipara after acupuncture. The sedation of the patients was significant. The duration of the delivery, particularly in the second and third stages was shortened. No adverse or harmful effect was noticed on either mother or child. It was concluded that acupuncture anesthesia is useful for delivery, especially because of its safety, despite more erratic and less potent results than conventional anesthetic techniques.


Atypical stromal hyperplasia of the prostate gland. Hyperplastic lesions of the prostatic stroma with atypical changes are presented and discussed. One lesion was a leiomyoma with atypical organization and a limited area of nuclear pleomorphism without mitotic figures. One was a lesion which in many portions was histologically indistinguishable from leiomyosarcoma. It, however, had certain features probably connoting less sinister behavior, and at autopsy 16 months after resection there was no evidence of recurrence or metastasis. One lesion histologically resembled fibroadenoma of the female breast. These three lesions occurred in patients more than 50 years who had symptoms and signs of prostatism. Reference is made to two previously reported lesions reminiscent of cystosarcoma phyllodes of the female breast. All the lesions were located in the craniad prostate, which is estrogen-influenced. A parallel is drawn between these atypical changes in prostatic fibromuscular stroma and atypical changes in the connective tissue stroma of the female breast.


Cytotoxic drug-induced lung disease.

Cytotoxic drug-induced lung disease. Cytotoxic drugs, principally bleomycin, methotrexate and busulfan, have been associated with pulmonary toxicity. Cytotoxic drug-induced lung disease may be difficult to establish with certainty because other causes of pulmonary disease are frequently present. We discuss the clinical, roentgenographic and histologic effects of the administration of bleomycin, methotrexate, busulfan and other cytotoxic agents on the lungs and suggest that these agents may also cause pulmonary malignancies. We note the importance of careful patient monitoring and withdrawal of a demonstrated offending agent.


Home observation for measurement of the environment: a validation study of screening efficiency. Home environments of 91 6-month-old infants were assessed with the Home Observation for Measurement of the Environment (HOME) Inventory. Multiple discriminant functions composed of the six subscale scores from the HOME Inventory were used to predict whether a child would be low IQ (below 70), low average (70 to 89), or average to superior (90 and above) at age 3 years. The mean vector of Home inventory subscales for the three IQ groups was significantly different (p less than .01). Significant univariate effects were observed for three HOME Inventory subscales: organization of the physical and temporal environment, provision of appropriate play materials, and maternal involvement with child. The discriminant function of HOME Inventory subscale scores correctly predicted 71 percent of all children who scored below 70 IQ. Results attest to the usefulness of the HOME Inventory in a comprehensive program of screening for developmental delay.


Passive immunization against viral hepatitis-- status and prospects. The value of conventional gamma globulin in prophylaxis of hepatitis A has not been confirmed in recent years but there is no evidence that ineffectiveness has been encountered as a result of declining immune experience among antibody donors in open populations. Fortunately, specific tests for hepatitis A antibody are becoming available as a means of estimating effectiveness of currently manufactured gamma globin. Hepatis B prophylaxis by conventional gamma globlin is much more uncertain but the negative evidence must be considered in light of rising anti-HBs titers of globin manufactured more recently. The latter have appeared to be effective in pre-exposure prophylaxis when nonparenteral transmission was implicated. Post-exposure prophylaxis against massive inocula of hepatitis B, as in transfusions, would appear to require large amounts of HBs antibody. Protection against hepatitis from small inocula accompanying accidental punctures with contaminated needles is under controlled study to determine whether the anti-HBs titer of special globulin preparations is a predictive index of protection. Results are expected by midyear, 1975.


Purification of human ovarian tumor-associated antigen and demonstration of circulating tumor antigen in patients with advanced ovarian malignancy. Human ovarian tumor-associated antigen (TAA) has been purified from ovarian tumor tissue by affinity chromatography on concanavallin A-Sepharose and three different gamma globulin-Sepharose columns. The resulting ovarian TAA appears to be contaminated by one normal antigen or family of antigens. Rabbit antiserum prepared against this purified ovarian TAA (antiserum 404) was coupled to CNBr-activated Sepharose 4B. This coupled Sepharose was added to fractionated serum from ovarian cancer patients with Stage III and IV malignancy. Bound protein was eluted with 0.2M glycine buffer and tested against antiserum 404. The bound protein contained TAA identical to the TAA isolated from ovarian tumor tissue.


False positive amniotic fluid alpha fetoprotein levels resulting from contamination with fetal blood: results of an experiment. The finding of an elevated level of alpha fetoprotein (AFP) in amniotic fluid is of value in the prenatal diagnosis of open neural tube defects. The present study was done to determine the amount of fetal blood required in amniotic fluid to produce a significant and misleading increase in AFP. Fetal blood was obtained at hysterotomy, and measured volumes were added to amniotic fluid samples. Bethe-Kleihauer tests, red cell counts, and AFP determinations were done. On the average, at 16 weeks' gestation, contamination of 5 ml. of amniotic fluid with 22 mul of fetal blood will results in an increase in AFP of 1.6 mg. per deciliter. Fetal cells in a much lower concentration can readily be detected by the Bethe-Kleihauer technique. A Bethe-Kleihauer test and red cell count should be done on all blood-stained amniotic fluid samples to determine the amount of fetal blood present. The contribution of the fetal blood AFP can then be estimated and must be considered in the interpretation of the total amniotic fluid AFP result.


Dysfunctional labor XII. Long-term effects on infant. Developmental studies were done at 3 and 4 years of age in a series of 656 children and the results were correlated with the preceding labor pattern and the type of delivery. It was determined that there were significant adverse effects among offspring delivered by midforceps procedures or born following labors characterized by prolonged deceleration, secondary arrest of dilatation, or arrest of descent.


Hepatitis B immune serum globulin and standard gamma globulin in prevention of hepatitis B infection among hospital staff: a preliminary report. In May 1973 a controlled double-blind clinical trail with prophylactic injects of hepatitis B immune serum globulin (antibody titer by passive hemagglutination 1:355,000) and standard gamma globulin (1:100) was started in Sahlgren's Hospital, Göteborg, Sweden. The annual attack rate of clinical hepatitis B in the three departments studied had been 5 to 8 per cent during recent years. A total of 118 members of the hospital staff were prophylactically treated while 125 staff members were unwilling to participate and received no prophylactic treatment. During the first 20 months of study nine cases of clinical hepatitis B with jaundice occurred within the untreated group (7.2 per cent) while three cases (2.5 per cent) were observed in prophylactically treated individuals. After decoding it was found that 60 individuals had received specific hepatitis B immune serum globulin while 58 had received standard gamma globulin. Two of the three clinical cases of hepatitis B occurred within the standard gamma globulin group. Both groups included two individuals with transient antigenemia only and the standard gamma globulin group also included four individuals with antibody seroconversion.


Reduction of stress between mothers and their handicapped children. This paper reports the results of videotaped baselines and a series of behavioral instruction sessions that involved 28 preschool handicapped children and their mothers. The behaviours of mother and child were analyzed from videotaped records before, immediately following, and nine months after the behavioral instruction sessions. The intervention, the instruction sessions, focused on enrichment of the mother-child interaction repertoire and was accomplished with immediate feedback to the mother by using the bug-in-the-ear device. The frequencies of the 216 measures of negative behaviours tested (12 behaviours in each of 18 dyads) decreased in 48 instances immediately following the instruction sessions. Forty of these changes were still present nine months later. The research indicates it is possible to reduce stressful, negative interaction and, in addition, to maintain the mother's behaviors of warmth and acceptance.


The chemical mediation of delayed hypersensitivity skin reactions. I. Purification of a macrophage-chemotactic factor from bovien gamma-globulin-induced skin reactions in guinea pigs. A macrophage-chemotactic factor (MCFS) was extracted in the pseudoglobulin fraction from delayed hypersensitivity skin lesions induced by bovine gamma-globulin in guinea pigs. Its chemotactic activity was estimated by a modification of Boyden's method using Nuclepore filter. After chromatography of the protein fraction using Sephadex G-50 and DEAE-cellulose, in that order, two chemotactic fractions were obtained. The chemotactic factor with stronger activity (MCFS-1) was further highly purified (488-fold) by chromatography on CM-Sephadex. This factor migrated in a single band on acrylamide disc gel electrophoresis and was found to be a protein that was free of nucleic acid. Gel filtration showed that its molecular weight was similar to that of IgG. Its chemotactic activity was heat labile. Intradermal injection of this factor into normal guinea pigs induced a pronounced mononuclear cell emigration from venules. These findings are pertinent to understanding macrophage reaction in the delayed hypersensitivity reactions. Am J Pathol 87:359-374, 1977).


The host antigen phenomenon in experimental murine schistosomiasis. III. Destruction of parasites transferred from mice to hamsters. The surgical transfer of 23- to 28-day-old Schistosoma mansoni from donor mice to the mesenteric vessels of outbred hamsters is followed by recovery of 70% of the transferred trematodes 30 days later. Prior immunization of hamsters with mouse erythrocytes results in anti-mouse erythrocyte antibody titers of greater than 1:4,096 and death of 98% of the parasites. Destruction is correlated with evidence of the presence of mouse antigenic determinants on the surfaces of schistosomes from donor mice.


A safe method of intrahepatic biliary drainage in obstructive jaundice. In malignant disease with severe obstructive jaundice, survival after operative intervention is extremely low. Simple external biliary drainage is desirable for these patients, as a preliminary procedure for radical operation or long-term palliation. Intrahepatic biliary drainage at the anterior edge of the liver can be performed easily and safely under local anesthesia in case of obstruction of the proximal bile ducts, just as cholecystostomy is indicated for obstruction of the common bile duct.


A simplified palliative method of bypassing inoperable cancer of the head of the pancreas. A plastic T tube has been used for internal drainage between the common bile duct and a loop of jejunum in six patients suffering from an advanced inoperable cancer of the head of the pancreas. The procedure proves to be very simple, without complications, and short in duration and offers certain advantages over other similar operative technics.


Vital staining of the corneal endothelium with rose bengal and alizarin red S. A new technique for the staining of the corneal endothelium is presented, in which the actions of the vital stain, rose bengal, and the intercellular stain, alizarin red S, are combined. The technique is an improvement over other simple evaluative methods, because it defines both healthy and damaged cells, and thereby permits an investigator to accurately quantify endothelial cell damage.


Granularity of cells in the juxtaglomerular apparatus in fetal rats after maternal nephrectomy or fetal unilateral nephrectomy. Granular cell indices (GCI: Dunihue and Robertson, '57) in kidneys of fetal rats one day after maternal nephrectomy of fetal unilateral nephrectomy on day 21 of gestation were determined by examining sections stained with Bowie's technique. Maternal nephrectomy induced an extreme increase of GCI in fetal kidneys with increased granularity of cells in the juxtaglomerular apparatus. Fetal unilateral nephrectomy did not cause any significant change.


Ultrastructural distinction between reticular and collagenous fibers with an ammoniacal silver stain. Reticular and collagenous fibers stain differently when subjected to ammoniacal silver reduction. A variety of tissues were subjected to such a "reticulin" technique and the association of reaction product with intercellular connective tissue elements was studied with the electron microscope. The reaction with reticular fibers was primarily associated with the interfibrillar matrix, and was globular in form having a wide variety of particle sizes. Conversely, in dermal collagen the unit fibrils were stained rather than the interfibrillar matrix. The precipitate was punctate in form and was associated with the cross striations of unit collagen fibrils. Large microfibrils also reacted positively with the stain, imparting a faint periodicity. Basement membranes were stained uniquely. The underlying plasmalemma and the lamina densa were heavily stained with silver while the lamina lucida was relatively unstained. The unit fibrils of the lamina reticularis stained in the same manner as dermal unit collagen while the ground substance remained unstained. This represents a clear distinction between the argentophilic characteristics of collagenous fibers, reticular fibers, and basement membranes.


Histochemical evidence of mucosubstances in the metaplastic epidermis and hair follicles produced in vitro in the presence of excess vitamin A. Pieces of upper lip and lower jaw from 13-day old mouse embryos grown in organ culture with excess vitamin A showed metaplastic changes in epidermis and hair follicles after 7 to 21 days. Changes were less marked in upper lip explants from 15-day old embryos. Areas of keratinizing epidermis showed a much higher incidence of Alcian blue-positive bodies when excess vitamin A was present. Histochemical tests with Alcian blue at critical electrolyte concentrations indicated moderately sulfated acidic mucosubstances in these bodies. Other patches of epidermis were transformed into stratified cuboidal epithelium producing PAS-positive, Alcian blue-negative, mucosubstances. The hair follicles, transformed by vitamin A into glands, developed three types of epithelium with apical granules, luminal borders and occasional goblet cells, all showing mucosubstances. Tests suggest that both metaplastic epidermis and glands secrete either neutral mucosubstances or non-sulfated acidic mucosubstances. Another response to vitamin A was a rapid loss of glycogen, particularly in hair follicles and the epidermal basal layer. It was concluded that excess vitamin A alters not only the morphogenesis but also the distribution and synthesis of polysaccharides in developing skin.


Comparison of electrophoretograms of normal canine serum and plasma and of serum and plasma of hemolyzed specimens. Comparison of the electrophoretograms of normal canine plasma and serum revealed a greater concentration of the beta3-fraction in plasma due to the presence of fibrinogen. When serum or plasma of hemolyzed canine blood was analyzed electrophoretically, there were slurring of the beta-globulin peaks due to the presence of free hemoglobin and increases in alpha2-globulins due to the formation of the haptoglobin-hemoglobin complex.


Analysis of serum proteins in clinically normal pet and colony cats, using agarose electrophoresis. The relative and absolute values of the electrophoretic fractions of serum proteins of 50 clinically normal cats were determined, using agarose as the supporting matrix. Six protein fractions were clearly and consistently resolved: albumin and alpha1-, alpha2-, beta1-, beta2-, and gamma-globulins. In many cats, the alpha1-, alpha2-, and beta2-fractions were each divided into 2 subfractions. Cats which lived in a research colony environment were found to have significantly increased levels of gamma-globulins as compared with the values in cats kept as house pets. The results of serum protein fractionation using this technique have been compared with the normal feline values reported in the literature.


Quantitative differences in goblet cells in the tracheal epithelium of male and female rats. The cause of higher morbidity rates among men than women from diseases of the respiratory tract may be complex and involve several factors, one of which may be structural differences within airways. In an attempt to determine whether such differences exist, 13 male rats and 45 female rats (15 each in proestrous, estrous, and diestrous) were evaluated. Tracheas were fixed in situ by injection of a mixture of formaldehyde and glutaraldehyde. Longitudinal sections cut from paraffin blocks were stained and combined alcian blue (pH 2.5) and periodic acid-Schiff stain to count goblet cells, or with Weigert's hematoxylin and eosin stain to determine epithelial thickness. In the normal rat trachea, cells containing periodic acid-Schiff-positive granules at their apices constituted a major population of goblet cells. The number of these goblet cells present in the trachea was greater in female than in male rats at each stage of the estrous cycle, with the values in the diestrous females closest to the value in the males. Among females, estrous and proestrous rats contained significantly more of these goblet cells than did diestrous animals. The tracheal epithelium of male rats was significantly thicker than that of female rats. These studies demonstrate that the tracheal epithelium differs in male and female rats and varies in the female rat as a function of hormonal cycles. These results raise the question of whether similar differences might be important in the pathogenesis of human disease, and they deserve further clarification in man.


Carcinoma of the oesophagus and cardia.

Carcinoma of the oesophagus and cardia. 234 patients, 146 with carcinoma of the oesophagus and 88 with carcinoma of the cardia are reported. There were 82 females and 152 males, mean age 62 years. The overall operability and resectability of the whole series was 38% and 23%. In cardiac carcinoma operability was 50% and resectability 32%, while in oesophageal carcinoma it was 31% and 18% respectively. 54 patients underwent resection, 44 received irradiation, and in 136 patients only palliative treatment was possible. The overall hospital mortality after resection was 15%, after oesophageal resection 12%, after cardiac resection 18%, and after palliative procedures 14%. Anastomotic leakage occurred in 9 patients (17%), four of whom died. The overall 5-year survival rate for the whole series was 4%, after resection 11%, and after radiotherapy 4%. No patient in the palliative group survived for 2 years. The mean survival time after irradiation was 11.5 months and after palliative procedures 5.5 months. The 5-year survival rate after oesophageal resection was 13% and after cardiac resection 6%.


[Differential expression of relevant Rous sarcoma tumor antigens in cultured cells]. Chickens bearing tumours induced by Rous sarcoma virus (RSV) are able to mount a cellular immune response against antigens associated with these neoplasms. Cultured Rous sarcoma (RS) cells, derived from the wings of chickens bearing tumors induced by RSV, were consistently more susceptible in cytotoxicity assays to killing by the splenic lymphocytes of RS-bearing chickens than were chicken embryo fibroblast (CEF) cells which had been transformed in vitro by RSV. In contrast, extracts (3M KCI-derived) and supernatant fluids of transformed CEF were equally or more capable of eliciting blastogenic responsiveness in circulating lymphocytes of birds with tumors than were similar extracts and supernatant fluids obtained from cultured RS cells. As measured by lymphocyte stimulation, the expression of this anti-tumour response was in some cases only short-lived, and varied between animals in terms of time following inoculation with RSV. These findings point to a differential expression of relevant RS-tumour antigens in these various cell types, and indicate that the use of various experimental techniques may yield quite different results.


[Correlation between tumor growth and proteic variations in interstitial liquid and serum]. The growth of four chemio-induced tumours has been studied in correlation with the proteic variations in interstitial subcutaneous liquid and serum revealed by polyacrylamide gel electrophoresis. We could notice important changes in three proteic groups: beta-lipoproteins, transferrin and alpha-globulins. A significant increase is recorded for these 3 proteic groups in intersitial fluid and only for alpha-globulins in serum for the tumours growing the slowest. By contrast, a significant decrease of these 3 proteic groups is recorded in interstitial liquid of mice which bear the faster-growing tumours.


[Triggering of human peripheral blood B cells by supernatants of activated T cells: the role of Ia-like determinants]. Human peripheral blood B lymphocytes, isolated by Sephadex G-200 anti-Fab column chromatography, were non specifically induced by either pokeweed mitogen (PWM) or soluble products of antigen stimulated T cells, to differenciate into plaque directed against human Ia-like antigens (anti-p 23-30) inhibited the differenciation of B cells into antibody forming cells. Thus, while PWM induced proliferation was only mildly reduced by anti-p 23-30, the PWM induced PFC response was totally abrogated. Conversely, the antiserum abolished both the proliferative and the PFC responses generated by products of activated T cells. Using both Ouchterlony plates and co-precipitation techniques, we were unable to detect p 23-30 molecules on the active products present in the T cells supernatants. These data suggest that the inhibitory effects are secondary to interaction of the antiserum with B cells determinants.


[Antigenic determinants of human immunoglobulin light and heavy chain variable regions. Comparison with animal species]. An antigenic analysis of human heavy and light chain variable region subgroups has been done on different animal species, by means of heterologous specific antisera using a hemagglutination-inhibition procedure. Excepted in lemur sera, where Vkappa III and Vlambda III are the only variable antigenic determinants found, all VL antigenic determinants tested were shown to be present in primates. In other mammals (carnivores, some rodents, some artiodactyls) several VL antigenic subgroup determinant were detected while others were not. No VL antigenic determinant was found in other classes studied. The VH III subgroup antigenic determinant was found among all primates, some mammals and avains. The results suggest that there has been more preservation in the variable region of immunoglobulin chains, and particularly VH III chain, than in the constant region of immuoglobulin molecule.


[H-2 specificity and auto-reactivity of autologous rosette-forming cells from adult thymectomized mice spleen cells]. We have previously shown that the number of autologous rosette-forming cells (A-RFC) found in adult thymectomized mice (A-Tx) spleens was 15 times higher than that found in spleens of intact controls. We have therefore investigated both the specificity of A-RFC and their relationship with autoreactivity. Immunoadsorption experiments showed that while the incubation on allogeneic monolayers did not bring any modification in A-RFC levels. This result suggests that the formation of autologous rosettes is the manifestation of a true recognition event associated with the H-2 complex. A-Tx mice spleen cells injected into syngeneic recipients induced an enlargement of the afferent popliteal lymph node (LN). Ficoll-Triosil A-RFC depleted A-Tx spleen cells lost their capacity to induce this popliteal proliferation. Conversely, A-RFC recovered spleen cell suspensions obtained from the pellet of the Ficoll Triosil gradient kept their capacity of inducing auto-reactivity. Thus, it seems that A-RFC and lymphocytes stimulating the afferent LN belong to the same sub-population.


[Biochemical and immunological characterization of a suppressor factor specific for the terpolymer GAT]. It has been possible to extract a suppressor factor specific for antigen from non-responder animals that have developed suppressor cells. This factor shows a high affinity for the antigen and cross-reacts with related antigens. It does not carry antigenic determinants of the constant region of immunoglobulin molecules but carries Ia determinants and has an affinity for the GAT comparable to the affinity of the anti-GAT antibodies.


[Artificial H-2 dependent carrier determinants of the insulin molecule]. The known tertiary structure of insulin allows the study of carrierdeterminants of insulin: their nature, their distance to antigenic determinants and their H-2 dependance. We examined the influence of "foreign " amino acids of insulins from two different species and the influence of chemically coupled new amino acids at the B-chain of insulin in congenic resistant mice. Three strains were immunized with bovine insulin and three derivatives: LeuB-insulin, LysB-insulin and GluB-insulin. H-2d mice were high responders to insulin and all derivatives, while H-2k mice showed no detectable antibodies. The H-2b strain had an intermediate antibody response to bovine insulin. LeuB-insulin, LysB-insulin and GluB-insulin produced similar titers as unmodified insulin in H-2d mice. In H-2b mice, GluB-insulin produced significantly more antibodies than did all other insulins tested with antibody specificities directed against A8-A10. Therefore Glu at position B0 acts as a carrierdeterminant and A8-A10 as antigenic determinant at the dose utilised in H-2b mice. The distance between both determinants is about 15-20 A, allowing therefore the cooperation of T and B cell.


[Modification of the immune response by a hepatic ferroglobulin: L alpha2-HF]. Alpha2-HF, foetal and tumorous isoferritin, the level of which is high in cancerous patients and in amniotic fluid during pregnancy, has an immunosuppressif effect on normal lymphocytic response. Its activity has been tested on blastic transformation induced by PHA, tuberculin, candidin and allgenic lymphocytes. The inhibition effect is proportional to the added quantity of alpha2-HF globulin. The antibody synthesis is depressed by alpha2-HF as demonstrated in vivo and in vitro. Iron is no responsible for the suppressif effect: the efficiency is identical with the native protein or the apo-protein. Crystallised ferritin, without sugar in its molecule on the contrary of alpha2-HF which is a glycoferroprotein, has no suppressif effect.


[Heterogeneity of L-valine pool in Actinomyces sp. 26-115 producing actinomycin C]. Free intracellular valine in Actinomyces sp. 26-115 producing actinomycin C its functionally heterogenous. There are at least 2 pools of free valine. One of them supplies valine for protein biosynthesis and the second for the antibiotic biosynthesis. The volume of the pools is estimated. Inadequate reaction of the pools to similar effects is indicative of differences in their properties. The pool participating in protein biosynthesis strives for preservation of its volume. The pool participating in the antibiotic biosynthesis is capable of enlarging its volume to various levels depending on the change in the volume of the common intracellular pool.


[Phylogeny of the e allotypic system of rabbit immunoglobulins: study of determinants recognized on ochotona IgG by anti-e15 antisera]. The phylogenetic studies of Cgamma allotypes already made in the Leporidae was extended to another family of lagomorphs, the Ochotonidae. The d allotypic system is only found in rabbits; thus, it appeared late in the lagomorphs evolution. The e system has two alleles (e14 and e15, present in rabbits and in another Leporidae genus (Sylvilagus). Previous studies on hare IgG showed that e15 pattern is composed of at least two " determinants " (or group of determinants) i and j. The hare has three allotypic patterns i+j+, i+j- and i-j-. All the studied ochotonae (from Afghanistan and Iran) possess the i determinant. From comparisons between results obtained with various genera of lagomorphs, and hypothetical scheme is proposed for the evolution of the Cgamma gene on the basis of the series allotypes.


Experimentally induced bleomycin sulfate pulmonary toxicity: histopathologic and ultrastructural study in the pheasant. Morphological alterations in the lungs of pheasants after prolonged high-dosage administration of bleomycin sulfate were studied by light and electron microscopy. Nontreated birds acted as controls, and their lungs showed no abnormalities. Lungs of bleomycin-treated pheasants revealed collapse alternating with overexpansion, marked cuboidalization of atrial epithelium, and incipient interstitial fibrosis. There were neither lymphoplasmacytic or eosinophilic infiltrates, nor evidence of vasculitis. Ultrastructurally, type 1 alveolar epithelial cells were either reactive or conspicuously absent in the air capillaries. Type 2 alveolar epithelial cells appeared hyperplastic with numerous lamellar bodies, many of which extruded into air spaces. Immature fibroblasts were noted in the vicinity of collagen fibrils or amorphous material resembling elastin. No immune deposits were present in basement membranes. These findings are consistent with a direct toxic effect of bleomycin to the pheasant lung rather than a drug hypersensitivity reaction. Reproduction of the bleomycin lesion in a nonmammalian species corroborates even further the high propensity of the drug to affect the lung.


Antiviral activities of acyl derivatives of 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine and 1-beta-D-arabinofuranosylcytosine in cell culture. Antiviral activities of acyl derivatives (3'-O-octanoyl and 3'-O-decanoyl) of 2,2'-anhydro-1-beta-d-arabinofuranosylcytosine (cyclo-C) and 1-beta-d-arabinofuranosylcytosine (Ara-C) were compared with other antiviral nucleosides, and some biological characteristics of the antiviral activity were investigated. Among those synthesized acyl derivatives, 3'-O-decanoyl ara-C was the most active against deoxyribonucleic acid viruses, with an activity comparable to that of Ara-C. Acyl derivatives of cyclo-C were somewhat less active than their Ara-C counterparts. In the value of therapeutic index, 1-beta-d-arabinofuranosyladenine was superior to the others, followed by 5-iodo-2'-deoxyuridine. In comparing the sensitivity of two serotypes of herpes simplex virus it was found that Ara-C and its ester, as well as its cyclo-C counterpart, were more active against the type 2 than the type 1 strain. The activity of 3'-O-decanoyl Ara-C, like that of its parent, was diminished by treatment with cytidine deaminase from mouse kidney, but 3'-O-decanoyl cyclo-C was resistant to this treatment. In comparative studies of 3'- and 5'-O-acyl Ara-C's, antivaccinia virus activity of 3'-O-palmitoyl Ara-C was significantly superior to its 5'-counterpart. The inhibitory activity of 5'-O-decanoyl Ara-C was markedly reduced by the presence of a threefold molar excess of eserine sulfate, a choline esterase inhibitor, whereas the 3'-acyl Ara-C was not affected by the inhibitor in any combination. This result indicates that enzymatic hydrolysis of the 3'-ester to Ara-C, which is inhibited by eserine sulfate, did not occur in this cell culture.


[Ultrastructural identifaction of human T lymphocytes using a peroxidase-conjugated anti-HTLA serum]. A horse antiserum rendered specific for human T lymphocytes was conjugated with peroxidase (PO) and used for identification of tonsilar T lymphocytes in electron microscopy. This conjugate stained nearly 50% of tonsilar lymphocytes, 96% of the T of the T cell-enriched population and 4% of the B cell-enriched population. The staining was only found on the cytoplasmic membrane as irregular small spots all over the cell surface. This conjugate was used for identification of the lymphocyte sub-populations extracted from skin infiltrates, and specially in Sezary's syndrome. PO-anti-HTLA serum stained all the cells showing morphological chracteristics of Sezary cells, which confirmed the thymus-derived origin of these cells.


[The regulation of the activation of cytotoxic lymphocytes may be mediated by a lymphokine]. MLC-CML reactivity declines after approximately the 7th day of culture. The experiments described were designed to probe the reason for this decline, envisaged as due to the signals (SD or LD determinants) required for CML activation. Either fresh stimulating cells or a lymphokine--blastogenic factor (BF)--were added daily to mixed cultures from the 5th to the 12th day of incubation. Whereas stimulating cells were without effect, added BF maintained both proliferative and cytotoxic activity of the cells in culture. These observations, together with previous results, were interpreted to suggest that helper cells may regulate the activation of cytotoxic lymphocytes by means of soluble mediators.


Histochemical and morphologic changes in skeletal muscle following cervical cord injury: a study of upper and lower motor neuron lesions. The effects of upper and lower motor neuron lesions on human skeletal muscles and muscle spindles were studied using histochemical and morphometric techniques. In the lower motor neuron lesions, the muscle fibers showed group atrophy, fiber type grouping and target fibers. The muscle spindle demonstrated thickening of the capsule, degeneration of the nuclear chain fibers, targeting and splitting of the bag fibers. In the upper motor neuron lesion, the muscles showed group atrophy with histochemical evidence of preferential type II fiber involvement. Histometrics, however, failed to demonstrate type II fiber atrophy but showed hypertrophy of type I fibers. The muscle spindles only showed increased number of intrafusal fibers.


Isolation and characterisation of oncornavirus from primary cultures of tissues from cattle with leukemia. The purpose of this investigation was to search for oncornavirus in primary cell cultures obtained from leukemic cattle organs and lymphocytes and to study their molecular-biological properties and role in the etiology of cattle leukemia. The investigation was carried out on 25 primary trypsinized cell culutres of lymph nodes, spleens, kidneys and lymphocytes from cattle with acute and chronic leukemia. It was demonstrated that all cell cultures from leukemic cattle (in contrast to cell cultures from healthy cattle) released oncornavirus into the culture medium. The virus possesses the main properties of oncornaviruses: it has a virion of C-type structure with a density of 1.16--1.18g/ml in a 20--60 per cent sucrose gradient, which may be induced by 5-bromodeoxyuridine, inhibited by Actino-mycin D, has reverse transcriptase activity, contains 60S RNA, that is annealed in the reaction of molecular hybridization with DNA of lymph nodes of cattle with leukemia. The propagation of the isolated oncornavirus in continuous cell lines of calf kidney culture was demonstrated. Experimental inoculation of purified oncornavirus was carried out on 60 baby calves and 15 lambs from leukosis free herds or flocks. Several of the calves later showed evidence of virus infection.


[Characteristics of morphogenesis of coronary arteriosclerosis in ischemic heart disease]. Characteristics of morphogenesis of plaques in the coronary arteries were studied in persons aged up to 50 years who had died of various forms of ischemic heart disease (IHD). It had been established to be different and in many respects to be dependent upon local and hemodynamic factors originating in connection with IHD. Hyalinized plaques were isolated, in their development a leading role was played by dysoric phenomena in the vascular wall developed because of acute hypoxia in the course of an attack of acute IHD. There were also revealed peculiar fibrous plaques formed in the distal regions of stenosed coronary arteries as a result of the overgrowth of the intima under conditions of hypovolemia. The authors failed to establish the morphogenesis of "old" plaques with lipid deposits.


Human red cell glyoxalase I polymorphism. Human erythrocyte glyoxalase I has been subjected to starch gel electrophoresis, and its isoenzymatic forms have been visualized by a new positive staining procedure. The enzyme exhibits polymorphism and holds promise as a useful new genetic marker.


Purification and properties of rabbit spermatozoal acrosomal neuraminidase. Treatment of rabbit spermatozoa with 50mM-MgCl2 removes the plasma and the outer acrosomal membranes. Subsequent treatment with the detergents Hyamine 2389 and Triton X-100 solubilizes spermatozoal neuraminidase bound to the inner acrosomal membrane. The enzyme was further purified by DEAE-cellulose, Sephadex G-150 and Bio-Gel P-300 column chromato. The enzyme showed a single major band, with the possibility of some minor contaminants, on disc-gel electrophoresis. It had a specific activity of 0.37 micronmal of sialic acid released/min per mg with purified boar Cowper's-gland mucin as the substrate. The enzyme had marked specificity for 2 leads to 6'-linked sialic acid in glycoproteins. The Km of spermatozoal neuraminidase was 1.72 X 10(-6)M with Cowper's-gland mucin, 1.17 X 10(-5)M with fetuin and 8.8 X 10(-4)M with sialyl-lactose as a substrates. The Vmax. was 0.112 micronmol/min per mg with the Cowper's-gland mucin, 0.071 micronmol/min per mg with fetuin and 0.033 micronmol/min per mg with sialyl-lactose as substrate. The enzyme hydrolysed sheep submaxillary-gland mucin as readily as the Cowper's-gland mucin. The optimum of enzyme activity was at pH 5.0 on the Cowper's-gland mucin and at pH4.3 on sialyl-lactose. The enzyme activity was unaffected by 20mM-Na+ and-K+, but was inhibited by 20mM-Ca2+,-Mn2+,-Co2+ and -Cu2+. The enzyme was unstable in dilute solutions, but could be stored indefinitely freeze-dried at --20 degrees C.


Characterization of a new reverse transcriptase of possibly cellular origin in the chicken system. The properties of an RNA-dependent DNA polymerase, which occurs ubiquitously in the allantoic fluid of uninfected, leukosis-virus-free eggs, are described. It is shown that the enzyme can synthesize faithful transcripts from natural RNA (globin mRNA). With biochemical and immunological methods, the enzyme can be clearly distinguished from the reverse transcriptases of the known chicken RNA tumour viruses and therefore seems to be a member of a so far unknown class of chicken polymerases. Our data show that in the chicken system reverse transcriptase can occur without connection to the replication of RNA tumour viruses and without relationship to the induction of malignancy.


Alpha-foetoprotein and carcinoembryonic antigen in germ cell neoplasms. Serum alpha-foetoprotein (AFP) and serum carcinoembryonic antigen (CEA) levels were measured, serially whenever possible, in 70 patients attending the Institute of Radiotherapy, Rotterdam, on account of testicular (65) or ovarian (4) germ cell tumours or, in one case, an endodermal sinus (yolk sac) tumour in the mediastinum. In 15 patients the disease was active; in the others it was in remission. Patients with active disease had raised serum AFP levels which correlated well with disease activity; no patient without evidence of active disease had raised serum AFP levels. None of the patients with active disease was found to have raised serum CEA levels. There was no correlation between serum AFP and CEA levels in patients with germ cell neoplasms, but good correlation between serum AFP levels and disease activity. Serum CEA levels did not correlate with disease activity, and serial determinations would therefore not be useful in monitoring progress in this group of diseases.


alpha-Fetoprotein levels in pregnancies complicated by gastrointestinal abnormalities of the fetus. alpha-Fetoprotein (AFP) levels have been measured in maternal serum and amniotic fluid in a variety of gastrointestinal abnormalities of the fetus. Maternal serum AFP levels were consistently elevated in abdominal wall defects of the fetus after 15 weeks gestation and the amniotic fluid levels were raised in 3 of the 4 patients measured. In atresia of the gastrointestinal tract and diaphragmatic hernia, serum AFP levels were usually normal unless there was an associated neural tube defect or multiple pregnancy, although the majority were not measured between 15 and 26 weeks gestation. If elevated amniotic fluid levels of AFP are used in the decision to terminate pregnancy on the assumption of a probable neural tube defect of the fetus, a proportion of terminations will be performed because of abdominal wall defects of the fetus.