Immunofluorescence study of the adenovirus type 2 single-stranded DNA binding protein in infected and transformed cells. High-titer monospecific antiserum against highly purified adenovirus 2 (Ad2) single-stranded DNA binding protein (DBP) was used to study, by indirect immunofluorescence (IF), the synthesis of DBP in Ad2-infected human cells and adenovirus-transformed rat, hamster, and human cell lines. In infected cells the synthesis of DBP was first detected in the cytoplasm at 2 to 4 h postinfection and reached a maximum intensity at 6 h postinfection. At this time DBP began to accumulate in the nucleus, where it reached maximum intensity at about 14 h postinfection. The cytoplasmic IF was diffuse, whereas nuclear IF appeared as dots that coalesced into large globules as infection progressed. In cells treated with 1-beta-d-arabinofuranosylcytosine to inhibit viral DNA synthesis, strong nuclear IF was observed in the form of dots, but the large fluorescent globules were not observed. The Ad2 (oncogenic group C) anti-DBP serum reacted very strongly by IF with Ad5 (group C)-infected, to a lesser extent with Ad7 and Ad11 (group B)-infected, and weakly with Ad12 and Ad18 (group A)-infected KB cells (treated with 1-beta-d-arabinofuranosylcytosine). These results may indicate that Ad2 DBP is closely related immunologically to DBPs induced early after infection by adenovirus serotypes in oncogenic group C, moderately related to DBPs of serotypes in oncogenic group B, and perhaps distantly related to DBPs of serotypes in oncogenic group A. The following adenovirus-transformed cell lines were examined for DBP synthesis by IF with the Ad2 anti-DBP serum: six rat cell lines (T2C4, F17, 8662, 8638, 8617, and F161) transformed by Ad2 virus, three hamster cell lines transformed by Ad2 virus (Ad2HT1) and Ad2-simian virus 40 hybrid virus (ND1HK1 and ND4HK4), and one rat (5RK) and one human (293-31) cell line transformed by transfection with Ad5 DNA. T2C4 and 8662 appeared weakly positive, whereas Ad2HT1 and ND4HK1 were strongly positive. The other transformed cell lines did not produce DBP detectable by IF. Thus, some but not all transformed cell lines produce DBP, which indicates that DBP is not required for maintenance of cell transformation and that transformed cells can express "nontransforming" viral genes as protein.


Ultrastrutural studies of vascular and muscular changes in ascorbic acid deficient guinea-pigs. Disorganization of muscle structures such as fragmentation of myofilaments with a loss of contrast in the Z bands, swelling of mitochondria and glycogenic infiltration, was seen in ascorbic acid deficient guinea-pigs. Vacuolar degeneration of external and internal endothelial cell membranes with accompanying dystrophic changes of the surrounding muscle and lack of collagen formation were consistent findings. Chondroblasts showed a marked dissolution of the matrix vesicle and a lack of hyaline droplets.


Rabies virus infection in mouse neuroblastoma cells. As part of an inquiry into factors that determine the virulence of fixed rabies virus, mouse neuroblastoma cells were infected in  culture with high virulence and low virulence strains of Flury HEP virus. Low virulence virus infection differed from high virulence virus infection in (1) its more rapid production of progeny virus in the early cycles of virus infection as shown by the number of extracellular virus particles and the infectivity of the supernatant fluid; (2) its earlier development of viral antigens on the cell surface; and (3) its earlier and more severe morphologic alteration of the cell surface. Where applicable, the differences were corroborated by scanning and transmission electron microscopy of the infected cells using the critical point drying technique on whole cells. The number of cells susceptible to complement-dependent immunolysis was almost proportional to the number of cells that were surface antigen-positive regardless of the strain of the virus used. Implications of the difference in the kinetics of virus production and of the development of surface antigens between low and high virulence strains are discussed.


Quantitative change of serum protein and immunoglobulin in patients with solid cancers. There are many quantitative changes of serum protein and immunoglobulin fractions in patients with cancer of various sites, excluding those with leukemic and lymphoproliferative disorders. The commonest change in serum proteins of patients with neoplastic disease is a reduction in albumin concentration and elevation of alpha globulins, especially alpha-2 fraction. Immunoglobulins (IgG, A,M) are a heterogenous group of proteins contained in the gamma, beta, and alpha-2 electrophoretic fractions of serum proteins. The IgG was found to be significantly increased in patients with cancer of the skin and lung, but decreased in patients with cancer of the prostate and breast. Serum IgM was reported to be elevated in patients with sarcoma, melanoma, brain tumors, but decreased in patients with carcinoma of the ovary. Serum IgA was found to be elevated in patients with cancer of epithelial secretory organs, such as skin, breast, head and neck, lung, gut, prostate, and uterine cervix. Whether these findings reflect specific changes of the humoral arm of tumor-host interaction remains to be investigated.


The pattern of food and mortality in Belgium. Belgians have been gradually shifting from a low ratio of polyunsaturated/saturated fat in their food to a higher one with lower total fat and cholesterol. This has occurred predominantly in the north, where the most obvious change is a decrease in butter consumption and an increase in margarine consumption. The northerners have a four to five times smaller intake of butter than the southerners and nearly double the intake of margarine. Evidence gathered over the past ten years reveals in the north a decreasing serum-cholesterol and in the south a significantly higher serum-cholesterol, associated with higher coronary morbidity and mortality. Life expectancy of males in the north is 2-4 years higher at birth and 2-2 years higher at the age of 30. It is concluded that the food habits of a population can be changed, with great benefit.


Radionuclide cystography in the investigation of vesicoureteric reflux in children. 50 children with urinary-tract infection and vesicoureteric reflux were investigated by direct radionuclide cystography (R.N.C.). Recent micturating cystourethrograms (M.C.U.) were used as controls. In 37 patients the results of both tests corresponded, 9 patients were M.C.U. positive only, and 4 were R.N.C. positive only. R.N.C. is associated with a considerably lower radiation dose than M.C.U.S. and intravenous urograms, it provides an accurate measurement of residual urine, and is simple to apply with equipment which is readily available. R.N.C. is a useful investigation in the diagnosis and management of reflux and a valuable complement to standard radiographic methods.


Radioimmunoassay of IgM, IgG, and IgA Brucella antibodies. A radioimmunoassay (R.I.A.) has been devised to measure the serum antibody against Brucella abortus in each of the immunoglobulin classes IgM, IgG, and IgA. This test was applied to 46 sera from individuals with various clinical types of brucellosis, and the results were compared with the results of conventional direct and indirect agglutination and complement-fixation tests. The R.I.A. provided a highly sensitive primary-type assay which avoided the difficulties with blocking or non-agglutinating antibody, and thus has many advantages in the diagnosis of acute and chronic stages of brucella infection in man. The R.I.A. was successful in detection of antibody in many instances in which conventional serological tests were negative, and such antibody could (if IgM) be associated with acute or (if IgG or IgA) with chronic cases of brucellosis. One case in which B. abortus was isolated by blood culture but which failed to yield antibody by conventional tests, nevertheless showed substantial levels of IgM and IgG antibody by R.I.A. In other cases the R.I.A. test helped to eliminate the diagnosis of brucellosis by revealing absent or low antibody levels.


Plasma-noradrenaline in essential hypertension. Plasma-noradrenaline (P.N.A.) has been determined in normotensive controls and in patients with essential hypertension while resting and after postural stimulation. A linear relationship was found between age and P.N.A. in normotensives during recumbency and in the upright posture. This relationship did not occur in the hypertensives and was due to raised P.N.A. levels in many younger patients. On standing, ten out of thirty-four patients under the age of 50 years with essential hypertension had significantly greater P.N.A. than the age-matched controls. No differences were found, however, between controls and patients in the older age-group. It is proposed that stimulation of the sympathetic nervous system by postural challenge provides a means for identifying a subgroup of younger patients with essential hypertension in whom sympathetic overactivity may play an important rule.


Burn excision by a caron-dioxide laser.

Burn excision by a caron-dioxide laser. When the 'Sharplan' 50 W carbon-dioxide laser was used for burn excision, blood-loss was reduced compared with that experienced during scalpel excision. This advantage was more than offset, however, by the increased operating-time and increased physical effort required to maintain a firm, prolonged pull on the burned tissue during excision. A more powerful laser might overcome these disadvantages.


Treatment of haemorrhoids in patients with inflammatory bowel disease. A retrospective review of outcome was undertaken in forty-two patients with ulcerative colitis and twenty patients with Crohn's disease who were treated for haemorrhoids and the inflammatory bowel disease between 1935 and 1975. Both surgical and conservative treatment of haemorrhoids in patients with ulcerative colitis had low complication-rates (4 complications after 58 courses of treatment). In Crohn's disease the complication-rate was high (11 complications after 26 courses of treatment). One of the forty-two patients with ulcerative colitis and six of the twenty with Crohn's disease required rectal excision for complications apparently dating from the treatment of haemorrhoids. These results suggest that treatment of symptomatic haemorrhoids is usually safe in patients with ulcerative colitis but is contraindicated in those with Crohn's disease.


Prepatency of giardiasis.

Prepatency of giardiasis. Recently acquired giardiasis was suspected in 199 patients because of typical symptoms following a trip to a known endemic area. In 130 cases giardiasis was confirmed by stool examination, although most of the samples obtained less than 3 wk after probable infection were negative for Giardia lamblia. Prepatency was documented in 35 patients who, after one or more negative stool examinations, started to excrete Giardia. The median prepatent period was 14 days, and in most cases the prepatent period was less than 3 wk. The median incubation time of giardiasis was 8 days, and in two-thirds of the cases the symptoms had continued for over a week before the parasite became detectable in faeces. A practical conclusion was that, in suspected cases of giardiasis with negative stool findings during the first 3 wk after possible exposure to Giardia, examination of repeated faecal samples is still effective in confirming the diagnosis.


Recovery of Paramyxovirus from the jejunum of patients with multiple sclerosis. Paramyxovirus, presumably measles, has been recovered by cocultivation or cell-fusion techniques from jejunal biopsy specimens of 6 consecutive patients with multiple sclerosis. Virus has been identified by immunofluorescence of antigen in infected HEp-2 and BSC-1 cells, by electron microscopy, and by haemagglutination of rhesus-monkey erythrocytes.


Jejunal immunopathology in amyotrophic lateral sclerosis and multiple sclerosis. Identification of viral antigens by immunofluorescence. Jejunal mucosa from 7 patients with amyotrophic lateral sclerosis (A.L.S.), 20 newly reported patients with multiple sclerosis (M.S.), and 35 control patients without either disease was studied by immunofluorescence. An immune reaction was present in all A.L.S. specimens and consisted of altered ratios of immunoglobulin-labelled cells in the lamina propria, complement-labelled cells in the same location, and, in some, immunoglobulin and complement deposits in the epithelial basement membrane. Poliovirus antigen was detected in 4 cases, and in 1 of the these cases measles antigen was also present. A fifth specimen showed large amounts of herpesvirus antigen. In 2 cases studied at necropsy, both viral infection and immunological change was confined to the proximal jejunum. Measles antigen was identified in every case of M.S., and in biopsy specimens from 16 of the 20 M.S. patients immunological reactions similar to those seen in A.L.S. were present. With 2 exceptions, the controls did not show these changes in the jejunal mucosa. The exceptions were a patient with Friedreich's ataxia, who had an increase of IgG-labelled cells and some complement-bearing cells in the lamina propria, and a patient diagnosed as having non-tropical sprue, in whom large quantities of herpes antigen were seen.


Different B lymphocyte alloantigens associated with multiple sclerosis in Arabs and North Europeans. The frequencies of HLA and B-lymphocyte alloantigens were investigated in 32 Arab patients with clinically definite or early probable multiple sclerosis (M.S.) and compared with those found in 43 healthy Arab controls. A significant association was found between M.S. and the B-lymphocyte alloantigen, BT 102; this contrasts with previous findings of an association between the B-lymphocyte alloantigen BT 101 and M.S. in North Europeans. It is suggested that this difference is due to the involvement of different environmental agents, possibly viruses, in the pathogenesis of M.S. in these populations.


Post-partum transient thyrotoxicosis with painless thyroiditis. 5 patients presented with transient thyrotoxicosis and painless thyroiditis in the post-partum period. Thyrotoxicosis developed within 1-6 months of delivery. All had small non-tender goitres. Initially, all patients had elevated values for thyroxine (T4), triiodothyronine (T3) uptake, and triiodothyronine by radioimmunoassay (T3[R.I.A.]). Radioactive-iodine uptake (R.A.I.U.) was suppressed in all. In all patients, thyrotoxicosis resolved within 4 months; subsequent transient hypothyroidism occurred in 4, 1 developing permanent myxoedema. 2 had persistently elevated thyroid-antibody titres and needle-biopsy findings compatible with chronic thyroiditis. 1 became permanently hypothyroid. The other 3 patients had serial clinical and laboratory findings suggestive of painless subacute thyroiditis. Serial thyrotrophin-releasing-hormone (T.R.H.) stimulation tests are also reported. The importance of the low R.A.I.U. in recognising painless thyroiditis is emphasised. Since the disorder is self-limited, conservative therapy should be given.


Subcuticular suturing after appendicectomy. The results of using interrupted nylon skin sutures or subcuticular polyglycolic acid (P.G.A.) sutures after appendicectomy were compared in a prospective controlled trial in 127 patients. Wound infections were significantly more common when subcuticular skin closure was used.


Complications of cancer immunotherapy with levamisole. In a group of 69 patients receiving levamisole the drug had to be discontinued in 15 (21-7%) because of intolerable but reversible side-effects including gastrointestinal upset, "flu-like" syndrome, central nervous system disturbances, and skin rash. Reversible agranulocytosis with life-threatening sepsis occurred in a patient receiving levamisole immunotherapy for colonic carcinoma. Neutrophils and platelets were both severely affected. Levamisole-dependent leucoagglutinins appeared with circulating immune complexes during the acute phase of the illness, suggesting an immune drug reaction.


Relief of Sudeck's atrophy by regional intravenous guanethidine. 17 consecutive cases of Sudeck's atrophy were treated with intravenous regional guanethidine. Results were encouraging, especially in the arm.


Haemorrhagic complications of heparin therapy. In a prospective trial 76 patients with venous thromboembolism have received intermittent constant-dosage heparin or continuously infused heparin with laboratory control. Frequencies of bleeding were similar in both groups. 32% of all patients bled, 13% severely. Retroperitoneal haemorrhage occurred in 5 patients. Major spontaneous bleeding was commoner in older patients and minor spontaneous bleeding in women. Bleeding was uncommon during the first 2 days of treatment, and its daily frequency was relatively constant thereafter. 21% of surgical wounds and 7% of arterial and venous puncture sites bled. These preliminary results illustrate the hazards of heparin therapy and suggest that bleeding complications are more closely related to duration of therapy, age, sex, and surgical trauma than to method of administration.


Oral contraceptives and hepatitis. A report from the Boston Collaborative Drug Surveillance Program, Boston University Medical Center. History of oral-contraceptive use was compared between 68 women with a hospital-discharge diagnosis of acute hepatitis and 1142 women who had been admitted for other reasons to the same hospitals during the same period. The risk of admission to hospital for hepatitis for users of oral contraceptives was estimated to be 3-3 times that for non-users (95% confidence interval, 1-8--6-3). This overall association was almost entirely attributable to a strong association among women under 25 years of age. Among users of oral contraceptives, duration of use tended to be shorter for hepatitis patients than for controls.


A prospective, randomised study of endoscopy and radiology in acute upper-gastrointestinal-tract bleeding. 318 patients admitted to hospital with acute upper-gastrointestinal-tract bleeding were entered into a prospective randomised comparison of investigation by either endoscopy or radiology. Although the diagnostic yield was higher in the endoscopy group than the radiology group, there was no difference between the two groups in management or survival, and the accuracy of the findings as judged independently at operation and/or necropsy was also similar in the two groups. These findings case doubt on the need to provide emergency endoscopic facilities for the investigation of patients with acute upper-gastrointestinal-tract bleeding where radiological services are already adequate.


Isolation of reovirus-like agents from patients with Crohn's disease. 220 nm filtrates of intestinal resections from 6 of 10 patients with Crohn's disease produced a cytopathic effect in WI-38 tissue-culture monolayers, whereas controls had no effect. Characterisation of the virus responsible has been completed in 3 of the 6 positive isolates and indicates that it is an R.N.A. virus, 55-60 nm in diameter, heat, ether, and acid stable, and antigenically related to Nebraska calf-diarrhoea virus. It therefore belongs to the Reoviridae family.


Clonidine withdrawal in hypertension. Changes in blood-pressure and plasma and urinary noradrenaline. Treatment was interrupted abruptly in 6 hypertensive patients receiving clonidine 0-45-5-4 mg daily. Blood-pressure rose to pretreatment levels within 24-48 h of withdrawal and was accompanied by insomnia, headache, flushing, sweating, and apprehension. These symptoms began 18-20 h after the last dose of clonidine. Plasma-noradrenaline levels and urinary catecholamine excretion increased 24-72 h after withdrawal of clonidine. The subjective symptoms were most prominent in patients on higher doses (greater than 1 mg/day) and in those who had previously been receiving treatment with other antihypertensive drugs. One patient on a very low daily dose (0-15 mg) of clonidine had no symptoms and no significant changes in blood-pressure or catecholamine production after drug withdrawal.


Ovarian function in patients receiving adjuvant chemotherapy for breast cancer. Plasma oestradiol-plus-oestron (E2 + E1), follicle-stimulating hormone (F.S.H.), luteinising hormone (L.H.), androstenedione (A2), and dehydroepiandrosterone sulphate (D.S.) were measured in 33 breast-cancer patients before and after adjuvant chemotherapy. Before treatment the plasma E2 + E1, A2, and D.S. levels were significantly higher and the L.H. and F.S.H. lower in the 16 premenopausal patients than in the 17 postmenopausal patients. After 6 mo of adjuvant chemotherapy the premenopausal patients, 11 of whom had become amenorrhoeic, showed striking reductions in plasma E2 + E1 and A2 and elevations in plasma L.H. and F.S.H. Further changes were evident after 12 mo of treatment. Plasma-A2 fell after chemotherapy in the postmenopausal group; the other hormones were unchanged. The beneficial effects of adjuvant chemotherapy for breast cancer may result, in part, from suppression of ovarian function.


Type-III Hyperlipoproteinaemia ("remnant removal disease"). Insight into the pathogenetic mechanism. The metabolism of very-low-density lipoprotein (V.L.D.L.) was studied in a patient with type-III hyperlipoproteinaemia. After injection of radioiodinated V.L.D.L. from a donor with endogenous hypertriglyceridaemia (in a type-IV pattern), clearance of radioactivity from the apoprotein-B moiety of V.L.D.L. was slow and appearance in low-density lipoprotein (L.D.L.) was delayed, suggesting defective catabolism of V.L.D.L. in type-III hyperlipoproteinaemia. Despite a 60% increase in the rate of V.L.D.L. production, therapy with oestrogen (ethinyloestradiol 1 microng/kg/day) resulted in a decrease in plasma-lipid concentrations, normalisation of lipoprotein composition, and correction of the defect in V.L.D.L. catabolism with increased conversion to L.D.L. Thus, in type-III hyperlipoproteinaemia, the primary defect seems to be impaired catabolism of V.L.D.L., which is corrected with oestrogen therapy.


Dialysis anaemia caused by subacute zinc toxicity. Nine out of ten patients dialysed in a satellite dialysis unit became severely anaemic over a 2-month period. The onset of anaemia coincided with the installation of a new galvanised-iron water softener in the dialysate water-supply system. An activated carbon filter was installed and haemoglobin levels returned towards previous values. Two patients on home dialysis showed similar falls in haemoglobin after the installation of galvanised iron piping in their dialysate water-supply systems; these problems also resolved after carbon filtration of the dialysis water. It is suggested that elution of zinc from galvanised iron can cause anaemia in dialysis patients. Carbon filtration removes of 95-99% of the zinc eluted.


Value of thyroid-stimulating-antibody determinations in predicting short-term thyrotoxic relapse in Graves' disease. Thirty consecutive patients with hyperthyroid Graves' disease received a 6-month course of antithyroid drugs. Sixteen patients relapsed within 6 months of the withdrawal of antithyroid therapy. All patients with high levels of thyroid-stimulating antibodies (TSAb) at the time of drug withdrawal relapsed within 2 months of discontinuing the antithyroid treatment while all patients with low or undetectable TSAb activity at the time of drug withdrawal remained in remission. It was not possible to predict the disease course in patients who had intermediate levels of TSAb when antithyroid therapy was stopped.


Clinical spectrum of gonococcal infection in women. The medical records of 278 women infected with Neisseria gonorrhoeae during a 6-month period were reviewed. These represented 75% of the infections in women at Boston City Hospital during this time. Women who presented to the venereal-disease clinic because they had had contact with an infected man and women who were found to be infected during routine examinations in the obstetrics-and-gynaecology clinic were usually free of symptoms or had non-specific symptoms such as vaginal discharge. However, these women accounted for only 108 (39%) of the 278 infections. Most of the infections were in women who presented to the emergency-care areas of the hospital with symptomatic gonococcal infections. At least 86 (31%) of the 278 infections were in women who had pelvic inflammatory disease. These data indicate that the clinical spectrum of gonococcal infection varies according to where the patients are seen and that the widely held concept that most gonococcal infections in women are asymptomatic may be erroneous.


Community education for cardiovascular health. To determine whether community health education can reduce the risk of cardiovascular disease, a field experiment was conducted in three northern California towns. In two of these communities there were extensive mass-media campaigns over a 2-year period, and in one of these, face-to-face counselling was also provided for a small subset of high-risk people. The third community served as a control. People from each community were interviewed and examined before the campaigns began and one and two years afterwards to assess knowledge and behaviour related to cardiovascular disease (e.g., diet and smoking) and also to measure physiological indicators of risk (e.g., blood-pressure, relative weight, and plasma-cholesterol). In the control community the risk of cardiovascular disease increased over the two years but in the treatment communities there was a substantial and sustained decrease in risk. In the community in which there was some face-to-face counselling the initial improvement was greater and health education was more successful in reducing cigarette smoking, but at the end of the second year the decrease in risk was similar in both treatment communities. These results strongly suggest that mass-media education campaigns directed at entire communities may be very effective in reducing the risk of cardiovascular disease.


Impact of new diagnostic methods on the differential diagnosis and treatment of secondary amenorrhoea. The development of homologous prolactin assays, multiple pituitary stimulation, tomography, and computerised axial tomography permit more detailed investigation of patients with secondary amenorrhoea than was formerly possible. 39% of 90 patients with secondary amenorrhoea had hyperprolactinaemia. 10 patients (11% of total) had pituitary tumours. 8 of these women had galactorrhoea (27% of those with galactorrhoea). For patients with hyperprolactinaemia but no tumour, bromocriptine is the treatment of first choice rather than clomiphene or human gonadotrophins. The best treatment for patients with detectable tumour is controversial, particularly when the tumour is confined to the sella turcica. Whether or not these tumors are true neoplasms remains to be determined. Clinically, a history of secondary anemorrhoea with or without galactorrhoea following withdrawal of oral contraceptives remains the commonest presenting syndrome.


Is duodenitis a dyspeptic myth?

Is duodenitis a dyspeptic myth? In 502 fibreoptic oesophagogastroduodenoscopies performed over 30 months, 14 cases (2.8%) of symptomatic duodenitis without an associated duodenal ulcer were diagnosed. Follow up (1 to 3-5 years) including repeat endoscopy and double-contrast barium meal showed that duodenal ulcers later developed in 6 patients. All have undergone surgery. A further 2 patients continued to complain of dyspepsis, and repeat endoscopy showed duodenitis, confirmed by conventional light microscopy (haematoxylin and eosin). The remaining patients are symptom-free. Repeat endoscopy and histological examination were either normal or showed mild inflammation of the duodenal mucosa. These findings suggest that duodenitis can cause symptoms and may be part of the pathophysiological spectrum of duodenal ulceration rather than a separate disease. It may represent both the production and healing phases of duodenal ulceration.


Jaw wiring in treatment of obesity.

Jaw wiring in treatment of obesity. 17 patients with severe (median percentage above ideal weight 100%) and resistant obesity underwent jaw wiring. There were no major complications and patients tolerated the procedure and subsequent minor inconveniences. All patients lost weight at a rate (median 25-3 kg in six months) comparable with that of intestinal bypass surgery and one achieved and maintained her ideal weight. Two-thirds of the patients, however, regained some weight after the wires were removed. Jaw wiring is a simple effective procedure which can be carried out in most hospitals, and has a place in an integrated approach to obesity.


Survival after cardiac arrest in hospital. A 10-year experience of cardiac arrests in a district general hospital is reviewed. 1063 arrests in the general areas of the hospital were studied, excluding the coronary and intensive care units. In 718 (67-5%) initial resuscitation was unsuccessful; in 252 (23-7%) the patient died later in hospital, 93 patients (8-7%) were discharged alive. After discharge from hospital there was a progressive annual mortality of about 7% for the first five years, but thereafter no patient died. Significant incapacity after discharge was also unusual. The probability of successful resuscitation was greater in patients with primary cardiac disease (11-8% survival), drug overdose (22-2% survival), or undergoing anaesthesia (20-0% survival). The success-rate was significantly greater in the accident and emergency department (7-9%) than on the wards (2-1%), but this difference was due entirely to the more successful resuscitation of patients with myocardial infarction in the accident and emergency department. Within each diagnostic category the survival-rate was independent of the age of the patient. Prolonged survival after resuscitation but ending in death before discharge was unusual.


Stimulation of growth of connective tissue by low-molecular-weight constituents from rapidly growing tissues. The effect of low-molecular-weight cell constituents from regenerating liver and granulation tissue on the growth of the connective tissue during skin wound healing has been investigated. Repeated injections (intravenous or subcutaneous) of these compounds greatly accelerated the growth of connective tissue by stimulation of both fibroblast proliferation and collagen biogenesis and thus promoted wound healing. These results suggest that the low-molecular-weight cell constituents from dividing cells contain internal factor(s) capable of committing resting cells to D.N.A. synthesis and division or of accelerating D.N.A. synthesis in committed cells.


Sperm/cervical-mucus crossed hostility testing and antisperm antibodies in the husband. The behaviour of sperms has been investigated in preovulatory cervical mucus in 44 infertile couples. In 22 couples, immobilising and agglutinating autoantibodies were detected in the husband's sera in high titres. In 10 couples, antisperm antibodies were detected in the husbands by indirect immunofluorescent testing. In 12 couples, no evidence of antisperm antibodies was found in either husbands or wives. The results obtained with husband and wife were compared with the behaviour of the husband's sperms in cervical mucus from fertile donors, and with the behaviour of sperms from fertile donors in the wives' mucus. This crossed hostility test indicated that high tires of immobilising and agglutinating antisperm antibodies in the husband effectively prevented the sperms from penetrating the cervical mucus, even though the sperms appeared normal on seminal analysis. Antibodies detected by indirect immunofluorescence did not have this effect. Poor penetration was also observed with low sperm motility or poor cervical mucus. It is concluded that this test, taken with the postcoital test, could provide a useful screen for immunological causes of infertility and an accurate test for the clinical relevance of antisperm antibody tests.


An in-vitro study of acidosis, platelet function, and perinatal cerebral intraventricular haemorrhage. Platelet aggregation in response to adenosine diphosphate was studied in umbilical-vein blood from 24 term infants. The pH of platelet-rich plasma was experimentally reduced by adding increasing concentrations of lactic acid or by exposure to carbon dioxide. Aggregation was significantly impaired by acidosis and there was a significant positive correlation between falling pH and impaired platelet aggregation in both experiments. Impaired platelet aggregation secondary to acidosis may be a factor in perinatal intracerebral haemorrhage.


Ethambutol plus isoniazid compared with rifampicin plus isoniazid in antituberculosis continuation treatment. Patients with bacteriologically positive pulmonary tuberculosis were treated initially for an average of three and a half months with isoniazid, rifampicin, and ethambutol and then a total of one year's treatment was completed with either rifampicin plus isoniazid (R+I) or with ethambutol plus isoniazid (E+I). 63 patients in each continuation group were followed up for at least one year, and no relapses occurred. Continuation treatment with E+I was as effective and acceptable as that with R+I and was much less costly.


A new syndrome characterised by absence of eosinophils and basophils. The clinical and laboratory findings in a patient constantly lacking eosinophil and basophil leucocytes in bone-marrow, blood, expectorates, and skin exudate are reported. He had repeated infections, asthma, haemolytic anaemia, vasomotor rhinitis, alopecia totalis, widespread scabies, and an extensive growth of warts. His IgA and IgE are low and this may account for some of the clinical features. When his plasma and serum were added in vitro the buffy coat of blood from other subjects, degranulation of eosinophils was seen within two hours. An immunological destruction of eosinophils and basophils is the most plausible explanation for their absence.


Intraosseous fluid administration in emergencies. 15 patients who needed prompt administration of fluids and in whom cannulation of a vein proved difficult were given various solutions and drugs by the intraosseous route. The results of this therapy were rewarding and no serious complications were attributed to the procedure.


Venepuncture nerve injuries.

Venepuncture nerve injuries. 6 patients seen in a blood-transfusion centre had painful peripheral-nerve injuries after venepuncture in the antecubital fossa. The nerves injured were the median nerve and the medial and lateral cutaneous nerves of the forearm in the antecubital fossa. The frequency of this injury was approximately 1/25 000 venepunctures. 3 patients were treated with carbamazepine, which relieved their pain. Although all patients recovered, early recognition of this complication of venepuncture is important, since successful treatment may obviate prolonged disabling symptoms and future litigation.


The great circulatory paradox.

The great circulatory paradox. A review of the relationship between infarction and arterial obstruction in four major vascular territories--brain, gut, leg, and heart--shows that infarction without demonstrable arterial stenosis is common in the brain and gut though rare in the heart and leg. The converse--arterial occlusion without infarction--is common in all four territories. Three factors are recognised as important causes of infarction without demonstrable arterial stenosis--embolism (with rapid disintegration of the clot), spasm, and acute circulatory failure. The importance of cerebral embolism and coronary spasm has only recently been established. An appreciation of the role of factors other than atheroma in the aetiology of infarction is essential for rational prevention and treatment.


Intravenous urography in the management of acute retention. A retrospective analysis of the frequency of requests for an intravenous urogram (I.V.P.) in men with acute retention of urine showed that this investigation was performed in 82%. In no instance, however, did the urographic findings influence the decision to operate or the type of operation performed. The introduction of a specialised urological service did not reduce the number of I.V.P.s requested because most referrals to the urologist were made after the I.V.P. Patients who had an I.V.P. waited on average 8 days from admission to operation compared with 3-5 days for those who did not. We conclude that no purpose is served by a routine I.V.P. in every male patient admitted to hospital with acute retention of urine.


Outbreaks of salmonella food-poisoning over a period of eight years from a common source. In an outbreak of turkey-borne food-poisoning lasting 8 years there were 185 cases and 1 death. 10 incidents were traced to one breeding establishment. The investigation of the outbreak revealed the advantage of close medicoveterinary collaboration.


Predicting the development of pregnancy-associated hypertension. The place of standardised blood-pressure measurement. 82 initially normotensive pregnant women with no known history of renal disease were seen at monthly intervals from 16 weeks' amenorrhoea onwards, and their blood-pressure (B.P.) was measured sitting and lying on their left side. 15 developed hypertension (B.P. greater than 135/85 mm Hg lying on the left side) in late pregnancy. When these women were compared with the 67 who remained normotensive throughout, their B.P.s were found to be significantly higher even in early pregnancy, although individual patients were not always separable in this way. When B.P. measured in this rigidly standardised manner was compared with routine antenatal clinic values, it was apparent that the latter did not detect the difference between the two groups. Women who develop hypertension in the third trimester of pregnancy (pre-eclampsia) may represent a separate group from entirely normal pregnant women from the beginning of pregnancy.


Two-stage operation for anatomical correction of transposition of the great arteries with intact interventricular septum. To allow redevelopment of the posterior ventricle in an infant with transposition of the great arteries and intact interventricular septum, at the age of 4 weeks the pulmonary artery was banded, an aortopulmonary shunt was fashioned proximal to the band, and atrial septectomy was performed. Peak systolic posterior ventricular pressure immediately rose to systemic level (70 mm Hg.) During the next 4 months the pressure drifted back to 55 mm Hg but rose to 72 mm Hg after angiography without a rise in end-diastolic pressure. When the child was six months old anatomical correction of the transposition was successfully performed, the aorta, pulmonary, and coronary arteries being reattached to the appropriate ventricles. Debanding was performed at the same time. For the first 48 hours after operation phenoxybenzamine was given to reduce overload. At 6-month follow-up the child remained symptomless and was not on any cardiac drugs; left-ventricular function was good. This two-stage technique should widen the application of anatomical correction from a small selected group with additional defects to include most patients with transposition of the great arteries.


Electrical bone-growth stimulation in an experimental model of delayed union. An experimental model has been devised for the consistent production of delayed bone healing of the tibia in adult dogs. A double-blind trial, with bias eliminated, was used to evaluate the use of a commercially available direct-current bone-growth stimulator with this model. The stimulator produced a statistically significant acceleration of bone healing at four weeks in the experimental model. Osteogenesis was normal, and no dysplastic, inflammatory, or neoplastic changes were found. This research has shown that electrical stimulation of bone is safe and augments bone formation. The bone-growth stimulator unit remains on trial, but in future it may alter the management of many difficult orthopaedic problems.


Longer term effects of live influenza vaccine in patients with chronic pulmonary disease. WRL 105 strain live influenza vaccine or placebo was given to patients with chronic bronchitis in a double-blind study. The twenty-one vaccinated and twenty-three placebo-treated patients made daily self-assessments of the severity of symptoms of cough, breathlessness, tightness, wheeze, and sputum production in the following 20 weeks. Symptom scores in the first 2 weeks after vaccination or treatment with placebo were used to calculate a baseline range for each patient. Comparison of symptoms in the two groups in the baseline period showed that symptoms were more often reported by vaccinated than by placebo-treated patients but the differences were not statistically significant. One patient who responded serologically to vaccination had a moderately severe influenzal illness starting on the day after vaccination. Comparison of symptom scores during the 18-week surveillance period with baseline values showed that symptoms of breathlessness, tightness, wheeze and cough were significantly more common in vaccinated than in placebo-treated patients and that antibiotic usage was more common in the vaccinated group.


Malignant brain tumours associated with adenylate kinase in cerebrospinal fluid. Adenylate-kinase activity was measured in cerebrospinal fluid (C.S.F.) from 35 healthy control subjects and 11 patients with brain tumours, of which 9 were malignant and 2 benign. No adenylate kinase could be detected in C.S.F. from the controls or from the patients with benign brain tumours. The enzyme was consistently found in C.S.F. from patients with malignant brain tumours.


Lunchtime gin and tonic a cause of reactive hypoglycaemia. 10 healthy young subjects drank, on three separate occasions, the equivalent of three gin and tonics containing 50 g alcohol and 60 g sucrose, gin and "Slimline" tonic containing 50 g alcohol and 0.5 g sucrose, or tonic alone containing 60 g sucrose. Their behaviour, symptoms, blood-glucose, and plasma-insulin were monitored for 5 hours. Both of the alcohol-containing drinks caused mild-to-moderate inebriation, but gin and slimline tonic had no significant effect on either blood-glucose or plasma-insulin levels. Gin and tonic provoked a greater insulinaemia and more profound reactive hypoglycaemic response than tonic alone, and in 3 of the subjects this was associated with the appearance of neuroglycopenic symptoms. Alcohol-mediated reactive hypoglycaemia may contribute significantly to motor-car accidents in the late afternoon at a time when blood-alcohol levels have fallen below the legal limit.


Renal transplantation and a positive serological cross-match. A renal transplant involving a recipient with a positive serological cross-match against donor lymphocytes generally results in hyperacute rejection of the graft. 13 cadaveric renal transplants were performed in recipients with a known positive serologic cross-match against donor B lymphocytes. 12 of these serological cross-matches were positive against donor blood, node, or spleen lymphocytes, but the reactivity was directed against donor B lymphocytes only. 3 transplants failed, 2 because of rejection and 1 because of renal-artery thrombosis. 10 transplants are functioning, 6 to 42 weeks after the operation. Of these 10 successful grafts, 3 had no acute rejection episodes, while 7 had an early acute rejection episode which responded to treatment. Histologically, the grafts showed a cellular rejection, similar to that in enhanced renal allografts in the rat. It is possible to transplant a kidney in a high-risk patient with a positive B lymphocyte cross-match with a low risk of failure. In addition active enhancement of the graft might sometimes occur.


Fluoridation of water and cancer mortality in the U.S.A. Authoritative statements that fluoridation of public water supplies is not associated with any increase in cancer have been challenged on the basis of data which, it is claimed, show that cancer mortality in the United States rose more sharply in cities with fluoridated water than in those without. However, during the period of study (1950-70) the population structures of these cities changed substantially. When account is taken of age, sex, and ethnic group the ratio between observed cancer mortality and expected cancer mortality fell slightly in the cities with fluoridated water and did not change in the non-fluoridated cities.


[Concept and first experiences of an oncologic therapy of head and neck carcinoma (author's transl)]. From the principle of an adjuvant chemotherapy evolved a concept of an oncologic therapy of head and neck carcinomas. Even according to the latest international publications there are no such studies until now (Clarysse, Kenis, and Mathé; Recent Results in Cancer Research, Vol. 53, p. 400; Springer, Berlin 1976). Without reducing or shifting the proved indications of curative operation or radiation we used in our clinic in the last years as an adjuvant different cytostatics applicating intra-arterial perfusions or synchronized radio-chemotherapy or polychemotherapy. Among the 200 patients treated hitherto the patients with oropharynx carcinomas conform at present the biggest collective group (intraarterial methotrexat perfusion). Now for the first time after more than two years of observation of 36 patients the efficacy of this treatment can be inferred from the survival rate respectively estimated for the period ahead. Comparing to other surveys it can be confirmed at present that for the total of all tumor stages the 2-year-survival-rate of our patients is 72% against 47% before whereas the survival-rate within the 5-year period can be estimated at 55% to 30%. On the other hand it turned out that 50% of the patients on radio-surgical therapy died after 1.7 years. After the application of adjuvant chemotherapy including operation and radio-therapy the death rate probably will be reached after 6-7 years.


[Morphological changes in rats during short-term chronic poisoning with Karbafos]. The animals were exposed to the shortened chronic poisoning with "Karbafos" in doses 20, 70, 250, and 850 ppm adminstered in fodder during 13 weeks. After the end of experiment, the animals were killed and their organs weighed. In the collected specimens, prepared histologically, were found the increase of the kidney mass and many nonspecific pathomorphotic changes. The pulmonary edema, parenchymatous degeneration in heart, kidneys and liver are--according to the authors--directly connected with "Karbafos" action. The intensification of changes was bound with the size of applied dose of preparation. The investigations allowed to fix the highest tolerance dose of "Karbafos" amounting to 20 ppm.


Staining mycobacteria with periodic acid-carbol-pararosanilin: principle and practice of the method. Mycobacteria may be acid-fast, non-acid-fast or even chromophobic in staining under different conditions. The pretreatments with oxidants including periodic acid increase effectually the acid-fastness of acid-fast bacilli. This is caused by additional free carboxyl groups resulting from non-acid-fast wax in the cell walls by demethylation with oxidants. Only by prolonged periodic oxidation the aldehyde groups formed as oxidation products of 1-amino-2-hydroxy groups in the cells can be demonstrated with carbol-fuchsin stain. This reaction is most probably attributable to the formation of Schiff's bases between fuchsin and aldehydes. Since pararosanilin is the active molecule in the diphenamine reaction, periodic acid (10%, 24 hours) followed by carbol-pararosanilin stain is a most sensitive and selective method to demonstrate mycobacteria including chromophobic forms.


Absorption of lead and carbon monoxide in Sydney traffic policemen. Examination of traffic policemen in Sydney showed that those exposed to motor vehicle emissions had blood lead levels within normal limits but marginally higher than those unexposed. Carboxyhaemoglobin levels depended only on cigarette smoking and were unrelated to exposure to motor vehicle emmissions.


The child with recurrent infections.

The child with recurrent infections. This review of the child with recurrent infection is taken from the point of view of an immunologist who investigates these patients. The interrelations of many of the parts of the immune defences have been described as well as the principles of the likely results of defects in major areas of the immune organization. An attempt has been made to answer the difficult question of who should be investigated, so that a large number of normal patients will not be investigated, but on the other hand the diagnosis of treatable conditions is not delayed. The management of the various immune defects has been summarized.


[TRH-test in hyperthyreoidism. Investigations of the TRH stimulated TSH-secretion in anti-thyroid drug treated primary hyperthyreoidism and in experimentally induced hyperthyreoidism (author's transl)]. Determinations in 11 patients with anti-thyroid drug therapy of hyperthyreoidism showed, that a pronounced lag period exist between normalisation of thyroid hormone level and TRH responsiveness. The lag period range between 5 and 27 weeks. During this time it is not necessary to give simultaneously thyroid hormones in antithyroid drug therapy to compensate hyperresponsiveness of TSH. - Investigations in 12 volunteers with experimental hyperthyreoidism induced by administration of thyroxine suggest a longterm suppression of the hypophysis to be the cause of the lag period of TSH-secretion. There are some similarities to the ACTH-suppression in therapy with corticosteroids and to the so-called "syndrome of oversuppression" in long lasting treatment with contraceptive drugs.


Accessibility of proteins in 50S ribosomal subunits of Escherichia coli to antibodies: an ultracentrifugation study. The accessibility of each of the proteins on the 50S ribosomal subunit of Escherichia coli was investigated by establishing whether immunoglobulins (IgG), specific for each of the 34 proteins from the 50S subunit, were able to bind to the 50S subunit. The main criterion for accessibility was the formation of specific antibody-50S subunit complexes that could be detected by means of analytical ultracentrifugation. The proteins fell into two main groups. Immunoglobulins against proteins L1, L2, L3, L4, L5, L6, L7/L12, L8, L9, L10, L11, L14, L15, L16, L17, L18, L19, L20, L21, L22, L23, L25, L26, L27 and L30 gave large amounts of complex (20-100%) and, therefore, these proteins were considered to be accessible on the surface of the 50S ribosomal subunit. The antibodies against the remaining proteins L13, L24, L28, L29 and L31 to L34 produced small amounts of complexes (10-20%). Since their effects were unequivocably stronger than those obtained with IgG's from sera of non-immunized animals, the results indicate that these proteins are probably also accessible. Nonetheless, from the ultracentrifugation studies alone definite conclusions about the exposure of the latter group of proteins could not be drawn.


The use of yeast cultures for the detection of environmental mutagens using a fluctuation test. A microbial fluctuation test, modified for the detection of environmental mutagens has been evaluated using a number of strains of the yeast Saccharomyces cerevisiae. Auxotrophic diploid cultures of yeast which produce prototrophic colonies by both mitotic gene conversion and mutation have been extensively utilized for the detection and evaluation of chemicals showing genetic activity. A number of the yeast strains utilized were shown to be suitable for use in the fluctuation test although the time scales of the experiments were considerably extended (up to 16 days) compared to those involving bacteria. The yeast strains respond to doses of mutagens at least a 100-fold lower than that required in a conventional short exposure treat and plate experiment. In experiments involving the induction of mitotic gene conversion at the tryptophan-5 and histidine-4 loci in the fluctuation test significant increases in prototrophic cells were produced in the presence of the insecticide Lindex (0.05 microng/ml), the preservative Thiomersal (0.0001 microng/ml), a mahogany hair dye (0.01 microng/ml), the herbicide Paraquat (0.02 microng/ml) and the alkylating agent ethyl methane sulphonate (0.1 microng/ml). The results demonstrate that the fluctuation test provides an extremely sensitive assay for the detection of chemicals which show genetic activity in yeast at non-toxic concentrations.


Bleomycin (NSC-125066) therapy of responsive solid tumors. 110 patients with far advanced head and neck squamous or testicular carcinoma were treated with bleomycin given by intravenous (i.v.) or intramuscular (i.m.) injection according to a randomized assignment. While responses were observed more frequently in patients treated by the intramuscular route, no superiority can be attributed clearly to intramuscular therapy. Responses were seen in 6.2% of head and neck squamous carcinoma patients (5/81; i.m. 3/38, 8%; i.v. 2/41, 5%) while 14% of testicular tumors responded (4/29; i.m. 4/13, 29%; i.v. 0/16, 0%). Toxicity was, in general, manageable.


Child automobile restraints: evaluation of health education. An experimental design was used to test the effectiveness of three modalities of instruction in pediatricians' offices. Parents in the experimental and control groups were asked if their children wore a car seat restraint on the way to the office. The parents in the experimental group were encouraged to have their children use restraints via one of the following methods: a pamphlet alone; a pamphlet and verbal instruction by the pediatrician; or a pamphlet, verbal instruction, and a brief slide-tape show. The parents were contacted by telephone, mail, or in person two weeks later and asked if their child used a restraint on their last car trip. There were no statistically significant changes in behavior in any of the gourps. Although the group that received all forms of instruction had the highest mean score, the greatest increase occurred with the control group.


Can we identify a group of children at age 2 who are at high risk for the development of behavior or emotional problems in kindergarten and first grade? A group of 198 children were followed from age 2 through first grade to see how consistent their behavior was across time and across settings. Measures of child behavior in the home were obtained when the children were ages 2, 4, and 5. Classroom behavior was ascertained when the children were in nursery school, kindergarten, and first grade. Correlations between early home and school behavior patterns were all quite low. Only when home and school measures were made close to the same point in time did relationships reach even a moderate level. Behavior within the same setting was more consistent over time than behavior across settings but even here relationships were not strong enough to be clinically useful for making predictions about individual children. It is concluded that early behavior in the home, as measured by these methods and for this population, is not be itself sufficiently predictive of later home or school behavior to warrant identifying the child or his family as being at "high risk" for future problems. Pediatrics 59.971-981, 1977, SOCIAL DEVELOPMENT, SCREENING, BEHAVIOR, CHILD DEVELOPMENT, HIGH RISK.


DNA-polymerase inhibitors. Rifamycin derivatives. Ten new derivatives of the antibiotic rifamycin with variable side chains at position 3 were synthesized. The inhibitory activity of these derivatives against DNA-polymerases isolated from avian myeloblastosis virus, E. coli and calf thymus were studied at various conditions. 3-(2,4,6-trinitrophenylhydrazone-(methyl) rifamycin SV is a strong inhibitor for all the polymerases tested and belongs to the C class inhibitors of reverse transcriptase. 3-(monoallylhydrazone-(methyl) rifamycin SV possesses a selective action on polymerases: at 0.1 mg/ml concentration it almost completely inhibits the reverse transcriptase and less than half of the bacterial and eukaryotic enzymes. A drug is found which strongly inhibits the DNA-polymerases from E. coli and calf thymus and weakly the viral enzyme. The inhibitory effect on reverse transcriptase is independent of the choice of template-primer; it could be overcome by the addition of excess enzyme but not of excess template-primer; the inhibition could be completely reversed by dilution of the drug-enzyme mixture. From Lineweaver-Burk analysis, the inhibition is noncompetitive with respect to the template-primer and, thus the drugs bind to the site different from the active site for the template-primer. From protective action of the template-primer and other data it might be suggested that the rifamycin derivatives act at an early step(s) in DNA synthesis catalyzed by reverse transcriptase. The obtained data are in agreement with the results for other derivatives of rifamycin SV described in literature.


Introduction of antigenic determining 2,4-dinitrophenyl residues into 4-thiouridine, N3-(3-L-amino-3-carboxypropyl) uridine and tRNA-Phe from E. coli. The introduction of antigenic determining 2,4-dinitrophenyl residues into the rare ribonucleosides 4-thiouridine (1a), and N3-(3-L-amino-3-carboxypropyl) uridine (2) as well as into tRNA-Phe from E. coli has been investigated. Alkylation of 1a with omega-bromo-2,4-dinitroacetophenone (3b) gives S-(2,4-dinitrophenacyl)-4-thiouridine (5A). Applying the reaction to the 5'-monophosphate of 1a, 5b is formed, but this product decomposes at pH 7. However, acylation of 2 with 2,4-dinitrobenzoic acid N-hydroxysuccinimide ester (4b) leads to N3-[3-carboxy-3-L-(2,4-dinitrobenzamido)propyl]uridine (6) which is stable in aqueous solution. The latter reaction was used for the introduction of an antigenic determining 2,4-dinitrophenyl residue into tRNA-Phe from E. coli. The modified tRNA-Phe was isolated and by degradation of the molecule with RNase T2 and alkaline phosphatase the nucleoside derivative 6 was obtained and found to be identical with the synthetic product.


Oligo(dG)12-18 aggregates result in non-homogeneity of oligo(dG)12-18.poly(C) type primer-template. Studies on the absorption spectra of equimolar solutions of oligo(dG)12-18 and poly(C), poly(Cm) or poly(Ce) showed that only 13%, 3% and 3% of base pairs, repectively, form complexes. Upon centrifugation of oligo(dG)12-18 with a molar excess of poly(C) of poly(Cm) in an analytical and a preparative centrifuge, it was found that only a part of oligodeoxynucleotide sediments with the polynucleotide, i.e. more rapidly than oligo(dG)12-18, poly(C) or poly(Cm). Products of binding of oligo(dG)12-18 with poly(C), poly(Cm) or poly (Ce) direct the synthesis of poly (dG) by AMV reverse transcriptas in accordance with the reported characteristics of these primer-templates, as well as of the enzyme. These observations suggest that the solutions of oligo(dG)12-18 with (polyC) or its analogues, commonly used as primer-templates of RNA- and DNA-directed DNA polymerases, contain a polynucleotide, to which oligo(dG)12-18 aggregates are bound through a few nucleotides chains shorter than 12-18 residues. These chains of oligo(dG)12-18 containing the 3'-OH ends are capable of of initiating the reaction with DNA POLYMERASES.


A theory for the displacement of proteins and viruses with polyethylene glycol. The displacement action of polyethylene glycol of different molecular weights may be linked to the ability of the polymers to form coiled particles in solution. From conclusions drawn from their sedimentating properties in centrifugal fields the polyethylene glycols of low molecular weights, as expected, are less randomly coiled than those of higher molecular weight. It is suggested that protein molecules have the ability to diffuse into the coils of the polyethylene glycol from which they are excluded when the random coiling increases with increasing polymer concentration. From considerations based on the interaction of the polymer filament with the displaced particle the distribution of the substance between the coils and the intermolecular spaces may be predicted semi-quantitatively.


Fallibilities, fragments, and frames: contemplation on 25 years of research in medical--surgical nursing. A critique of articles on medical-surgical nursing which appeared in NURSING RESEARCH during the past 25 years discusses problems reflected in the reports and raises questions regarding the future of literature of the specialty field.


tRNATrp (bovine) binding to the reverse transcriptase of avian myeloblastosis virus and function as a heterologous primer. The primary structures for tTNATrp (bovine) and primer tRNATrp (avian) show only minor differences in nucleotide sequence. The heterologous tRNATrp (bovine) appears to have properties similar to the tRNATrp (avian) in its ability to bind the alphabeta from of RNA-dependent DNA nucleotidyltransferase of avian myeloblastosis virus. A stable enzyme-tRNA complex has been isolated by gel filtration. In addition, tRNATrp (bovine) can hydridize to the avian viral 35S RNA and act as a primer for transcription of the RNA. tRNATrp (bovine) can be obtained in larger amounts than the avian primer and can be used to study the interactions between the primer and the viral enzyme.


Terminal redundancy and the origin of replication of Rous sarcoma virus RNA. In vitro synthesis of Rous sarcoma virus DNA by the virion endogenous DNA polymerase activity is initiated on a tRNAtrp primer located near the 5' end of the genome. A major product of such synthesis is a piece of DNA 101 nucleotides long (strong stop DNA) which can be isolated covalently bound to the tRNA primer. Here we show that the strong stop DNA is complementary to the extreme 5' end of the genome. We also show that the 5' and 3' termini of the Rous sarcoma virus genome, excluding the cap and the poly(A), have the identical sequence. We propose that the function of this sequence is to facilitate elongation from the 3' end of DNA chains initiated elsewhere on the virus genome.


Binding to idiotypic determinants of large proportions of thymus-derived lymphocytes in idiotypically suppressed mice. All A/J mice immunized with a conjugate of p-azophenylarsonate groups to keyhole limpet hemocyanin produce antibodies against azophenylarsonate, some of which share a crossreactive idiotype. The appearance of the idiotype can be suppressed, without reducing the response against azophenylarsonate, by injecting rabbit anti-idiotypic antibodies prior to immunization. We have now observed that mice suppressed in this way, or by adoptive transfer of leukocytes from other suppressed mice, and then immunized with the hemocyanin-azophenylarsonate conjugate, possess high proportions (up to 14%) of lymphocytes that form rosettes with A/J erythrocytes coated with Fab fragments possessing the idiotype. Idiotypic specificity was demonstrated by various experiments. Most of all of the rosette-forming lymphocytes appear to be thymus-derived lymphocytes (T cells). Treatment of T cells with trypsin eliminated the capacity to form rosettes, which was restored on standing overnight in medium. Thus, the receptors are synthesized by the cells and are not passively adsorbed. Treatment of mice with anti-idiotypic antiserum without antigenic stimulation did not elicit substantial numbers of rosette-forming cells. The requirement for antigen suggests that antigen-idiotype complexes may be a stimulatory agent. A prolonged rest period after immunization of suppressed mice was required for the induction of high percentages of rosette-forming cells. Rosette formation provides a convenient method for studying factors that induce the formation of idiotype-specific T cells.


Nature of the antigenic complex recognized by T lymphocytes: specific sensitization by antigens associated with allogeneic macrophages. Alloreactive guinea pig thymus-derived (T) cells generated in vitro were rendered unresponsive to allogeneic macrophages by treatment with bromodeoxyuridine and light. The remaining T cells were subsequently primed and rechallenged in tissue culture with trinitrophenyl (Tnp)-modified syngeneic or allogeneic macrophages. By this procedure we found that the remaining T cells primed with Tnp-modified allogeneic macrophages could be restimulated only with Tnp-modified allogeneic, not syngeneic, macrophages. Similarily, if the remaining T cells were primed with Tnp-modified syngeneic macrophages, they could be restimulated only by Tnp-modified syngeneic, and not by allogeneic, macrophages. In contrast, no T cell sensitization with Tnp-modified syngeneic or allogeneic macrophages occurred if the alloreactive T cells were treated with light alone, suggesting that an uninhibited mixed leukocyte reaction causes nonspecific suppression of antigen-specific T cell priming. These results indicate that the genetic restriction of T cell-macrophage interactions is imposed by the type of macrophage used for initial sensitization rather than by a requirement for self-recognition through cellular interaction structures.


Antigenic relatedness of the DNA polymerase of human breast cancer particles to the enzyme of the Mason-Pfizer monkey virus. We have previously reported [(Ohno, T., Sweet, R.W., Hu, R., DeJak, D. & Spiegelman, S. (1977) Proc. Natl. Acad. Sci. USA 74, 764-768)] on the purification and characterization of the DNA polymerase from human breast cancer particles. Its preference for certain synthetic templates and its ability to use a viral RNA to fashion a faithful DNA transcript identify it as a reverse transcriptase similar to that found in the mouse mammary tumor virus and in the Mason-Pfizer monkey virus (MPMV). We report here that the human breast cancer enzyme crossreacts immunologically with the reverse transcriptase of MPMV. The crossreactivity was shown both by inhibition of enzyme activity and by complex formation between purified enzyme and isolated IgG against MPMV polymerase. No such interactions were observed with other oncornavirus reverse transcriptases of avian, murine, feline, or simian origin. Further, the IgG failed to neutralize the reverse transcriptases from human mesenchymal neoplasias (leukemias and lymphomas) or the activities of normal cellular DNA polymerases (alpha, beta, gamma).


[Surgery of therapy-resistant pain due to peripheral nerve injury]. 1. The forms of peripherally triggered or localized pains are differentiated: Local pain of a neuromatous character, propagated pain, sympathalgia, phantom pain, causalgia, and combined forms. 2. Surgical operations are performed locally, to the spinal cord, brain, and sympathicus, as well as by neurostimulation on all levels. 3. The areas of indication differ according to the localization of pain and its probable cause. 4. Serving the prevention of pain after peripheral nerve injuries are the particular topical treatment of a fresh injury, psychic guidance, specific aftercare and physiotherapy, elimination of pension payment problems, and optimum reintegration into normal working life]


Chemotherapy in testicular tumors.

Chemotherapy in testicular tumors. Surprisingly good clinical results are obtained by means of the so-called synchronized treatment with vincristine or bleomycin or adriamycin combined with Ifosfamid when cell-kinetic conditioning factors are taken into consideration. The results could neither be obtained with monotherapy nor by the aid of various combined therapies. Of 22 patients affected by metastasizing malignant testicular tumors a complete remission could be achieved in 14 continuing up to a period of 18 months. Six patients died. The answer to what extent these therapeutic results will be confirmed over a longer observation period, has, however, to be put off until a later date.


Palliative cryotherapy in inoperable prostate carcinoma. Cryotherapy was applied by us as a palliative in 91 cases of carcinoma of the prostate. 1. Disobstruction was achieved in 87% of patients. 2. Results proved stable over time. 3. Operating mortality, survival curve, number of deaths, etc. was not statistically different in patients treated with cryotherapy compared with patients undergoing other treatments. 4. Precutions are required to combat infection of cryotherapy patients in the first few weeks. We feel authorized to pursue cryotherapy in the future exploiting all its immunologic possibilities.


Reflex sympathetic dystrophy.

Reflex sympathetic dystrophy. This paper describes a patient with typical post-traumatic Sudeck's atrophy of the right foot, who subsequently developed an atraumatic, painful osteoporosis of the left foot and right knee. It is suggested that cases of 'migrating osteolysis' and 'transient osteoporosis' of the lower limbs be grouped with classical Sudeck's atrophy as a reflex sympathetic dystrophy; Theories of pathogenesis have been reviewed and a possible theory of causation in atraumatic cases is presented.


[Immunopathological circumstances in the structure of complications appearing after smallpox vaccination]. Investigations were carried out concerning the dynamics of antivaccinal antibodies and the structure of serum proteins in relation to the clinical manifestations following upon smallpox vaccination. In general, immunity is not apparently influenced by postvaccinal complications may be associated with immunoprotein perturbations, manifested by an increase in the alpha2-globulin fraction and, inconstantly, in the gamma-globulin fraction. Immunoelectrophoretic determinations revealed a relatively constant IgM and IgG deficiency. Postvaccinal dysglobulinemia may accompany various clinical forms, suggesting a temporary deficient immunological response. In one case of agammaglobulinemia, revaccination produced a deep vaccinal ulcer, with extensive necrosis (giant necrotic vaccinia). In order to decipher the substrate of the reaction in the clinical forms with distal manifestations or generalized vaccinia, skin biopsies were performed. The lesional vasculoallergic substrate of the skin lesions does not exclude the local aggression of the vaccinal virus, which was isolated by viral determinations.


Antigen recognition by T lymphocytes (status of the minimal hypothesis). Data of recent studies based upon three approaches to the problem of the T cell receptor for antigen, namely, use of "anti-receptor" (= anti-idiotype) antibodies, utilization of antisera made against circulating antibodies in association with physiochemical characterization procedures, and phylogenetic investigations, support the conclusion that this recognition molecule is an immunoglobulin, but that it represents as isotype distinct from usual circulating antibodies and B cell surface IgM- and IgD-like molecules.


Phosphatases and bone growth.

Phosphatases and bone growth. By mapping the distribution of resorptive and appositional surfaces in rat skull bones with the help of in vivo staining with alizarin red S. it has been possible to study the connection between patterns of bone growth and alkaline and acid phosphatase activity on bone surfaces. Alkaline phosphatase activity obviously bears no specific relation to appositional and resorptive surfaces as all surfaces react strongly. Acid phosphatase activity, in contrast, is most marked at sites of resorption.


Actual aspects of cold agglutination.

Actual aspects of cold agglutination. Cold agglutinins (CA) can be directed against antigens of the I/i system and the Pr complex. In addition, anti-Gd CA have been recently described. The CA immunoglobulins, serological specificities and the antigen immunochemistry are reviewed. CA permitted studies on interrelations between antibody structures and specificities. The significance of subgroup preferences and cross-idiotypic specificities is discussed. Interrelations between CA specificities and certain virus infections are pointed out, and recent results obtained from studies using CA as indicators for membrane alterations of other than red cells are reviewed.


Distribution of some hydrocarbons in ambient air near Delft and the influence on the formation of secondary air pollutants. The relative concentrations of hydrocarbons in the atmosphere may provide information concerning their origin. It appears that the hydrocarbon composition measured in Delft (The Netherlands) is entirely different for northern and southern wind directions. This points to different sources. The most important sources for this area are natural gas leaks, traffic, and (petrochemical) industries. It appears that the relative potential of the precursor mix to form peroxyacetylnitrate (PAN) and ozone is also different for both wind directions.


Immunological reactivity of peripheral lymphocytes in kidney transplant patients. The in vitro lymphocyte response to mitogens (PHA, PWM) and specific antigens (PPD, LPS, histocompatibility antigens), as well as their capacity to form spontaneous SRBC rosettes, was evaluated in 24 renal transplant patients; of these, 13 were studied both before and after kidney graft. The results of our tests, compared to the range of values obtained from healthy controls, show that continuous immunosuppressive therapy does not significantly depress the in vitro mitotic potentiality of lymphocytes in spite of greatly reduced levels of circulating T cells. The in vitro escape of lymphocytes from the action of immunosuppressive drugs frustrated the aim of calibrating the immunodepressive therapy for each patient. A better understanding of the immunosuppression in an individual will perhaps be obtained from a more prolonged observation of the in vitro lymphocyte reactivity in a larger number of patients.


Evaluation of 125I-DNA for detecting anti-DNA antibodies in the diagnosis of systemic lupus erythematosus. A 125I-DNA preparation for the detection of human anti-DNA antibodies (ADA) was evaluated as a diagnostic test for systemic lupus erythematosus (SLE). A normal range of 0-25 U/ml was established. Serum ADA level greater than 110 U/ml were diagnostic in clinically active SLE and levels greater than 45 U/ml were found in 75% of patients with inactive disease. This value was significantly greater than that found in rheumatoid arthritis, renal disease caused by non-immune mechanisms, post-streptococcal glomerulonephritis and a miscellaneous group of disorders comprising connective tissue diseases, auto-immune disorders and chronic active hepatitis. Anti-nuclear factor (ANF) titres greater than 1/160 and LE cells were found in 85% of these patients. In inactive disease the ADA levels ranged between 25 and 98 U/ml, ANF titres varied from 1/40 to 1/640, and LE cells were detected in only 20% of the cases. In 3 patients investigated during the course of the disease, the ADA levels correlated best with clinical improvement. Two patients with apparent active lupus nephritis showed intermediate ADA levels, which were probably caused by antigen-antibody formation and immune complex deposition in the kidneys.


Rheumatoid factor in non-rheumatoid black patients. A total of 301 Black patients without rheumatic diseases was studied to estimate the prevalence and causes of positive rheumatoid factor. The latex slide test was positive in 25% of patients and 21% had a 'diagnostic' titre of 80 or more. A significant relationship between gamma-globulin levels and rheumatoid factor positivity was demonstrated. IgG appeared to be the most important in determining this relationship. The most common ailments among sero-positive patients were cirrhosis and tuberculosis.


Fluorescence analysis of late DNA replication in human metaphase chromosomes. Thymidine incorporated as a terminal pulse into chromosomes otherwise substituted with 5-bromodeoxyuridine can be detected by associated bright 33258 Hoechst fluorescence. The location of metaphase chromosome regions identified by this method as last to complete DNA synthesis is consistent with the results of autoradiographic analyses with tritiated thymidine. The very late-replicating regions correspond to a subset of those which appear as bands after chromosomes are stained by quinacrine or modified Giemsa techniques. The high resolution of the 33258 Hoechst fluorescence pattern within individual cells is especially useful for revealing variations in the order of terminal replication. Both homolog asynchrony and fluctuations in the distribution of bright 33258 Hoechst fluorescence within chromosomes from different cells are apparent and localized to individual bands. The results are consistent with the possibility that these bands constitute units of chromosome replication as well as structure.


Gastric bypass of upper oesophageal carcinoma: a case report. A case is presented in which an oesophagogastric bypass was constructed in the neck for palliation of an unresectable carcinoma of the oesophagus at the level of the aortic arch.


Drusen of the optic disc.

Drusen of the optic disc. Although optic disc drusen have been of interest to ophthalmologists for more than 100 years, their etiology and many aspects of their relationship to other clinical conditions remain obscure. They have been clinically observed in 0.3% of the population, although autopsy studies suggest an incidence of 2%. Drusen are seldom accompanied by visual symptoms; however, decreased vision and visual field changes may occur. The historical and epidemiological aspects of drusen are reviewed; clinical and histological features, as well as special diagnostic techniques (ultrasonography and fluorescein angiography) are discussed in detail.


Preparation and antigenic properties of 5alpha-dihydrotestosterone-11-(O-carboxymethyl) oxime-BSA conjugate. The C-11 (O-carboxymethyl) oxime derivative of 5-alphadihydrotestosterone (5alphaDHT) has been prepared. Due to steric hindrance at C-11, a novel two step procedure was used to introduce the (O-carboxymethyl) oxime at this position. Condensation of this oxime to bovine serum albumin afforded a conjugate which produced anti-5alphaDHT sera inoculated rabbits. Apart from a 30% cross reaction with testosterone, the antisera was reasonably specific for 5alphaDHT.


Quantitative serological analysis of a rabbit anti-rat lymphocyte serum and preliminary biochemical characterisation of the major antigen recognised. Rabbit antisera to rat thoracic duct lymphocytes were examined by absorption analysis with quantitative radioimmunoassays to determine the tissue distribution of the antigens recognised and the amount of antibody against different specificities. Seven of eight sera were remarkably specific for leucocytes and one serum was analysed in detail. In this serum about 70 per cent of the antibody was leucocyte specific and most was against determinants on thymocytes, bone marrow cells, peripheral lymphocytes, and macrophages. This specificity is referred to as the leucocyte-common antigen. Smaller amounts of antibody were specific for antigens on peripheral lymphocytes but not thymocytes, and this could be subdivided into two antigens, one present on bone marrow cells and the other not. For preliminary biochemical analysis of the leucocyte-common antigen, thymocyte membrane was solubilized in deoxycholate. The homogeneity and apparent size of the antigen was determined by gel filtration and zone sedimentation on sucrose gradients. The activity behaved as a single component with the following hydrodynamic properties: sedimentation coefficient, 5.9S; partial specific volume, 0.71 ml/g; and Stokes radius, 7.5 nm. The molecular weight (including any bound deoxycholate) was calculated to be 172,000 and the frictional ratio 2.05. All activity bound to a lentil lectin affinity column and was eluted by methyl alpha-D-glucopyranoside, suggesting that the antigen is a glycoprotein.


Separate Ia-like determinants in human lymphocytes and macrophages. Some human alloantisera cytotoxic for B-lymphocyte preparations lost their reactivity when the number of contaminating monocytes was decreased by treatment with carbonyl iron. Such sera were found to react with the corresponding monocyte preparations isolated by adherence to Petri dishes. Macrophage antibodies were present in 38% of random sera from multiparous women and in 70% of sera from kidney transplant recipients. They could not be absorbed with B-lymphocyte preparations, thus suggesting that determinants expressed in macrophages were not present in B lymphocytes. Macrophages stimulate in mixed lymphocyte culture and participate in immune reactions. It is possible that alloantigens of macrophages, as observed in the present experiments, are products of genes associated with these histocompatibility-controlled functions.


Close association between Fc receptor and HLA-D-associated (Ia-like) determinants on human lymphoid cells. The inhibitory effect of HLA antisera on Fc receptors of human lymphoid FcRFC and K cells was investigated. Antisera recognizing determinants of the HLA-A, -B, and -C series had no effect on FcRFC, while specific inhibition was observed with an antiserum reacting with determinants closely associated to HLA-DW2. This inhibitory effect was also demonstrated by the Fab' fragments. Specific inhibition of K cells was observed with all HLA antisera, but this effect was lost in the Fab' fragments. We concluded that the Fc receptor of FcRFC may be closely associated with products of the HLA-D region. This is analogous to the association between the Fc receptor and the Ia antigens on murine splenic B lymphocytes.


HLA-D-locus determinants detected by sperm-lymphocyte culture. Twenty-seven sperm from 17 donors were tested against a random panel of sperm donors' lymphocytes and others and used to identify HTC-defined HLA-D determinants as well new SLC-defined determinants including DW Fes 5; the latter was confirmed as a new D-locus specificity by family studies.


Simplification of B-cell antisera of the Merrit system with platelets and lymphoblastoid cell lines. Human sera with anti-HLA and anti-Merrit B-cell reactivities were absorbed with different volumes of a pool of packed outdated human platelets obtained from 237 donors. After absorption, each serum was tested against a panel of CLL cells and normal unfractionated peripheral blood lymphocytes that had given positive reactions with the same serum prior to absorption. The optimal platelet volume for complete absorption of anti-HLA and full preservation of anti-Merrit B-cell activities in these sera was found to be 1/10 to 1/5 of the volume of serum. Higher volumes of packed platelets, especially over 1/1, in most instances reduced anti-B-cell activity "nonspecifically." Among the platelet absorbed sera, those showing no HLA and strong anti-Merrit B-cell cytotoxicity were used for cross-absorption studies with cultured human lymphoid cell lines. Multi-specific anti-Merrit sera could be simplified by this method. Cultured lymphoblastoid cell lines represent a valuable resource, since large volumes of cells may be needed for absorption and simplification of human sera containing allogeneic B-lymphocyte antibodies.


The role of B-lymphocyte antigens in MLC stimulation. A total of 950 MLC combinations were set up out of which 259 were classified as low MLC response. An attempt was made to predict which of the combinations would give low response by matching the B-lymphocyte specificities and the HLA-A and -B antigens. A statistically significant prediction of a low response was noted for the B-lymphocyte specificities as well as for HLA-A and -B antigens. The fraction of the low response, which was correctly found, was, however, greater with the B-cell specificities than the HLA-A and -B locus antigens. It is concluded that the B-lymphocyte specificities may be either identical or closely linked to the DW specificities. To what extent they are associated with the strong transplantation antigens of man remains to be determined.


HLA typing and primary cadaver graft survival. Analysis of 463 consecutive primary cadaver renal transplants showed no influence of HLA match grade on renal allograft survival. Additional categorization according to HLA match grade and degree of presensitization again showed no correlation between match grade and graft survival. Mismatches and matches of specific antigens, cross-reacting groups of antigens, and effect of matching at both locus A and B were also evaluated. There was no significant effect on graft survival except when mismatches against donor A2 and cross-reacting group A2, A28 occurred. A trend toward better graft survival was suggested in recipients matched for A9 and cross-reacting group A9, Aw 23, Aw 24. Although HLA match grade did not influence ultimate graft survival, HLA typing remains important, especially to avoid mismatch against donor A2 antigen. In addition, subsequent detection of new specificities, particularly in other than the A and B loci, may provide significance in the future.


Antigenic specificities detected on papainized human granulocytes by microgranulocytotoxicity. A reliable and routine identification of human granulocyte antigens is possible with an improved microgranulocytotoxicity assay. Freshly isolated, papainized granulocytes, an extended incubation period, and alcohol to prevent the adherence of cells are important factors enhancing cellular reactivity. Absorption studies indicate an absence of B-lymphocyte alloantigens on granulocytes. Five tentative granulocyte specificities were defined with granulocytotoxic non-HLA alloantisera. Sib-pair studies suggest the independent chromosomal segregation of the granulocyte and HLA antigen systems.


Allograft-infiltrating killer cells.

Allograft-infiltrating killer cells. The allograft is infiltrated by several classes of killer cells carrying the relevant idiotypic receptor for alloantigen and being specifically cytotoxic to cells carrying the graft antigens.


In vitro correlates of rejection. I. Suppressive effect and specificity in mixed lymphocyte interaction of alloantiserum producing hyperacute rejection. A hyperimmune antiserum from WfBN F1 hybrid rats primed to hyperacutely reject LBN F1 cardiac allografts has been studied. A large volume of antiserum will cause allograft rejection in less than 1 day. In the in vitro MLI, concentrations of this antiserum as low as 0.05% are markedly suppressive. This suppression is dose-dependent and immunizing-strain-specific at concentrations less than 1%. The suppressive activity is in the globulin fraction. After in vivo absorption, donor-strain specificity is clearly shown, with some cross-reactivity with third-party ACI strain. Moderate suppression of the rat MLI was seen with some normal rat sera, and augmentation of the MLI was seen in some experiments when very dilute concentrations of hyperimmune serum were used. Since suppression or augmentation of the MLI can occur as a function of antiserum dose and presumably antibody concentration, single measurements of MLI blocking factors may be misleading, and MLI suppression is not necessarily a correlate of allograft enhancement.


Suppression of specific MLC responsiveness during skin allograft rejection in rats. During the effector phase of allograft rejection a specific MLC unresponsiveness of PBL has been observed in skin-grafted rats. This unresponsiveness is caused by a suppressive effect that is dependent on a cooperative interaction between macrophages and alloantigen-activated T cells. The interaction is mediated by a soluble factor released from the alloantigen-activated T cells on exposure to the specific antigen. The suppression itself is nonspecific.


[Effect of various antimicrotubular drugs on the osmotic water flow through the wall of frog's urinary bladder]. The action of antimicrotubular drugs (colchicine, vinblastine and copper) on the osmotic water flow through the wall of the urinary bladder of Rana temporaria has been studied. The osmotic gradient was made by five- or tenfold dilution of the internal Ringer solution. The water flow was estimated gravimetrically. The water flow was induced by pituitrin (50 milliunits/ml), cyclic AMP (cAMP, 0.5-10(-3) M) and nystatine (3.5-10(-5) M). Pituitrin and cAMP and all the antimicrotubular drugs were added from the serosal surface of the bladder. Nystatine was introduced with the help of a fixed polyethylene tube. Preincubation with colchicine lasted 4 hours and that with vinblastine and copper (CuSO4), 1 hour. The drug concentrations varied between 10(-5)--10(-4) M. All the drugs studied showed a significant inhibitory effect toward pituitrin. The action of cAMP on the water flow was seen inhibited in the presence of colchicine and copper. The nystatine induced water flow was supressed by copper, colchicine being in this case inactive. A conclusion is drawn that the inhibition of cAMP formation does not cause a decreased pituitrine effect in the presence of antimicrotubular drugs. It has been assumed that the microtubules may be involved in the directed water flow within the cell.


[C- and Q-chromatin of the experimentally condensed human interphase chromosomes]. Condensed interphase chromosomes of the cultured human lymphocytes obtained by the fusion of interphase and metaphase cells were studied using C- and Q-bands techniques. The appearance and localization of the constitutive heterochromatin blocks on condensed chromosomes at G1-period were the same as on the metaphase ones. These characters were used for a group and individual identification of some chromosomes condensed at G1-period and for a study of the association of the constitutive heterochromatin blocks in the interphase nuclei. The fluorescent analysis of the chromosomes condensed at G1-period detected some bright fluorescent blocks of the constitutive heterochromatin.


[Cytospectrophotometric analysis of various color reactions for acid and basis proteins in nerve tissue cells]. Polyvinyl formal films soaked with various concentrations of proteins as well as Carnoy-fixed paraffin sections of rat brain were stained with various colour reactions for acidic and basic proteins. Sufficient specificity, reproductivity, sensitivity and applicability for cytospectrophotometric determinations have been shown for the staining of acidic proteins with Toluidine blue 0 (pH 9.0) or with Fast green FCF (pH 2.6), and for the staining of basic proteins with Alcian blue (pH 10.0), or with Fast green FCF (pH 8.2). Importance of cytophotometric analysis of individual protein fractions is outlined for the functional cytochemistry of the nervous system.


Cross-resistance in M. tuberculosis to kanamycin, capreomycin and viomycin. Drug resistant mutants to streptomycin, kanamycin, viomycin, capreomycin, and rifampicin were isolated from four strains of Mycobacterium tuberculosis. The mutants isolated from each parent were then tested for evidence of development of cross-resistance to other drugs. There was no cross-resistance between either streptomycin or rifampicin and any of the other drugs. Complete cross-resistance between viomycin and capreomycin was found. Cross-resistance between kanamycin and capreomycin, and kanamycin and viomycin was variable. A review of the medical histories of 27 patients with kanamycin-resistant tubercle bacilli indicated that cross-resistance with capreomycin and viomycin occurs, but is unpredictable. Because of this variability in cross-resistance and the fact that kanamycin is a more toxic drug than capreomycin, it is suggested that capreomycin be used in the first retreatment regimen for tuberculosis when streptomycin resistance has been demonstrated.


[Ability of blood protein, typical of normal growth, to activate glycolysis and inhibit the Pasteur reaction]. Formation of lactic acid by the extracts from the healthy rabbit muscles was studied as affected by the sera of embryos, newborn rabbits and pregnant female rabbits. The blood sera and beta-globulin isolated from them are established to activate anaerobic glycolysis and inhibit the Pasteur reaction. It is shown that protein typical of normal growth, belonging to beta-globulins and circulating in blood of the embryos, newborn rabbits from the first to the fifteenth day of development is "responsible" for this phenomena. Correlation is found between the precipitation test for detecting this protein and its biological effect on glycolysis and the Pasteur reaction.


[Distribution of antibodies to DNA in the tissues of rats with sarcoma-45]. Distribution of a label was studied in nuclear fraction and in tissues of rats with transplanted sarcoma 45 within a day after an administration of immune and nonimmune 131I-gamma-globulins. When gamma-globulins, containing antibodies to one-stranded DNA, were administered the more intensive accumulation of the label was observed in nuclei of malignant tissue as compared with other tissues (liver, heart, thymus and muscles). The diffuse distribution of the label was found if nonimmune gamma-globulins were used. The phenomenon was apparently related to the active penetration of labelled antibodies to the replicating matrix and binding of them with one-stranded DNA sites. The suggestion is discussed that the effect of accumulation of immune gamma-globulin in proliferating tissue might be used for depression of the proliferative process.


[Use of synthetic steroids, inhibitors of microsomal enzymes, for retention of hexenal in the body and for prolongation of hexenal anesthesia under experimental conditions]. 17alpha-hydroxydeoxycorticosterone and its acetate derivative inhibited the activity of rat liver microsomal enzymes. The inhibitory effect of steroids was not accompanied by induction of the enzyme synthesis, which was characteristic for the other known inhibitors of mixed function oxydases (SKF 525-A, DPEA, MPDK). These properties of the steroids suggested their use for prolongation of the effect of drugs, which are inactivated by microsomal enzymes. The suggestion was tested using hexobarbital as an example. The transformation of hexobarbital in vitro by the rat liver microsomal enzymes was completely inhibited by the equimolar amount of the steroid acetate. Treatment of rats with the steroid acetate almost doubled the life-time of the hexobarbital in rat blood and resulted in the 1.5-fold increase of the sleeping time. The most effective dose of the steroid acetate was 5 mg per 100 g of body weight, the drug being injected 15 min before hexobarbital administration.


[Clinical significance and problems of technique in the immunochemical determination of the third complement component C 3 (beta 1 C/beta 1 A protein) (author's transl)]. Immunochemical determination of the third complement (C) component C 3 as beta 1 C/beta 1 A protein has found extensive use in the clinical evaluation of immunopathological conditions. C 3 changes are associated with inborn C defects and acquired diseases. In the latter case, diminished C3 levels are of the greatest practical relevance. Reduced C 3 values are not necessarily due to "classical" antibody-mediated C activation, as in immune-complex diseases, but may be caused also by "alternative" pathway activation and decreased C 3 synthesis. In addition, important technique factors have to be considered in the evaluation of immunochemically-determined C 3 values. Since the antigenic pattern of C 3 changes during in vitro ageing, not only the state of conversion of C 3 in the sample and in the reference serum (standard), but above all, the specificity of the anti-C 3-serum plays an important role in critically influencing the total error of the method. In order to avoid this error C 3 can be determined as beta 1 C protein using a beta 1 C standard which is, however, not easily available. On the other hand, beta 1 A quantitation causes less problems since standard sera usually contain C 3 as beta 1 A portein. However, an incubation period of 7 days at + 37 degrees C is necessary for complete C 3 conversion. This undesirable time delay has not yet been satisfactorily overcome by in vitro acceleration of C 3 conversion using different substances.


[Disorders of blood coagulatiion during haemoperfusion (author's transl)]. Charcoal haemoperfusion of patient may cause a fall in thrombocyte and fibrinogen levels. The possible cause of these changes in haemostasis was investigated by means of five haemoperfusion devices which were filled with 2000 ml ACD fresh blood and perfused for three hours. A continous reduction in the thrombocytes and the plasma coagulation proteins resulted, while the ethanol test and the level of fibrin degradation products stayed within normal levels. These results indicate the adsorption of thrombocytes and protein on to the surface of the charcoal haemoperfusion device. An activation of the coagulation system (i. e. disseminated intravasal coagulation, fibrinolysis) appears unlikely.


[Effect of proteolytic enzymes on the antitrypsin activity of blood serum in the postoperative period]. An antitryptic activity and effect of trypsin and chymotrypsin, administered parenterally, on the activity were studied in blood serum of patients, subjected to surgical operations. The antitryptic activity and content of alpha1- and alpha2-globulins were shown to increase in blood serum of patients within 5 days of the postoperative period. Intramuscular administration of the proteolytic enzymes within 5 days decreased the anti-tryptic activity and content of alpha1- and alpha2-globulins in blood serum.


[Recurrent herpes simplex. The situation in the United States]. At present, there is no drug marketed in the United States for the treatment of herpes simplex, except for idoxuridine for the treatment of herpetic keratitis. The recent enthusiasm for the use of heterocyclice fluorescent dyes in conjunction with exposure to light (photodynamic inactivation) has diminished, and the efficacy of all available topical measures is being questioned. Of the numerous antiviral drugs being investigated, the following seem to show promise: idoxuridine, adenin arabinoside, trifluorothymidine, phosphonoacetic acid, and ribavirin. There are no vaccines available. Measures to stimulate immune response concern the use of levamisole hydrochloride, Interferon, Inosiplex and Transfer factor. Only adenine arabinoside will be available in the near future, and then only to serious life threatening infections. The marketing of other medications is several years in the future.