Genetic subtypes of unipolar primary depressive illness distinguished by hypothalamic-pituitary-adrenal axis activity. Serum-cortisol response to the 1 mg overnight dexamethasone suppression test was investigated in 86 patients with unipolar primary depressive illness and 80 non-depressed controls (45 with mania and 35 with schizophrenia). The depressed patients were assigned to one of three genetic subtypes according to the family psychiatric history. Resistance to suppression of serum-cortisol by dexamethasone was found in 37 of 86 (43%) depressives and none of the 80 controls. Non-suppression distinguished the three genetic subtypes of depression, being found in 23 of 28 (82%) patients with familial pure depressive disease (F.P.D.D.), 13 of 35 (37%) patients with sporadic depressive disease (S.D.D.), and 1 of 23 (4%) patients with depression spectrum disease (D.S.D.). The three genetic subtypes were further distinguished by the age of onset, with S.D.D. the oldest, and by the number of previous depressive episodes, with F.P.D.D. the most. Severity of depression did not separate the three subtypes. This is the first report of a distinct neuroendocrine abnormality which supports an objectively defined classification of unipolar primary depressive illness. It is suggested that unipolar primary depressive illness is three or more separate illnesses, each with a potentially distinctive mode of inheritance, pathophysiology, neurochemistry, clinical course, and treatment response.


Prevention of early recurrence of spontaneous subarachnoid haemorrhage by epsilon-aminocaproic acid. A controlled clinical trial of epsilon-aminocaproic acid (E.A.C.A.), 36 g/day, was undertaken to assess its effectiveness in reducing immediate recurrence in patients with spontaneous subarachnoid haemorrhage (S.A.H.) proved by lumbar puncture. Of 83 patients treated with E.A.C.A., 3 (4%) had recurrent haemorrhage, and 1 (33%) of these died. Of 82 control patients who were not given any antifibrinolytic drug, 22 (26%) had recurrent haemorrhage, and 10 (45%) of these patients died. E.A.C.A. produced a striking reduction in the early recurrence of S.A.H. No serious side-effect resulted.


Oral-contraceptive use in relation to myocardial infarction. The effect of oral-contraceptive use on the risk of myocardial infarction and, in particular, the possible accentuation of that effect by cigarette smoking, was investigated in 234 premenopausal women with a first infarction and 1742 hospital controls. The overall rate ratio estimate of acute myocardial infarction for women who had used oral contraceptives in the preceding month was 4.0 (95% confidence interval, 2.5--6.3). Women who smoked heavily and used oral contraceptives had a point estimate of 39 (lower two-sided 95% confidence limit, 22) compared with those who did neither. This value was appreciably larger than could be accounted for by the separate effects of cigarettes and oral contraceptives, and this suggests a considerable accentuation by cigarette smoking of the effect of oral contraceptive use on myocardial infarction.


Impaired hypothalamic control of prolactin secretion in massive obesity. Intravenous insulin tolerance tests and thyrotropin-releasing hormone (T.R.H.) stimulation tests were performed in nine massively obese women and six lean female controls and the prolactin, growth hormone, and cortisol responses were measured. A combined pituitary function test (insulin, T.R.H., and gonadotropin-releasing hormone) was performed in eleven other massively obese women. In the obese women to whom insulin was given separately there was no prolactin release, and growth hormone and cortisol responses were impaired. T.R.H. stimulation produced a prolactin response which was subnormal. These changes were not apparent in the obese women in whom a combined pituitary function test was performed. The results suggest an alteration of hypothalamic function in massive obesity.


Isolation of Legionella pneumophila from blood. Legionella pneumophila has been isolated, with an in-vitro method, from the blood of a patient with fatal legionnaires' disease.


Internal fistula as a route of infection in acute suppurative thyroiditis. Seven cases of acute suppurative thyroiditis are described. Six patients had a recurrent painful swelling of the left anterior neck and one was seen at her first episode of the disease. A barium meal revealed a fistula originating from the apex of the left pyriform sinus in all cases. The fistula, a remnant of the fourth pharyngeal pouch, thus seems to be a common route of infection in acute suppurative thyroiditis, allowing bacterial infection to begin in the perithyroidal space and spread to the thyroid gland. Complete extirpation of the fistula is required for a permanent cure.


Dietary cholesterol is co-carcinogenic for human colon cancer. Colorectal carcinoma is becoming the most common form of visceral cancer in Western populations. A fat-related dietary factor is implicated in its pathogenesis, and evidence in man suggests that this factor may be cholesterol. Dietary cholesterol is co-carcinogenic in animals with colon cancer, and there is indirect evidence for a similar role in man. It is proposed that prolonged exposure to dietary cholesterol is co-carcinogenic for human colon cancer in that it facilitates the development, growth, and spread of this disease.


Relation between aflatoxin, hepatitis-B virus, and hepatocellular carcinoma. A new role is postulated for aflatoxin in the production of hepatocellular carcinoma. Rather than acting as a primary carcinogen, as it seems to do in animals, it is suggested that aflatoxin suppresses cell-mediated immunity. This effect on the immune system would allow the hepatitis-B virus, highly endemic in certain populations, to maintain itself more easily in the liver, to produce more chronic infection and cirrhosis, and in the long term to lead to a high incidence of hepatocellular carcinoma.


Role of carotid-body chemoreceptors and their reflex interactions in bradycardia and cardiac arrest. Stimulation of the carotid-body chemo-receptors by asphyxia during an apnoeic episode may contribute to the vagally mediated cardiac arrest and sudden death that sometimes occurs in man. Apnoeic asphyxia may be induced centrally or reflexly by stimulation of upper airways receptors. Conditions associated with apnoeic asphyxia and in which the risk is likely to be greatest include intubation, laryngoscopy and bronchoscopy; accidents involving underwater swimming; inhalation of sympathomimetic amines in aerosols by asthmatic patients; and chronic hypoventilation syndromes. These reflexes may be responsible for some victims of sudden infant death syndrome. Stimulation of the carotid bodies normally produces hyperventilation and bradycardia. When apnoea occurs centrally or reflexly, carotid chemoreceptor excitation resulting from asphyxia now causes a much enhanced bradycardia and even cardiac arrest, but paradoxically does not usually affect respiration. These reflexes and their interactions normally serve protective and purposeful functions, but may under certain circumstances become exaggerated and put the patient's life at risk.


Legionnaires' disease in a prepaid medical-care group in Seattle 1963--75. The community incidence of legionnaires' disease (L.D.) was estimated by a retrospective study of stored paired sera from 500 patients treated for pneumonia in Seattle in 1963--75. The patients were all members of a prepaid medical-care group; 84% were treated as outpatients. Only 5 (1%) had a fourfold rise in antibody titre to the L.D. antigen. Seroconversion to influenza A virus also occurred in 3 of the 5 cases. The course of illness in 4 of the 5 patients with confirmed infection was milder than that previously reported with legionnaires' disease. In addition, 1 child had a fourfold fall in titre, and 23 patients had titres of greater than or equal to 256 without significant change in titre. Only 8 of the 23 had their first serum collected later than 2 weeks after onset of illness, which suggests that the majority had acquired their antibodies before their attack of pneumonia. Prevalence of antibody in the 500 patients was not affected by age, sex, or year in which illness occurred. The incidence of legionnaires' disease based on 5 patients with rises in titre was estimated to be 0.4--2.8/10 000 persons/year.


Gradual reintroduction of full-strength milk after acute gastroenteritis in children. 46 children (26 boys and 20 girls) admitted with mild acute gastroenteritis were randomly allocated to a regimen of continuing on full-strength milk, or to one of taking clear fluids until the diarrhoea settled before full-strength milk was reintroduced either immediately, or gradually in quarter-strength steps. There was no difference in length of hospital stay between the three groups.


Association between hepatobiliary cancer and typhoid carrier state. A case-control study of deceased typhoid carriers registered by the New York City Health Department between 1922 and 1975 was carried out to test for an association between the typhoid-carrier state and death due to hepatobiliary cancer. 471 carriers were matched with 942 controls for sex, age at death, year of death, borough in which the carrier died, and where they were born. The results show that chronic typhoid carriers die of hepatobiliary cancer six times more often than the matched controls and that this difference is significant (P less than 0.001) by simple chi2 test and by the Mantel-Haenszel method of chi2 for matched triples. Possible mechanisms for this association are discussed.


Identification of gallbladder typhoid carriers by a string device. The efficiency of a gelatin capsule containing a nylon string for collection of duodenal specimens was investigated in carriers of Salmonella typhosa (typhi). Cultures of duodenal specimens obtained by means of the string capsule were compared with cultures of duodenal specimens obtained by a conventional duodenal tube and with stool cultures Duodenal contents obtained with either the string or tube were more often positive for S. typhosa than were stool cultures. The string, which is as efficient as tube collection but simpler and more comfortable, may be useful in identifying carriers of S. typhosa.


HLA-A,B compatibility in parents of offspring with neural-tube defects or couples experiencing involuntary fetal wastage. To test the contribution of a putative human analogue of the murine T locus to neural-tube defects (N.T.D.) and involuntary fetal wastage, HLA-A, B compatibility between husband and wife was studied in a group of 77 couples with known obstetric histories. The frequency of sharing of HLA-A,B antigens was significantly higher in 13 couples with recurrent fetal loss at one gestational age and in 11 couples whose offspring had had a lethal N.T.D. than in 17 couples with three or more normal pregnancies. The extent of HLA compatibility--that is, the number of antigens shared by husbands and wives--was significantly higher in 16 couples with one spontaneous abortion, 23 couples with recurrent spontaneous abortions, and 21 couples with N.T.D. offspring than in controls. These data are consistent with a contribution of a locus in or near the HLA complex to N.T.D. and involuntary fetal wastage.


Treatment of Paget's disease with (3-amino-1-hydroxypropylidene)-1, 1-bisphosphonate (A.P.D.). 18 patients with Paget's disease were treated orally with (3-amino-1-hydroxypropylidene)-1, 1-bisphosphonate (A.P.D.). In most cases bone resorption became normal within a week of treatment, whereas the return to normal bone formation took 3-6 months; this difference produced a transient imbalance between resorption and formation. In biopsy specimens taken during treatment the numbers of osteoclasts and osteoblasts decreased towards normal and excess osteoid disappeared.


Inhibition of osteolytic bone lesions by (3-amino-1-hydroxypropylidene)-1, 1-bisphosphonate (A.P.D.). 14 patients with osteolytic bone disease due to breast cancer or myeloma, 7 of whom had hypercalcaemia, received oral treatment with (3-amino-1-hydroxypropylidene)-1, 1-bisphosphonate (A.P.D.). Serum-calcium dropped to low normal values in all 14 patients, accompanied by a decrease in urine calcium and hydroxyproline excretion-rate. The results show that A.P.D. may inhibit tumour-induced osteolysis.


Urinary beta 2 microglobulin in upper and lower urinary-tract infections. Beta 2-- microglobulin excretion in 24 h urine collections and beta2- microglobulin clearance were significantly increased in patients with upper-urinary-tract infections, but beta 2- microglobulin clearance and excretion were normal in patients with cystitis. Beta 2-microglobulin estimation may be used to distinguish between upper and lower urinary-tract infections, except when pre-existing tubular damage is present. Voided urine must have a pH above 6 . 0, since beta 2- microglobulin is rapidly degraded in the bladder at low pH.


Minimum effective dose of intermediate factor-VIII concentrate in haemophiliacs on home therapy. The minimum effective dose of intermediate factor-VIII concentrate required for the successful home treatment of spontaneous joint bleeds in six haemophiliacs has been investigated in a randomised trial. 207 episodes of bleeding were included. 5 . 7 units/kg controlled 85% of bleeds, but with a dose of 3 .0 units/kg the risk of failure doubled. This lower dose is inadequate for treatment of bleeds other than those regarded subjectively by the patient as mild. The implications of these findings in terms of availability and usage of factor VIII in this centre are discussed.


Possible virus in schizophrenia and some neurological disorders. Cerebrospinal fluid from 13 of 38 patients with schizophrenia had a cytopathic effect in cultures of MRC5 cells. The cytopathic agent passed a 100 nm but not a 50 nm filter and was unaffected by heat at 56 degrees C for 30 min, treatment with chloroform, or the presence in cultures of bromodeoxyuridine. The agent could not be propagated serially in a satisfactory manner but its properties were those of a virus. A similar cytopathic effect was induced by cerebrospinal fluid from 8 of 11 patients with serious or chronic nervous system disease but only 1 of 25 patients with surgical or general medical conditions.


Characteristics of patients with schizophrenia or neurological disorder and virus-like agent in cerebrospinal fluid. A virus-like agent (V.L.A.) with a cytopathic effect on cultured cells was found in the cerebrospinal fluid of 18 of 47 patients with schizophrenia, of whom 10 had nuclear schizophrenic symptoms. In most patients with V.L.A., blood and C.S.F. protein concentrations were normal. Patients with and without V.L.A. had similar clinical characteristics but serum IgA levels were higher in those with V.L.A. V.L.A. was also detected in the C.S.F. of 8 of 11 patients with serious or chronic neurological disease (Huntington's chorea, multiple sclerosis, and unexplained alterations of consciousness).


Evidence of cadmium toxicity in a population living in a zinc-mining area. Pilot survey of Shipham residents. 22 of 31 residents of a Somerset village where soil levels of cadmium were high had raised blood-cadmium levels, and some had clinical and biochemical findings (including hypertension and biochemical evidence of renal tubular damage) indicating toxic effects which could be attributed to the metal. It is suggested that more detailed studies should be carried out as a matter of urgency and that advice on avoiding local garden produce and not smoking should be emphasised. Probably more serious, however, is the summation effect with industrial exposure.


Antenatal diagnosis of Duchenne muscular dystrophy. As a means of assessing the value of fetal serum-creatine-kinase (S.C.K.) levels in the antenatal diagnosis of Duchenne muscular dystrophy (D.M.D.), fetal muscle from control and at-risk fetuses was studied histologically and the findings were related to fetal S.C.K. levels. Of 7 at-risk fetuses 4 were believed to have normal muscle and all these had normal S.C.K. levels. However, of 3 fetuses with abnormal muscle only 1 had a raised S.C.K. level. At present caution should be exercised in offering antenatal diagnosis in D.M.D. on the basis of fetal S.C.K. levels.


A rapid technique for distinguishing herpes-simplex virus type 1 from type 2 by restriction-enzyme technology. A rapid simplified technique, based on restriction-endonuclease analysis of radioactively labelled D.N.A. is described; it distinguishes herpes-simplex virus type 1 strains from herpes-simplex virus type 2 unambiguously. Large numbers of isolates can be screened in 4--5 days.


Tuberculous peritonitis and role of diagnostic laparoscopy. Eleven patients with tuberculous peritonitis were treated in a London hospital between 1971 and 1978. All the patients were immigrants (mean age 30 years). The history of abdominal symptoms was often short and sometimes difficult to distinguish from that of Crohn's disease or neoplasm. The diagnosis was made by laparoscopy and target peritoneal biopsy in eight of these patients. Laparoscopy is a safe and effective method of obtaining an early diagnosis in patients with suspected tuberculous peritonitis.


Relation of reduction in pressure to first myocardial infarction in patients receiving treatment for severe hypertension. In order to examine the widely held belief that the aim of antihypertensive therapy should be to restore "normality," the relative risk of myocardial infarction and sudden death was related to the extent of pressure reduction in a survey of 169 patients with uncomplicated essential hypertension followed-up under treatment over a mean period of 6.25 years. Apart from the effects of the hypotensive agents, there were no statistically significant differences in coronary heart-disease (C.H.D.) risk factors between the patients who had and those who did not have an infarction. Overall average values for final diastolic pressure (F.D.P.), as last recorded before the end of the study, were almost the same in the two groups. But the relative risk of myocardial infarction in the patients with F.D.P. reduced to less than 90 mm Hg was more than five times that in the patients with F.D.P. 100--109 mm Hg (P less than 0.01), while in those who had developed infarcts with F.D.P.S of less then or equal to 90 mmHg the pressure falls were all markedly greater than in unaffected controls matched for C.H.D. risk factors that included form of treatment, age, sex, and established pre-treatment diastolic pressure (E.D.P.). Thus it would seem that, in severe middle-aged hypertensives, attempts at "normalisation" of high blood-pressure may precipitate as many infarctions as it prevents. Other cardiovascular complications did not exceed the incidence expected during treatment. The findings suggest that the blood-pressure in such patients should seldom be reduced by more than 22% or to diastolic levels less than 104--110 mm Hg.


Simple and effective measures for control of enteric cross-infection in a children's hospital. This report shows how simple measures have reduced the rate of enteric cross-infection from 61 cases a year to close to zero in an old and architecturally unsatisfactory children's hospital.


Cytochemical specificity of acridine red towards RNA and depolymerised DNA. The paper contains an account of the use of the basic dye, acridine red, of the xanthene group, for staining RNA and depolymerised DNA. The in situ absorption curve of nuclei stained with acridine red indicates a peak of maximum absorption at 560 nm, whereas in vitro absorption characteristics of an aqueous solution of the dye indicate the peak at 550nm. The possibility of using acridine red as a substitute for pyronin, when staining is required for RNA only or in methyl green-acridine red sequence for localising DNA and RNA has been discussed.


Modified Feulgen staining of DNA with aqueous solution of pinacyanol. The paper reports on the use of a quinoline dye, pinacyanol, towards staining of acid hydrolysed DNA. The dye as an aqueous solution can be used after treatment of mammalian tissue sections in concentrated phosphoric acid at 5 degrees C for 20 min followed by hydrolysis in 6N HCl at room temperature for 15 min, for staining DNA-aldehyde molecules. It has also been observed that staining of DNA-phosphate groups is also possible in sections treated with cold concentrated phosphoric acid after selective extraction of RNA. Both in situ absorption characteristics of stained nuclei as well as in vitro absorption data of an aqueous solution of the dye have been presented. It has been suggested that staining DNA-aldehydes with pinacyanol, without any primary amino group in its molecules is due to a modified Feulgen reaction.


[Methodical investigations for quantitative image analysis on cells of the female genital tract (author's transl)]. An earlier published [8] image analysis system for cytology is tested on gynecological material. At first the question for the staining method which is optimal for scanning-photometrical measurements is investigated. In addition the wavelength of the light which reproduces best the nuclear structure must be found. Feulgen-stained preparations scanned at 570nm allow a more secure sorting of superficial cells against intermediary cells than those in the classical Papanicolaou-stain at white light. Discoloring of Papanicolaou-preparations and Feulgen staining afterwards was accomplished without technical problems and there were not detectable any qualitative differences with directly Feulgen-stained preparations by means of image analysis. With this method it is possible to recognize structural changes in nuclei of vaginal epithelium during cell differentation.


Are audiotapes cheaper than lectures?

Are audiotapes cheaper than lectures? First year pre-clinical medical students were taught about blood grouping and haemostasis using four audiotapes and associated booklets as the sole method of formal instruction. The audiotapes were readily accepted by the great majority of students as a replacement for lectures and those who listened to the tapes scored significantly higher in a multiple choice test 10 months later than did a previous years's student who had covered the same topics by means of lectures. If booklets are provided for each student, tapes are more expensive than lectures in terms of the time and running costs involved. By contrast, if booklets are sold or made available on loan with the audiotapes, then costs become equivalent when tapes are distributed to four to six average-sized medical schools and become increasingly cheaper as the number distributed increases. Other less readily quantifiable benefits of audiotape learning are discussed and it is concluded that in terms of both costs and effectiveness of learning, audiotapes can usefully replace a proportion of lectures in a conventional course. Consideration should be given to the provision of more space for audiotape tuition and less for formal lectures.


[Clinical results with granulocyte transfusion (author's transl)]. 16 adult patients with granulocytopenia and septicemia resistant to antibiotics received 42 granulocyte transfusions. The granulocytes were obtained from healthy donors with a blood cell separator by continuous flow centrifugation. Adding hydroxyethyl-starch an average of 1.8 X 10(10) leukocytes with 69% granulocytes were harvested in 3.5 hours. A small leukocyte increment after the transfusion was seen in half of the recipients. No correlation could be found between fever lysis and survival of the infection, which occurred in half of the cases too. A granulocyte transfusion is indicated in patients, who have granulocytopenia, sepsis and no evidence of bone marrow recovery.


Demonstration of HLA restricted killer cells in patients with acute measles. The relationship between HLA determinants on effector and target cells and cell-mediated cytotoxicity was studied using the release of 51Cr from measles virus-infected PHA-blasts. HLA compatibility between effector and target cells was not required if effector lymphocytes were derived from measles seropositive adults, from a patient with SSPE, and from children after live measles vaccination. Cytotoxicity was always abolished after removal of Fc receptor-bearing lymphoid cells. In these donors, the effect is, therefore, probably due to K cells. In contrast, lymphocytes from children with acute measles preferentially killed those virus-infected target cells with which they shared HLA antigens. Selective lytic activity was still observed after elimination of Fc receptor-bearing lymphoid cells. It is suggested that HLA-dependent killer cells represent specific cytotoxic T lymphocytes. These cells seem to be limited to the acute phase of measles.


[Staining of the X chromatin].

[Staining of the X chromatin]. A staining method suitable for the selective demonstration of X-chromation and other types of chromatins is described. On the basis of the behaviour of chromations four types of cells (in males only two) can be distinguished. From the changes of the proportion various types of cells, conclusions can be drawn concerning the alteratins of cell kinetics. These changes raise the question of the existence of a general basical biological rhythm. The duration of a cycle in this rhythm is 73 days. These cycles considerably modify the course of different diseases and the efficacy of the therapy applied. Thus the investigation of the chromatin is a useful tool for the prognosis and the therapy. The chronic myeloid leukaemia was detaily analyzed. Practical importance of the data obtained seems to be obvious.


Genetic toxicology of bleomycin.

Genetic toxicology of bleomycin. Bleomycin (BLM), an antibiotic obtained from Streptomyces verticillus, is of significance as an antineoplastic agent. The compound is actually the mixture of some 200 related forms which differ from each other in the amine moiety. The drug, at low concentrations, can cause elimination of bases, particularly thymine. This causes strand breakage of DNA and inhibition of cell growth. The influence of BLM on cell growth may be unrelated to the effects on DNA. In general, mitotically dividing cells show more DNA damage than non-dividing cells. G2 seems to be the most sensitive phase indicating that cell death may not be related to a direct effect of BLM on DNA replication. The antibiotic shows specific effects on chromatin and causes chromosomal damage in all sub-phases of interphase. It can affect early prophase chromosomes also. Suggestion has been made that BLM-induced breakage and cell death are similar to those induced by densely ionizing radiations. Whereas the antibiotic affects the frequency of somatic crossing over and produces micronuclei, the data on mutation induction and production of sister-chromatid exchanges do not permit classifying BLM as a potent inducer of these phenomena. The genetic effects of BLM can be modified quantitatively by thiol compounds, caffeine, hyperthermia and H2O2. It is concluded that the available data do not permit assessment of genetic damage in the offsprings of BLM-treated patients. Such studies are urgently needed, as are the studies to find out the effects of BLM on meiotic phenomena.


Ineffectiveness of topical adenine arabinoside 5'-monophosphate in the treatment of recurrent herpes simplex labialis. The ability of topical 10 per cent adenine arabinoside 5'-monophosphate to decrease the severity and frequency of recurrent herpes simplex labialis was evaluated in a double-blind, randomized study of 233 patients at three collaborating institutions. Nine clinical and four virologic measurements were used to evaluate drug efficacy during a single episode. No statistically significant improvement in any measurement was seen in the drug-treated patients. Analyses according to institution and age, stage and size of lesion before therapy also indicated no benefit attributable to the drug. There was no effect of the drug on the rate of recurrence of herpes simplex labialis. We conclude that, despite activity against herpes simplex virus infection in tissue culture and in some laboratory animal models, topical use of the drug is ineffective against recurrent herpes simplex labialis. This may be due to failure of the drug to penetrate the skin.


[Perichordal necroses. Contribution to the understanding of the spinal column morphogenesis]. In 12--15 days old rat embryos and 12 days old mouse embryos vitally stained by acridin orange, a perichordal necrosis appears, showing metameric intensifications at the level of the dense sclerotomites. Similar aspects were detected in serially sectioned rabbit and human embryos (6--7 mm c.r. length). The authors correlate the necrotic zones mentioned with the inductive functions of the notochord.


Growth factors derived from human serum, platelets, and pituitary: properties and immunologic cross-reactivity. A cationic polypeptide growth factor, isolated from human serum and purified to homogeneity, has stimulated the replication of density-inhibited BALB/c 3T3 cells. It has a molecular weight of 1.3 x 10(4) daltons and an isoelectric point of 9.7. Trypsin or chymotrypsin digestion reduces the growth-stimulatory activity by 75%, whereas 2-mercaptoehanol completely abolishes it. The growth factor is heat-stable (100 degrees C X 10 min) and free of insulin-like activity. The highly purified serum growth factor has been labeled with 125I, and an antiserum to the growth factor was produced in the rabbit. A specific, highly sensitive radioimmunoassay has been developed. Factors with growth-stimulating activity have also been detected in human platelets and human pituitary gland extracts. Platelets and pituitary glands have antigenic determinants that are recognized by antibodies to the serum growth factor. The platelet and pituitary gland growth factors are also cationic and heat stable, and are destroyed by 2-mercaptoethanol. Thus the human serum, platelet, and pituitary gland growth factors have similar properties.


Prostate cancer: normal prostate from human and hamster. "Prostatic acid phosphatase" is a term that has been used widely and ambiguously to refer to acid phosphatase, which 1) is elevated in the sera of patients with various diseases of the prostate, 2) is inhibited by one or more specific inhibitors, 3) attacks one or more specific substrates, 4) has certain unique antigenic properties, 5) is extracted from homogenates of prostate, and 6) is obtained from prostate secretions, etc. Most of the data adduced to justify this term is indirect. We have purified specific kinds of cells from prostates and other tissues. These purified cells have served as sources of enzymes known to be derived from particular kinds of cells. We studied several substrates and one inhibitor that have been claimed useful for the measurement of prostatic acid phosphatase. None of the substrates or inhibitors studied appeared to offer much "specificity," which would allow us to distinguish acid phosphatase activity from prostatic epithelial cells from acid phosphatase activities from several other kinds of purified cells.


Specificity and effector-target interaction. When effector cells were tested on a number of target cells, the most obvious effect observed was a nonselective cytotoxicity that is now known as natural cell-mediated cytotoxicity. The apparent nonselectivity was a result of specific cytotoxic activity against many different antigens on target cells. This specificity was demonstrated in the cross-competition assay in which target cells sharing common antigens selectively inhibited natural cytotoxicity.


Immunochemical determination of human chorionic gonadotropin and alpha-fetoprotein in sera and tumors of patients with testicular cancer. In several prospective studies during the past 5 years, we evaluated 400 patients with nonseminomatous and 60 with seminomatous testicular tumors with the use of serum and cellular AFP and HCG at the NCI. Ninety percent of the patients with nonseminomatous testicular tumors had elevated levels of either HCG and/or AFP that have been useful in detection, staging, prognosis, and monitoring the efficacy of the therapeutic modalities. Although 5% of the patients with pure seminoma had an elevated level of serum HCG, one must search for elements of nonseminomatous testicular tumor in these patients by serial section of the seminoma specimen. Elevated serum AFP in patients with designations of seminoma indicates the presence of an element of embryonal carcinoma and/or teratoma. We have localized these markers in various tumor cells by using the technique of indirect immunoperoxidase. The HCG is localized in syncytiotrophoblastic component of choriocarcinoma and syncytiotrophoblastic giant cells occasionally found in association with embryonal carcinoma, teratoma, and seminoma. The AFP is localized in embryonal and endodermal sinus tumor.


Serum alpha-fetoprotein and human chorionic gonadotropin in the management of testicular tumors. The new radioimmunoassays for AFP and beta-HCG are highly specific for nonseminomatous, germ-cell testicular tumor in genitourinary patients who do not have liver disease or other cancers. When used together, they are an accurate and sensitive indicator of metastases and are helpful in determining the effectiveness of therapy. However, they are not very useful in the differential diagnosis of scrotal masses.


Specificity of cell membrane antigens in prostate cancer. Male CD2F1 mice bearing an MCAM-7 transplant in the right leg underwent surgical excision of the tumor and showed specific resistance to subsequent challenges with that identical tumor line. An in vivo response to tumor-specific antigens (MCAM-7 antigen) solubilized by hypertonic potassium chloride was measured by 24-hour footpad swelling response in male CD2F1 mice immunized to the tumor from which the antigens were extracted. These observations suggested that the transplantable MCAM-7 fibrosarcoma could produce immunity toward the solubilized MCAM-7 tumors antigens and that this tumor immunity could be measured by footpad swelling response to injection of the solubilized antigens, an indication of cell-mediated immunity. The footpad swelling response was also monitored in relation to the extent of tumor growth. Similar techniques have been applied to patients bearing adenocarcinoma of the prostate for whom skin testing was substituted for the measurement of footpad swelling in animals. Four of 10 patients, who had known prostate carcinoma and were given intradermal injections of soluble tumor antigens extracted from their tumors, exhibited a cutaneous, delayed type hypersensitivity response to the injected autologous tumor extracts. No positive reactions were observed in response to solubilized components of control tissues, including BPH. These observations suggest that some patients bearing adenocarcinoma of the prostate can exhibit an immunologic response to specific antigens present in their neoplasms.


Rat prostate carcinoma 11095-A: profile of organ- and tumor-specific antigens. The 11095-A squamous cell tumor is a transplantable prostate carcinoma of the F344 rat. No tumor-specific antigens could be demonstrated for this carcinoma by serologic tests or in host protection experiments. Preliminary data from two other assay systems indicate that tumor-specific antigens may be weakly expressed in this model.


Antigenic properties of a cell line from human prostate carcinoma (EB 33). Evidence for tumor-specific transplantation antigens of human prostate carcinoma was gained by others from in vivo sensitization. The fact that these antigens have not been detected by in vitro methods prompted us to investigate whether EB 33 cells, originated from a human prostate carcinoma by one of us (F.H.S.), expressed these antigens. Using 3-M potassium chloride extracts of EB 33 cells for immunization of New Zealand white rabbits, we obtained xenogeneic antibodies. Further analysis of their specificity was achieved by indirect immunofluorescence and by measurement of their cytotoxicity in a [51Cr]-release test. Xenogeneic antibodies were cytotoxic for EB 33 cells. However, the extent of cell lysis depended on the passage number of EB 33 target cells, thus reflecting an alteration of the antigenicity of the EB 33 cell population during culture. Formation of nonspecific antibodies could be absorbed with HeLa cells. As HLA were not detectable on EB 33 cells, results obtained from absorption experiments with homogenates of normal and malignant prostate tissue may argue for organ-specific and tumor-related transplantation antigens on EB 33 cells.


Prostate and transitional cell carcinoma: radioimmunoassay of viral tumor-associated antigens. Partially purified extracts from human urothelial tumors were utilized as competing antigens in competition radioimmunoassays in conjunction with purified RNA viral interspecies proteins and the respective antibodies to these viral proteins in efforts to detect the presence of one of the structural components of type C RNA viruses, the p30 core protein. Some antigen present in extracts of 25% of the bladder and 22% of the prostate tissues assayed demonstrated cross-reactivity with the viral p30 protein used in the radioimmunoassay system. These findings suggest that some human urothelial tissues contain a protein similar to the p30 core protein of the C-type RNA viruses and that this protein might prove useful in clinical surveys of patients with urogenital tumors.


Detection of antigens on transitional cell carcinoma with a xenogeneic antiserum. An antiserum against T24 was raised in rabbits. One serum that was tested by complement-dependent cytotoxicity and absorption analysis appeared to distinguish functionally between bladder cancer cell lines and other cell lines.


Measurement of acid phosphatase activity in various tissues and cultured cells. Acid phosphatase activity has been measured in various tissues and in extracts of cultured cells. Cells were solubilized with NP40 at neutral pH, and thymolphthalein monophosphate was used as substrate. Reproducible assays were possible with a few as 10(6) cells.


Transplantation of human prostate neoplasia into the nude mouse. Cells derived from human prostates have been successfully transplanted from tissue culture and from primary surgical specimens into nude mice. Techniques of transplantation and results are discussed.


[Role of alpha 1-antitrypsin and alpha-2 macroglobulin in hepatopathies]. Two pictures of alpha 1-antitrypsin deficiency, one associated with alpha 2-macroglobulin deficiency and one isolated case of the latter deficiency have been observed in three patients suffering from cirrhosis of the liver and/or hepatoma. On the basis of these cases, the literature on the subject is reviewed. The unusually high incidence of such anti-enzymatic deficiencies (three cases in the first eleven patients studied) in severe liver pathology, calls for a reassessment of such research and suggests that these tests should be carried out on a routine basis in cases of cryptogenetic cirrhosis and probably for long-term prognosis in cases of viral hepatitis.


Localization of aortic cells in the nodose ganglion by HRP retrograde transport in the cat. Localization of the aortic cells in the nodose ganglion was attempted in the cat using retrograde axonal transport of horseradish peroxidase (HRP). Following dissection of the aortic nerve from the vago-aortic trunk, the cut ends of the aortic fibers were immersed in a HRP solution for 23--46 h. Labelled cells were found in the nodose ganglion and were located mainly in the medial border of the ganglion.


Immunologic and biochemical studies on the carcinoembryonic antigen-like substance in human neuroblastoma. Several authors have observed that the plasma levels of carcinoembryonic antigen (CEA) in patients with neuroblastoma were significantly elevated. The present study was undertaken to investigate the nature of CEA activity in neuroblastoma tissue. This tumor tissue contains a small amount of CEA-like substance reacting with anti-CEA serum which is characterized by gamma-globulin electrophoretic mobility, a molecular weight that is approximately equal to that of albumin (4.6S) by gel filtration, and a glycoprotein staining with periodic acid-Schiff (PAS). According to the double immunodiffusion method, this antigen is partially identical to purified CEA of colon carcinoma, and is completely identical to nonspecific crossreacting antigen (NCA). This antigen is, therefore, referred to not as the CEA as described by Gold, but as NCA in neuroblastoma tissue. The elevation of plasma CEA activity in patients with neuroblastoma may be due to the release of NCA from tumor cells, or to the destruction tissues by metastasis, of normal which are rich in NCA, or to a combination of both.


Effects of resuscitation for patients with metastatic cancers and chronic heart disease. When records of 29 chronic heart disease and 34 metastatic cancer patients were studied for results of resuscitation efforts versus supportive care only efforts, 26 (90 percent) of the heart patients were given resuscitation while 3 (9 percent) of the cancer patients received such care. One (3 percent) heart patient received supportive care only and expired. Thirty (88 percent) of the cancer patients who received supportive care only expired. Of the patients who received resuscitation effort, 17 heart patients died immediately, 5 lived hours or days following the effort, and 4 were discharged from the hospital. Of the cancer patients who received resuscitative care, 2 expired immediately and 1 lived a few hours or days after the effort.


The use of 2450 megahertz of microwave in cancer therapy; a pilot study. Contraindications to microwave diathermy traditionally include malignant tumors. This paper describes a pilot study of tissue hyperthermia treatment (average 42.5 degrees C, 108.5 degrees F) for superficial cancers, using 2450 megahertz of microwave diathermy. Tissue temperatures were recorded for prolonged periods of time, and tumor responses to heat alone, or to heat combined with radiation therapy, were observed. Such treatments were tolerated by the patients, but were not without side effects. Preliminary results of this pilot study, as well as those of other investigators, showed that tissue hyperthermia would be a useful treatment modality for cancer therapy. The familiarity of physical therapists with microwave diathermy may be an asset to them as clinicians. Physical therapists, however, should not attempt to treat cancer patients alone. Further clinical research in the area should be conducted in the proper setting under the guidance of an oncologist.


Results of behavior modification in the treatment of chronic pain. Two hundred patients with chronic pain were treated in an in-patient program in which behavior modification was the major therapeutic modality. The patients were characterized by having had pain of many years' duration, multiple operations, treatment failures, prolonged disability, compensation factors, and dependency on medication. At hospital dismissal, 59% of the patients had achieved moderate improvement or better. At a 3-mo follow-up, 40% of the admitted patients (75% of those successfully treated) were still doing well, and after 1 yr, 25% of those originally admitted continued to do well (65% of those successfully treated).


The binding of thyroxine and tri-iodothyronine to plasma proteins in the chicken at the physiological pH. Amounts of 125I-labelled thyroxine (T4) and triiodothyronine (T3), representing approximately 50 per cent of the plasma concentration, were incubated with chicken plasma or serum, the proteins were separated by polyacrylamide gel electrophoresis at pH 7.4 and the distribution of the hormones determined. Seventy to 75 per cent of T4 migrated with albumin, about 10 per cent with the alpha-globulin and most of the remainder with a pre-albumin fraction. The percentage attached to the pre-albumin tended to increase with age. Neither barbiturate nor 8-anilino-1-naphthalene sulphonic acid (ANS) affected the distribution. About 50 per cent of T3 was associated with albumin, 30 to 40 per cent with the main alpha-globulin and most of the remainder with an adjacent globulin band. ANS reduced the percentage attached to albumin and increased that associated with the alpha-globulin. Barbiturate had no effect.


Pain relief by surgery in chronic pancreatitis? Relationship between pain relief, pancreatic dysfunction, and alcohol withdrawal. Since 1963, 57 consecutive patients with chronic pancreatitis, 44 of them alcoholics who had been operated upon for recurrent severe pain, have been controlled regularly for an average of 6 years. Thirty-two of them had a cyst drainage procedure (group A), and 25 had a ductal drainage procedure and/or distal pancreatectomy (group B). Ten patients died within 2 years (group A, n = 5). Lasting pain relief by surgery occurred in 19 patients only. Of 28 patients with pain relapses after surgery (group A, n = 15), however, 22 (78.6%) obtained late pain relief 1-8 years after surgery in association with marked increase of pancreatic dysfunction (group A, n = 12). Pain relief was associated with pancreatic calcifications in 71-86% of the alcoholics. Cyst drainage procedures were successful in preventing pain relapses mainly in patients with either advanced pancreatic dysfunction or in non-alcoholic pancreatitis. The data suggest that in chronic pancreatitis lasting pain relief is more often due to marked pancreatic dysfunction than to surgery. Alcohol abstinence after surgery was probably an additional factor for lasting pain relief in some patients.


V and C gene contribution in creating anti-alpha-1,3 dextran antibodies in mice. I. Characteristics of Ig-lal prototype responses. The light (L) and heavy (H) chain and the antigenic, idiotypic (Id) composition of the antibody (Ab) plaque-forming cells (PFC) and serum Ab specific for alpha-1,3 dextran have been characterized in Ig-lal BALB/c prototype mice, in Ig-la- [30] mice, and in BALB/c congenic and recombinant strains. Four distinct Ab Id specificities were identified by using criteria of Id relatedness to three Id-distinct, alpha-1,3 dextran-binding BALB/c myeloma proteins (MP), all associated, in the Ig-lal mice with the lambda (lambda) chains: a major, common IdX in 40--90% of the molecules; three minor, individual IdI in 1--49% of the molecules; and a fifth, Id-undefined one. These specificities were expressed at the PFC and serum level in the mu and gamma isotypes. A minor, kappa (kappa), Id-negative Ab was discerned only at the PFC level. The Ig-la- CBA and C3H mice responded with anti-alpha-1,3 dextran, kappa Id-negative Ab. The BALB/c, congenic strain CB20 (BALB/c Ig-lb, carrying the C57Bl/Ka, Ig-lb variable H (VH) gene complement and CH phenotype, made anti-alpha-1,3 dextran kappaId-negative Ab of the Ig-lb prototype. The recombinant BAB/14, carrying in the C57Bl/Ka CH-Ig-lb phenotype the BALB/c Ig-lal VH gene(s) controlling anti-alpha-1,3 dextran lambda Ab responsiveness and Id specificity (VH-DEX+), express the BALB/c lambdaId repertoire.


V and C gene contribution in creating anti-alpha-1,3 dextran antibodies in mice. II. Characteristics of Ig-lb to e prototype responses. The light (L) and heavy (H) chain and the idiotypic (Id) composition of the antibody (Ab) plaque-forming cells (PFC) and serum Ab specific for alpha-1,3 dextran have been characterized in murine strains exhibiting the CH-Ig-lb to e allotypes and in their F1 hybrids with Ig-la1, BALB/c prototypes. The Ab response of the Ig-lb to e mice to the alpha-1,3 dextran was low in the kappa (kappa) L chain class with only a minor, sporadic Ab in the lambda (lambda) L chain class discernible after prolonged immunization. Two of a total of sixty-eight C57Bl/6 Ig-lb mice, in a total of 318 Ig-lb to e mice tested, exhibited, in late responses, a significantly elevated Ab in the lambda L class at both serum and PFC levels, equalling at the PFC level the total non-specific lambda PFC values. An Id analysis showed this lambda Ab and the kappa Ab to lack the Id relatedness to the three BALB/c alpha-1,3 dextran-binding myeloma proteins (MP) Ab prototypes, J-558, 104 E, and UPC-102, exhibited by the lambda Id+ Ab of the Ig-la1 BALB/c prototypes and their F1 hybrids with the Ig-lb to e prototypes. Furthermore, affinity differences could be detected by alpha-1,3 nigerodextrans, PFC inhibition analysis, between the late C57Bl/6 anti-alpha-1,3 dextran lambda Id--Ab PFC and the lambda Id+ Ab PFC of the BALB/c and their F1 progeny.


Demonstration of electrophoretic heterogeneity of serum beta 2-microglobulin in systemic lupus erythematosus and rheumatoid arthritis: evidence against autoantibodies to beta 2-microglobulin. A sensitive crossed radioimmunoelectrophoretic method (CRIE), originally developed to study lymphocyte-associated beta 2-microglobulin (beta 2m), was applied in the study of serum beta 2m in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In six of seven patients with SLE and nineteen of twenty-seven patients with RA a considerable electrophoretic heterogeneity of serum beta 2m was found. In addition to the normally seen symmetric beta 2m precipitate, a beta 2m precipitate exhibiting complete immunochemical identity was found in the alpha-electrophoretic region. Binding of isolated 125I-labelled beta 2m to the abnormal precipitate was demonstrated in crossed immunoelectrophoresis. After gel filtration of sera exhibiting the above-mentioned beta 2m binding, all beta 2m was eluted in low molecular weight fractions corresponding to free beta 2m. By application of appropriate antisera and a glycoprotein-binding lectin in intermediate gels in CRIE, it was shown that the possible beta 2m-binding ligand is not an antibody, not a major constituent of normal human serum, and not unmodified HLA alloantigen. The abnormality was not restricted to patients with high disease activity but was found more frequently and was more pronounced (mean score 1.6 arbitrary units against 0.57 arbitrary units, P less than 0.01) in such patients. Thus our data exclude the possibility that autoantibodies to beta 2m were present in serum from patients with SLE and RA.


Effects of anti-guinea-pig beta 2-microgloblin antibodies on lymphocyte transformation induced by specific antigens or mitogens. The effects of a goat anti-guinea-pig beta 2-microglobulin antiserum (a beta 2m) on lymphocyte transformation, induced by specific antigens or mitogens, were studied. a beta 2m was found to exert inhibitory effects on antigen stimulation, with three different antigens (purified protein devivative, hen egg-white lysozyme, and ovalbumin), and on stimulation induced by the 'T-cell mitogens', concanavalin A and phytohaemagglutinin, and the 'mixed mitogen', pokeweed mitogen. Stimulation induced by the 'B-cell mitogens', dextran sulphate and bacterial lipopolysaccharide, did not seem to be inhibited to the same extent by a beta 2m. The inhibitory effects seemed specific, as they were not seen with a beta 2m that had been absorbed on a column with insolubilized purified guinea-pig beta 2m nor with normal goat serum. Time studies indicated that the inhibitions started already during the first day of culture.


Demonstration of rheumatoid factor idiotypic antigens on peripheral blood B and T lymphocytes from patients with rheumatoid arthritis. Antisera were raised against three polyclonal IgM rheumatoid factors (RF). After adequate absorptions, the antisera were rendered idiotype-specific, as assayed by haemagglutination technique. By using the anti-idiotype antisera in indirect immunofluorescence on peripheral blood lymphocytes from the patients used as donors for the immunizing RF, it was demonstrated that 3-14% of the lymphocytes were stained, and thus had membrane-bound structures with idiotypic antigens similar to those of the circulating IgM RF of the same patients. While most of these idiotype-positive lymphocyte were B lymphocytes, it was demonstrated in one patient that about 7% of the T lymphocytes also had the same idiotypic antigens.


Changes in histamine and cyclic nucleotide levels after bronchoprovocation in patients with extrinsic asthma. The contents of histamine and cyclic nucleotides were studied in leukocytes before and after a bronchoprovocation test on patients with extrinsic asthma. The bronchospastic response correlated significantly with the reduction of the amount of histamine in leukocytes isolated after the provocation. The leukocytes cyclic AMP and cyclic GMP contents were slightly reduced after the provocation, while the plasma level of cyclic AMP was markedly increased. The beta-adrenoceptor response was tested on leukocytes, before the provocation. A normal elevation of the cyclic AMP content was obtained when the leukocytes were stimulated with isoprenaline, but after the provocation, isoprenaline had no significant effect. Only when a phosphodiesterase inhibitor was present did isoprenaline increase the cyclic AMP level in the postprovocation tests. It is suggested that the mediator release from the immunologic target cells is of importance for the bronchospastic response and that a desensitization of the beta-adrenoceptors of these cells is evident after bronchoprovocation.


Simultaneous production of Q and R bands after staining with chromomycin A3 or olivomycin. Human and mouse chromosomes, stained with either chromomycin A3 or olivomycin, which bind preferentially to G - C-rich DNA (where G is guanosine and C is cytosine), exhibit a Q or a reverse banding pattern, depending on the wavelength used for excitation. The two complementary banding patterns can be observed in the same metaphase simply by changing the combination of excitation filters. These data suggest, therefore, that in addition to base composition, other factors are involved in the production of chromosome banding by chromomycin A3 and olivomycin.


Chloroxymorphamine, and opioid receptor site-directed alkylating agent having narcotic agonist activity. Chloroxymorphamine, the 6beta-N,N-bis(2-chloroethyl) derivative of oxymorphone, is a potent nonequilibrium narcotic agonist in the longitudinal muscle preparation of guinea pig ileum. The corresponding naltrexone analog,chlornaltrexamine, is a potent nonequilibrium antagonist of morphine. These receptor sitedirected alkylating agents possess considerable potenial as pharmacologic and biochemical probes of apoid receptors.


DNA polymerase with characteristics of reverse transcriptase purified from human milk. A DNA polymerase purified from a particulate fraction of human milk has biochemical and biophysical properties similar to those of viral reverse transcriptases. This enzyme is immunologically distinct from cellular DNA polymerases obtained from a variety of human sources.


Inhibition of mast cell histamine secretion by N-substituteed derivatives of phosphatidylserine. The structural basis for the highly specific action of phosphatidylserine in enhancing mast cell histamine secretion induced by concanavalin A was investigated by studying the activities of three N-substituted derivatives: N-acetyl phosphatidylserine, N-1-dimethylaminonaphthalene-5-sulfonly phosphatidylserine, and N-4-nitrobenzo-2-oxa-1,3-diazole phosphatidylserine. None of the derivatives was capable of activating concanavalin A-induced histamine secretion at concentrations two to three times that required for maximal activation by phosphatidylserine. Instead, the derivatives were found to inhibit the secretory response of mast cells to the calcium ionophore A23187 as well as to concanavalin A. The inhibition was noncytotoxic, partially reversible by washing, and associated with binding of N-substituted phosphatidylserine to the mast cell.


Residual effectiveness of insecticidal deposits on various wall surfaces. The effectiveness of three chemicals DDT, malathion and Dursban was evaluated against larvae and adults of C. p. fatigans. When larvae and adult mosquitoes were tested for susceptibility, they were susceptible to malathion and Dursban. These insecticides were sprayed onto various wall surfaces at a dose of 2 gm per square metre and the residual effect on C. p. fatigans were studied. Dursban residue was superior on all sufaces, giving effective kill for 10-30 weeks, malathion gave satisfactory result on thatch, plywood and galvanized iron while DDT residue failed to produce effective kills.


[Individuality of human chromosome polymorphism revealed by Q-staining]. The G-polymorphism of metaphase chromosomes of peripheral human lymphocytes and its inheritance in 32 families (268 persons) and 315 unrelated persons after G-staining has been studied. The site of Q-heterochromatine, its size and the length of secondary constrictions were accepted as morphological signs of Q-polymorphic variants of chromosomes. All the three chromosome signs are shown to be inherited according to codominant type and are characteristic features of each separate chromosome. No identical patterns of Q-polymorphic chromosome variants are found among all the persons studied, except the monozygotic twins. According to the data obtained, the question of individualization of each chromosome in the karyotype (3, 4, 13--15, 21, 22) and of each personal individuality in relation to Q-polymorphism is discussed.


Properties of neutrophils collected by discontinuous-flow centrifugation leukapheresis employing hydroxyethyl starch. The properties of neutrophils, collected by discontinuous-flow centrifugation leukapheresis in the presence of hydroxyethyl starch and citrate were studied in an attempt to insure that cells harvested in this fashion are suitable for transfusion. Neutrophils obtained from leukocyte units prepared for transfusion by leukapheresis were found to perform similarly to those isolated from the venous blood of corresponding donors prior to the pheresis procedures when assessed by morphology, viability, hexose monophosphate shunt activity, superoxide anion generation, nitroblue tetrazolium dye reduction, chemiluminescence, adherence to nylon fibers, random mobility, chemotaxis and staphylococcal killing. The results compared favorably with values previously established for healthy control subjects. Neutrophils prepared in this manner should serve as a satisfactory blood component.


[Reaction of the cerebral cortical neurons to complete ischemia]. Changes of morphological and neurophysiological characteristics of pyramidal neurons in response to complete ischemia have been studied by means of vital microscopy of cat and rabbit cortex neurons in addition to some other cytological methods. These responses were found to be complex involving phasic changes in the neuron size, membrane potential and redox potential. Neurons of particular types responded to normo- and hypothermic ischemia differently. Pyramidal neurons retained their vital ability for the whole prolonged period of the complete ischemia (up to 40--60 min).


Auto anti-Kpb associated with weakened antigenicity in the Kell blood group system: a second example. An 84-year-old woman with intestinal bleeding had marked reduction of red blood cell antigenicity in the Kell system, and a positive direct antiglobulin test caused by auto-anti-Kpb. KX antigen activity of her cell was increased, an observation which supports the belief that KX marks a precursor structure utilized in the normal Kell biosynthetic pathway. It is postulated that reduced Kell antigenicity was an acquired change that resulted from enzymatic degradation, possibly of bacterial origin.


The Can serum: demonstrating further polymorphism of M and N blood group antigens. An antibody defining an antigen that is very similar in structure to M is described. The reactions of this antibody are considered in the light of what is now known of the biochemical structure of the M and N blood group antigens.


Allo-anti-C in a patient who had previously made an autoantibody mimicking anti-C. A patient, previously studied by us, who had produced a benign autoantibody with a specificity that mimicked anti-C, has now produced allo-anti-C that is not of the mimicking type. She is no longer producing any serologically demonstrable autoantibody. It is highly probable that conversion from auto to alloantibody production in this patient was prompted by the introduction of additional foreign immunogen on fetal red blood cells during her third pregnancy.


[Physicochemical and immunochemical properties of submolecular structures of immunoglobulin G characteristic of cancer]. Studies in physicochemical and immunochemical properties of polipeptide chains fragments of immunoglobulin G malignant growth permitted detecting the location site for a specific determinant which adds a unique feature to the whole molecule of immunoglobulin G. The specific antigenic determinant is defined by a group of amino acids located in the heavy chain site corresponding to Fd-fragment. During papain and trypsin hydrolysis of specific immunoglobulin G obtained from different patients the formed sets of fragments and peptides are different. This testifies to the fact that the immunoglobulin under study may belong to any of four subclasses of immunoglobulin G, that is confirmed by the immunochemical analysis with application of monospecific antisera against certain subclasses of immunoglobulin G.


Effect of transurethral resection on coagulation in carcinoma of prostate. Eleven patients with cancer of the prostate and 10 patients with benign prostatic hypertrophy (BPH) had thirteen parameters of coagulation evaluated before and after transurethral resection (TUR). Changes in fibrinogen and fibrin split products in both groups suggested potential incipient disseminated intravascular coagulation (DIC). It is concluded that prostatic cancer patients are no more susceptible to DIC than patients with BPH.


Significance of protein-bound neuraminic acid levels in patients with prostatic and bladder carcinoma. The role of plasma N-acetyl neuraminic acid (NANA) level in detection and staging prostatic and bladder carcinomas was evaluated. Multiple determinations were obtained in 73 male subjects, including normal controls, patients with prostatic or bladder carcinoma or with benign prostatic hyperplasia. Patients with prostatic or bladder carcinoma had significantly higher NANA levels than normal individuals. Further, in patients with prostatic carcinoma, NANA values correlated well with both the stage of the disease and the response to therapy.


[Combined chemotherapy of the metastases of testicular teratoblastomas]. Sixty two patients with metastases of testicular teratoblastoma were subjected to combination chemotherapy. Forty nine patients were treated with an association of bleomycin and vincaalkaloids. An objective effect was gained in 77.5%. Ten patients were treated with a combination of bleomycin, vinblastine, natulane, dactinomycin, an effect being gained in 60% of the patients. The treatment with cis-diamini-dichloroplatinum was effective in 8 of 11 patients (72.7%). In 6 of 10 patients treated with olivomycin and cyclophosphane the effect was obtained (in 60%), when they were resistant to bleomycin combinations. Evidence is presented of high-effectiveness of the combinations including bleomycin as well as of the effect of cis-diamini-dichloroplatinum in treatment of testicular teratoblastomas. With pharmaceutical resistance to bleomycin it is recommended to continue olivomycin and cyclophosphane chemotherapy.


[Further comment on the lipotropic action of niacin]. An investigation into the total lipids, fatty acids, total phospholipids and ATP content in the liver of rats given nicotinamide, separately and together with hydrocortisone, showed that the disclosed shifts mutually correlate well and may be explained in keeping within the bounds of the idea as to the lipotropic action of the preparations. The coincidence of the corticosteroids and nicotinamide effects in regards to mobilization of lipids and their oxidation in the liver presumes a hormonal causation of shifts on the level of lipids metabolism.


[Group and strain-specific determinants of the influenza virus nucleoprotein]. An antiserum to a purified nucleoprotein preparation of influenza virus recombinant A/MRC/11 obtained from A/Port Chalmers/1/73 and A/PR/8/34 strains, was examined for the presence of antibody before and after its adsorption with sodium sarcolysil sulphate-disrupted influenza. A viruses by the methods of radial and double immunodiffusion. The antiserum was found to contain both group- and strain-specific (for MRC-11 nucleoprotein) antibodies. In radial immunodiffusion tests MRC-11 nucleoprotein showed the greatest affinity to A/PR/8/34 nucleoprotein and differed from A/Scotland/860/74 and A/USSR/090/77.


[Diagnosis and therapy of pancreatic carcinoma (author's transl)]. Report of 143 cases of pancreatic carcinoma and the operations carried out. In 14 cases (operability rate 10%) a pancreaticoduodenectomy was  performed. The operative lethality rate came to 14,3%. The longest survival time was 7 1/4 years, the shortest 11 months. Early diagnosis, early laparotomy and operation as radical as possible are emphasized.


[2 new fluorochromation methods for blood smears and chromosomes using berberine sulfate following deoxyribonucleoprotein denaturation]. The authors reported a Berberine sulfate technique based on DNP-denaturation with modifications for the purposes of fluorescent cytochemistry in cytology of blood and vaginal smears. A similar fluorochromation technique for staining of metaphase chromosomes and chromosomes in meiotic division has been applied. The fluorescent specificities, probably due to the differences in the denaturation properties of the hetero- and euchromatin desoxyribonucleoprotein-complexes, are discussed in comparison with other fluorochrome techniques and in relation with differences in distribution of hetero- and euchromatin and amounts of proteins in DNP, as far as DNA denaturation and tinction properties are concerned. The weaker fluorescence of immature (or leucemic) nuclei in blood smears and certain chromosomal regions would be due to the greater amount of active euchromatin (DNA which is slow reassociating or unstable to denaturation), which obviously does not bind to a sufficient degree the fluorochrome applied. The differences established in the fluorescence of active euchromatin and inactive heterochromatin zones by post-denaturing fluorochromation with Berberine sulfate gave grounds to recommend the application of these techniques in haematological and cytological (normal and abnormal) practice and for the cytogenetical and microfluorimetrical analyses.


[Distribution pattern in the guinea pig cochlea of intravitally injected peroxidase]. Following perilymphatic perfusion and injection into the cisterna cerebello-medullaris, respectively, the distribution pattern of horseradish peroxidase in the cochlea of the guinea pig was studied light and electron microscopically. The findings prove effective tight junctions (zonulae occludentes) between the cells of the epithelial lining of the endolymphatic compartment. At the level of the reticular membrane the tight junctions are far more extended than elsewhere at the cochlear duct epithelium. From the findings a fairly rapid exchange is suggestive between the lymphatic space of the organ of Corti and the tympanic scale. Various types of cells of the cochlear duct actively take up considerable amounts of peroxidase. However, endocytosis of peroxidase by hair cells and particularly by the outer ones is rather scanty. Passive permeation of the tracer through the membran of undamaged hair cells was disproven.


[Intratypical antigenic differentiation of poliovirus strains circulating in Mali by means of cross-adsorbed sera]. The intratypic antigenic differentiation of poliovirus strains isolated from sick or healthy children in Mali in 1975-1976 was performed. The method is based on the use of cross-adsorbed sera in the neutralization tests in which the virus is titrated by the plaque procedure or by the cytopathic effect. All the examined strains of serologic types I, II, and III were distinguished by the antigenic structure from the vaccine strains and were classified as "wild". Quantitative differences in the antigenic structure of type I strains isolated in different towns of Mali were found.


Antigenic analysis by agglutination of Trypanosoma brucei brucei parasitemias initiated in mice with in vitro-produced metacyclics. Trypanosomes from 14 first-peak parasitemias initiated in mice by injection of in vitro-produced metacyclics were stabilated. Strains derived from these stabilates were analyzed for their antigenic composition by cross-agglutination with immune sera produced in rabbits against 12 of the stabilates. The antigenic composition of the 14 stabilates was compared also with two first-peak parasitemias from mice inoculated with fly-derived metacyclics, the variant-specific antigen of the strain used to initiate the cultures that ultimately became infective, and the antigenic variant that was used to infect the flies. One variant-specific, presumably basic, antigen was found, either as the predominant (nine parasitemias) or as a minor (seven parasitemias) antigen, in all first peak-parasitemia strain initiated with culture- or fly-derived metacyclics; it was absent, however, from the strains (not first-peak parasitemias) used to start the cultures or to infect the flies. Only one of the first-peak parasitemias appeared to have the basic antigen alone. The remaining parasitemia populations seemed to have from about two to six antigens, some of which were common to culture- and fly-derived infections. There was very little, if any, antigenic relationship between the foregoing populations and the strains employed for initiation of cultures or for infection of flies. It is evident from the results that much antigenic similarity exists between the culture- and tsetse fly-derived first-peak parasitemias.


[Participation of species specific and group specific ornithosis antigens in immune reactions]. The immunogenic properties of the species-specific antigen localized in the elementary particle membrane and group-specific or inner antigen of the causative agent of ornithosis were studied. The species specific antigen was shown to induce the antibody neutralizing the infectious properties of the agent as well as those agglutinating elementary bodies, inhibiting hemagglutination, and complement-fixing antibody detectable in the direct and indirect complement-fixation tests. The results indicate that the antigens most clearly defining the species-specific properties of the causative agent of ornithosis are localized in the elementary particle membrane. These antigens may be used for differential diagnosis studies employing not only CFT but also other antibody tests.


Identification of fetal blood stains by radioimmunoassay of alpha 1-fetoprotein. Radioimmunoassay of alpha 1-fetoprotein(AFP) for medico-legal identification of fetal blood stains using a commercial kit is described. The AFP content in fetal blood stains on filter paper ranged from 21--320 ng/9 mm2. The protein was detected in stains of adult blood and retroplacental blood in only negligible amounts. Aging of the blood stains did not influence the values up to 1 month. The method is simple and sensitive enough for application to medico-legal-practice.


[Craniopharyngioma--comparison of postoperative course following tumor and palliative surgery]. The results of surgical treatment of 86 craniopharyngioma patients are followed up in the postoperative and later periods. Under the indication of progressive impairment of vision by direct pressure on optical structures the direct tumour operation was carried out in 50 cases. The postoperative lethality of 32%, the total lethality within one year of 36% and within 5 years of 44% correspond to the world level and show an increasing improvement in the last few years. The relative independency of the postoperative lethality rate of the degree of radicality speaks for a correct appraisal of the operability limit which is given by the vicinity of the diencephalic structures. With the indication of prevailing cerebral compression and the formation of hydrocephalus by a blocking of the foramen of Monro a spinal-fluid draining operation instead of a tumour operation was carried out in 33 cases. The results of bilateral Torkildsen drainage are compared with those obtained with valve draining. It appears that the bilateral placing of a Cordis-Hakim valve is the best method, especially because no functional impairment due to a possible increase in rachialbumin need be expected.


[Cervical tractotomy V, IX, X and VII and accompanying rhizotomy in incurable pain due to malignant tumors of the facial-cervical reagion]. For the elimination of incurable pain in the faciocervical region caused by malignant tumours a transverse separation of the tract of the cerebral nerves V, IX, X and VII is carried out after minute stimulation at several levels under local anaesthesia. In addition, the sensitive cervical roots 1 to 3 are severed. The extent of the separation depends on the extent of the painful region and the effect of the individual separations. The method was successfully employed in 13 patients: 4 laryngeal carcinomas, 2 parotid carcinomas, 2 tongue carcinomas, 1 carcinoma of the pharynx, 1 of the maxilla, 1 of the lip, 1 of the tonsil and 1 of the Os occipitale, in most cases with submandibular metastases.


[Antilymphocytic immunoglobulin with an associated antibacterial orientation. I. The production and experimental laboratory study of the preparation]. Immunoglobulin was obtained from rabbit sera following immunization of the animals with a complex antigen composed of a suspension of human thymocytes and killed microbe polyvaccine. The preparation possessed not only antilymphocytic activity in vitro, but also protected the animals after their artificial infection.


The use of trypan blue for counterstaining in the Sepharose bead immunofluorescence test. The application of the test for the demonstration of primate retrovirus-specific antibodies and antigens. The Sepharose bead immunoflurorescence test was performed by counterstaining the beads with trypan blue. This results in a red staining of negative beads which allows an easy distinction from positive green-fluorescent beads. Sepharose beads conjugated with viral proteins or antiviral antibodies were used to demonstrate Mason-Pfizer monkey virus (MPMW)- and simian sarcoma virus (SSV) - specific antigens or antibodies. The test shows a high sensitivity and specificity and needs a small amount of material.


The effect of sexual hormones on skin graft survival, thymic morphology and serum levels of glycoproteins and albumin in mice. Inbred mice of the B10LP strain were injected subcutaneously over a period of 28 days with chloromadinone acetate, mestranol, both hormones together, and the carrier alone. Treatment with the gestagen chloromadinone acetate alone or in combination with mestranol caused a significant prolongation of the H-2 different skin graft survival. This was not seen after mestranol treatment alone. All the hormone-treated mice developed characteristic cysts in the thymic medulla and changes in the concentration of some plasma proteins, e.g. a fall of albumin level and a simultaneous increase of glycoprotein level. Therefore, it is necessary to look for such side-effects in humans also to prevent or to notice early alterations of immunological surveillance.


[Therapeutic indications in hyperthyroidism (author's transl)]. The administration of synthetic antithyroid drugs or of l131, and subtotal resection of the thyroid gland remain the treatments of hyperthyroidism. Precise criteria will determine the choice. Surgery is the treatment of large goitres, of associated ophthalmic disorders and of recurrence after medical treatment. Drugs are indicated at the first occurrence of hyperthyroidism in young subjects with a small goitre; it will also be used as a preparation for surgery associated to Lugol and Levothyroxine. Finally l131 is indicated in medium size hyperthyroid goitres in patients over 45 years. Each treatment has advantages and drawbacks which must be taken into account for the therapeutic choice and the follow-up.


Renal handling of beta-2-microglobulin, amylase and albumin in acute pancreatitis. The renal handling of beta-2-microglobulin, amylase and albumin was studied in patients with acute pancreatitis. The data were compared with results obtained from patients with glomerular proteinuria and from patients with tubular proteinuria. Initially during acute pancreatitis, the clearance ratio (clearance protein/clearance creatinine) for beta-2-microglobulin was increased dramatically (77-fold) compared to normals. After four to seven days this ratio had fallen and was elevated only 7-fold. The corresponding figures for amylase were 3.3 and 1.8 times and for albumin 9 and 5 times respectively. In glomerular disease, the clearance ratios for beta-2-microglobulin, amylase and albumin were increased 6, 1.1, and 154 times and in tubular disease 448, 1.1, and 28 times, respectively. The electrophoretic pattern of the urinary proteins during pancreatitis was mostly normal. In a few cases, slight tubular proteinuria was noticed. Amylase activity in serum and urine from patients with pancreatitis was found to sediment, (S20,W = 4.6) in a sucrose gradient, identical to amylase from normal serum and urine. The marked increase in the excretion of beta-2-microglobulin probably reflects interference of the kidney function at the proximal tubular level. Determinations of this protein in urine may be of value in studies of kidney dysfunction that can accompany pancreatitis.


Hepatic uptake of desialylated testosterone-oestradiol-binding globulin in the rat. Testosterone-oestradiol-binding globulin (TeBG) isolated from bovine serum was desialylated by treatment with neuraminidase and its properties were compared with intact TeBG. No significant differences were observed in the testosterone-binding capacity or antigenic determinant, but electrophoretic mobility of asialo-TeBG decreased slightly. When injected into rat vein, 125I-labelled asialo-TeBG was rapidly taken up by the liver, whereas 125-labelled intact TeBG remained in the circulation for a much longer period. Galactose oxidase treatment of asialo-TeBG, which presumably oxidized the primary alcohol of galactose at C-6 to an aldehyde, caused a reversion of its survival time in the blood to that of intact TeBG. When incubated with isolated rat liver cells at 20 degrees C, the desialylated, but not intact, TeBG was rapidly taken up, and its uptake was inhibited by excess amount of asialo-orosomucoid. Under these conditions in vitro, [3H]testosterone bound to asialo-TeBG was taken up by the liver cells together with the asialo-TeBG.


Hormone blood levels and their inter-relationships in normal men and men with benign prostatic hyperplasia (BPH). In 128 non-hospitalized men (age range 36-65 years) rectal palpation revealed in 54 cases an enlargement of the prostate (group II), which was very distinct in 20 cases (group III). The measurement of testosterone (T), 5alpha-dihydrotestosterone (DHT), 5alpha-androstane-3alpha,17beta-diol (3alpha-diol) oestradiol (Oe2), sex-hormone-binding-globulin binding capacity (SHBG), luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (Prl) in the blood of normal men (group I) and those with BPH (group II or III) demonstrated no significant differences between the three groups when respective age ranges were compared. A significant increase of FSH and decrease of 3alpha-diol with age was seen in the normal group (I), which was similar but less pronounced in BPH (groups II and III). A distinct increase of DHT with age was found in BPH (group II), which was not so dominant in normal men (group I). From these data it is concluded that the conversion of DHT to 3alpha-diol might be reduced in older males independent from the occurrence of BPH and that the hyperplastic prostate possibly secretes significant amounts of DHT into the circulation. These results are discussed with respect to their possible role in the pathogenesis of BPH.


Isolation of highly purified sex hormone binding globulin (SHBG): evidence for microheterogeneity. Highly purified sex hormone binding globulin (SHBG) was isolated in milligram amounts from a human serum fraction (Cohn IV-4). The final preparation was homogeneous by the criteria of polyacrylamide-gel electrophoresis. Immunological evidence for purity could be given by double diffusion according to Ouchterlony. However, following gel isoelectric focusing highly purified SHBG displayed four different bands, as could be demonstrated by staining as well as by a photoscan of the [3H]5alpha-dihydrotestosterone-SHBG complex. After incubation with neuraminidase the microheterogeneity of SHBG disappeared and the asialo-SHBG showed only one band.


The morphologic identification of Pneumocystis carinii. The diagnosis of Pneumocystis carinii infection is dependent upon morphologic identification of the organism, making the staining properties of P. carinii important to the cytologist engaged in clinical service or research. Several special stains specific for P. carinii are described; in addition, the staining characteristics of the organism in Papanicolaou and in hematoxylin and eosin stains are described. The successful identification of P. carinii with the latter two stains has not been reported previously. Because these stains are often used on lung preparations, it may be possible to identify P. carinii when using these latter two techniques; however, for optimal results, we feel that it is essential to utilize one or more of the special stains discussed herein.


Location of iron and porphyrin in the liver in porphyria cutanea tarda. Porphyrin and iron distributions in the liver biopsies of patients with Porphyria cutanea tarda (PCT) were investigated by comparison of composite photographs from fluorescence microscope and after iron stain. Three distinct areas are visible: 1. red fluorescent areas with porphyrins; 2. blue areas corresponding to iron; 3. areas with neither iron nor porphyrin. The areas with iron or porphyrin do not overlap, therefore, this experiment indicates lack of direct correlation between iron and prophyrin distribution in livers of PCT patients.


Use of cis-Pt(II)-uracil for electron microscopic cytochemistry of rat brain nucleic acids. Cis-Pt(II)-uracil staining reveals nucleic acids in a relatively specific manner when applied alone for 1 h to rat brain tissue specimens. Poor contrast and resolution are observed when glutaraldehyde-fixed and epoxyembedded thin sections are post-stained with cis-Pt(II)-uracil alone. Counterstaining thin sections with uranyl acetate decreases staining specificity by revealing many tissue proteins. Synapses did not stain, which suggests that they do not contain significant amounts of large RNA molecules. Technical procedures must be carefully regulated to avoid artifactual staining of cellular components other than nucleic acids.


Age-related changes in the seminal vesicles of a Brazilian (Nelore) zebu. Age changes in the structure of the seminal vesicles and in the rate of production of fructose and citric acid have been studied in a Brazilian (Nelore) zebu, from the fetal period to 36 months of age. At 3 and 6 months, the microscopic anatomy of the gland resembled that of the fetus; the tubules of the seminal vesicles had a reduced diameter and a low epithelial layer; only a few presented traces of secretion, and tissue contents of fructose and citric acid were accordingly low. At 12 months, the tubules were more ramified and had a larger diameter. In the 18-month-old animals the seminal vesicles presented substantial modifications; the tubules were large, with irregular lumina and surrounded by narrow stroma, the epithelial layer was higher than that of previous stages and its columnar cells had nuclei located basally. Tissue levels of fructose increased rapidly between 12 and 18 months. At 24 months, the seminal vesicles had reached the adult condition characterized by intense proliferation of tubules with irregular lumina and abundant secretory material. Numerous dark columnar cells were found in the epithelium. Seminal vesicles of Nelore zebus contain less fructose and citric acid than those of taurine bulls of comparable age.


Histochemistry of mucins in the submaxillary salivary gland of buffalo (Bubalus bubalis). The histochemistry of mucins in the submaxillary salivary gland has been studied in 10 buffaloes of different age groups. The acidic mucins exhibited moderate to intense reaction in new-born and young animals; in adult animals, these were noticed in patches. Neutral and non-sulphated mucins were observed in traces and in mild amounts, respectively, in the mucous secretory end-pieces of different age groups; sialomucins were seen in moderate to intense concentrations. The seromucous end-pieces revealed traces of neutral mucins in new-born buffalo calves and moderate to intense concentrations in young and adult animals. These structures showed mild concentration of acidic mucins, hyaluronic acid and sialomucins. Sulphated and non-sulphated mucins were observed in traces in the seromucous end-pieces. The apical border of the lining cells of the intra- and interlobular ducts contained moderate to intense concentrations of acidic mucins. In young and adult animals, the epithelial cells showed mild to moderate reaction for neutral mucins. Goblet cells of the interlobular ducts exhibited the presence of mild and intense concentrations of sialo- and sulphomucins, respectively.


Localized regressive articular cartilage changes in the hip joint of the rabbit following an induced synovitis. A talcum induced synovitis in the hip joint of the rabbit, which is known to cause articular cartilage hyperplasia followed by femoral head protrusion and joint incongruency, has in the present experiment also been shown to lead to localized regressive articular cartilage changes. The articular cartilage of the hip joints in 40 rabbits was examined histologically, at intervals, following induction of such a talcum synovitis. Regressive changes in the form of loss of surface chondrocytes and glycosaminoglycans sometimes accompanied by fibrillation, were found in the area of the femoral head articular cartilage which had become flattened following the head protrusion. Chondrocyte cloning facilitated subsequent cartilage repair. The biomechanical disturbance in the joint following the induced synovitis is felt to have caused the regressive changes. The experiment is considered to have some significance in connection with Legg-Calvé-Perthes' Syndrome (L.C.P.S.) in children.


[Polish hydroxyethyl starch preparation: a clinical study]. The 6% solution of hydroxyethyl starch (MS = 0.47-0.7, Mw = 120,000-220,000) prepared at the Department of Biochemistry, Institute of Haematology in Warsaw was administered in infusions to a group of surgical patients. It was found that the preparation complied with the conditions and requirements for plasma-replacing agents. In none of the treated patients any side effects were observed. Further investigations will be continued infusing greater volumes of HES to patients with hypovolaemia of different origin.


Serology of Neisseria gonorrhoeae. Demonstration of strain-specific antigens by immunoelectrophoresis, immunofluorescence and co-agglutination techniques. Among a group of four selected strains of Neisseria gonorrhaeae, common and strain-specific antigens were demonstrated by immunoelectrophoresis, indirect immunofluorescence (IFL) and co-agglutination (COA). In preparations of ultrasonically-disrupted organisms, the strain-specific antigens appeared in crossed-line immunoelectrophoresis (C-LIE) with antigen containing intermediate agar gel as a two-peak precipitin line, one peak close to the antigen well, the other towards the anode. A similar pattern was found for each of the four strains studied. These strain-specific precipitin lines were also identified in rocket-line immunoelectrophoresis (R-LIE) tests, which were found useful for comparative studies. Using whole cells, strain-specific antigens were also demonstrated by COA and IFL tests with the use of cross-absorbed antibodies. The results corresponded to those obtained with C-LIE and R-LIE. Immunosorption experiments indicated identity between the strain-specific antigens shown by COA tests and those demonstrated by C-LIE and R-LIE tests.


Catabolite repression in Aspergillus nidulans; the role of glutamine synthetase. A mutant (nit8) with a lowered activity of glutamine synthetase (GS) was isolated in Aspergillus nidulans. The levels of GS and of an arginine catabolic enzyme, ornithine transaminase (OTA) were assayed under a variety of growth conditions leading to repression, depression and induction of OTA in the wild type, nit8 and several regulatory mutants. The results obtained appear to exclude the possibility of involvement of GS in the regulation of arginine catabolism in A. nidulans.


Genetic mapping of the chromosome of Rhizobium trifolii. Cultures of the wild strain and auxotrophic mutants of Rhizobium trifolii T37 synchronized by means of phenylethanol have been mutagenized with nitrosoguanidine. Fifteen genetic markers were characterized in respect of their order and the time of replication based on the peaks of mutations of the genes. The time of R. trifolii chromosome replication was estimated using inhibitors of the initiation of DNA replication: rifampicin, chloramphenicol and phenylethanol. The replicative map of R. trifolii chromosome has been constructed. Taking into account the replicative map, linkages of the genes, and the bidirectional model of the Rhizobium chromosome replication, a circular genetic map of the chromosome of R. trifolii T37 was elaborated.


Replication of plasmid R6K in DNA polymerase deficient mutants of Escherichia coli. The plasmid R6K has been introduced into a number of Escherichia coli polymerase deficient (pol) mutants. In polCts mutants transferred to the nonpermissive temperature to inactivate polymerase III, R6K replicates but the replication products have a density in dye-CsCl gradients intermediate between supercoiled and linear forms. This aberrant replication requires normal cellular levels of polymerase I since it does not occur in polA polCts mutants. Normal R6K replication and maintenance occur in a polA polB polC+ host, however, we cannot tell from our experiments wheather polymerase I or III replicates R6K in polA+ polC+ host. Polymerase II, the polB gene product, has no detectable role in R6K replication.


Genetic properties of the Salmonella enteritidis R404 plasmid aggregate. III. Entry exclusion features of its separative forms. The genetic relationship of four plasmids separated from R404 plasmid aggregate has been characterized by investigating entry exclusion and intracellular incompatibility. It has been found that the four plasmids exist in an autonomous state in cells carrying the aggregate. They are compatible and the two conjugative plasmids possess different traS genes.


Restoration of effectiveness of R. meliloti ineffective mutants by transduction of high level streptomycin resistance. Rhizobium meliloti lysine dependent mutant, L5-30lys, was ineffective and this mutation was not cotransducible to lys. Transduction of chloramphenicol and linked temperature sensitive mutations did not change its symbiotic properties. Subsequent transduction of high level streptomycin resistance restored its effectiveness. Streptomycin resistance marker was linked to chloramphenicol resistance and temperature sensitive markers.


Ultraviolet induced mutations in Aspergillus wentii. Aspergillus wentii (IMI 17295) and its three nutritional mutant strains were irradiated with UV rays. New mutants obtained differed from the parent strains in colour of the conidia, growth factor requirements and amylase activity. Arginine deficient strains showed greater amylase activity.


Mutants of Streptococcus lactis subsp. diacetylactis lacking diacetyl reductase activity. Three strains of Streptococcus lactis subsp. diacetylactis, namely DRC-1, DRC-2 and DRC-3 which produced diacetyl up to 120 h of incubation were exposed to the ultraviolet irradiation as well as N-methyl-N'-nitro-N-nitrosoguanidine (NTG) to isolate mutants lacking diacetyl reductase activity. UV irradiation did not produce any isolate completely devoid of diacetyl reductase activity, though, 99.5% loss in activity could be achieved. NTG treatment proved to be more effective and seven survivors exhibiting complete loss of diacetyl reductase activity were recovered. These altered characteristics were retained on repeated subculturing.


Polypeptide antibiotic 26a from Bacillus subtilis. III. Physicochemical and biological in vitro properties. Antibiotic 26a, a weakly basic (pK1 3.85 and pK2 7.1) polypeptide compound, has been recovered from the fermentation fluids of bacillus subtilis cultures as hydrochloride salt easily soluble in water and dimethylsulphoxide, sparingly soluble in lower alcohols and insoluble in several organic solvents. At low concentrations 26a was effective against gram-positive bacteria, mainly micrococci and corynebacteria, moderately active against mycobacteria, and inactive against gram-negative bacteria, yeasts and moulds even at 300 microgram/ml concentration. From the viewpoint of elemental analysis, electrometric titration, optical rotation, UV, IR and NMR spectra, amino acid composition, molecular weight and biological observations, 26a can be considered as an antibiotic, if not identical, then closely related to bacitracin family polypeptides.


Polypeptide antibiotic 26a from Bacillus subtilis. IV. Evaluation of biological in vivo activity. The studies performed with the antibiotic 26a, which has a close resemblance to bacitracin family polypeptide antibiotics, revealed a prominent therapeutic and protective actions. The antibiotic is characterized by a moderately low toxicity, lack of cytotoxic and cytostatic effects on several tissue cultures, and therapeutic effectiveness in lethal streptococcal infections in mice, and corynebacterial infections in guinea pigs.


Studies on alkaline phosphatase in normal and nitrofurantoin resistant Vibrio el tor. Activity of alkaline phosphatase as well as its substrate specificity in Vibrio el tor and in nitrofurantoin resistant Vibrio el tor have been studied. A lower level of activity is observed in Vibrio el tor after its acquisition of resistance towards nitrofurantoin. The enzyme activity in both the strains is significantly inhibited by EDTA, and also by metal ions like Mg++, Zn++ and Mn++. The normal strain is found to possess two isoenzymes for alkaline phosphatase whereas the resistant strain has only one isoenzyme.


Septal ultrastructure in Candida albicans. Fine structural studies on the septa of Candida albicans in vitro (when leading a saprophytic existence) and the organism in its invasive form (as a pathogen in oral candidosis) have shown that in the former the septum exhibits a unique central perforation resembling an aggregate of fine canaliculi connecting one cell to the other. In the invasive form the septum is non-perforated and appears as a solid structure. Septal ultrastructure is well characterised in many pathogenic fungi. Our observations on Candida albicans do not resemble any previous studies carried out on other deutromycetous fungi.


Nitrification of industrial wastewaters with high nitrogen concentration. Industrial wastes from the production of nitrogen fertilizers, containing about 900 mg N/1, (450 mg NH4-N, 300 mg urea-N and 150 mg NO3-N), showed high activity of I stage nitrifying bacteria. The addition of phosphorus to the wastes increases the intensity of nitrification two-fold and also increase the rate of urea hydrolysis. An attempt was made to obtain a nitrifying activated sludge. CaCO3 and Fe(OH)3 were used as carriers and the culture was aerated with air enriched with CO2. After 90 days an activated sludge was obtained which nitrified an average of 80% NH4-N and urea-N with 4-day aeration time of the wastes. In contrast to the activated sludge, the presence of nitrification phase I and II in biological bed was observed, but the efficiency of the process was considerably low (about 38%).


Three-dimensional architecture of the golgi apparatus in Sertoli cells of the rat. Glutaraldehyde-fixed testes were stained "en bloc" with the Ur-Pb-Cu technique of Thiéry and Rambourg ('76) or post-fixed and stained with the osmium tetroxide-potassium ferrocyanide method of Karnovsky ('71). Thin or thick (up to 3 micron) sections were examined with the Philips (301 or 400) EM or the high voltage EM. Stereopairs were prepared with photographs of tilted specimens (+/- 7 degrees). At low magnification, in thick sections (0.5-3 micron) stained with Ur-Pb-Cu, the whole Golgi apparatus formed a single network of interconnected wavy ribbon or platelike structures extending from the juxtanuclear region toward the apex of the cell. At higher magnifications, with the two staining techniques, this Golgi network showed two distinct types of regions: the "saccular region" corresponding to the conventional stack of saccules and the "intersaccular connecting region" made up of anastomotic tubules which bridge adjacent stacks. In the saccurlar regions, there was, on the cis-face of the stack, a tight polygonal meshwork of anastomotic tubules (osmiophilic element). Underlying it there were three to seven closely apposed saccules perforated with pores of various diameters, and finally, on the trans-face, a network of tubules was usually connected to the last saccule of the stack, which seemed to peel off" from the pile. The intersaccular connecting regions showed proximal and distal zones with regard to the associated stacks. The proximal zone was made up of superimposed and parallel polygonal networks of membranous tubules which were continuous with corresponding saccules of the stack. In the distal zone they interdigitated, intertwined, anastomosed and bridged adjacent saccular regions; others turned at right angles and established connections with tubular extensions arising at various levels of the same stack. While cisternae of endoplasmic reticulum were contiguous with tubules or saccules located on the transface of the Golgi apparatus, a close association between the ER cisternae and the cis-face of the stacks was not usually observed.