Cellular immune responses in familial medullary thyroid carcinoma. We studied prospectively 46 members of a kindred with familial medullary thyroid carcinoma to determine the importance of possible cellular immune reactivity to tumor antigen. We evaluated in vitro production of macrophage-migration-inhibitory factor and 3H-thymidine uptake by lymphocytes from patients, family members and normal subjects in response to extracts of medullary thyroid carcinoma and normal thyroid tissue. Lymphocytes from 12 of 18 patients with medullary thyroid carcinoma and four of seven patients with C-cell hyperplasia produced migration inhibitory factor or proliferated (or both) in response to tumor antigen. In contrast, cells from only two of 25 normal subjects and two of nine family members not genetically at risk for medullary thyroid carcinoma made migration inhibitory factor and proliferated to tumor antigen. Of particular interest, lymphocytes from six of 12 clinically normal family members genetically at risk for medullary thyroid carcinoma exhibited cellular immune reactivity to tumor antigen.


"Somatostatinoma": a somatostatin-containing tumor of the endocrine pancreas. We studied the pancreatic and enteric hormone profile of a 46-year-old woman who had hyperglycemia and a pancreatic tumor. Before operation, there was no evidence of overproduction of glucagon or insulin. The tumor's ultrastructure had a distinctive endocrine morphology, resembling D cells. Prompted by the recent demonstration of somatostatin in D cells of pancreatic islets, we analyzed the tumor and found a large quantity of immunoreactive somatostatin (301 ng per milligram of tissue). Insulin, glucagon, gastrin, vasoactive intestinal polypeptide and human pancreatic polypeptide were present in only trace quantities. The tumor cells were cultured in monolayers, which remained viable up to 51 days and released somatostatin into the culture medium. In seven insulinomas and two glucagonomas, we found the somatostatin content either much lower (less than 0.6 ng per milligram of tissue) or undetectable. After complete resection of the tumor, our patient became euglycemic and has remained so for the past 20 months.


Examination of the effect of age and acquired immunity on the susceptibility of mice to infection with Aspergillus fumigatus. Adult CBA mice showed considerably greater resistance to experimental infection with Aspergillus fumigatus than young animals of the same strain (P less than 0.01). Furthermore, in contrast with the young mice, the susceptibility of the adults was only moderately increased by treatment with cortico-steroids. On the other hand, immunosuppressive treatments producing severe depression of lymphocyte function greatly increased susceptibility to lethal infection and promoted fungal growth in a wide range of tissues. These observations suggested a role for specific acquired immunity in the relatively high resistance to experimental aspergillosis shown by older mice.


Counterimmunoelectrophoresis and opportunistic fungal infections. Sera from 35 apparently normal humans, 37 compromised human patients, 30 hedgehogs and 30 sheep, were examined for precipitating antibodies to four opportunistic fungi - Absidia corymbifera, Aspergillus fumigatus, Candida albicans and Rhizopus arrhizus-using counterimmunoelectrophoresis (CIE). Precipitins to A. fumigatus were almost exclusively confined to specimens obtained from the compromised human group (51% of those examined) while Candida precipitating antibodies were detected in the sera of both normal (26%) and compromised (49%) humans and in 10% of the hedgehog specimens. Serum precipitins against the two phycomycetes included in the investigations were rare. Because of the complexity of most fungal antigen extracts, it appears the two phycomycetes included in the investigations were rare. Beause of the complexity of most fungal antigen extracts, it appears essential that sera be tested against a number of different antigen concentrations if CIE is to be used with confidence in fungal serology.


[Membrane permeability and antibiotic resistance in bacteria]. The resistance of mainly gram-negative bacteria against antibiotics is discussed with respect to new discoveries on the permeability barrier of the outer membrane. Proteins originally characterized as virus receptors have been found to be involved in the translocation of certain substrates across the membrane. Antibiotics can reach their target by the same "pores".


Proteinuria following renal transplantation. Proteinuria was studied in ten renal allograft recipients; it was defined as: (a) glomerular--characterized by predominant albumin excretion; (b) tubular--significant excretion of both albumin and low molecular weight (LMW) proteins; and (c) glomerulo-tubular or mixed type, a combination of the two. LMW protein and albumin were quantitated by polyacrylamide gel electrophoresis with sodium dodecyl sulfate. In the immediate posttransplant period, LMW protein and albumin excretion, expressed as a percentage of creatinine clearance, were high, revealing a mixed pattern, and excretion of both protein classes was higher than during both acute tubular necrosis and acute rejection crisis. Tubular proteinuria was observed in acute tubular necrosis; a glomerulo-tubular or mixed pattern of protein excretion in acute rejection crises.


Electrographic and clinical effects of intracarotid sodium amobarbital on bilateral myoclonic status epilepticus. The effects of rapid intracarotid injection of 20 to 100 mg of sodium amobarbital were studied in three patients with bilateral myoclonic status epilepticus due to Jakob-Creutzfeldt disease, sequelae to anoxic encephalopathy, and hepatic coma, respectively. In each instance, the drug produced prompt abatement of clonic jerks contralaterally and attenuation of electroencephalographic epileptiform discharges ipsilaterally. These results suggest that the cerebral cortex actively participates in the elaboration of certain types of bilateral myoclonus in human beings.


Drug interactions during anticonvulsant therapy in childhood: diphenylhydantoin, primidone, phenobarbitone, clonazepam, nitrazepam, carbamazepin and dipropylacetate. It is well known that the concomitant use of different drugs may alter the reactions of the body towards the individual components. This is particularly important in long-term anticonvulsant therapy which is frequently a combined therapy. By carrying out statistical analysis of more than 6000 assays of the serum levels of antiepileptic drugs an attempt was made to gain insight into the possible drug interactions. The following results were obtained: 1. There was an increase in serum levels of diphenylhydantoin when either clonazepam or dipropylacetate (short-term therapy) was given concomitantly. 2. There was a decrease in serum levels of diphenylhydantoin when carbamazepine, primidone or dipropylacetate (long-term therapy) were administered concomitantly. 3. There was an increase in the serum level of phenobarbitone when it was administered together with diphenylhydantoin. 4. There was an increase in the serum level of primidone when it was administered together with clonazepam. 5. There was a decrease in the serum level of primidone if it was administered concomitantly with either carbamazepine or dipropylacetate (long-term therapy).


[Anamnestic questionnaire of the Italian Diagnostic Center]. A model of computerized clinical history is presented for physicians and anyone else interested in automatic information processing. The questionnaire should be compiled by the patient, controlled and examined by paramedical and medical staff, processed and managed by computer and organized into an output report. In addition to historiddition to historical data, this report includes the results of fun ctional and laboratory findings. In such a context, the purpose of anamnesis is to provide a complete clinical history in the interests of the better "classification" of the patient. Its logic and structure, however, also lends itself well to clinical and statistical uses and to a standardization of the clinical card.


[Combination of antimetabolites and alkylating agents in the treatment of advanced breast cancer]. An association of 5-fluoruracyl (or methotrexate) and cyclophosphamide was used in the treatment of 20 cases of hormone-resistant breast cancer. Five objective regressions were obtained. Mean survival here was 28.25 (S.D. 2.87) months, as opposed to 12.75 (S.D. 6.93) months in the remainder. Side-effects of various kinds were noted in 9 patients.


[Combination antimetabolite-alkylating agent-vinblastine in the treatment of advanced breast cancer]. The results obtained in 14 patients suffering from hormone-resistant metastatic breast cancer treated with the following association: methotrexate (5-fluorouracyl in case of methotrexate intolerance), cyclophosphamide, vinblastin administered i.v. once every 10-13 days, are reported. 4 objective regression (29%) were observed but survival did not very appreciably differing therapy. In 9 cases (65%) intolerance of various types was observed but in 8 these signs regressed in a short time and the therapy was resumed.


[Use of dimethothiazine in the prevention of hemicrania]. The best results in the prevention of migraine have so far been obtained with tricyclic antihistamine, anti-5HT drugs. Experimentation of dimethothiazine--already widely employed in the management of essential headache--in this field is reported. Results obtained in a double-blind trial with a placebo on randomised levels and on a large series evaluated with Pearson's scatter index showed that the drug was effective, especially in the prevention of classic migraine. It was also usuable during attacks and in the prevention of cluster headache. Good tolerance and the absence of side-effects suggest the adoption of a standard course of 60 mg/day for not less than 2 to 3-4 months. Other therapeutic courses may be alternated during the year.


[Pharmacokinetic and clinical research on a new antibiotic combination (amoxicillin and flucloxacillin in equivalent-weight dose)]. A controlled double-blind biometric and an open clinical trial were conducted to determine the therapeutic effectiveness of a new equal-dose w/w association of amoxicillin and flucloxacillin. The following conclusions were drawn. Both antibiotics were present in high serum levels; those of flucloxacillin were higher and more persistent. Analysis of variance on 89 patients pointed to the superiority of the association by comparison with amoxicillin alone. The clinical study made it clear that the broad and complementary spectrum of the association, its synergy, absence of toxicity and good gastric tolerance make it a valuable and effective therapeutic aid, also in presence of germs that produce beta-lactase.


[Pharmacokinetics and clinical aspects of a new ampicillin]. The chemical, physical, kinetic features, spectrum and clinical employment of amoxicillin (alpha-amino-p-hydroxbenzylpenicillin) are described. A kinetic study on 48 volunteers indicated its rapid gastroenteric absorption. In addition, the new drug quickly reached serum levels that were able double those obtained with corresponding ampicillin doses of equal weight. A very satisfactory therapeutic response and no more than trivial side-effects were noted in a clinical trial on 106 patients, most of whom presented bacterial infection of the upper and lower airways.


Pituitary responses in LH secretion to LHRH during pregnancy. Thirty-six pregnant women and 15 normally menstruating women were each given 100 microng of synthetic luteinizing hormone releasing hormone (LHRH) by a single intravenous injection. Human chorionic gonadotropin (hCG), luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels were determined by specific radioimmunoassay (RIA) technics. For the determination of the serum LH levels, the LHbeta-RIA method, which is unaffected by hCG at sample levels as high as 500 IU/ml, was used. Serum concentrations of LH and FSH were lower in pregnant women than in the normal women in the follicular and luteal phases. While the release of LH was observed in pregnant women following the administration of LHRH, the average net increase was less than that seen in both the follicular and luteal phases. During pregnancy, there was a progressive decrease in the LH response to LHRH, but no release of FSH.


A critical review of the frequency of lymph node metastasis and death from microinvasive carcinoma of the cervix. The lack of a uniform, specific definition of microinvasive carcinoma of the cervix has made it difficult to extract from the literature a sufficient number of cases similarly defined from which to estimate the risk of nodal metastasis or death from tumor. Factors potentially biasing the frequency of nodal metastasis and death from tumor are examined, and series lacking such factors are used to provide estimates of the risk of metastasis or death from tumor for various specific definitions, but the number of cases fitting each definition are too few at present to give reliable estimates.


[Latticed or dendritic lines on the periphery of the retina]. Latticed or dendritic lines (true white lines) on the periphery of the retina. Vitreo-retinal adherences between the ora and equator correspond to former embryonal blood vessels to the vitreous (or retinal vessels) attaching to the retina. Between attachments of vitreous consolidations coming from in front and behind as a congenital anomaly of the retina, the latter is either loosened or replaced by connective tissue, or there is a defect, wedge-shaped from within outwards (colobomatous). These are obviously very frequently comgenital. The vitreous between and above the vitreous-retinal attachments is always liquefied and structureless. With increasing age, there is a reactive proliferation of the connective tissue (vessel-vitreous medullary cells) and pigmented epithelium. This new tissue either replaces the retina or rests on it distinctly localized, and has a strong tendency to hyalinization and sclerosis (sclerotic degenerative area). The latticed or dendritic lines (true white lines) on the periphery of the retina which for preference appear in the region of the degenerative sclerotic area sometimes consist of obliterated vessels with hyalinized walls and sometimes of hyaline connective tissue threads which are independent of the vessels. Frequently the vitreous fibre strands (vitreo-retinal adherences) may also continue through the inner retinal layers as far as these dendritic hyaline (white) retinal threads of connective tissue.


Assessment of calcium dobesilate in diabetic retinopathy. A double-blind clinical investigation. In this double-blind, randomized trial, which lasted for 2 years, the authors investigated the efficacy of calcium dobesilate on diabetic retinopathy. 68 patients (51 on the active substance, 17 on placebo) participated in the study. The statistical analysis of the results indicate that calcium dobesilate acts as a potent angioprotector, capable of preventing both intra and extraretinal hemorrhages. The drug also lowers the incidence of exudate formation and improves visual acuity.


Surgical correction of the atrophic alveolar ridge. A preliminary report on a new concept of treatment. Inferior repositioning of the atrophic maxillary edentulous alveolar ridge by LeFort I osteotomy and simulataneous bone grafting, and superior repositioning of the atrophic mandibular edentulous ridge by horizontal osteotomy of the mandibular body and simultaneous bone grafting have been accomplished successfully. These two new surgical procedures add a new dimension to treatment of severe atrophy of the alveolar ridges in edentulous or partially edentulous patients.


A mandibular cystlike lesion in a prehistoric American Indian. A possible multilocular cyst or ameloblastoma is reported in a 1,200-year-old prehistoric American Indian. A description of this lesion and its incidence in early populations is reviewed.


[Short and long term behaviour of pleural effusion cultures. (Report of 200 cases) (author's transl)]. Pleural effusions from 200 patients with benign or malignant pleural involvement have been cultured in vitro and observed from 48 hours to 9 months. The morphology and "social behavior" of the different types of cells are described. Mesothelial cells settle down quickly and come into contact with each other by long cytoplasmic processes. The tendency of epithelial malignant cells is to clump and grow in clusters. These "balls" of varying size are freed into the culture medium. Similar clusters may be found in benign effusions showing mesothelial hyperplasia. In case of malignant primary tumor of the pleura, the morphology of cultured cells is similar to that of mesothelial cells. In 3 cases, typical malignant epithelial cells have allowed us to discard the diagnosis of malignant mesothelioma. Discrepancies between conventional cytology and cell culture were found in 13 cases: in 6 cases, positive for malignant cells using conventional cytology, cell culture was negative. In 7 cases with negative routine techniques, cell culture disclosed malignant cells. Large multinucleated syncytia were observed in 15 cultures. They suggest a cytopathic effect similar to that seen in myxovirus infected cells. Correlation with the etiology of pleural effusions in these cases is described.


[Humoral study of human parasitic diseases. Interest of ELIEDA. (Enzyme--linked--immuno--electro--diffusion--assay) (author's transl)]. In order to sensitize the reaction of immuno-electro-diffusion (IED) and to define the class of immuno-globulins implied in the antigen-antibody reaction, we have completed the technique of IED by coupling it to an enzymatic technique. In such a way the immune complexes are treated by enzyme labeled antibodies specific to each class of immunoglobulin. This association realizes the technique of ELIEDA (enzyme-linked-immuno-electro-diffusion-assay). The sensitivity and the specificity of this method allow the follow up of the qualitative evolution of antibodies during natural or experimental parasitic diseases.


[The cellularity of fibrillated articular cartilage. A comparative study of age-related and osteoarthrotic cartilage lesions from the human femoral head]. The cellularity of human femoral head cartilage has been studied in age-related and osteoarthrotic fibrillated samples and control intact samples. Age-related fibrillated cartilage shows a marked increase of the cell density which is directly related to the proliferation of cell clusters and to cartilage thinning. In osteoarthrotic cartilage lesions multicellular clusters are less frequent and cell density is decreased. A smooth aspect of the exposed cartilage surface and an increased subchondral bone mass are only found in osteoar/hrotic samples. The findings suggest that age-related and osteoarthrotic cartilage lesions are due to different mechanical stresses governing the cellularity of the tissue.


[Anticomplementary activity of a polyanion: polyanion: pentosan-poly-sulfoester. I. "In vitro" study and "in vivo" trial in human glomerulonephritis (author's transl)]. The drug, pentosan-poly-sulfoester (PPS), has an anticomplementary activity (ACA) on human serum both in vitro and in vivo, as judged by a reduction in total hemolytic complement activity (CH 50). In vitro, this ACA is very potent, immediate and temperature independent. In vivo this ACA obtained with a IV dose of 100 mg per 8 hours eg 300 mg/24 h, increases with the duration of treatment (mean time:30 days), suggesting a cumulative effect. Eleven patients with glomerulonephritis (GN) received such a treatment (8 with acute post-streptococcal GN and 3 with mesangio-proliferative GN). In patients with already marked hypocomplementemia, the ACA is difficult to establish, while in patients with normal complement activity or moderate hypocomplementemia, the decrease of CH 50 level in serum is obvious. There was no significant change inthe serum level of C3, C4, properdin factor B as measured by radial immunodiffusion technique. The clinical course of these GN was apparently not affected by this treatment. Neverthless, the in vivo ACA of PPS is firmly established and we can speculate that this functional depletion in complement may prevent or decrease the liberation of humoral mediators of inflammation.


Crystalloid nature of mineral deposits in Bowman's capsule of the human glomerulus. Study by X-ray microanalysis and electron microdiffraction. Abnormal crystalline mineral deposits are often observed in the basement membrane of Bowman's capsule in the human glomerulus. The nature of these deposits has been the subject of much discussion. By means of electron probe microanalysis and electron diffraction techniques, we have identified these abnormal deposits as whitlockite (beta-calcium-orthophosphate).


[Inherited and familial bisalbuminemia. Acquired transient bisalbuminemia (author's transl)]. The present study is a survey of the different types of bisalbuminemia. In the inherited and familial form, the anomaly is fortuitously discovered and not associated with disease. The abnormal albumin fraction only differs from the normal one in a slight alteration in the aminoacid sequence, responsible for increased ("fast type") or decreased ("slow type") electrophoretic mobility. The anomaly is genetically determined and is transmitted as an autosomal codominant character. The condition is relatively rare, but has been observed in most parts of the world, with some higher incidence in many American Indian tribes. In the acquired transient biaslbuminemia, the abnormal component of the albumin is always of the fast type and occurs in patients either receiving large amounts of beta-lactamine type antibiotics, or suffering from pancreas diseases.


[Levamisole, stimulant of the immune system in animal and man (author's transl)]. Levamisole, a drug initially used for its antihelminthic properties has been recently emphasized when Renoux proved its immunostimulating effects in mice en 1971. Since this date, numerous publications concerned the immunological activity of this drug in animals and men. These come to the conclusion that levamisole is capable of restoring cellular immunity as demonstrated by clinical and biological tests (restoration of delayed skin hypersensitivity, increase of the percentage of rosette forming cells and PHA transformed cells). In men, its seems possible to confirm the therapeutic activity of this molecule in a wide range of disease with suspected or proven immunological deficiency. In different forms of cancer, when most of the tumor volume is first reduced, levamisole therapy significantly increases both remission and survival. In auto immune diseases (rheumatoid arthritis, systemic lupus erythematosus), levamisole seems to be strikingly effective. In viral infections (zoster, recurrent herpes, aphthous stomatitis) levamisole is able to reduce the duration of outbreaks and prolong the disease free interval. Finally, encouraging results have been obtained in patients with lepromatous leprosis. Other conditions, where an immunological deficiency is suspected are under study with levamisole therapy. This low molecular weight synthetic drug is perhaps the first pharmacological agent which acts on the host defense mechanisms.


[Serodiagnosis of gram-negative urinary infections (author's transl)]. The authors recall the interest of serodiagnosis of urinary infection in children for the diagnosis of pyelonephritis and supervision during treatment. They then give details of the technic of estimation of specific antibodies for Gram negative bacilli isolated during past and present infections.


[Study of magnesium level in myocardium and aorta tissues from subjects free of ishemic necrosis (author's transl)]. Before carrying out a study on the levels of magnesium in the myocardium and the aorta in subjects who had died of coronary thrombosis, we determined the reference levels of magnesium in the right and left ventricles and in the aorta of sixteen normal subjects. The samples were homogenized and digested with nitric acid/hydrochloric acid mixture before the measurement itself was made; this was carried out by atomic absorption spectrophotometry. The magnesium values are expressed in microng/g of wet tissue, in mg/g of tissular proteins, in mg/ of total lipids in the aortic wall. The differences between the concentrations of proteins or magnesium in the left and right ventricles are significant magnesium in the left and right ventricles are significant (P less than 0,001). They probably derive from anatomic and physiological differences. We have found a correlation which is significantly positive between magnesium level and protein level in the ventricle. In the aorta, the results for proteins, lipids and magnesium are extremely dispersed because of the heterogeneous nature of biochemical composition of this tissue according to age and area which it has been taken from.


[Anticomplementary activity of a polyanion: pentosan-poly-sulfoester, II.--Mode of action and "in vitro " inhibition of human complement hemolytic activity (author's transl)]. The drug, pentosan-poly-sulfoester (PPS), is a potent in vitro inhibitor of the human complement hemolytic activity. This CH 50 inhibition represents a real anticomplementary activity (ACA), because this drug has no effect on sensitized sheep red blood cells (EA). The inhibition curve of human serum CH 50, by PPS is sigmoidal. The 50% inhibition is obtained for a 1: 650 dilution of PPS, which corresponds to a concentration of 0.08 mg/ml in normal human serum. Hemolytic titrations of C1, C4, C2, C3, and C5 showed a complete inhibition of C4, C2 and C3, and a partial inhibition of C1 (C1q, C1r, C1s, Ca++) and C5, by this drug. The mechanism of such functional inactivation of the different complement components is not yet elucidated.


[Allogenic bone marrow grafts (author's transl)]. Bone marrow transplantation is a major therapeutic approach for treatment of patients with severe aplastic anemia or acute leukemia refractory to chemotherapy. It is possible only if an HLA matched sibing is found. ABO compatibility is not necessary. The conditionning regimen includes high doses of cyclophosphamide associated or not with a 1 000 rads total body irradiation. In acute leukemia, the two year percentage survival is 17%, in aplastic anemia it is 40%. Complications are immunologic : rejection, graft versus host disease and persistent severe immune deficiency.


[Regulation of cell renewal in the gastrointestinal mucosa (author's transl)]. The renewal of the digestive mucosa is the most efficient process assuming the maintenance of the gastrointestinal barrier. The mucous and absorptive cells, born in the proliferative zone, are migrating to the surface and they extrude duirng meals, living 4 to 6 days. Hyperphagia, pregnancy, lactation and intestinal resection induce a hypertrophic state. Fasting, ageing, germ free status provoke a hypoplasia. The ulcerogenic and antimitotic drugs decrease the proliferative activity. The gastrointestinal cell renewal is controlled by hormonal, vitaminic and nervous agents. Gastrin and growth hormone are the major trophic factors, secretom amd cprtocpsteroids act as antitrophic agents. The vitamins A, D and B12, and the nervous transmittors participate in the feed back control assuming a steady state between proliferation and extrusion. Chalones and immunologic factors are probably the most important but unknown inhibitors. The pathological events concerned with abnormal renewal are peptic ulcer, atrophic gastritis, intestinal villous atrophy and digestive cancer.


[Sensitivity of "Haemophilus influenzae" to 5 antibiotics and rapid detection of its resistance to ampicilin (author's transl)]. Sensitivity of Haemophilus influenzae to 5 antibiotics has been determined by the agar dilution method. Two strains out of 165 are resistant to ampicillin and 5% to tetracycline. All strains were sensitive to chloramphenicol, cotrimoxazole and cefuroxime. A simple test for rapid detection of beta-lactamase with a chromogenic cephalosporin and sensitivity testing by an agar diffusion method were evaluated for Haemophilus.


[Refractory sideroblastic anemia, three cases with the same extra marker chromosome (47, Mar +) (author's transl)]. Three very similar cases of sideroblastic idiopathic anemia were respectively observed for 105, 57 and 69 months. The cytogenetic blood study was normal. But the medullary genetic findings showed marker extra-chromosome, having the same aspect in each metaphase = 47 Mar +. It was respectively found in 13 mitoses/32, 2/45 and 1/30. The study of chromosome showed that it was not a normal cytogenetic C-chromosome at all, even it seemed to be a C - X type chromosome at first. The long arms had about the same size as the one of the C- type. But the short arms were really shorter. The study on R- bands showed a chromosomic marking unkown so far. The cytogenetic abnormalities described during the sideroblastic idiopathic anemias, the rare sideroblastic idiopathic anemias where were found a C- type chromosome really identified, then the well-defined myeloproliferative disorders having an extra- C chromosome, have been looked over again through the litterature. In each of our three studies we can think that these myelodysplasia are real mysloproliferative disorders because of the same marker extra-chromosome, but even after nine months we did'nt observe any chromosomal sign of blastic transformation.


Management of the obese adolescent.

Management of the obese adolescent. Obesity as a health problem appears to be increasing in incidence. Adolescent obesity is generally exogenous in type. The teenagers are basically healthy with advanced sexual and bone maturation. They suffer from peer ridicule and exclusion from activities. The weight problem bars them from successful adult adjustment in their social lives and career choice. To the physician who treats the obese adolescent, it would be wise to review the pitfalls of previous programs. The multidisciplinary approach is an attempt to combine dietary restriction and increased physical activity to gradually mobilize fat stores and provide psychologic support. Motivation is reinforced by a committed staff and by the patients' own obese peers with whom they meet weekly. Despite the repeated record of failure in adolescent weight reduction programs, it is hoped that the challenge of obesity management spurs the interest of physicians to increase their knowledge of nutrition and to intervene with early effective preventive measures.


Nutritional management of the chronically ill child. Congenital heart disease and myelomeningocele. We have presented some of the nutritional complications encountered in two major pediatric congenital disorders. Although these conditions represent two more common major defects, it is unlikely that many health care providers will manage large numbers of these patients. Nevertheless, the nutrition principles apply to other nutritional dilemmas of chronically ill children. When an infant consumes a low volume intake, regardless of etiology, concerns such as provision of adequate nutrition, within the confines of the infant's water balance, become paramount. Methods have been discussed for increasing caloric density and for monitoring dietary safety and adequacy. When an infant has a propensity for becoming obese one needs to consider preventive measures such as providing sound nutrition information, support, and follow-up for both patient and family. Nutritional problems can become magnified unless adequate support is provided for total health and social needs of the family. The role of the dietitian must be one active participation within the the framework of an interdisciplianry team so that appropriate innovative nutrition programs can be developed and implemented.


Federal nutrition support programs for children. In summary, the physician as a concerned citizen, contributing taxpayer, and key provider of child health care can provide responsible leadership in assuring that nutrition support services for children include assessment of their nutritional status, provision of a safe food supply adequate in quality and quantity, nutrition counseling for specific nutritional problems, and sound nutrition education for children, parents, and all other caretakers of children.


Office assessment of nutritional status. The standard components of nutritional assessment-anthropometry, clinical examination, dietary intake, and biochemical analysis--have been discussed in the context of "office or clinic practice." With appropriate modifications of these tehcniques, nutritional assessment can become a basic and integral part of pediatric care.


Commercial infant foods: content and composition. The relative contribution of strained foods to total dietary caloric distribution is important when assessing the appropriateness of a particular food choice. Because protein intakes by most infants in the United States are generous, the high carbohydrate content of the typical strained food can be helpful in adjusting the distribution of calories. The fat content of most strained foods is low and those foods higher in fat are also comparatively high in protein content. Therefore it is difficult to find strained foods to contribute greater amounts of dietary fat without also increasing the percentage of calories in the form of protein. For this reason it is not possible to achieve a satisfactory distribution of calories in the diet of an infant fed skim milk. With the exception of home-prepared fruits with low sugar content, baby food prepared in the home will probably have a higher caloric density than commercial products. Care should be taken not to overfeed infants when feeding home-prepared baby foods. The appropriateness of United States baby foods for use in developing countries and a physiological rationale for age of introduction of strained foods were discussed. A basic need is to ensure that the strained foods of the future are formulated with emphasis given to nutritional need and least cost, as well as to mother's taste and to the manufacturer's profit.


Decrease in size of intrathoracic meningocele following insertion of a ventriculo-venous shunt. A case of spontaneous disappearance of an intrathoracic meningocele following insertion of a ventriculo-venous shunt is reported. The shunt was performed for treatment of hydrocephalus secondary to Arnold-Chiari malformation. The intrathoracic meningocele reappeared when the shunt obstructed and decreased in size when the obstruction was relieved.


Prevention of recurrent urinary tract infections in girls. Eighteen girls between the ages of 3 and 13 years--with a history of at least three culture-documented episodes of bacteriuria in the previous year, but without radiologic evidence of major urinary tract abnormality--were placed on a double-blind, crossover study comparing the effectiveness of nitrofurantoin macrocrystals against a placebo in preventing the recurrence of bacteriuria. Each child was placed on a daily low dose of nitrofurantoin (1.2 to 2.4 mg/kg/day) or an identical-appearing placebo for six months. Each child was then placed on the opposite capsule for a similar period. There were 35 episodes of bacteriuria (4.2 episodes/patient/yr) in the patients taking the placebo, which compared with a rate of 3.8 episodes/patient/yr during the year prior to the study. Only two episodes (0.2 episodes/patient/yr) occurred in the patients taking the drug. The difference in the rate of recurrent bacteriuria between the girls on placebo and on medication is significant at the 0.01 level using the Wilcoxin matched-pairs test. There were no adverse reactions to the drug. Nitrofurantoin macrocrystals in a single daily low dose appear to be a safe, effective method of preventing recurrent bacteriuria in girls at high risk.


Serial neurologic examination of hyperactive children. Forty-four of 102 children undergoing pharmacologic treatment of hyperactivity received serial neurologic examinations on five separate occasions. The responses to three of the "soft" neurologic signs administered were analyzed: heel gait, toe gait, and diadochokinesis. A high degree of variability of response within individuals was documented. There was no evidence of interaction between treatment and the subjects' responses. The degree of variability was such that to have used these data as measures of "improvement" (i.e., drug effect) would have been misleading. The value of these signs for purposes of diagnosis or assessment of therapy is doubtful.


[Value of anticonvulsant level determination in the treatment of epilepsies]. Phenobarbital and diphenylhydantoin were estimated in treated epileptics. An initial measurement was made in 457 patients. 96% were taking phenobarbital and 53% diphenylhydantoin. Only 37% of the phenobarbital levels and 18% of the diphenhlhydantoin levels were in a therapeutic range. Correlations between the levels, the stability of the epilepsy and signs of overdosage are discussed. Intolerance to phenobarbital reported in some patients, which appears to be real, is not reflected by "normal" or even low blood levels. By contrast, high levels of phenobarbital appear to be well tolerated. Signs of overdosage were quasi-constant when levels of diphenylhydantoin were greater than 15 mg/1. Doses of phenobarbital and of diphenylhydantoin were altered, levels assessed and the clinical condition evaluated in 134 patients. Bringing levels to within the therapeutic range resulted in the disappearance of attacks in 55% of cases for phenobarbital and 30% for diphenylhydantoin. Reduction of doses responsible for excessively high blood concentrations (overdosage) was practically never associated with an increase in the number of attacks. This adjustment is easy for phenobarbital though much more difficult for diphenylhydantoin. In this study, therapeutic levels were 15 to 25 mg/1 for phenobarbital, and 7 to 15 mg/1 for diphenylhydantoin.


[Current aspects of human heart transplantation. II. Postoperative surveillance and results]. The cardiac transplantation program of the Pitié-Salpêtrière Hospital has, since October 1973, involved 17 transplants with 15 recipients. Seven patients are alive. Real progress has been achieved in all areas: --selection of the recipient, now more strict is dependent upon precise criteria; --choice of the donor should take into account the best possible tissue and haemodynamic compatibility; --immuno-depressive therapy involves the combination of corticosteroids, azathioprine, antilymphocytic globulins and heparin. It is varied as necessary in relation to episodes of rejection; --the diagnosis of rejection is based upon clinical, radiological and electrical criteria, but also upon new and precise haemodynamic and biological criteria; --long term control is facilitated by regular telephone transmission of the electrocardiogram. The prognosis remains reserved but with socio-professional rehabilitation to help in overcoming the initial slight degree of "hospitalism", the sensation of a new life is such that cardiac transplantation represents an acceptable solution in the treatment of certain cardiac diseases.


[The relation between anti-hypertensive action and plasmatic concentration of pindolol. Preliminary study]. A correlation study between the antihypertensive effect and the plasma level of pindolol was performed in 10 patients with permanent essential hypertension. Pindolol was given orally (20 mg/day) during 9 days. The highly significant fall in blood pressure (delta SBP and delta DBP) is directly correlated negatively correlated, to the pretreatment pressure (p less than 0.02 for deltaSBP and p less than 0.05 deltaDBP) and negatively correlated to the pindolol plasma level (P less than 0.001 for delta SBP and p less than 0.05 for delta DBP). Multiple regression analysis shows, for delta SBP, a stronger influence of plasma level than of basal blood pressure. These results suggest that pindolol could have a specific effect in some hypertensive patients.


Complementable fraction and complemented enzyme of mutant M15 from Escherichia coli: partial purification by affinity chromatography. The technique of affinity chromatography has been used in the partial purification of complementable fractions and complemented enzyme of beta-galactosidase from Escherichia coli mutant M15. The crude extract of mutant M15 was incubated with fragment CM-B. The complemented enzyme and complementable fractions were passed through a small column of p-aminophenyl-beta-D-thiogalactoside to which inhibitors had been covalently attached. A high percentage of the nonspecific protein passed directly through the affinity column while the specific enzymatic protein remained bound to the gel. Phosphate buffer with NaCl was used to elute the complementable fractions from the column. Sodium borate buffer was used to elute the bound complemented enzyme from the affinity support. The results of this study show that 100% of the complemented enzyme was bound to the column. The partially purified enzyme had the same position in disc gel electrophoresis as beta-galactosidase from E. coli.


[Functional activity of the thyroid gland after immunization with the homologous tissue of the pancreas]. An insufficiency of the insular apparatus of the pancreas developed in rabbits in response to the immunization with a homologous tissue of the pancreas. A correlation existed between the thyroid gland function and the endocrine portion of the pancreas. The results of study of the functional activity of the thyroid gland under conditions of immunization with a homologous tissue of the pancreas are presented. The data obtained in the course of the experiment pointed to the changes in the thyroid gland characteristic of the intensification of its function: the height of the epithelium increased, the diametre of the follicles and the index of the colloid accumulation diminished. Experimental results confirmed the literature data on the existence of an inverse relationship between the functional activity of the insular apparatus of the pancreas and the thyroid gland function.


Isomeric aminoacyl-tRNAs are both bound by elongation factor Tu. Recent suggestions that elongation factor Tu (EF-Tu) is specific for 2'-O-aminoacyl-tRNA, as compared with the 3'-isomer, prompted us to assay [3H]aminoacyl-tRNAs from Escherichia coli terminating in 2'- or 3'-deoxyadenosine for binding to EF-Tu to determine the possible positional specificity of the factor. Binding of modified aminaocyl-tRNAs to EF-Tu-GTP was measured both as a function of the ability of EF-Tu-GTP to diminish the rate of chemical deacylation of [3H]aminoacyl-tRNAs and by gel filtration of the individual ternary complexes. Fifteen different tRNA isoacceptors were tested by the deacylation procedure, including three (tRNAAsp, tRNACys, and tRNATyr) for which isomeric modified aminoacyl-tRNAs were available. All of the modified aminoacyl-tRNAs were protected fromdeacylation, although generally to a lesser extent than the corresponding unmodified species. Six modified tRNA isoacceptors (including tRNATrp and tRNATyr, for which both modified aminoacyl-tRNAs were accessible by enzymatic aminoacylation) were used in gel filtration experiments to permit direct measurement of the individual aminoacyl-tRNA-EF-Tu-GTP complexes. These experiments were also done in the presence of equimolar amounts of the corresponding unmodified [14C]aminoacyl-tRNAs, and the relative affinities for a limiting amount of EF-Tu-GTP were measured. The results were completely consistent with those obtained by the deacylation procedure and indicated that EF-Tu can bind to both positional isomers of aminoacyl-tRNA with no obvious preference for either.


Preparation and characterization of a modified form of beta2 subunit of Escherichia coli tryptophan synthetase suitable for investigating protein folding. Globular proteins often appear to consist of distinct compact "domains," and the assumption is frequently implicitly made that these domains correspond to intermediate structures in the folding process. If this assumption is correct, the polypeptide fragment that builds up a domain should be able to spontaneously fold into its native conformation even when isolated. In an attempt to isolate and study such a fragment, the beta2 subunit of tryptophan synthetase [tryptophan synthase, L-serine hydro-lyase (adding indoleglycerol-phosphate), EC 4.2.1.20] has been subjected to controlled proteolysis. The resulting protein is shown to be a dimer, the protomer of which contains two nonoverlapping polypeptide chains of molecular weights 12,000 and 29,000. Though inactive, the nicked protein is shown to be in a conformation that closely resembles that of the original enzyme, since it still can form an enzyme-bound intermediate of the catalytic reactions. The fluorescence of this intermediate is used to characterize the binding sites for the cofactor (pyridoxal-P) and substrates, which are shown to exist on the nicked protein. The possibility is discussed of using the fragments isolated from the nicked protein to study individual steps of the enzymatic reaction, intracistronic complementation, and the folding process in the normal beta2 subunit.


[Insulin content in the erythrocytes and blood serum of patients with acromegaly and Sheehan's syndrome]. Insulin content was studied by radioimmunological and histochemical methods in the erythrocytes and the blood serum of patients with acromegaly and the postpartum panhypopituitrism (Sheehan's syndrome) in comparison with that in healthy persons on fasting stomach and after glucose-tolerance test (GTT). It appeared that the erythrocytes of healthy persons contained 50 times more insulin on fasting stomach than the blood serum. In persons with acromegaly complicated by diabetes mellitus insulin content in the blood serum was almost double that in healthy individuals. But this "hyperinsulinism" was only seeming, since the hormone reserves in the organism (erythrocyte insulin content) were sharply diminished. Sheehan's syndrome was characterized by hypoinsulinemia (both in the serum and in the erythrocytes). After the GTT the insulin content rose in the serum, and decreased in the erythrocytes. This indicated that erythrocytes participated in the homeostasis regulation of glycemia.


Lipid and protein segregation in Escherichia coli membrane: morphological and structural study of different cytoplasmic membrane fractions. Lipid and protein segregations can be induced in E. coli cytoplasmic membranes by conformational transitions of their lipid hydrocarbon chains from a disordered to an ordered state. For E. coli strain K 1059 (an unsaturated fatty acid auxotroph) supplemented with linolenic acid, the segregation leads to large areas of membrane surfaces having distinctly different morphological characteristics (smooth compared with strongly particulated fracture faces, as visualized by freeze fracture electron microscopy). The different regions are physically separated by osmotic lysis of spheroplasts at temperatures below those of the order-disorder transition of the lipid hydrocarbon chains. The analysis of the different cytoplasmic membrane fractions provides a direct demonstration and allows a direct analysis of the segregation. As compared to the nonfractionated membranes, the membrane regions corresponding to the smooth fracture surfaces are poor in proteins, rich in lipids, and enriched in saturated fatty acids, while the membrane regions corresponding to the strongly particulated fracture surfaces are rich in proteins, poor in lipids, and enriched in unsaturated fatty acids. Quantitative information about the extent of these segregations is obtained from high-angle x-ray diffraction of the different membrane fractions and of the corresponding total lipid extracts.


[Effect of clomiphene on the restoration of ovulation in androgen-sterile rats]. In the androgen-sterile rats given 10-250 mug of testosterone-propionate there was observed at the early postnatal period a reduction in the LH-RP level in the hypothalamus, of the LH in the hypophysis and the blood, of the weight of the ovaries and of the corporal luteum count in them, as well as an increase in the dopamine level in the anterior portion of the hypothalamus. Klomiphen administration for 5 days in a dose of 20 mug led to the normalization of these indices and to the appearance of ovulation, but failed to restore the capacity to pregnancy. Prolonged klomiphen administration (20 mug every 3 days for a period of 1 month) also failed to restore this capacity.


Conditionally lethal ribosomal protein mutants: characterization of a locus required for modification of 50S subunit proteins. Mutagenized P1 bacteriophage were used to transduce a marker (aroE) adjacent to the cluster or ribosomal protein genes located at 72 min on the Escherichia coli chromosome. Linked temperature-sensitive transductants were isolated and characterized. A mutant unable to grow at 44 degrees was found to be defective in protein synthesis both in vivo and in vitro. At the restrictive temperature mutant cells lost all polyribosomes. Analysis of the ribosomal proteins revealed alterations in at least four 50S subunit proteins. The mutation (called rimE1, ribosomal protein modification) mapped between rpsE and aroE. It is suggested that the rimE locus is the structural gene for an activity that modifies a selected number of ribosomal proteins.


Functional expression of cloned yeast DNA in Escherichia coli. A collection of hybrid circular DNAs was constructed in vitro using the poly(dA-dT) "connector" method: each hybrid circle contained one molecule of poly(dT)-tailed DNA of plasmid ColE1 (made linear by digestion with EcoRI endonuclease) annealed to a poly(dA)-tailed fragment of yeast (Saccharomyces cerevisiae) DNA, produced originally by shearing total yeast DNA to an average size of 8 X 10(6) daltons. This DNA preparation was used to transform E. coli cells, selecting colicin-E1-resistant clones that contain hybrid ColE1-yeast DNA plasmids. Sufficient numbers of transformant clones were obtained to ensure that the hybrid plasmid population was representative of the entire yeast genome. Various hybrid ColE1-yeast DNA plasmids capable of complementing E. coli auxotrophic mutations were selected from this population. Plasmid pYeleu 10 complements several different point or deletion mutations in the E. coli or S. typhimurium leuB gene (beta-isopropylmalate dehydrogenase); plasmids pYeleu11, pYeleu12, and pYeleu17 are specific suppressors of the leuB6 mutation in E. coli C600. Plasmid pYehis2 complements a deletion in the E. coli hisB gene (imidazole glycerol phosphate dehydratase). Complementation of bacterial mutations by yeast DNA segments does not appear to be a rare phenomenon.


Isolation of a multi-enzyme complex of fatty acid oxidation from Escherichia coli. A multi-enzyme complex of fatty acid oxidation has been isolated from E. coli B cells and has been purified to near homogeneity by a simple two-step procedure. The complex exhibits thiolase (EC 2.3.1.9), enoyl-CoA hydratase (EC 4.2.1.17), and 3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.35) activities towards short-, medium-, and long-chain substrates. The complex has been estimated to have a molecular weight of approximately 300,000 and is apparently composed of two types of subunits with molecular weights of 78,000 and 42,000.


Virion-associated RNA polymerase required for bacteriophage N4 development. Escherichia coli phage N4 transcription is resistant to rifampicin, an inhibitor of the host RNA polymerase, even when the drug is added prior to infection. A rifampicin-resistant RNA polymerase has been detected in disrupted N4 virions. This enzyme shows a requirement for the four ribonucleoside 5'-triphosphates and exogenous denatured DNA. With denatured N4 DNA, the preferred template, transcription is asymmetric. The virion RNA polymerase apparently is necessary for phage development because a conditional lethal N4 mutant shows temperature-sensitive RNA synthesis in vivo as well as a temperature-sensitive RNA polymerase in disrupted virions.


Identification of a protein methyltransferase as the cheR gene product in the bacterial sensing system. Methylation of membrane-bound proteins with apparent molecular weights around 65,000 does not occur in mutants of the generally nonchemotactic cheR class of Salmonella typhimurium. This was shown to be due to the lack of a protein methyltransferase in these mutants by means of an in vitro assay using soluble proteins, membranes, and S-adenosylmethionine as the methyl donor. The methylase from the wild type was purified, characterized, and shown to be of molecular weight 38,000. It is specific for proteins in S. typhimurium and Escherichia coli membranes. The methylase is not required for tumbling but appears to be essential for maintaining the appropriate rate constants and levels of the regulator of the chemotactic response.


Homology among acid proteases: comparison of crystal structures at 3A resolution of acid proteases from Rhizopus chinensis and Endothia parasitica. The molecular structures of two fungal acid proteases at 3 A resolution have been compared, and found to have similar secondary and tertiary folding. These enzymes are bilobal and have a pronounced cleft between the two lobes. This cleft has been identified as the active site region from inhibitor binding studies. The results of the comparison are discussed in terms of homology among the acid proteases in general.


Surface differentiation antigens of human mammary epithelial cells carried on the human milk fat globule. Rabbit antibodies against components of the human milk fat globule bind specifically to normal human breast epithelial cells and cell lines derived from breast carcinomas, as well as to the outer surface of the human milk fat globule. Variation in indirect immunofluorescence staining in both intensity per cell and percentage of cells stained is observed for the different brest cell lines. Cells derived from other epithelial and other ectodermal tissues, fetal fibroblasts, cells of the blood buffy coat, and even fibroblasts of the breast itself do not bind the antibodies. This suggests that these antibodies are detecting cell-type-specific antigens. These normal breast epithelial cell antigens are on the cell surface and their expression is stable in long-term cultured cell lines, even after much chromosomal variation in a given line. By affinity chromatography, three distinct antigenic components can be isolated from the milk fat globule, one of which contains carbohydrate. These differentiation antigens of the human breast epithelial cell are not only useful as specific cell-type markers, but also can provide a tool to study the role of the cell surface in normal and neoplastic mammary development.


Cells reconstituted from cell fragments of two different species multiply and form colonies. Nuclei (minicells) prepared by cytochalasin-induced enucleation of rat myoblasts (L6) were fused with inactivated Sendai virus to preparations of cytoplasms from mouse fibroblasts (A9). Cell colonies arising from such fusion mixtures were examined 5 days after fusion. In the presence of virus a new type of colony was obtained. The cells in these colonies were derived from reconstituted cells capable of undergoing repeated cell divisions.


Free calcium increases explosively in activating medaka eggs. We have used the calcium-specific light-emitting protein aequorin to follow changes in free calcium concentration during fertilization and cleavage of eggs from medaka, a fresh-water fish. Aequorin-injected medaka eggs show a very low resting glow before they are fertilized, indicating a low calcium concentration in the resting state. Upon activation by sperm, the calcium-mediated light emission increases to a level some 10,000 times the resting level with a 1 to 2 sec time constant for an e-fold increase, and then slowly retruns to the resting level. Upon activation by the ionophore A23187, the early rise in luminescence is much slower, but once a threshold has been reached the subsequent  rise becomes as rapid as the normal sperm-induced response. We infer that the explosive rise in calcium involves calcium-stimulated calcium release, and that a sperm normally triggers this rise by somehow inducing a more modest and localized rise in calcium.


Calcium dependence of glucocorticoid-induced lymphocytolysis. A potent glucocorticoid, triamcinolone acetonide (9alpha-fluoro-11beta, 16alpha,17alpha, 21-tetrahydroxypregna-1,4-diene-3,20-dione-16,17-acetonide) and a divalent cation ionophore (A23187) had similar effects in vitro on [3H]uridine uptake and on lysis of thymocytes of adrenalectomized rats. Removal of Ca2+ from the medium blunted the cytolytic action of triamcinolone acetonide and virtually eliminated that of A23187. In Ca2+-free media, treatment of the thymocytes for 15 hr with triamcinolone acetonide or A23187 followed by re-introduction of Ca2+ resulted in a rapid decrease in cell survival. Based on the time courses of the responses, triamcinolone acetonide and A23187 evoked proportionate increases in 45Ca uptake and lysis of the thymocytes. These findings implicate enhanced Ca2+ uptake in glucocorticoid-dependent lymphocytolysis.


Localization of bovine brain filament antibody on intermediate (100 A) filaments in guinea pig vascular endothelial cells and chick cardiac muscle cells. Guinea pig vascular endothelial cells contain naturally occurring rings of intermediate filaments that completely encircle the nucleus. Indirect immunofluorescence staining showed that these perinuclear rings bound antibody prepared against protein from bovine brain 9-nm filaments. In endothelial cells grown in the presence of 1 muM demecolcine (Colcemid) the perinuclear ring "coils" into a juxtanuclear "cap". Throughout this process we could demonstrate staining of the intermediate filaments. Chick cardiac muscle cells in culture stained diffusely with the antibody. After treatment for 24 hr with 1 muM demecolcine the cardiac cells accumulated large bands of intermediate filaments. These bands stained intensely with the antibody. Our findings suggest that intermediate filaments in guinea pig endothelial cells and those induced in chick cardiac muscle cells are antigenically similar to bovine brain filaments. The staining of these filaments is not affected by treatment with demecolcine.


Biosynthesis of type I and III collagens by cultured smooth muscle cells from human aorta. The synthesis of collagen by human aortic smooth muscle cells was studied after incubating the cells with [3H]proline and [3H]glycine for 48 hr. The culture medium and cells were lyophilized and then digested with cyanogen bromide (CNBr) in 70% (wt/vol) formic acid. The resultant peptides were subjected to ion exchange chromatography on CM-cellulose and gel filtration on agarose. On the basis of the molar ratios of the alpha1(I)-CB8 and alpha1(III)-CB8 peptides of the alpha1(I) and alpha1(III) chains, approximately one quarter of the collagen synthesized by these cells was identified as type III and three quarters as type I. These data indicate that the smooth muscle can synthesize at least two types of collagen found in the arterial wall.


Effects of ribosomal mutations on the read-through of a chain termination signal: studies on the synthesis of bacteriophage lambda O gene protein in vitro. In a DNA-dependent protein-synthesizing system that contains streptomycin-sensitive ribosomes, lambda DNA directs the synthesis of two proteins that are products of the O gene. The larger is produced as a result of read-through of a UGA termination codon. In the system containing streptomycin-resistant ribosomes this read-through protein is not synthesized, indicating that the mutational alteration in the ribosomal protein S12 restricts the read-through. The mutant ribosomes also fail to synthesize the read-through coat protein of RNA phage Qbeta. In addition, the mutant ribosomes restrict suppression of amber mutations in vitro, similar to their effect in vivo.


Deletions affecting the transposition of an antibiotic resistance gene. The structural gene for plasmid-mediated ampicillin resistance resides upon a 3.2 X 10(6) dalton transposable sequence (TnA) flanked by short inverted repeated sequences that accompany its insertion. TnA was transposed to pMB8, a 1.8 X 10(6) dalton derivative of the colicingenic plasmid ColE1. Random deletions were introduced in the resultant 5 X 10(6) dalton recombinant plasmid by a combination of nuclease treatments in vitro. From this set of deletions a subset was isolated that contained deletions affecting the transposition of TnA. The deletions were mapped by digestion with restriction nucleases and electron microscopic analysis of DNA hetero-duplexes and were found to include one of the inverted repeated sequences or lie in the central portion of TnA. Complementation experiments were attempted between these plasmids and another compatible plasmid carrying a deletion in TnA that abolished its ampicillin resistance. The results of the deletion data indicate that approximately 2 X 10(6) daltons of TnA is required for transposition; the complementation experiments suggest that the terminal inverted repetition and the central region of TnA play different essential roles in TnA transposition.


Demonstration of terminal deoxynucleotidyl transferase in thymocytes by immunofluorescence. The cellular and subcellular distribution of terminal deoxynucleotidyl transferase (DNA nucleotidylexotransferase; nucleosidetriphosphate:DNA deoxynucleotidylexotransferase, EC 2.7.7.31) in thymocytes and peripheral lymphocytes from rat, mouse, and calf was studied by immunofluorescence using rabbit antiserum to homogeneous transferase from calf. Terminal transferase was readily detected in approximately 75% of cortical thymocytes, but not in medullary thymocytes or lymph node lymphocytes. The enzyme appeared to be present predominantly in the cytoplasm of positive thymocytes in ethanol-fixed cell smears and frozen sections. The reactivity of anti-terminal-transferase for thymocytes could be neutralized with purified calf enzyme. Results of experiments in which thymocytes were separated on 7-step discontinuous Ficoll density gradients suggested that cortical thymocytes are heterogeneous with respect to terminal deoxynucleotidyl transferase content.


Amino acid sequence for the peptide extension on the prolipoprotein of the Escherichia coli outer membrane. The messenger RNA for the lipoprotein of the E. coli outer membrane was found to code for a putative precursor, prolipoprotein, which has 20 additional amino acid residues extending from the amino terminus of the lipoprotein. Using the prolipoprotein synthesized in an E. coli cell-free system directed by purified messenger RNA for the lipoprotein, the complete amino acid sequence of the amino-terminal precursor region was determined to be as follows: (formula: see text). It was also found that the prolipoprotein that accumulates in toluene-treated cells has the same sequence. The significance of the amino acid sequence is discussed in terms of the mechanism of biosynthesis and assembly of the lipoprotein in the E. coli outer membrane.


High-resolution proton magnetic resonance study of the secondary structure of the 3'-terminal 49-nucleotide fragment of 16S rRNA from Escherichia coli. The 3' terminus of 16S rRNA has been implicated in the recognition of mRNA's by the ribosome. A fragment containing the 3'-terminal 49 nucleotides cleaved from the rRNA by cloacin DF13 was isolated in a pure form. The secondary structure of this fragment has been studied by measuring the high-resolution proton magnetic resonance spectra. The resonances observed at low field can be assigned to hydrogen-bonded iminoprotons of base-pairs present in the fragment. From the data we conclude that the rRNA fragment, under the conditions used, exists as a hairpin consisting of eight intramolecular base-pairs, the 3'-terminal dodecanucleotide being unpaired. The implications of these findings with respect to the function of the ribosomal protein S1 are discussed.


Bidirection replication from a unique origin in a mini-F plasmid. Replicating molecules of the mini F-kanamycin resistance plasmid, pML31, derived from F'lac, have been isolated from Escherichia coli as covalently-closed circular DNA molecules. These molecules were examined in the electron microscope after digestion with either EcoRI or BamHI restriction endonuclease. The structure of the majority of the molecules replicating was consistent with a bidirectional mode of replication starting at a unique origin on the F-fragment. This origin is located approximately 2.3 kilobases from one of the EcoRI sites. Orientation of the F-fragment relative to the physical map of F showed the position of the origin to be at 42.6 kilobases. A small proportion of molecules appeared to be replicating unidirectionally in either direction from this origin. Termination of replication of pML31 apparently occurs in the fragment containing the locus for kanamycin resistance in a unique region opposite the origin in the circular DNA molecule.


A protease inhibitor blocks SOS functions in Escherichia coli: antipain prevents lambda repressor inactivation, ultraviolet mutagenesis, and filamentous growth. Inhibition of DNA synthesis in E. coli by treatment with carcinogenic and mutagenic agents results in the coordinate expression of a group of diverse functions (SOS functions) including lambda prophage induction, filamentous growth, and an error-prone DNA repair activity (SOS repair) believed to be responsible for ultraviolet mutagenesis. It has been proposed that this SOS induction proceeds via irreversible proteolytic inactivation of repressor(s) for SOS functions. To test this hypothesis, we investigated the effect of a protease inhibitor, antipain [(1-carboxy-2-phenylethyl)carbamoyl-L-arginyl-L-valylargininal], on SOS induction. We found that 0.5 mM antipain (which has no effect on cell growth, overall RNA and protein synthesis, or induction of beta-galactosidase) drastically decreases mutagenesis. Antipain also blocks expression of thermally induced mutator activity (another manifestation of SOS repair) and filamentous growth in a tif-1 mutant that expresses SOS functions at 42 degrees without inhibition of DNA synthesis or detectable DNA damage. Furthermore, antipain inhibits thermal induction of lambda prophage in the tif-1 mutant without affecting the kinetics of thermal induction of lambdacI857 prophage. This lambda mutant codes a temperature-sensitive repressor that is directly destroyed by heat and does not require the SOS induction pathway for inactivation at 42 degrees. From our results we conclude that antipain inhibits lambda prophage induction by blocking proteolytic inactivation of lambda repressor and that it inhibits the induction or expression of SOS repair and filamentous growth. Our results suggest a role for proteolytic cleavage in the regulation of SOS functions.


Interaction between mutations of ribosomes and RNA polymerase: a pair of strA and rif mutants individually temperature-insensitive but temperature-sensitive in combination. A temperature-sensitive lethal mutant of Escherichia coli has been constructed by combining two temperature-insensitive mutations: a rif180 mutation that modifies RNA polymerase (RNA nucleotidyltransferase; nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) and a strA24 mutation that modifies the ribosomal protein S12. The temperature sensitivity is a property of the combination of these two particular alleles; replacement of either of the alleles relieves the temperature sensitivity. An isogenic strain containing a different strA mutation (i.e., rif180 strA11) is not temperature sensitive. Evidently ribosomes modified by the particular strA24 polymerase altered by the rif180 mutation, which suggests that in vivo there may exist some interaction between structures of ribosomes and the RNA polymerase.


Isolation and characterization of conditional-lethal rho mutants of Escherichia coli. Temperature-sensitive nitA (rho) mutants of E. coli were isolated; one of them was characterized as an amber mutant. These strains show the Nit phenotype (transcription of phage lambda DNA independent of the N gene) at low temperatures and are inviable at high temperatures. The mutated sites appear to be between cya and metE on the chromosome. Temperature-sensitive nitA bacteria not only permit leftward transcription of the lambda genome at a high rate in the absence of the lambda N protein, but also allow lambda growth at low temperatures. At high temperatures, phages lambda and T4 are incapable of normal development in these cells, while growth of T7 is not affected. The production of thermally unstable rho by the nitA temperature-sensitive mutant suggests that nitA is the structural gene for rho.


Magnification of genes coding for ribosomal RNA in Saccharomyces cerevisiae. When a strain of Saccharomyces cerevisiae monosomic for chromosome I and initially deficient for 25% of the genes coding for ribosomal RNA is repeatedly subcultured, the number of these genes increases to and remains stable at the number in the wild type. This strain shows 2:2; viable: inviable first division segregation and hemizygosity for the ade1 gene (a chromosome I marker), evidence that the strain is still monosomic for chromosome I. The increase in the number of genes coding for ribosomal RNA in yeast may be analogous to the magnification of the ribosomal RNA genes in Drosophila melanogaster bobbed mutants.


Physical mapping of a DNA sequence common to plasmids of incompatibility group F I. We have mapped a region of homology within a 2.2 kilobase segment of plasmids of incompatibility group F I, WHICH IS CONTAINED IN AN EcoRI restriction enzyme fragment bearing genes for autonomous replication; The coordinates of the 2.2 kilobase segment are 46.4F-48.6F on the physical map of the F plasmid. The orgin of vegetative replication has been mapped at 42.5F, at which site F has no sequence homology with other group F I plasmids. Plasmids belonging to other incompatibility groups have no homology with the 46.4-48.6 F segment. Possible mechanisms underlying incompatibility are discussed. We think that incompatibility is due to either a limitation in a common equipartitioning mechanism or a limitation in a common replication control. In either case, the common mechanism is specific for plasmids belonging to a given incompatibility group.


Endotoxin-induced serum factor controlling differentiation of bone-marrow-derived lymphocytes. Serum from bacillus Calmette-Guerin-infected mice injected with endotoxin induces the appearance of surface immunoglobulin, Ia antigen, and complement receptor on the surface of precursor bone-marrow-derived (B) cells. While endotoxin itself causes phenotypic conversion of both thymus-derived (T) cells and B cells in vitro, the endotoxin-induced serum factor was found to be a selective inducer of B cell differentiation. Spleen cells rendered immunodeficient by removal of B cells bearing the complement receptor regained the capacity to cooperate with helper T cells and to produce antibody against red cell antigens in vitro upon upon addition of the serum factor to the culture medium. Thus, a factor that controls selective phenotypic and functional differentiation of B cells has been identified and can now be characterized,


Thymic activity in severe combined immunodeficiency diseases. Thymic function was evaluated by quantitation of circulating thymic factor in patients with several forms of severe infantile immunodeficiency diseases. Direct quantitation of thymic factor in serum of patients with severe combined immunodeficiency revealed heterogeneity of this syndrome by this parameter, as was also shown by study of susceptibility of the marrow cells to differentiation in vitro. Thymic factor was not detectable in one patient with severe combined immunodeficiency, but was present in normal or near-normal concentrations in three others. Circulating levels of this hormonal activity were also not detectable in a patient with DiGeorge athymic syndrome. Following marrow or fetal liver transplantation, which corrected the severe combined immunodeficiency thymic factor levels either increased slightly or did not change appreciably. Fetal thymic transplantation, which together with fetal liver transplantation corrected the immunodeficiency in one patient with severe combined immunodeficiency, was associated with increase of thymic factor to normal levels. Fetal thymus transplantation alone, which was employed to correct the immunodeficiency of DiGeorge athymic syndrome, caused an increase in thymic factor activity to normal or near normal levels in this patient.


Effects of naloxone on experimentally induced ischemic pain and on mood in human subjects. The hypothesis that painful stimuli activate the endogenous opioid (endorphin) system in humans was tested by examining the effect of the opiate antagonist naloxone on experimentally induced ischemic pain and on subjective mood ratings. Intravenous injections of saline or naloxone hydrochloride (2 and 10 mg) were administered under double-blind conditions to 12 subjects. Naloxone did not affect the pain ratings. However, a significant dose-related effect of naloxone on tension-anxiety was found, suggesting that the endorphins. like exogenously administered opiates, may have antianxiety properties.


Eukaryote ribosomes possess a binding site for concanavalin A. Ribosomes prepared from chicken liver or rabbit reticulocytes bound concanavalin A in a molar ratio of approximately 1:1. This binding is to the large subunit of the eukaryote ribosomes with a dissociation constant of 5 X 10(-7) M (0 degrees). The binding of concanavalin A to Escherichia coli ribosomes was much less. Binding to the RNA or to possible membrane contaminants was ruled out in control experiments. Chicken liver ribosomes were labeled in vivo with 3H-labeled amino acids, purified, and dissociated in sodium dodecyl sulfate. Affinity chromatography of this preparation made it possible to isolate the small proportion of the ribosomal proteins (about 1.5%) containing the concanavalin A binding site. This protein moved as a single band during electrophoresis on polyacrylamide gels containing sodium dodecyl sulfate and showed an apparent molecular weight of 31,000.


Aminoglycoside-modifying enzyme of an antibiotic-producing bacterium acts as a determinant of antibiotic resistance in Escherichia coli. Bacillus circulans NRRL B-3312, a nonpathogenic bacterium that produces the aminoglycoside antibiotic butirosin, is known to contain an aminoglycoside phosphotransferase that is similar to the neomycin phosphotransferases of clinically isolated antibiotic-resistant bacteria. Purified DNAs from B. circulans and the plasmid ColE1-ApR were digested with EcoRI endonuclease and the resulting fragments covalently joined with polynucleotide ligase. The recombined DNA was used to transform E. coli and ampicillin-neomycin resistant colonies were selected. Analysis of several clones indicated that neomycin resistance in the E. coli transformants was due to the presence of the B. circulans phosphotransferase gene. This observation is consistent with the notion that anitbiotic-modifying enzymes from antibiotic-producing organisms may be the sources of antibiotic resistance in plasmid-containing bacteria.


Schedule dependent changes in operant responding after lesions of the dorsal tegmental noradrenergic projection. The present experiments examined the role of the dorsal tegmental noradrenergic bundle (DTNB) in operant responding for food under various schedules of reinforcement. This catecholaminergic neuronal system originates in the nucleus locus coeruleus and has diffuse projections to hippocampus and cerebral cortex. Bilateral stereotaxic injections of 6-hydroxydopamine into the DTNB of rats reduced hippocampal-cortical noradrenaline to less than 5% of control levels. Animals with these lesions acquired a continuously reinforced (CRF) bar-press response at the same rate as controls. Compared to controls rats with DTNB lesions responded at significantly lower rates on a variable interval 30 (VI 30) schedule. Extinction after VI 30 responding did not differ significantly between control and lesioned animals. In another experiment no significant difference was observed between DTNB lesioned and control groups on the rate of responding on a fixed ratio 30 (FR 30) schedule. The results are discussed with reference to previous reports indicating changes in operant responding after intraventricular injections of 6-hydroxydopamine. The data failed to support the hypothesis that the DTNB is critically involved in learning and memory.


Behavioral and biochemical effects of knife cuts that preferentially interrupt principal afferent and efferent connections of the striatum in the rat. Knife cuts were made that preferentially interrupted (a) the nigrostriatal pathway; (b) pallidofugal projections to the lower brainstem; (c) caudate-pallidal interconnections; and (d) fibers entering or leaving the striatum ventrally. The effects of these cuts on conditioned (shuttle box) avoidance, passive avoidance, swimming escape, sucrose-rewarded alley running, locomotor activity, and various measures of sensory-motor function were examined. The norepinephrine, dopamine and serotonin content of the striatum, residual forebrain and hypothalamus were determined following the completion of behavioral testing. The pattern of results suggests that striatal functions which are significantly influenced by several afferent and efferent connections are essential for the acquisition and, perhaps, execution of complex behavior in appetitive as well as aversive test paradigms. A special role for the dopaminergic afferents to the striatum was not established in these tests.


Spasticity: its physiology and management. Part IV. Current and projected treatment procedures for spasticity. Today's prescriptions for treating spasticity may include pharmacological, surgical, or physical procedures. All derive their rationale from the classical concepts of decerebrate rigidity and of brain organization as discussed in Part I. This paper describes the advantages and disadvantages of these current treatment procedures and proposes that recent discoveries about the "recovery" capabilities of the central nervous system may influence the means for managing spasticity in the future.


The acquired auricular deformity. A systematic approach to its analysis and reconstruction. Acquired ear deformities present unique and varied problems which tax the ingenuity of the plastic surgeon. Case individualization is necessary, and a systematic assessment of the residual tissues is a requisite when planning an appropriate reconstruction. Cases performed by one surgeon have been used to demonstrate the basic principles of these repairs. A systematic approach to the reconstruction of these acquired deformities is presented.


Comparison of free flaps with pedicled flaps for coverage of defects of the leg or foot. The use of free flaps to repair defects of the leg or foot is a viable alternative to cross-leg flaps because (1) the total time of immobilization and hospitalization is less, (2) the total number of general anesthetics is less, and (3) the morbidity and cost are less. Increased experience will enhance the survival statistics for free flaps, making their use the method of choice for the reconstruction of defects in the distal part of the lower extremity.


Surgical treatment of erythroplasia of Queyrat. An operative technique is described for the treatment of large lesions of erythroplasia of the penis. The defect on the glans and on the coronary sulcus is covered by a flap prepared from the external part of the prepuce. This therapy has been effective and has given a good functional result.


Myocutaneous flaps in lip reconstruction. Applications of the Karapandzic principle. Our experiences with the reconstruction of lips by the use of innervated myocutaneous flaps is described. We present the technique and some illustrative cases.


Repairing defects of the lower eyelid with a free chondromucosal graft. A method is presented for the repair of full-thickness defects of the eyelid. The lining and tarsal plate are replaced by a free chondromucosal graft from the nasal septum, in which the cartilage is thinned and perforated. Cover is provided by a compound, bipedicled flap of skin and muscle from the opposite lid.


Effects of crowding of mice on humoral antibody formation and protection to lethal antigenic challenge. The effects of grouping (crowding) on humoral antibody response to typhoid paratyphoid vaccine and subsequent protection from a minimal lethal challenge dose of Salmonella typhimurium were studied in white Swiss-Webster mice. The data show a trend between the degree of crowding and antibody response. Geometric mean titers of high density grouped mice were significantly lower than the geometric mean titers of the less crowded mice. Also, there were significantly less antibody responders in the high density grouped mice than in the less crowded mice. However, challenged with a minimal LD50 dose of Salmonella thphimurium, no deaths occurred in the immunized study group, regardless of measurable antibody level. In the nonimmunized controls, which were under the same stressor conditions, there was a significant difference between the level of crowding and death to challenge. The data show that nonimmunized mice in this study exhibited a marked increase in susceptibility to an infectious agent when under the stressor effect of crowding.


Recurrent urinary tract infections in infants and children. Urinary tract infection is the most common abnormality found in the urinary tract of children, and it is as dangerous as it is common. The infections usually commence in infancy, especially in neonates. Of special interest to the radiologist is the fact that radiologic examination is the only way to assess damage to the kidneys and to determine the long term risk to the child.


[Problems and experiences with computerized coding of radiological findings in pneumoconioses (author's transl)]. For medical surveillance of dust workers, correlation of anatomical and radiological findings in silicosis and asbestosis is an assumption for computerized application of the ILO U/C 1971 classification of pneumoconiosis. The new regulations of insurance companies for preventive examinations in workers exposed to asbestos are described, and their results presented. Practicability and preliminary data suggest important information for the future.


[Physiology of bile formation (author's transl)]. Generation of bile flow in humans depends mainly on two transport mechanisms of the hepatocyte. One of these is responsible for secretion of bile acids, the other for transport of sodium into the bile canaliculi. Accordingly, a bile acid dependent fraction of hepatocytic bile can be distinguished from a bile acid independent fraction. Many endogenous and exogenous substances, including x-ray contrast media, are secreted into hepatocytic bile by more or less specific transport systems. The bile produced by the liver cells is then modified by admixture of ductular bile and by reabsorptive processes in the biliary passages and in the gallbladder. Increased knowledge about these mechanisms represents one of the requirements for progress in oral and intravenous cholangiography.


[Physiology of biliary excretion of roentgenographic contrast media (author's transl)]. Contrast agents for oral and intravenous cholecysto-cholangiography are iodinized lipophilic compounds with marked albumin binding. Their selective uptake by the liver occurs because of the presence of a membrane transport system and preferential binding to the hepatic cytoplasmatic proteins. Peroral contrast agents are conjugated. The canalicular excretion is an active carrier-mediated process limited by a transport maximum. Intravenous contrast agents are potent choleretics. Bile salts are important for intestinal absorption and hepatic excretion of the contrast agents. Pharmacological agents do not improve the biliary excretion of contrast compounds. The value of various investigation techniques is discussed.


[A contribution to the rate of side-effects of hepatotropic contrast media. A clinical comparative study of iodoxamate (Endomirabil) and ioglycamid (Bilivistan) (author's transl)]. The new substance Iodoxamate (Endomirabil) is a hepatotropic contrast medium. In a clinical comparative study, the contrast of the biliary ducts and gall bladder is equivalent compared with Ioglycamid (Bilivistan). Assuming equal conditions of injection and in conformity with animal experimental studies, the rate of side effects of Iodoxamate is distinctly lower than that of the referring substance Iolgycamid (Bilivistan).


Subtraction technique in intravenous aortography. Excretory urography using the subtraction technique (100 ml of 60% urographic media injected in 10-12 seconds) demonstrated the aorta and its major branches well enough to prove useful clinically. The method is fast and graphic, and risk seems no greater than that associated with the standard urographic examination.


Occult malignant tumors in dermatologic disease. The futility of radiological search. Analysis of 102 patients with dermatomyositis, polymyositis, bullous pemphigoid, and dermatitis herpetiformis was undertaken to determine: (a) the incidence of occult malignant tumors in these diseases, and (b) the value of radiological screening to detect unsuspected malignant neoplasms. The incidence of internal malignant disease was no higher than that encountered in a control population. Radiological screening procedures routinely performed for patients with these disorders failed to disclose any occult neoplasms. A radiological tumor search has no place in the evaluation of these patients unless specific clinical findings suggest carcinoma in a particular organ system.


Computer-aided medical decision making in radiotherapy. Radiotherapy departments are becoming sophisticated in working with computers for isodose computations, treatment machine verifications and administrative and medical records. The next step lies in computer-assisted medical decision making. The logic for a patient's diagnostic work-up and treatment protocol can be stored in a computer. It can then be used as an aid in making the diagnosis, in prescribing the treatment and for quality control. For patients who fit established protocols the computer can select and list treatment using the logic of that protocol. Such a system has been implemented for the postoperative radiotherapy of breast cancer on a trial basis. Its potential usefulness is illustrated by results in 25 consecutive patients. Physician acceptance and costs of the program are under investigation.


Cellular responses to combinations of hyperthermia and radiation. The two principal rationales for applying hyperthermia in cancer therapy are that: (a) the S phase, which is relatively radioresistant, is the most sensitive phase to hyperthermia, and can be selectively radiosensitized by combining hyperthermia with x-irradiation; the cycling tumor cells in S phase which would normally survive an x-ray dose could thus be killed by subjecting these cells to hyperthermia; and (b) the relatively radioresistant hypoxic cells in the tumor may be selectively destroyed by combinations of hyperthermia and x-irradiation. Both of these rationales have been mentioned as reasons for using high LET irradiation in cancer therapy; therefore where such irradiation may be of use, hyperthermia may also be advantageous.


Hyperthermic effects on animal tissues.

Hyperthermic effects on animal tissues. TCD50 values for thermally resistant tumors have been significantly reduced. The therapeutic ratio has been improved for some tumor-normal tissue situations and treatment protocols, but not for others. The oxygen enhancement ratio (OER) for hyperthermic damage may be congruent to 1; if this is true for tumor cells in vivo, the combination of hyperthermia and radiation should improve the therapeutic ratio to the extent that hypoxic cells are critical. There does not appear to be a differential response to hyperthermia by the normal foot or tumor growing in the foot pad for the following two parameters: (a) relationship between heating time to produce the specified response and the level of heating, and (b) effect of fractionation of hyperthermia.


Prospects for hyperthermia in human cancer therapy. Part I: hyperthermic effects in man and spontaneous animal tumors. Systemic hyperthermia in man may occur by accident, as in heat stroke or malignant hyperthermia during general anesthesia, or it may be therapeutically induced (fever therapy). The latter has been used infrequently since the advent of antibiotics, except recently for treatment of cancer. Local or regional heating combined with x irradiation for human cancer therapy has been sporadically reported for over 60 years, but has not found its place in clinical medicine possibly due to technical limitations in heat production and dosimetry. Preliminary results are reported for treatment of spontaneous animal tumors with radiofrequency current fields and x irradiation.


Prospects for hyperthermia in human cancer therapy. Part II: implications of biological and physical data for applications of hyperthermia to man. Laboratory data from studies of hyperthermia as a potential antitumor agent indicate that: (a) tumor cells may be more sensitive to heat than normal tissue; (b) hyperthermia enhances response to irradiation and can increase the therapeutic ratio; (c) cells are most sensitive to hyperthermia during the S-phase, when they are resistant to ionizing radiations; (d) the oxygen effect is absent for hyperthermic cell killing, and radiation effects are less oxygen-dependent when potentiated by heat treatment; and (e) biological damage changes more rapidly at temperatures above 43 degrees C. Methods of heat production and dosimetry need to be refined further before these findings can be put to practical use in tumor therapy.


Stop-action cardiac computed tomography. Computed tomographic (CT) cardiac imaging in vivo has been hampered by motion of the heart during its cardiac cycle. A technique of post data-acquisition correlation of the angular projection data using the electrocardiogram as a reference signal is described. This method produced seven "stop action" images of the heart and resulted in delineating morphological detail not recognizable on the conventional CT scan.


Radioimmunoassays of drugs of abuse in humans: a review. Only recently has radioimmunoassay been used for the detection of drugs of abuse in body fluids. While conventional assay methods are time-consuming, relatively insensitive, and require a larger sample volume, the radioimmunoassay method is rapid, sensitive, specific, and can be performed with a minimum of sample. Performance of individual assays is identical, and requires about 1 hour to complete. Herein are reviewed the radioimmunoassays which have been developed for measurement of drugs of abuse in humans. These new techniques are of importance in screening and in further research into the effect of these drugs on the functions of the human body.


Detection of chemical mutagens use of concentration gradient plates in a high capacity screen. A method is described which makes possible the rapid screening of chemicals for mutagenic potential. Ten fold concentration gradients of test compound in agar are prepared in square petri dishes. Ten strains of bacteria including both histidine auxotrophs and tryptophane auxotrophs are then streaked on the surface. In the activated phase of the test an overlay of 9000 g liver homogenate in agar is applied to the gradient plate before the organisms are streaked. After incubation, the plates are scored by observing the concentration range over which the test compound produces mutant colonies in each of the ten organisms. With this technique it is possible to determine on only eight plates the mutagenic potential of a substance against ten different bacterial strains, both with and without microsomal activation and over a 10,000 fold concentration range. The minimum concentration at which growth of the auxotroph is inhibited is also noted. The method has been found to be very useful for preliminary screening of large numbers of chemicals.


Floctafenine: a new analgesic for use in rheumatic diseases. In a double-blind, single-dose, multiple cross-over study, floctafenine (200 mg) was shown to be an active analgesic and similar in potency to aspirin (600 mg). A graphic rating scale was used to measure pain relief. The use of such a scale without cut-off points at each end led to problems in the distribution of results.


A double-blind trial of flurbiprofen and aspirin in soft-tissue trauma. A double-blind trial of flurbiprofen (150 mg daily) and aspirin (3.6 g daily) for six days was carried out in 52 soft-tissue injuries in 28 professional footballers. An analysis of daily pain scores in both injury categories (trauma and sprains) showed that players taking flurbiprofen had significantly lower pain scores from day 2 onwards compared to the aspirin group (P less than 0.01), the effect being more marked in the trauma subgroup. Flurbiprofen was significantly better than aspirin in reducing the time taken to achieve both training and match fitness, and 65% of the players taking flurbiprofen were able to train within three days of injury compared to 35% taking aspirin (P less than 0.05). The possible effects of both anti-inflammatory agents on prostaglandin metabolism are discussed, and their role in soft-tissue trauma outlined.


[Anti-deoxyribonucleic acid antibodies: comparison of results provided by 3 research methods]. Three methods of determination of anti-DNA antibodies were compared. The indirect immunofluorescence method after exposure to animal DNA (IF) and Farr's radio-immunological method with bacterial DNA labelled with C14, gave highly similar results, although there were some cases in which Farr's method gave a negative and the IF method a positive result. In part, this discordance appears to be accounted for by the variable affinity of the anti-DNA antibodies for DNA. The counter-immuno-electrophoresis method (CIEP) on the other hand, gave very different results: positive reactions in a large proportion of normal sera and a considerable proportion of false-positive and false-negative results in disseminated lupus erythematosus. It is concluded that until the CIEP method is made more reliable by technical refinement, determination of anti-DNA antibodies may be carried out by either the IF or the radio-immunological method, but a double-check, by application of the two methods at the same time, is highly advisable.


[Treatment of rheumatoid arthritis by levamisole. First results]. Twenty selected patients suffering from severe, long-standing rhumatoid arthritis (RA) not controlled by anti-inflammatory drugs (19 cases) and from disseminated lupus erythematosis (DLE) (1 case) were treated with levamisole. The subjects were divided into 2 groups: Group I comprised fourteen patients (13 RA and 1 DLE) treated continuously by levamisole 150 mg/day for 3 or 6 months then on an intermittent regime (150 mg/day-3 days per week). Group II comprised 6 RA patients treated on the intermittent regime from the beginning. In Group I, following average treatment of 9 months (5-12 months), clinical results assessed according to precise clinical criteria were favorable in 9 out of eleven cases. In the other 2 cases no change was noted. Side effects included reversible agranulocytosis in 9 cases, on 3 occasions this necessitated the discontinuation of treatment. A signifcant reduction in sedimentation rate was noticed in 5 cases out of eleven and in 3 patients the Rose-Waller test turned negative. A monoclonal disglobulinemia of IgG lambda appeared under treatment in 1 patient who was deficient in IgA. Skin tests carried out periodically showed a significant augmentation of the response to candida. Lymphocyte culture in the presence of mitogens gave highly variable results from one control to the other in the same subject, as well as in the treated subjects as in the group of RA not receiving levamisole. These results are compared with those previously published; the mechanism of action and possible indications for levamisole in RA are discussed.


Enzymes as denture cleansers.

Enzymes as denture cleansers. It was the purpose of the study to test the efficiency of dextranase, mutanase, and protease in removing denture plaque. The study group comprised 100 denture-wearers with denture stomatitis. The enzymes were dispensed as dissolvent tablets either in pure or in mixed preparations. Placebo tablets and Steradent, a commercial denture cleanser, were used as control tablets. The following parameters were studied: the amount of denture plaque, the degree of palatal erythema, and the concentration of yeast cells and inflammatory cells in mucosal and denture smears. The study was designed and carried out as a double-blind study. The dissolvent tablets containing the enzymes in mixed preparations were more effective than the tablets containing the pure enzymes, the placebo tablets, or the Steradent tablets. The beneficial effect of the mixed enzyme preparations included a significant reduction of the amount of denture plaque and an improvement of the clinical condition of the palatal mucosa.