Chromatographic pattern of gut glucagon-like immunoreactivity (GLI) in plasma before and during glucose absorption.

In this work we have studied the chromatographic pattern on Bio-Gel P-30 columns of the glucagon-like immunoreactivity (GLI) present in unextracted plasma from normal dogs in the basal state and after intraduodenal administration of glucose. Basal plasma GLI, measured by R-8 antiserum, was distributed in four distinct fractions, whose approximate molecular weights were: greater than 30000 delta (Fraction I), 10000 delta (Fraction II), 3500 delta (Fraction III) and 2000 delta (Fraction IV). Fraction I accounted for the highest percent of total immunoreactivity. The increase in plasma GLI during glucose absorption was due to a significant increase of Fraction II, which may well correspond to tissue GLI Peak I, while no significant changes were evident in the other three fractions. The fact that tissue Peak I (or plasma Fraction II) ssems to be the factor secreted during glucose absorption puts the material/s of this molecular size in the first place for further investigation.


Pancreatic exocrine secretion in the pig following test meals of different composition and intra-duodenal loads of glucose and maltose.

Eleven pigs were fitted with pancreatic and duodenal fistulae, and pancreatic juice collected permanently. Amylase, chymotrypsin, lipase and total proteins were determined in juice collected within 2 and 6 hours after different test-meals or intraduodenal loads of glucose and maltose. In the pancreatic juice of pigs adapted to a high-lipid diet and submitted to a high-carbohydrate test-meal the activity of amylase was increased by 50%. When the consumption of the high-lipid meal was associated with an intraduodenal load of 100 g of glucose all the enzyme activities were stimulated when compared to the effect of meal alone, but only the activity of amylase was significantly increased (+ 82%). In the juice of pigs adapted to a balanced diet and submitted to intraduodenal loads of 150 ml of water, 50 g of glucose, 50 g of maltose and 150 g of maltose, the enzyme activities remained almost constant with the load of water and 50 g of maltose but with 50 g of glucose and 150 g of maltose loads, amylase activity was increased by 20% and 30% respectively. It is suggested, that the exocrine pancreas of the pig adapts itself rapidly to the changes in the size of the intestinal pool of starch hydrolysis products.


Amino acid transport in the exocrine pancreas. IV. Do glucagon or insulin mediate the in vivo effect of caerulein on amino acid transport and incorporation?

The direct in vitro effect of caerulein on pancreatic protein synthesis and amino acid transport has been investigated. In contrast to in vivo conditions we were unable to demonstrate any effect on alpha-aminoisobutyric acid and leucine uptake and on leucine incorporation usin rat pancreatic lobules. Insulin and glucagon were therefore examined as possible mediators for the in vivo effect of caerulein. Insulin (1--5 microM) slightly enhanced AIB uptake (16% but did not change uptake and incorporation of leucine. Glucagon (0.01--1 microM) was ineffective. Both islet hormones had no influence on the formation of cyclic GMP induced by secretagogue either in rat (40% increase) or in guinea pig lobules (500% increase). It seems unlikely that the two islet hormones exert any direct effect on the exocrine pancreas and thus could serve as mediators for the in vivo synthetic effect of caerulein.


Propranolol inhibits the in vitro conversion of thyroxine into triiodothyronine by isolated rat liver parenchymal cells.

A model for the in vitro study of the conversion of thyroxine into triiodothyronine using isolated rat liver parenchymal cells is described. Isolated liver cells (mean protein content 18 mg/ml) convert approximately 0.8% of 1.3 microM exogenously added T4 into T3 during thirty minutes incubation. Carbimazole (50 microM) has no effect on the conversion process, whereas propylthiouracil (50 microM) inhibits the conversion. The beta-adrenoceptor blocking agent propranolol lowers the conversion ratio when added in concentrations of 580 and 1160 microM, but has no inhibitory effect when 290 microM is added.


Radioimmunoassay for human parathyroid hormone for differentiation between patients with hypoparathyroidism, hyperparathyroidism and normals.

A RIA system for human PTH is presented using a goat antibody (Code name 017-spring-78) against C-terminal hPTH fragments, as well as a human PTH standard from hemodiafiltration of a hyperparathyroid patient. It proved to be useful for the differentiation not only between hyperparathyroid patients and normals, but even within the normal range and hypoparathyroid states.


The relationship between maximal oxygen uptake and glucose tolerance/insulin response ratio in normal young men.

Maximal oxygen uptake (VO2max.), glucose tolerance (K-value), and insulin response (IRI-area) were studied in seventeen young, non-obese, non-diabetic males. The ratio between K-value and IRI-area correlated significantly with VO2 max. (r = 0.70, p less than 0.01) also when differences in body fat mass were eliminated by partial correlation analysis (r = 0.56, p less than 0.05). Subjects with a high VO2 max. thus maintained a given glucose tolerance with a lower insulin response than did subjects in whom VO2 max. was low.


Modification by oral contraceptives in rat of 14C acetate incorporation into platelet lipids.

The in vitro incorporation of acetate 14C in platelets lipids was compared in control female rats (Gr. I) to rats treated for 4 days either by an oral contraceptive ethinyl oestradiol + lynestrenol (Gr. II), or by ethinyl oestradiol alone (Gr. III) or lynestrenol alone (Gr. IV). An increase of 43--45% in the incorporation of acetate could be observed in the two groups (II and III) which received ethinyl oestradiol, while the incorporation in group IV was similar to that of the controls. The lipid fractions of which the synthesis was the most considerably stimulated by the oestrogen treatment, were the neutral lipids as separated from the other lipids by TLC. In groups II and III the incorporation in cholesterol and cholesterol esters was increased by 8 fold and by 10 fold in the free fatty acid fraction. In these two groups, even in the phospholipid fractions PS + PI and PE, the radioactivity was significantly increased. The observed effect of the oral contraceptive studied here on platelet lipid synthesis in female rats, appears to be essentially due to the estrogens, since lynestrenol had only minimal effects in that respect.


Substance P plasma levels in pregnancy and in various clinical disorders.

Using radioimmunoassay, immunoreactive SP (iSP) has been measured in the plasma of 162 hospital patients with various disorders and in the plasma of 67 pregnant women. In pregnancy, iSP was undetectable in 40% women as compared to 12% in other hospital patients. The mean iSP plasma level in pregnancy was 37.8 +/- 4.6 (SEM) as compared to 77.1 +/- 4.9 (SEM) pg/ml in other hospital patients. The results support earlier observations based on bioassay, suggesting that the blood of pregnant women contains higher concentrations of a SP-inactivating factor. Of the hospital patients, elevated levels of iSP were found in patients with chronic leukaemia, in one patient with a basaloid carcinoma of the anus, and in one patient with toxic liver damage and pancreatic insufficiency. No correlation was found between thyroid function and iSP plasma levels. ISP plasma levels in various gastrointestinal disorders were similar to those found in normal subjects.


Studies of growth hormone secretion in juvenile diabetes.

To further investigate the GH secretion in juvenile diabetics, blood glucose (BG) and plasma growth hormone (GH) were determined during controlled exercise performed in basal condition and under glucose infusion, in 7 controls and 22 juvenile diabetics aged 12--35 years, 10 of them with fundal vascular lesions. In controls, glucose infusion significantly lowered the exercise induced GH rise observed under basal conditions. In diabetics, under basal conditions, diabetics with low basal BG (BG less than 100 mg/100ml) had higher GH secretion than those with high basal BG (BG greater than 140 mg/100 ml; p less than 0.05). Under glucose infusion, diabetics with normal BG peak values (not different from controls: BG = 284 +/- (SK) 45 mg/100 ml) had significantly higher plasma GH levels than controls (p less than 0.01). In contrast, in diabetics with BG peak value higher than controls (BG greater than 374 ng/100 ml), plasma GH levels were not different from control values. This study indicates that exercise induced GH secretion in diabetics is mainly related to actual BG levels. Furthermore, we found no relation between the magnitude of GH secretion and the presence of retinopathy in diabetics.


Adenohypophyseal hormone response to chronic stress in dexamethasone-treated rats.

The influence of dexamethasone treatment on the basal values of corticosterone, GH, prolactin (PRL), LH and FSH, as well as on the adenohypophyseal hormone response to chronic stress was studied in female rats. Dexamethasone acetate (25 micrograms/100 b.w.), given by gavage twice daily for 10 days, decreased the resting plasma levels of corticosterone, GH, LH and PRL, whereas the FSH titers remained normal. The secretion of ACTH (evaluated indirectly through corticosterone concentrations) and of GH appeared to be most sensitive to the suppressive effect of dexamethasone. The same hormonal response pattern was induced by 8 h of daily immobilization for 10 days, except that ACTH release was enhanced and the plasma LH titers dropped more drastically. Dexamethasone administration in combination with restraint did not alter the characteristic hormonal profile of chronic stress, despite the fact that ACTH secretion was completely blocked. These data suggest that the inhibition of PRL, LH and GH secretion following severe, chronic stress is not causally related to the sustained elevation of plasma ACTH.


Long-term cimetidine does not alter serum prolactin.

The effect of repeated cimetidine ingestion on serum prolactin values was studied prospectively in 17 men with proven duodenal ulcers. These patients received 400 mg of cimetidine twice daily for 12 weeks but showed no alteration in their mean serum prolactin levels. Cimetidine-induced hyperprolactinaemia is not the explanation for the development of gynaecomastia in men exposed to this drug.


Effect of oral contraceptive used by technician on sensitivity of progesterone radioimmunoassay.

Gonadotropin and steroid radioimmunoassays (RIAs) have been run in our laboratory for the past 6 years. Recently, the progesterone RIA was unpredictable when performed by one technician. After checking the mechanics and reagents, it was discovered that the technician had changed from Ortho Novum 1 + 50 to Ovral about the time the RIA became erratic. Standard curves of progesterone RIAs performed while the technician was taking either Ortho Novum 1 + 50 or Ovral, or on no contraceptive are reported. The data suggest that a probably exhaled metabolic product of norgestrel, the synthetic progestin in Ovral, interferes with the progesterone RIA and indicate an additional variable investigators must eliminate in performing RIAs.


Counteraction of testosterone-induced suppression of the pituitary-ovarian axis in rats by flutamide.

Daily administration of 100 micrograms of testosterone to unilaterally ovariectomized rats for 18 days caused a significant decrease in compensatory ovarian hypertrophy. The number of corpora lutea was markedly reduced and many cystic follicles were noticeable. Administration of graded doses (0.5, 1 and 3 mg daily) of flutamide over the same period did not cause any significant change in the weight and histology of the ovary in untreated unilaterally ovariectomized animals. However, treatment with the same doses of flutamide prevented the changes observed in the reamining ovary of testosterone-treated animals.


Estradiol metabolism by liver homogenates and microsomes of normal and cirrhotic male rats.

Incubation experiments show that homogenates and microsomes obtained from CCl4-induced cirrhotic livers of male rats metabolize an estradiol load at a much slower rate than preparations from normal livers. The decreased metabolic capacity results in a slower disappearance of estradiol from the incubation medium, and in a slower transformation of metabolized estradiol to polar extractable and to highly polar nonextractable metabolites.


Proposition 13: experience in one community mental health center.

The impact of Proposition 13 on one community mental health center in California is described. Although the center has had no layoffs as a result of its passage, the measure has had a serious effect on staff morale, which was already at a low point because of pre-existing budgetary constrictions that led to staff reductions despite increased demands for services. It has also generated several changes in treatment programs designed to reduce overhead costs and make more efficient use of staff time. The author emphasizes that because of the supplemental funds made available by the state from its surplus during fiscal year 1978-79, the full impact of Proposition 13 on local service programs is still to be felt.


Psychiatrists and primary physicians: collaborative learning experiences in delivering primary care.

Psychiatric and primary care residents can benefit from taking part of their training together in a primary care setting such as a neighborhood health center or a health maintenance organization. The training in such organized settings can best focus on the comprehensive appraisal of patients' multiple health, mental health, and health-related social service needs; the coordination of care to devise nonfragmented treatment plans for multi-problem patients; the effective collaboration between health generalists and mental health specialists; and the efficient use of limited resources to meet a population's health care needs. Such a coordinated training experience also helps overcome interprofessional antagonisms that often inhibit collaboration between psychiatrists and other physicians.


Private-sector services for low-income psychiatric outpatients. D.C. Institute of Mental Hygiene Washington, D.C.

A community-based, nonprofit outpatient clinic in Washington, D.C., has been successful in using the medical model to provide high-quality services to low-income patients. In 13 years it has grown from five staff members and 17 patients to a part-time staff of 74 and a patient population of 1500. Hours of direct service have increased from 1000 to more than 40,000 per year. The clinic has matched the services provided in the city's public mental health clinics at a fraction of the cost. It receives no direct federal funding and only minimal assistance from state and local governments. It exemplifies the contribution the private sector can make in creatively serving the economically disadvantaged. Fiscal reality and patient demand emphasize the need for a strong and ongoing partnership between the private and public sectors if that population is to be served.


New reporting system aids epidemiologists.

The feedback loop reporting system lifts the burden of reporting communicable diseases from the physician's shoulders and ensures more efficient, and more frequent, reporting.


Area agencies ensure success of disaster drill.

Salem County (NJ) Memorial Hospital cooperated in an areawide disaster drill and found that it took large doses of planning and cooperation to coordinate the effort.


Food service researched in special project.

Regional research project, funded by the Department of Agriculture and staffed by specialists, is conducting studies of food quality, food sanitation, and energy conservation.


Pharmacists' clinical role expanded.

A hospital used management engineering to achieve more effective utilization of its pharmacy staff so that pharmacists' clinical role could be expanded without increases in staff or costs.


Energy situation is precarious.

Given the uncertain future that lies ahead for meeting the nation's energy needs, many hospitals are assuming a posture of vigilance and preparedness. If they are not, they should be, experts say.


What are the antitrust implications of shared purchasing for hospitals?

Although it can be argued that shared purchasing arrangements are lawful in most circumstances, competent legal counsel should examine the agreements to be sure. Courts are likely to examine such arrangements to distinguish managerial reform from anticompetitive actions.


The possible dream: the Navajo Nation Health Foundation.

The dream of high-quality health care for the Navajo began in Ganado, AZ, some 70 years ago. Now it has gone a step further through the work of the only hospital and clinic system in the United States that is owned and operated by American Indians.


It's not that kind of a job.

The duties of the corporation president and the hospital administrator are less publicly visible than those of the senator and the physician, but that doesn't make them less valuable.


Hypertension clinic proves effective.

Hypertension can best be combatted through patient education and early detection. A screening clinic can be an excellent way of reaching the public if follow-up is diligent.


Center for Life provides accessible maternity care.

Providing good, comprehensive, accessible maternity care to the underserved can help solve a hospital's declining OB census and can support a pro-life philosophy.


Hospital buildings have few alternative uses.

A year ago HEW published guidelines regulating hospital beds and occupancy rates. Reluctant to close their doors, administrators have sought conversion alternatives, most of them impractical and economically impossible. A go-slow attitude is recommended, as population increases will dictate hospitals' proper response.


Responding to consumer demand: a study of alternative birth centers.

Responding to consumer demands, many hospitals are setting up ABCs for couples who desire a more self-directed, family-centered experience. Such programs require that administrators and staff anticipate potential problems for personnel and clients.


Analyzing the hospice market.

Hospitals should base decisions about hospice services on need rather than on subjective feelings. Marketing methods can be used to identify the potential population for hospice care.


Storeroom procedures that conserve assets.

As nonlabor costs in health care increase disproportionately, changes in storeroom operations will become an important cost containment tool.


The 1979 CHA survey of pastoral care programs.

Pastoral care programs have grown and matured in the 10 years since The Catholic Hospital Association and the National Association of Catholic Chaplains issued their "Guidelines for Establishing a Department of Religion in a Catholic-Sponsored Hospital." CHA's 1979 survey of 370 institutions points out that while pastoral care departments are recognized as important, budgets for personnel and programs are unrealistic. The shortage of pastoral care personnel is an acute challenge to Catholic facilities, and alternative staffing methods must be sought.


Recognition mechanisms in infectious disease.

Recent studies have begun to elucidate the nature of pathogen-host recognition mechanisms. Not only is our understanding of the nature of infection thereby growing, but there is promise of an entirely new approach to treatment--by inhibiting or preventing the contact between pathogen and target cell, the first step in the infectious process. Models have largely been elucidated for shigella infections and cholera.


Systemic lupus erythematosus.

SLE often presents such a confusing clinical picture that diagnosis is long delayed, and it remains a disease of unknown cause. But early diagnosis and carefully planned therapy can enable many patients to lead nearly normal lives. Recent advances are outlined.


Malabsorption in the elderly.

Age-related deficiencies in gastrointestinal function do occur, but the evidence suggests that their contribution to malabsorption syndromes is usually trivial. Symptoms of malabsorption in elderly patients therefore probably do not simply reflect "old age," but some underlying problem(s). An orderly approach to diagnosis, emphasizing disorders likely to be present in the geriatric population, can lead to effective treatment.


Skeletal scintigraphy in the diagnosis of acute osteomyelitis.

Bone scans detect osteomyelitis earlier, sometimes several days earlier, than x-rays. Prompt institution of therapy, before significant bone damage has developed, thus becomes possible. A positive scintigram is, however, nonspecific, and firm diagnosis requires radiologic and other confirmation. Moreover, because the technique is so new, many open questions remain both about its optimal utilization and about its potential.


The quantitative analysis of polymorphism on human chromosomes 1, 9, 16, and Y. II. Comparison of the C segments in male and female individuals (group characteristics).

Comparative analysis of the polymorphism of C segments on chromosomes 1, 9, 16, and Y was conducted in 50 normal boys and 50 normal girls. Quantitative methods revealed that the mean lengths of C segments, their variability, and their distribution on the chromosomes mentioned are quite identical in the two groups. Methodological problems related to the study of chromosome polymorphism are discussed.


The quantitative analysis of polymorphism on human chromosomes 1, 9, 16, and Y. III. Study of relationships of C segments' lengths in individual karyotypes.

The correlation relationship of the lengths of C segments on chromosomes 1, 9, 16, and Y was studied in a group of normal boys and girls (50 boys and 50 girls). No correlation was found between the C segment lengths, either on homologs or on chromosomes of various pairs. This confirms the idea of random combinations of the said chromosomes with C segments of different lengths in an individual karyotype.


Short rib-polydactyly syndrome, Majewski type, in two male siblings.

Two male siblings with a short rib-polydactyly syndrome, Majewski type (Majewski syndrome), are reported. To our knowledge, the present report is the first one of siblings each confirmed to be affected by Majewski syndrome, and it may therefore contribute to establishing the mode of inheritance.


Partial trisomy for the long arm of chromosome 7 due to familial balanced translocation.

A partial trisomy for the distal segment of the long arm of chromosome 7 (bands q32 replaced by qter) was observed in a severely retarded child with somatic and CNS anomalies. The phenotypically normal father and paternal grandmother had a balanced reciprocal translocation between the long arm of a chromosome 2 and the long arm of a chromosome 7: 46,XX-XY,t(2;7) (q37;q32). The clinical features of the child at birth and at the ages of 5 months and 2 years are compared with those previously reported in cases of partial trisomy 7q.


Simultaneous staining of sister chromatid exchanges and Q-bands in human chromosomes after treatment with methyl methane sulphonate, quinacrine mustard, and quinacrine.

Human peripheral lymphocyte chromosomes were stained simultaneously for sister chromatid exchanges (SCEs) and Q-banding. No effect of treatment with MMS, QM, and Q on the distribution of SCEs in chromosomes was found compared with controls. The SCEs were distributed between chromosomes roughly according to metaphase length, with the shorter chromosomes underrepresented. The majority of SCEs were located to pale bands, while a few occurred in bright bands and at interfaces between pale and bright bands. A greater frequency than expected of SCEs had occurred at identical sites in homologous chromosomes. This frequency was significantly increased after treatment with MMS.


Chromosome lesions in amniotic fluid cell cultures.

The frequencies of chromosome lesions were determined on 3537 mitoses in samples of varying sizes from cultures of 25 amniotic fluid specimens taken from patients at cytogenetic risk. The average percentage values of aberrant cells, including and excluding gaps, were 12.5 and 4.9, respectively. The corresponding values for fibroblasts and peripheral blood lymphocytes from normal adult donors, calculated under the same laboratory conditions, were 5.0 (including gaps) and 2.4 (excluding gaps) and 2.4 (including gaps) and 1.0 (excluding gaps), respectively. The hypothesis of a correlation between the increased incidence of chromosome lesions and the occurrence of abnormal karyotypes in amniotic fluid cell cultures is discussed.


Intracellular phenylalanine and tyrosine concentrations in 19 heterozygotes for phenylketonuria (PKU) and 26 normals. Do the higher values in heterozygotes explain their lowered intellectual level?

Intracellular phenylalanine and tyrosine was determined in lymphocytes of 10 heterozygotes (parents) for PKU and in 26 randomly collected apparently normal persons. In cells from the heterozygotes the concentrations of both phenylalanine and tyrosine were higher than in those from the normals, the difference being statistically highly significant. It is argued that this could be responsible for the slight, though statistically significant, intellectual inferiority of heterozygotes for PKU.


Genetic variation in parotid basic proteins (Pb) in the Bozo (Mali, West Africa).

The frequency of variants in the Pb system was studied in 71 individuals from the Bozo tribe in the Bani-Niger area (Mali, West Africa), in 25 male students from different African countries, and in 110 Dutch students. The frequency of the Pb2 allele was 0.20 in the Bozo and 0.00 in the Dutch population. A comparison is made with the results of a study among American blacks and with a Japanese study. The Pb 2--2 phenotypes observed in this study favour the hypothesis that the Pb-2 c protein is derived from a larger precursor in a manner analogous to the generation of the Pb-1 b protein from Pb-1 protein e.


Partial trisomy 17q. Karyotype: 46,XY,der(21),t(17;21)(q22;p13).

A 15-year-old deeply mentally retarded male is described with partial distal 17q trisomy (17q22 replaced by 17qter),as the result of a de novo 17q/21p translocation. Differential Ag-staining showed that the satellites of chromosome 21 were included in the translocation chromosome.


C3 polymorphism in some Indian populations.

The distribution of C'3 phenotypes was studied in one tribal and three urban populations from India. The C'3F gene was found low in frequency compared to European and West Asian populations. Quantitatively also, the concentration of the C3 component in the Indian region was found significantly low to the European and West Asian populations reported previously.


Genetic linkage analysis of hemoglobin variants in 175 families.

Linkage analysis using the LIPED program developed by Ott for the analysis of whole family data was performed on 175 families with variants of the hemoglobin beta- or gamma-chain. Comparison of our results with those in the literature indicate that there is little evidence for linkage with any of the currently used markers, although there is considerable heterogeneity in lod scores between sexes for the Duffy and MNS blood groups. It is suggested that the most successful approach in the future will be to analyze markers known to be localized on chromosomes which have been indicated as likely sites of the beta-chain locus from hybridization studies.


Polymorphism of glyoxalase I in Vienna.

Phenotype and gene frequencies of the GLO I polymorphism in Vienna are given. No exception to the postulated rule of inheritance could be found in 23 families with 51 children and 132 mother-child pairs. Linkage with the HLA system is confirmed, but no linkage disequilibrium between GLO alleles and HLA-A, B, C genes was detected. The use of the GLO I polymorphism in paternity cases is discussed.


Polymorphism of red cell glutamic-pyruvic transaminase in Japanese: gene frequencies in samples from Northern Japan.

The genetic polymorphism of red cell GPT was investigated by starch-gel electrophoresis in four samples from northern Japan including a sample of the Ainu of Hokkaido. The distribution of the Gpt1 gene frequencies among 10 samples excluding the Ainu so far examined showed heterogeneity. The geographical cline of Gpt1 gene frequency reported in southern Japan was not observed in northern Japan.


Seven cases of branchial cyst and sinuses in four generations.

7 cases of isolated branchial anomalies distributed in four consecutive generations of a Central Indian family are described: 6 were males and 1 was female. 3 members had a left-sided branchial sinus, 1 had a right-sided sinus, 2 had bilateral sinuses, and 1 had a right-sided cyst. The family shows that branchial (lateral cervical) cysts and sinuses are inherited as autosomal dominant characters, and that the two anomalies are indistinguishable genetically.


Glyoxalase 1: a possible 'null' allele.

A three-generation family, ascertained through the presence of two diabetic sibs, provides segregation data suggestive of the existence of a null allele at the glyoxalase (GLO) locus. This conclusion is supported by the GLO 1 phenotype in two children from a GLO 2 father. These two children inherited the same paternal HLA allele, while two other sibs received GLO 2 with the other paternal HLA haplotype. The rest of the pedigree is in agreement with this suggestion, while the segregation of all other informative markers does not suggest nonpaternity.


A study of the linkage relations of epidermolysis bullosa dystrophica.

Two large families from the Faroe Islands presenting epidermolysis bullosa of the dystrophic type were subjected to extensive linkage analyses with 22 serological markers. No significant evidence in support of linkage with any of these loci was provided. It was found to be very unlikely that the gene or genes causing the present types of epidermolysis bullosa belong to the EBS1 locus known to be closely linked to the GPT locus.


Human alpha-L-fucosidase: a common polymorphic variant for low serum enzyme activity, studies of serum and leukocyte enzyme.

Serum alpha-L-fucosidase was assayed in 422 individuals. Extremely low levels of enzyme activity were found in 26 individuals. This variant enzyme has increased heat lability. The remaining samples exhibited a bimodal frequency distribution. Family studies suggest that the variant is inherited as a Mendelian recessive character. The variant leukocyte enzyme exhibits normal activity yet increased heat lability. Serum and leukocyte samples from individuals who do not possess the low activity variant are heterogeneous with respect to the heat lability of alpha-L-fucosidase. This common polymorphism may be useful for mapping purposes in family studies.


Genetic and nongenetic influences on the ABH and Lea antigen levels of saliva and milk.

The saliva and milk of 250 parturient women were studied in relation to ABH antigen levels; part of the sample was also investigated for the Lewis (Lea) substance. The levels of A and B are higher in saliva, and those of H and Lea higher in milk. The H average salivary titers presented the relationship O greater than A2 greater than A1 greater than B greater than AB, but these differences were not present in milk. In addition, the salivary levels of A and B are similar in individuals of these groups but B greater than A in AB persons, and A1 greater than A2; while in milk A greater than B in A, B and AB subjects, and A1 approximately equal to A2. The amount of Lea substance depends of the ABH secretor status in both secretions; but independently of this difference, the average titers were always higher in milk. Correlation coefficients between the levels observed in the two secretions are statistically significant for the A substance in A persons (0.46), H in B (0.58) and Lea in all subjects tested (0.47). A stepwise multiple regression analysis performed to verify the influence of four genetic and six nongenetic variables in the ABH levels of both fluids indicated only one consistent modifying factor: ABO type.


Metabolism of mannose and fucose in cultured fibroblasts from patients with mannosidosis and mucolipidosis.

The incorporation of 14C-D-mannose or 14C-L-fucose into cultured fibroblasts from controls and patients with mannosidosis and mucolipidosis type II was studied. Mannose-containing oligosaccharide chains retarded on Sephadex G-25 were accumulated in cells from both patients. Fucose-containing oligosaccharides retarded on G-25 were also accumulated in cells from the patient with mucolipidosis. Besides there was an increase of macromolecular fucose-containing material in the cells from the patient with mucolipidosis. Conditioned medium of the cells from controls and the different patients exhibited about the same pattern as found in the cells, which might indicate leakage of the cellular material due to cell damage or death.


On the population genetics of beta2-glycoprotein I.

Beta2-glycoprotein I typings on 152 healthy Germans and 150 patients with atopic diseases did not show any differences in the serum protein concentrations or in the phenotype and gene frequencies. Compared to these German samples, Philippinos (n = 88) as well as healthy Negroes from South Africa (n = 192) revealed statistically significant lower concentrations of this serum protein. They differ also from the Germans with regard to phenotype and gene frequencies. A most striking result was found in the comparison of healthy and leprous Negroes (n = 250) from South Africa. In these, quite different and statistically significant beta 2-Glycoprotein I concentrations, respectively, phenotype and gene frequencies were seen, which may be due to this disease. The possible reasons for these observations as well as for the observed population differences are discussed.


A microtechnique for the rapid analysis of macromolecule synthesis in minicultures of mammalian cells.

A new micromethod, called the Stanzen technique, is described for the rapid determination of DNA and protein content as well as the incorporation rates of radioactively labeled precursors into macromolecules in cells growing in replica minicultures on plastic petri dishes. The procedure yielded reproducible results assaying only minimal cell numbers per sample and was applied for studying both primary or early passaged cell cultures (mouse epidermal cells and fibroblasts) and a malignantly transformed epidermal cell line. In four well defined circular areas (called Stanzen) marked on the bottom of tissue-culture plastic petri dishes (by heated stamps), 0.2 to 4 x 10(5) cells per area were plated and grown as four individual cultures in one dish. Both treatment and labeling with radioactive precursors of these Stanzen cultures were performed as with normal petri dishes. After fixation and extraction of the cultures, the singular Stanzen areas (with the cells fixed onto them) were sawed out and transferred into vials for liquid-scintillation counting or determination of DNA and protein. The obtained values of specific activity corresponded well whether the samples compared were derived from the minicultures of the same dish or from several dishes. By modifications of the known colorimetric methods for DNA and protein determination, the sensitivity of these procedures was improved down to values of 1 microgram DNA or 5 micrograms protein per individual culture. These micromodifications yielded the same values as the standard methods whether applied to cell suspensions or to cell cultures. Finally, cell proliferation was not influenced by the growth conditions in the small Stanzen areas and proceeded as in normal dishes or larger areas similarly stamped on the bottom of petri dishes. Since this method proved valuable for biochemical studies using primary cultures of mouse epidermal cells (saving cell material by a factor of 10, test substances and time), it might also be advantageous for other purposes as well where the availability of cells or test substances are limiting factors for large test series.


Mutagenic effect on L5178Y mouse lymphoma cells by growth in ethylene oxide-sterilized polycarbonate flasks.

The mutation frequency of L5178Y mouse lymphoma cells to resistance to 5'-bromo-2'-deoxyuridine increased 6- to 14-fold after growth in ethylene oxide-sterilized polycarbonate culture flasks compared to growth in glass flasks. No comparable increase was observed when L5178Y cells were grown in identical polycarbonate culture flasks sterilized by autoclaving.


Biological properties of human melanoma cells in culture.

Three human melanoma cell lines derived from one primary and two metastatic tumors from three different patients were characterized for growth properties usually associated with malignant transformation; these include cell morphology, growth rate, saturation density, growth in semisolid media, colony-forming ability on contact-inhibited monolayers of normal fibroblasts and epithelial cells, and tumorigenicity in immunosuppressed mice. Variations in expression of aberrant properties were evident among the lines. One of the metastatic lines satisfied all the parameters of malignancy tested and the other showed a number of these properties, whereas the primary essentially fulfilled only one. These results suggest that cultured melanoma cells reflect the clinical variability often observed among melanoma patients and that metastatic melanoma seems to display a higher degree of malignant transformation than the primary.


Normal human endometrium in cell culture. II. A microspectrophotometric study of polyploid nuclei in short-term primary epithelial cultures.

The growth of short-term primary cultures of endometrial epithelium has been studied using Feulgen microspectrophotometry. A gradual increase in the number of polyploid nuclei up to 64C has been observed and is associated with a decline in the growth capacity of the cultures. The specific mechanism(s) of this polyploidization is not known.


The use of agarose in the determination of anchorage-independent growth.

At the present time, growth in agar suspension is one of the best in vitro correlates of tumorigenicity. Growth in agarose, however, has not been evaluated extensively as an in vitro criterion for tumorigenicity. In the present study we have tested 19 cell lines, including six mouse-human hybrids, for growth in agarose and agar in the presence and absence of exogenous hypoxanthine. None of the six nontumorigenic cell lines grew in agar or agarose. Ten of the 13 tumorigenic cell lines grew in both agar and agarose with about equal efficiency. The remaining three tumorigenic cell lines grew well in agarose but poorly or not at all in agar. Hypoxanthine did not stimulate the growth in agar or agarose of any of the cell lines except BHK. We conclude that growth in agarose may be a more sensitive marker for tumorigenicity than growth in agar and that BHK is exceptional in its sensitivity to supplemental purines.


Selection of a chemically defined medium for culturing adult newt forelimb regenerates.

Three commercially available tissue-culture media were evaluated for their ability to support continued growth and differentiation of 14-day regenerates of adult newt forelimbs. Serums, embryo extracts, egg ultrafiltrates, and antimicrobial agents were avoided in this analysis. The hormones insulin and L-thyroxine were added to these chemically defined media to enhance continued cellular metabolism and growth. The optimum conditions appeared to be cultivated at 25 degrees C (pH 7.2 to 7.4) in media osmotically adjusted to conditions approximating amphibian blood values (i.e. 225 m0SM for 199, 244 m0SM for CMRL-1066, and 262 m0SM FOR L-15).


Polarographic measurement of oxygen uptake by astrocytes in primary cultures using the tissue-culture flask as the respirometer chamber.

Oxygen uptake was measured in primary cultures of astrocytes from the brain hemispheres of newborn DBA mice by the aid of an oxygen electrode inserted directly into the culture flask, i.e. using the flask, completely filled with MEM medium, as the respirometer chamber. The respiration was initially intense (300 mumol per hr per 100 mg protein) but declined somewhat during the 6 hr of measurement, probably due to a depletion of intermediary metabolites released to the large surplus of medium. The respiratory rates were approximately identical in the presence of a CO2/bicarbonate and a HEPES buffer. Exposure to a high concentration of potassium led to a transient stimulation of the oxygen uptake to almost 100%, a response that was very easily observed using the present method. Since no mechanical damage was inflicted upon the cells, culturing could be continued, if so desired, after the measurement.


Sensitivity of cultured rat hepatocytes to aflatoxin B1 and benzo(a)pyrene.

We have tested the sensitivity of a cloned rat hepatocyte line, RL-PR-C, to aflatoxin B1 and benzo(a)pyrene as a function of population-doubling level. The cells were much more sensitive to the cytotoxic action of these agents subsequent to 230 population doublings. This sensitivity corresponded to the enhanced inducibility of aryl hydrocarbon hydroxylase activity by 3-methylcholanthrene.


[Determination of the bactericidal activity of peritoneal macrophages: a new method (author's transl)].

A new method to estimate the bactericidal activity of peritoneal macrophages is described. This method allows to calculate with great accuracy the number of phagocytised bacteria per macrophage. In serial experiments different degrees of activation of macrophages in respect to their bactericidal activity against listeria monocytogenes has been shown.


[Studies on normal range of serum IgE concentration (author's transl)].

To obtain information about the normal range of IgE concentration in serum a random population of male and female patients was divided into 14 age groups. Based on the mean values (x +/- 1s) an age dependency is clearly recognizable with an increase of the IgE concentration at one and two years of age, a constant IgE concentration during the middle age period, and a decrease of the IgE level in the 40th year of age which becomes especially obvious after the 60th and 80th year of age. From the distribution pattern of IgE levels within the different age groups it is evident that only the curves of newborns and persons over 80 years resemble a normal Gaussian distribution. The other age groups show 2 or 3 peaks of IgE. However, these peaks represent only 50% of the total IgE concentration. A similar distribution pattern was obtained by IgE determinations in 100 "healthy" blood donors which showed no clinical evidence of allergy. The age dependent normal ranges given in this paper make it possible to evaluate increased IgE levels accordingly.


Chemotactic factor inactivator release from rat leukocytes.

Rat neutrophils, alveolar macrophages, and peritoneal macrophages each released chemotactic factor inactivator (CFI) activities under conditions of endocytosis (uptake of opsonized zymosan particles and preformed immune complexes). CFI activities in supernatant fluids from phagocytizing leukocytes were found for the chemotactic factors from the third (C3) and the fifth (C5) components of complement and for the bacterial chemotactic factor (present in culture supernatant fluids from Escherichia coli.) CFI activity could also be demonstrated in homogenates obtained from disrupted leukocytes. CFI release from intact leukocytes was dependent on the duration of incubation of leukocytes with the phagocytic stimulus. No quantitative relationships were noted between the amount of CFI activity and the amount of beta-glucuronidase in phagocytic supernatant fluids released from leukocytes. The release of CFI activities from phagocytizing leukocytes may represent a regulatory ("turn-off") mechanism for the inflammatory response.


An assay procedure for the comparative irritancy testing of esters in the tigliane and daphnane series.

A method is described for testing of diterpene esters for irritancy. The technique involves the application of acetone solutions of the toxins to the inside ears of female LACA mice. The number of mice responding per group and the log10 dose data were evaluated using probit analysis with the assistance of a computer program. This evaluation has the advantage that approximations inherent with an arithmetical evaluation were eliminated, and limits may be placed upon the standard deviation of the irritant dose 50% (ID50). In addition, the use of a chi2 test automatically eliminated results which were not attributed to random biological variation. Observations of the time to onset and the persistence of the inflammation have led to the suggestion that daphnane orthoester diterpenes may elicit their effect by means of a direct action at a receptor site in skin, whereas the tigliane O-acyl esters may in part act by causing more general tissue damage.


The effect of selected amino acids on gelatin-induced inflammation in adult male mice.

Several studies have indicated to us that certain amino acids may exhibit antiinflammatory activity. In the present study we attempted to evaluate the inhibitory effect of various amino acids on gelatin-induced abdominal inflammation in mice using peritoneal fluid cytology as the diagnostic tool. The L-amino acids tested were tryptophan, phenylalanine, alanine, cystine, hydroxyproline, tyrosine, citrulline, leucine, and valine. Hydrocortisone was used as an antiphlogistic steroid control. Tryptophan, phenylalanine, alanine, cystine, hydroxyproline, and tyrosine all significantly decreased the inflammation. Citrulline and valine, however, both exhibited strong antiiflammatory responses. Based on these results, three related dipeptides were also screened: L-valy-L-alanine, L-valyl-L-tryptophan, and L-tyrosl-L-valine. Valyl alanine was found to produce a strong antiinflammatory effect. In a final test, the combination of the steroid, hydrocortisone, and the amino acid, cystine, was screened for a synergistic effect. The combined treatment inhibited the gelatin-induced inflammation more than either the amino acid or the steroid administered alone.


Acute induction of joint inflammation in the rat by poly I . poly C.

Intraarticular injection of interferon inducer, double-stranded polyinosinate-polycytidylate (Poly I . C) caused acute synovitis in rats. This acute inflammatory response was accompanied by an increased concentration of prostaglandin E (PGE) in the synovial tissue. Double-stranded polyadenylate-polyuridylate (Poly A . Poly U) was less potent than Poly I . Poly C in inducing synovitis and increasing PGE concentration, while single-stranded polyinosinate (Poly I) or polycytidylate (Poly C) were inactive in these respects. Intraarticular injection of partially purified mouse fibroblast interferon also induced synovial inflammation. The present results suggest that interferon may be a mediator of viral inflammatory responses.


Pulmonary macrophage growth factor.

Pulmonary macrophage growth factor (MCF) can be purified from the "used" serum-free medium of cultures of mouse lung cells by concentration and dialysis over a 30,000-dalton Amicon ultrafilter and subjecting the retentate to isoelectric focusing. This yields a protein fraction with an isolelectric point of pH 4.2, which contains all the MGF activity. Upon electrophoresis of this fraction in analytical gels, one large and four small bands could be visualized. All bands were biologically active. This same "heterogenous" fraction ran as one band (mol wt 68,000) in SDS analytical gel electrophoresis, suggesting the ordered aggregation of this monomer. This was confirmed by reelectrophoresis of the first (and largest) band demonstrating the same 5-banded pattern as the initial material.


Investigations into the skin-irritant properties of resiniferonol ortho esters.

A series of esters were produced by partial synthesis from 9,13,14-orthophenylacetyl-resiniferonol. These compounds were tested for irritant effects by means of a mouse ear assay. All of the derivatives, including the parent compound, produced short-term inflammation of mice ears within 1-2 h and the effects did not persist for 24 h. This is in contrast to esters of structurally related tigliane diterpenes which produce a longer-term on mice ears. Highly potent irritants were synthesized which exhibited irritant doses 50% in the 0.0012-0.00021 nmol range. These esters were all substituted phenylacetates of the C-20 position of 9,13,14-orthophenylacethyl-resiniferonol. The meta or para positions of the phenylacetate moiety were substituted with electronegative groups for maximum activity. Compounds exhibiting substituted phenyl propionates at C20 were not irritants in the test used.


Effect of inflammatory and noninflammatory stress on plasma ketone bodies and free fatty acids and on glucagon and insulin in peripheral and portal blood.

Inflammatory stress as characterized by infection with Streptococcus pneumoniae, administration of endotoxin, or the induction of a turpentine abscess is characterized by the inhibition of the ketosis assoicated with fasting and a decline in the level of free fatty acids in the plasma. Moreover, rats subjectd to these inflammatory stresses demonstrate a significant rise in peripheral and portal insulin and glucagon. Rats subjected to noninflammatory stresses, screen-restraint, or noninvasive femoral fracture did not demonstrate the inhibition of ketosis but did show a decrease in plasma free fatty acids. The noninflammatroy stresses did not show an abnormal elevation of plasma or portal insulin or glucagon.


Leukocyte migration inhibition activity of nonimmune acute inflammatory pleural exudate.

Material with leuckocyte migration inhibition (LMI) activity has been demonstrated in various types of nonimmunologically induced acute pleural inflammatory exudates. This activity is present in inflammatory cell-free exudate and appears to involved the deposition of fibrin around the migrating leukocyte, resulting in "cell-trapping." This is supported by the fact that removal or inhibition of fibrin formation leads to loss of exudate LMI activity. Both fibrinogen and complement as well as vitamin K-dependent clotting factors appear to be required for LMI activity. The mechanism involved in the LMI reaction and its significance in nonimmune and cell-mediated immune inflammation are discussed.


Neutrophil enzyme activities in rheumatoid inflammation.

This study analyzed the neutrophils and sera of patients with rheumatoid arthritis and of normal controls. No significant differences were found in the activities of the granular enzymes beta-glucuronidase and lysozyme or the cytoplasmic enzyme lactic dehydrogenase (LDH). Normal neutrophils were found to release significant (P less than 0.05) amounts of the granular enzymes, but not of LDH in response to immunoglobulin G aggregates. There was no difference in the percent release exhibited by rheumatoid versus control neutrophils. Studies delineating the effects of rheumatoid factor sera and normal sera on aggregate-induced enzyme release revealed a significant negative correlation between the amount of rheumatoid factor in the sera and the percent release of beta-glucuronidase and lysozyme but not of LDH. These studies thus demonstrate no abnormalities in rheumatoid neutrophil or rheumatoid serum enzyme activities or in neutrophil response to immunoglobulin G aggregates. They suggest, however, that rheumatoid factor may partially inhibit the release of lysosomal enzymes, thus suppressing this important component of the rheumatoid inflammatory process.


Bone healing in rabbits after compression osteosynthesis: a comparative study between the radiological and histological findings.

The relationship between the radiological and histological findings was studied in a series of rabbit osteotomies and fractures stabilized with plates with and without longitudinal compression. When compression was employed, the gap varied between 10 and 200 micrometers and no radiologically visible callus was seen. After 4 weeks the smallest gaps of 10--30 micrometers were filled histologically with structureless material, while the larger gaps contained 'cortical' bone derived from periosteal and endosteal proliferation. The degree of union could not be assessed from X-ray examination, as there was no correlation between the histological and radiological appearances. When no compression was employed, the gap varied between 200--1200 micrometers; radiologically visible periosteal callus and filling of the gap indicated that consolidation had appeared in four weeks. Gaps of 200--500 micrometers were filled with bone derived from the periosteum and endosteum of lamellar structure which had invaded the original cortical bone ('plugging'). When the gaps were more than 500 micrometers, islands of cartilage and connective tissue were found. In all cases studied, many 'anchoring osteons' passed from the endosteal and periosteal callus into the original cortical bone. It is concluded that a 'compression internal fixation' of cortical bone will not necessarily secure union, as histologically confirmed, even when the formation of radiologically visible callus is suppressed. The lack of periosteal callus appears to be the result of a small gap and rigid fixation, rather than related to strains induced in the bone.


Internal fixation of fractures of the proximal end of the radius in adults.

Eight cases of internal fixation for fractures of the proximal end of the radius in adults are discussed. The reasons for this procedure, after considering the patient's age and activity and the type of fracture, was to avoid the sequelae of resection of the radial head. By following an appropriate technique, and provided that there are no compications, the results obtained have been excellent.


A universal snap-fit endoprosthesis for the treatment of subcapital fractures of the femur: a preliminary report.

A new endoprosthesis for the treatment of subcapital fractures is described. It is hemispherical with a high density polyethylene (HDP) core which is snap-fitted onto a Charnley-type femoral prosthesis. The aim is to prevent acetabular erosion by its virtual lack of movement of the cartilage-metal interface. If this should occur then conversion to a total hip is readily performed without removing the femoral stem. So far 14 have been inserted without any complications. In fact, they are easily mobilized with very little pain.


Internal fixation of fractures of the neck of the femur in hemiplegic patients.

There was a history of hemiplegia due to stroke in 97 (6.5 per cent) of 1483 consecutive patients with fresh fractures of the neck of the femur. Both cervical and trochanteric features occurred significantly more often on the hemiplegic side. Internal fixation was technically satisfactory in trochanteric fractures, but failed frequently in cervical fractures.


Varus deformity in supracondylar fractures of the humerus in children.

Eighty cases of supracondylar fracture of the humerus at the elbow in children have been analysed. The post-reduction radiograph of the fracture was classified depending on the residual deformity present and related to the loss of carrying angle and cubitus varus deformity at the time of follow-up. Fifty-four percent of the displaced fractures showed a loss of carrying angle greater than 5 degrees, and of these 23 per cent developed cubitus varus deformity. Eighty-five per cent of those cases with a loss of carrying angle greater than 10 degrees showed either residual tilt or medial rotation on the post-reduction radiograph. All cases in which there was residual medial tilt after manipulation and 40 per cent of those with medial rotation on the post-reduction radiograph developed cubitus varus. In our series, there was no evidence of epiphyseal injury causing the deformity and in none of the cases was the deformity progressive. It is suggested that, in order to reduce the incidence of varus deformity in suprocondylar fractures, open reduction and internal fixation is indicated in those fractures in which tilt or medial rotation cannot be reduced by conservative means.


The unstable shoulder: recurring subluxation.

A review of operative repairs for recurring dislocation of the shoulder revealed that a significant proportion of these operations was being done for what could best be described as recurring subluxation of the shoulder. The presenting complaint was of the shoulder 'going out of joint', but no significant trauma was recalled, dislocation was never shown on the radiograph and none required manual reduction. The only physical finding was apprehension on external rotation of the shoulder in abduction. Radiographs were frequently normal and arthrography and cineradiography were not helpful in confirming anterior displacement. The most useful preoperative information was obtained by manipulation of the shoulder under general anaesthesia just before the surgical repair. In all instances anterior instability could be demonstrated. Of 99 Magnuson-Stack repairs drawn from the records of the Vancouver General Hospital in a 3-year period, 34 proved to be examples of recurring subluxation. This high proportion of such patients contradicts the teaching in standard orthopaedic textbooks, but substantiates the warning of Rowe (1963) to beware of the patient whose shoulder 'dislocates' initially with little evidence of injury. It also substantiates Saha's concept (1971) of inherent shoulder instability as a contributor to the incidence of recurring dislocation.


Entonox in the emergency department.

The use Entonox (BOC Medishield) was examined in a large accident and emergency department and was found to give satisfactory relief from pain in 92 per cent of cases. This compares favourably with reports of its results in other applications.


Ankle injuries caused by seat belts.

Two cases of tri-malleolar frautures of the ankle caused by feet becoming entangled in loose seat belts are reported. Open reduction and internal fixation of all three malleolar fragments was carried out in each case with a satisfactory end result.


A six-month review of motorcycle accidents.

Ther were over 1000 fatal motorcycle accidents in Britain during 1976, which cost the taxpayer over pounds 40 million. There has been a 50 per cent increase in the number of motocyclists treated at Newcastle General Hospital Casualty Department over the past six months. Most accidents occur with young inexperienced male drivers, making elementary driving errors. Suggestions for positive prevention of motorcycle accidents are made. Of paramount importance is the need for consideration of compulsory formal training and enactment of the motorcycle lighting-up law.


Cell-mediated immune responses to the hemagglutinin and neuraminidase antigens of influenza A virus after immunization in humans.

Humoral and cell-mediated immunity (CMI) were evaluated in groups of school children after immunization with inactivated influenza virus vaccines. A conventional biphasic strain (H3ChN2Ch) of Port Chalmers influenza virus (X-41), a recombinant influenza virus specific for the neuraminidase antigen (Heq1N2Ch) of Port Chambers influenza A virus (X-42), and a placebo were employed for immunization. The techniques of hemagglutination inhibition and neuraminidase inhibition were used to determine serum antibody titers. The CMI responses were evaluated by the in vitro lymphocyte transformation assay employing HavN2Ch, Heq1Neq1, H3ChNeq1, and H3ChN2Ch influenza A virus strains as stimulants. Specific HAI antibody and CMI responses to H3Ch were observed in X-41 but not in X-42 vaccinees. Specific anti-neuraminidase antibodies and CMI responses to N2Ch were manifested by both X-41 and X-42 vaccinees. Immunization with the placebo resulted in no influenza-specific immune responses. The CMI response was first detectable 10 days after immunization and then declined. These observations demonstrate the induction of CMI responses to the HA and NA influenza surface antigens after immunization. These responses may be important in antiviral immunity and the recovery from influenza infection.


Immunological specificity of heat-stable opsonins in immune and nonimmune sera and their interaction with non-encapsulated and encapsulated strains of Staphylococcus aureus.

The in vitro interactions between strains of Staphylococcus aureus and human polymorphonuclear leukocytes in the presence of immune and nonimmune sera were studied. Evidence indicated that phagocytosis of encapsulated strains occurred in the presence of specific homologous antiserum, whereas non-encapsulated strains were readily phagocytized by polymorphonuclear leukocytes in the presence of both normal and immune sera. Immunological analyses demonstrated that normal serum opsonins, which reacted with the non-encapsulated strains, were specifically directed against exposed mucopeptide moieties of the organisms. Sera rich in antimucopeptide antibodies were obtained from rabbits immunized with heterologous bacteria such as Escherichia coli and group A-variant streptococci and were shown to be effective in opsonizing the non-encapsulated strains of S. aureus. Fresh clinical isolates of S. aureus were noticeably more resistant to the opsonizing effects of the antimucopeptide antibodies. Results were presented which suggest that the surface structures of these clinical isolates are more diverse than laboratory-propagated strains and that these antiphagocytic surface antigens may be significant factors in masking the opsonizing effects of the mucopeptide opsonins which are present in most sera.


Purification and characterization of Clostridium difficile toxin.

Recent evidence indicates that toxigenic Clostridium difficile strains are a major cause of antimicrobial-associated ileocecitis in laboratory animals and pseudomembranous colitis in humans. C. difficile ATCC 9689 was cultivated in a synthetic medium to which 3% ultrafiltrated proteose peptone was added. Purification of the toxin from broth filtrate was accomplished through ultrafiltration (100,000 nominal-molecular-weight-limit membrane), precipitation with 75% (NH4)2SO4, and chromatographic separation using Bio-Gel A 5m followed by ion-exchange chromatography on a diethylaminoethyl-Sephadex A-25 column. The purified toxin displayed only one band on polyacrylamide gel electrophoresis, and approximately 170 pg was cytopathic for human amnion cells. The isolated toxin was neutralized by Clostridium sordelli antitoxin, heat labile (56 degrees C for 30 min), and inactivated at pH 4 and 9; it had an isoelectric point of 5.0, increased vascular permeability in rabbits, and caused ileocecitis in hamsters when injected intracecally. Treatment of the toxin with trypsin, chymotrypsin, pronase, amylase, or ethylmercurithiosalicylate caused inactivation, whereas lipase had no effect. By gel filtration, its molecular weight was estimated as 530,000. Upon reduction and denaturation, the toxin dissociated into 185,000- and 50,000-molecular-weight components, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Extensive dissociation yielded only the 50,000-molecular-weight component. The toxin appears to be protoplasmic and is released into the surrounding environment upon autolysis of the cells. Attempts to correlate specific enzymatic activity with the toxin have been unsuccessful. These studies will help delineate the role of C. difficile toxin in antimicrobial-associated colitis and diarrhea.


Flagella-induced immunity against experimental cholera in adult rabbits.

The adult rabbit ligated ileal loop model was used to evaluate the prophylactic potential of a crude flagellar (CF) vaccine produced from the classical. Inaba strain CA401. A greater than 1,000-fold increase in the challenge inoculum was required to induce an intestinal fluid response in actively immunized adult rabbits equivalent to that produced in unimmunized animals. Similar protection was afforded against challenge with classical and El Tor biotypes of both Inaba and Ogawa serotypes. Highly virulent 35S-labeled vibrios were inhibited in their ability to associated with the intestinal mucosa of CF-immunized rabbits. The protection conferred by CF immunization was found to be superior to that of a commercial bivalent vaccine and also to that of glutaraldehyde-treated cholera toxoid. The critical immunogenic component of CF appears to be a flagella-derived protein. The immunogenicity of CF was destroyed by heat treatment, and absorption of CF-immune serum with aflagellated mutant vibrios did not diminish its ability to confer a high level of passive protection. The intestinal protection of CF-immunized rabbits was completely reversed by the introduction of both goat anti-rabbit immunoglobulins A and G, but by neither alone.


Immunosuppression and isolation of rubella virus from human lymphocytes after vaccination with two rubella vaccines.

Two groups of young rubella-susceptible women were vaccinated with two rubella vaccines. Heparinized blood samples were taken from all individuals the day of vaccination and 5, 7, 15, 21, 30, 35, and 42 days later. Purified lymphocytes from these samples were cocultivated with AGMK cells for rubella virus isolation. Parallel samples of lymphocytes were stimulated with phytohemagglutinin, and the rate of [14C]thymidine incorporation was determined. Rubella virus was isolated from lymphocytes collected on days 7, 15, and 21 after RA27/3 vaccination in contrast to days 7 to 35 after HPV77 vaccination. The lymphocyte response to phytohemagglutinin was markedly suppressed from day 5 to 15. Normal lymphocyte responses were restored within 1 month after vaccination with RA27/3, but even later (1 week) after HPV77 vaccine. Lymphocytes from rubella-susceptible persons infected invitro with rubella virus vaccines and stimulated with phytohemagglutin displayed a decrease in their responsiveness to the mitogen similar to that observed with lymphocytes from vaccinees. The transient immunosuppression observed in vaccinees is probably due to virus-induced functional damage of the lymphocytes since no direct cytocidal effect of rubella vaccine has been demonstrated on human lymphocytes.


Efficacy of antimicrobial therapy in experimental rat pneumonia: antibiotic treatment schedules in rats with impaired phagocytosis.

Pneumococcal pneumonia in rats with intact host defense mechanisms could be successfully cured by penicillin. The efficacy of this antibiotic therapy was lost in cobra venom factor-treated rats which had selectively impaired phagocytic functions. In these animals the effect of penicillin therapy was improved by increasing the daily dose and the frequency of injections and by earlier initiation of the therapy. The efficacy of penicillin in the cobra venom facttor-treated rats was restored either by markedly increasing the daily dose of penicillin or by increasing the daily dose in combination with a reduced interval of the penicillin injections.


Rabies virus immunity in genetically selected high- and low-responder lines of mice.

The antibody responsiveness to and the specific vaccination effect of rabies virus infection were investigated in high- and low-responder lines of mice produced by two-way selective breedings for quantitative production of antibodies to flagellar (H/f and L/f lines) or somatic (H/s and L/s lines) antigens of salmonellae. After specific immunization, both high lines were more resistant to rabies virus infection than were the low lines, and the protector effect was related to the level of antibody produced, as demonstrated by neutralizing serum activity. The present findings confirm the nonspecific genetic modification of the general antibody responsiveness induced in high- and low-responder lines selected for quantitative antibody production.


Animal model of neutropenia suitable for the study of dual-phagocyte systems.

When two sets of phagocytic cells participate simultaneously in the inflammatory process and bacterial killing, the relative contribution of each cell type is difficult to ascertain. The use of cell-specific antibody will permit selective depletion of one phagocyte population. We describe an experimental model of granulocytopenia which utilizes the immunoglobulin G fraction of an antigranulocyte serum. This material markedly depleted circulating polymorphonuclear leukocytes (PMN); within 2 h after injection of antigranulocyte globulin, PMN counts were at 19% of original levels and remained significantly depressed for 24 h. Granulocyte recruitment was also impaired, with only 5 x 10(3) PMN appearing in the lungs in response to an aerosol of Klebsiella, compared to 4.17 x 10(5) PMN in control animals (P less than 0.01). Most importantly, alveolar macrophages retained normal viability (97% versus 94% for control value, P not significant) normal phagocytic function, and normal bactericidal capacity. Antigranulocyte globulin is thus a valuable tool for the study of bacterial defense mechanisms.


Analysis of the effects of lipopolysaccharide on macrophages: differential phagocytic responses of C3H/HeN and C3H/HeJ macrophages in vitro.

The phenomenon of lipopolysaccharide (LPS)-induced in vitro macrophage cytotoxicity has been reported by a number of investigators but has often been difficult to reproduce and to quantitate. In this report, we have examined the effect of LPS on the ability of macrophages to ingest 51Cr-labeled, opsonized sheep erythrocytes as a method for examining the direct toxic effects of LPS on macrophages in vitro. By using this assy, we can clearly discriminate between LPS responder C3H/HeN macrophages and LPS nonresponder C3H/HeJ macrophages and demonstrate that LPS induces a profound inhibition of Fc-mediated phagocytosis in LPS responsive macrophages. Furthermore, low concentrations of LPS stimulate phagocytosis in macrophages derived for C3H/HeJ mice. The lipid A moiety of the LPS is responsible for the observed enhancement or inhibition of Fc-mediated phagocytosis. This assay was more sensitive than LPS-induced cytotoxicity, since inhibition of phagocytosis was detectable in cultures of LPS-sensitive macrophages even when cytotoxicity, assessed by trypan blue exclusion, was not. Thus, this assay represents an extremely sensitive method for analyzing the direct effects of LPS on macrophages.


Efficacy of antimicrobial therapy in experimental rat pneumonia: effects of impaired phagocytosis.

The importance of intact host defense mechanisms for successful antimicrobial therapy was investigated in an animal model. Recovery from lobar pneumococcal pneumonia as a result of penicillin therapy was studied in normal rats and in rats treated with cobra venom factor. This factor was used to selectively suppress the phagocytosis of pneumococci as a result of complement depletion. Although complete recovery from the infection occurred in normal rats after appropriate penicillin therapy, this was not the case in cobra venom factor-treated rats. Within the limitations of this study, evidence is presented for loss of antibiotic activity as a consequence of impaired phagocytosis.


Enhancement of generation of monocyte tissue thromboplastin by bacterial phagocytosis: possible pathway for fibrin formation on infected vegetations in bacterial endocarditis.

The deposition of fibrin on infected vegetations and the presence of mononuclear phagocytes that have phagocytized bacteria are remarkabe features in experimental bacterial endocarditis. In a study in vitro, we show that phagocytosis of bacteria by human monocytes enhances thromboplastin generation by these cells. Maximal enhancement of the generation of thromboplastin by monocytes was about six times compared with that in the control experiment without bacteria, and it was obtained by preincubation of the monocytes with 5 to 10 bacteria per monocyte. No quantitative difference was observed between Staphylococcus epidermidis and Streptococcus sanguis as to the enhancement of the monocyte thromboplastin generation. An enhancement of the procoagulant activity generation was also observed after addition of bacteria to human or rabbit whole blood. Probably, this generation was also due to synthesis of thromboplastin by monocytes. It is conceivable that fibrin deposition on infected vegetations during bacterial endocarditis is mediated by thromboplastin synthesis by monocytes.


Infection of chicken erythrocytes with influenza and other viruses.

Chicken erythrocytes can be infected by the fowl plague (Rostock) strain (FP/R) of influenza type A, Newcastle disease virus (NDV), and Semliki Forest virus (SFV). Only NDV and SFV produced infectious progeny, albeit at low levels. Infection by FP/R was monitored by de novo synthesis of viral proteins, and the proteins synthesized could be identified by comparison with infected chicken fibroblast cells. FP/R synthesized far greater amounts of viral protein than did NDV or SFV.


Stimulation of peroxidase by chlamydial infection: cytochemistry of guinea pig conjunctival epithelium.

Guinea pig inclusion conjunctivitis, a naturally occurring chlamydial disease of guinea pigs, resolves spontaneously after 3 to 4 weeks. The factors responsible for curbing the infection have not yet been specifically defined. Since Iwata (Invest. Ophthalmol. 15:297-301, 1976) reported cytochemical activity for peroxidase in the conjunctival epithelium of the normal rat, we undertook these studies to determine whether a similar activity exists in the guinea pig, and if so, whether it functions in the elimination of this Chlamydia psittaci infection. Tarsal conjunctivas of 14 normal guinea pigs, 34 infected ones, and 7 control guinea pigs (inoculated with yolk sac only) were excised and tested for peroxidase by the Graham and Karnovsky method (J. Histochem. Cytochem. 14:291-302, 1966). We found that peroxidase activity, virtually absent in normal animals, was intensely stimulated by the infection. This enzymatic activity appeared 2 days after inoculation of the conjunctiva with chlamydia and persisted for 6 to 7 weeks. The enzyme was localized in the rough endoplasmic reticulum and perinuclear cisternae of all layers of the conjunctival epithelium from the external surface to the basal lamina, including cells with no apparent inclusions as well as those heavily parasitized. Reaction in the Golgi complex was variable. No reaction, however, was ever evident in the chlamydial vacuoles or lysosomes, and the organisms continued to grow and multiply during peak enzymatic activity. We therefore concluded that the stimulated enzyme is apparently not directly responsible for the waning of the infection, but instead reflects an alteration of host metabolism that occurs as a consequence of the infection.


Immunization of mice against coccidioidomycosis with a subcellular vaccine.

In vitro-cultivated spherules of Coccidioides immitis were disrupted in a Braun homogenizer. The resultant wall fragments were separated from cell sap and endospores by centrifugation. Extraction of the walls with phosphate-buffered saline yielded a subcellular fraction that was immunogenic in mice. This fraction, which contained polysaccharide and protein, gave substantial protection against intranasal challenge with a usually lethal dose (1,000) of arthrospores, provided that it was administered with adjuvant.


Cytochalasin B does not inhibit ingestion of Chlamydia psittaci by mouse fibroblasts (L cells) and mouse peritoneal macrophages.

Cytochalasin B did not inhibit ingestion of Chlamydia psittaci by either mouse fibroblasts (L cells) or mouse peritoneal macrophages in concentrations that produced distinctive morphological changes and inhibited phagocytosis of polystyrene latex beads and Escherichia coli K-12.


Interferon induction by the immunomodulating polyanion lambda carrageenan.

The lambda fraction of carrageenan induced murine interferon, which was characterized by sensitivity to trypsin and inhibition by pretreatment of target cells with actinomycin D.


Macrophage activation by bacterial cell walls and related synthetic compounds.

Activation of peritoneal macrophages from guinea pigs by various bacterial cell walls, M-1 endo-N-acetylmuramidase enzymatically digested bacterial cell walls and synthetic muramyl dipeptides was studied in terms of stimulation of [14C] glucosamine incorporation. All test bacterial cell wall preparations significantly increased a [14C]glucosamine uptake by the macrophages. Some of the water-soluble M-1 enzyme digests also exerted stimulating effects on macrophages, although the activity of the digests was found to be weaker than those of original cell walls. Furthermore, an adjuvant-active synthetic MurNAc-L-Ala-D-isoGln (MDP) showed a weak but significant activity, whereas an adjuvant-inactive analog, MurNAc-L-Ala-L-iso-Gln, did not show a significant activity, at least with the dose of 100 microgram. Additional studies with 6-O-acyl derivatives of MDP revealed that 6-O-(2-tetradecylhexadecanoyl)-MDP and 6-O-(3-hydroxy-2-tetradecyl-octadecanoyl)-MDP exhibit stronger macrophage-stimulating effects than MDP. It can be concluded from the above findings that MDP is the essential structure responsible for stimulating the activity of cell walls on guinea pig peritoneal macrophages, but it requires a particle state, which results from an additive character of lipophilicity, to exert the activity fully and effectively.


Use of HeLa cell guanine nucleotides by Chlamydia psittaci.

Exogenous guanine was found to be incorporated into the nucleic acids of Chlamydia psittaci when the parasite was grown in HeLa cells containing hypoxanthine guanine phosphoribosyltransferase (EC 2.4.2.8) activity but not when the parasite was grown in transferase-deficient HeLa cells. No evidence for a chlamydia-specific transferase activity was found in either transferase-containing or transferase-deficient infected HeLa cells. It is concluded that C. psittaci is incapable of metabolizing guanine, but that the parasite can use host-generated guanine nucleotides as precursors for nucleic acid synthesis.


The sensitivity of gentamicin-resistant gram-negative bacilli to cefotaxime, other cephalosporins and aminoglycosides.

The sensitivities of 80 gentamicin-resistant gram-negative bacilli to cefotaxime, cefuroxime, cefoxitin, cefamandole, cefazolin, tobramycin, netilmicin and amikacin were determined. Amikacin was the most active amino-glycoside. However, the percentage sensitivity to cefotaxime of most of the species was higher than, or equal to any of the other antibiotics tested. Cefotaxime was particulary active against Providencia spp., Serratia spp., Klebsiella spp., and Pseudomonas maltophilia, being 16 to 256 times more active than the next best cephalosporin or cephamycin. Clinical trials of cefotaxime are now required.


Comparative study of the binding of acylureidopenicillins and carbenicillin to human serum proteins.

The binding of the acylureidopenicillins azlocillin and mezlocillin to serum proteins was investigated by means of equilibrium dialysis and ultracentrifugation. The penicillin concentrations were determined by the agar diffusion test and by circular dichroism. The degree of binding is dependent on the penicillin concentration. At a mean penicillin concentration of 20 microgram/ml 39% of azlocillin is bound by serum proteins and 35% of mezlocillin. The acylureidopenicillins are bound to about the same degree by the two proteins albumin and gamma globulin, which occur in different concentrations in serum. The binding affinity delta F degree for the interaction between azlocillin and mezlocillin to human albumin is equal to -15,389 J/mol. The corresponding values for the binding of ampicillin and carbenicillin are -17,340 and -16,800 J/mol. Albumin has one binding site of a high affinity and two binding sites of a low affinity for the acylureidopenicillins. Measurements of partition coefficients of the penicillins for isobutanol and aqueous solution show that the interaction between acylureidopenicillins and serum is mainly hydrophobic in nature. This can be deduced from the fact that for example in the presence of sisomicin azlocillin is not displaced from its albumin binding site, in contrast to carbenicillin. The reason for this difference in behaviour lies in the fact that carbenicillin, like sisomicin, is bound to the serum proteins mainly by ionic bonds. In the case of azlocillin, however, hydrophobic bounds predominate which are not influenced by the ionic bonds of sisomicin.


Bactericidal or bacteristatic effects of two sulphonamide plus trimethoprim preparations in human urine.

Rrine collections were made by ten volunteers taking cotrimoxazole and a sulphamoxole/trimethoprim combination on a cross-over basis. The latter was given in approximately half the dose of cotrimoxazole. Following collection of urine and its sterile filtration, the trimethoprim and sulphonamide concentrations were estimated. The urines were then inoculated with various species of Enterobacteriaceae whose minimum inhibitory concentrations had been previously determined. The viable counts in these urines were followed for 24 hours and from these the times to kill 90% of bacteria were calculated. These were very reproducible for any one experiment but showed no correlation with drug concentration, source of the urine or organism sensitivity, except for one organism which had high resistance to both sulphonamide and trimethoprim. When the organism was sensitive to at least trimethoprim a slow bactericidal effect was generally seen with either combination. We concluded that in this type of experiment the higher dosed combination showed no advantage contrary to a previous report, but in agreement with another. This brings into question the current dosage regime of cotrimoxazole when used to treat urinary tract infections in that its higher dosage over certain other sulphonamide/trimethoprim combinations appears to confer no advantage in our experiments.


Propionibacterium acnes pneumonia in a patient with lymphoma.

A 57 year-old male with lymphocytic lymphoma developed symptoms of cough, fever and progressive dyspnea accompanied by a diffuse lower lung infiltrate. Open lung biopsy revealed multiple micro-abscesses surrounding small bronchioles which yielded a pure growth of Propionibacterium acnes.


[Tissue penetration of erythromycin (author's transl)].

Although erythromycin has been used in therapy for more than 25 years, until now there has been no paper summarizing the data on tissue penetration. The present review documents in detail dose- and time-related peak serum levels of erythromycin derivatives after oral administration, in addition to the erythromycin tissue levels. The erythromycin tissue levels often manifoldly exceed the corresponding MIC values of pathogens sensitive to erythromycin. However, erythromycin does not penetrate the central nervous system, or only penetrates in small, incalculable amounts. The same applies for the placental passage of erythromycin. The tissue levels confirm, with respect to the MIC values of the pathogen spectrum, clinical experience with erythromycin in the treatment of ear, nose and throat infections, respiratory tract infections and, with some limitations Chlamydia urethritis.


[Legionnaires' disease in Germany (author's transl)].

In February 1979 a 51 year old man fell will in Munich, displaying symptoms of an influenza-like illness which developed into pneumonia. The patient died eight days later of circulatory collapse which failed to respond to treatment, accompanied by high temperature, leucopenia and agranulocytosis. Typical rods detected in the lung tissue and histological sections by immunofluorescence indicated the possibility of a Legionella pneumophila infection. The pathogen isolated from the lung tissue on CYE agar was identified as L. pneumophila, serogroup I. The diagnosis was confirmed by the CDC, Atlanta. This is the first time this organism has been isolated in Central Europe from a case with a fatal outcome.


Sex differences in daydreaming and related mental activity from the late teens to the early nineties.

Using the Imaginal Processes Inventory, aspects of daydreaming and associated mental activity were examined for sex differences in 1200 well educated middle and upper-middle class whites aged seventeen to ninety-two ninety-two years. Females reported higher levels of daydreaming and nightdreaming frequency and emotional reactions to daydreaming as well as more daydreams of a problem solving nature. Females also reported lower levels of daydreams of a sexual, bizarre-improbable, heroic and achievement-oriented nature. Most sex differences persisted over the life span with the difference for sexual daydreams increasing with increasing age level. Except for problem-solving daydreams, all daydreaming contents investigated decreased with increases in age. Across the lifespan problem-solving daydreams were the most likely for both sexes except for seventeen to twenty-nine year old males where such daydreams were second most likely; from age seventeen to twenty-nine sexual daydreams were most likely for males. After age forty, achievement oriented daydreams were relatively more important for females than for males. Females across the lifespan also reported more interpersonal curiosity than males while males exhibited more curiosity about things. Unexpectedly, male curiosity about things was equally as strong as their curiosity about people.


The outer limits of the welfare state: discrimination, racism and their effect on human services.

The European social democracies have been more generous than the United States in social provision, including services to aged. The momentum of provision has slowed down in recent years. We suggest that prosperity which has led to use of foreign laborers in menial jobs has caused this slow down. The dynamics are similar to the historical U.S. use of "non-100% Americans" as our menial workers. Changes in social policy strategies are needed: 1) universal provision, rather than programs aimed at minorities, is needed to enlist support of stable working and middle classes; 2) tax reforms, which lower progressive income-tax structures for middle incomes, and value-added tax, may be necessary to overcome anti-tax ideologies; 3) clear priorities as to most necessary services must be established by the gerontological community.


Attitudes toward the elderly in Sweden: correlates and age group comparisons.

The objectives were to examine attitudes toward societal relations of the elderly in two age-stratified random samples, aged thirty to sixty-five, and seventy to seventy-five (both groups expressed attitudes toward the latter group), and to explore which of various correlates were associated with the attitudes. Six attitudinal dimensions were analyzed by means of group comparisons and linear regression. The younger group appeared positive toward interactive behavior, the elderly in turn being positive toward previous roles though reluctant to engagement in new activities. Some significant correlates were distinguished, although in a diversified manner over groups and dimensions: Positive attitudes among the younger were associated with low age, high education, and being female. No such clear pattern was found among the elderly, where instead work commitment and contacts with peers were particularly indicative of positive attitudes toward social activities.


Recirculation dialysis (RD) (20 to 40 liters of dialysate) with venous bicarbonate buffering - an alternative procedure to hemofiltration (HF).

We report about a dialysis procedure, the circulation stability of which is comparable to hemofiltration treatment. Hemodynamic parameters were measured invasively and different procedures were compared for each patient. In RD and HF significant reduction in cardiac output (HF: --20%, RD: --21.5%), stroke volume (HF: --20%, RD: --17%), pulmonary artery pressure (HF: --57%, RD: --45:6%) and plasma volume (HF: --12%, RD: --15%) were found. Blood pressure and heart rate (HF: --1%, RD: --3%) remained stable despite the high utrafiltration rate. Peripheral resistance rose significantly (HF: + 20%, RD: + 25.9%). Compared with HG, the most important advantage during RD is the improved tolerance to treatment without typical hemodialysis-induced symptoms. In comparison to that, we found under conventional dialysis an inadequate increase in peripheral resistance (HD: + 6.1%). A following strong compensatory hyperventilation with drop in PCO2 was paralleled with typical symptoms like nausea and headache. Because of resttriction of this compensatory mechanism, hypotension and arrhythmia will be induced of the following peripheral tissue perfusion and central acidosis.


Effects of 1-alpha OH D3 therapy in uremic patients in conservative or dialytic treatment.

The effects of phosphate restriction and of 1 alpha OH D3 administration were investigated in patients with advanced chronic renal failure. Few modifications of the various biochemical parameters in the patients were achieved with the restriction of dietary phosphate while better results were obtained with 1 alpha OH D3 administration. In dialyzed patients the treatment with this drug resulted in a normalization in serum calcium and alkaline phosphatase levels and in a remarkable significant decline in plasma parathyroid hormone and a reduction in the bone disease associated with uremia. This treatment in dialyzed uremic patients could avoid the employment of higher dialysate calcium concentration potentially dangerous for postdialysis hypercalcemia with the risk of metastatic calcifications.


The exponential model for a regulatory enzyme: a computer program to determine the constants for the binding of a single ligand.

The paper describes a non-linear multiple regression program to analyse data arising from the binding of a single ligand by a protein under the assumption that the reaction can be represented by the exponential model for a regulatory enzyme.


A data storage and retrieval system for clinical research.

A data storage and retrieval system is presented that can be used for clinical research studies. The system is designed in such a way that the programs are independent of the application. It can be used by non-computer experts via a simple query language. Since it is bulit up in a modular way extensions can be easily made. The system is implemented on a PDP 11/70 under FORTRAN.


[Analytical study and physiological consequences of a model of respiration].

The author, starting from the pattern established by Brocas and Cherruault (1973), develops new equations by considering the dynamics of breathing. He distinguishes space without exhanges, called 'blower' and space with exchanges, called 'exchanger'. The equations are studied and explicit solutions are found by an original method. The necessity for a neutral gas is proved. The author develops periodic functions for ventilation, for gas pressures in the air and in the blood and control functions such as differences of pressure between aerial- and blood-dissolved gas at the bottom of the alveola, consumption of O2 and excretion of CO2 and remaining CO2 in blood. The control functions oscillate around zero for the differences and around constants for the others. Examining the effects of frequency of breathing, blood flow, variations of transerval diffusivities, atmospheric pressure, variation of the dimensions connected with fever, infections, altitude and depth, sclerosis and even emotions, he again determines the pathologies, their auscultation symptoms and other aspects.


Results of simulation of non-homogeneous ventilatory mechanics for a patient-computer arrangement.

A model of the ventilatory mechanic system was realised on the MEDA TC 41 analogue computer; it consists of 2 structurally identical compartments, differing in the values of their coefficients. By changing the values of coefficients and the relations between the 2 compartments, it was possible to simulate the non-homogeneity of a real, pathologically-changed system of the body afflicted by disease. Complex resistance loops with phase shifts. identical with those really registered from patients, were realised; this was impossible for models with only 1 compartment. By changing the non-homogeneity of the model., it was possible to simulate the past and future development of the state of the diseased patient with sufficient reliability.


The application of robust non-linear regression methods for fitting hyperbolic Scatchard plots.

The Scatchard plot is an essential tool for the estimation of binding parameters in biochemistry. In certain situations the fitting of a hyperbolic line is required in this context. It is proposed to solve this non-linear regression problem by robust methods. A method according to Huber and Dutter (1974) is outlined and its good applicability is demonstrated.


Cell-mediated cytotoxicity for cultured autologous melanoma cells.

Peripheral blood lymphocytes from 32 patients with malignant melanoma were tested for cell-mediated cytotoxicity (CMC) against cultured autologous melanoma cells. Effector cells were prepared from venous blood by defibrination, gel sedimentation, nylon column filtration, and lysis of remaining erythrocytes with NH4Cl. Melanoma cells prelabelled with [3H])proline were used as target cells in a 40-h assay and CMC was evaluated against standards obtained with blood lymphocytes from the least reactive normal donor. Reproducible autologous CMC was detected in 18 of 32 patients in a series of 367 total tests. CMC correlated with tumor volume (5-500 cm3) but not with tumor stage or DNCB reactivity. Preliminary results indicated that autologous CMC was not affected by treatment with DTIC, dexamethasone, intralesional BCG, radiation therapy, or partial surgical excision. Lack of consistent CMC in 14 patients could not be attributed to a measurable decrease in general immune capacity or to increased resistance of the patients' melanoma cells to CMC in general. Fibroblasts were more resistant to CMC than melanoma cells, and therefore of questionable value for defining specificity in direct tests.


Enhancement of carcinoembryonic antigen expression by interferon.

Human interferon decreased DNA but not RNA synthesis in a human colon carcinoma cell line, WiDr; in addition, there was a two- to three-fold increase in the expression of a tumor-associated antigen, carcinoembryonic antigen. In contrast, interferon had no effect on a normal human diploid cell line, WI-38. Thus, in addition to its anti-cellular effect against tumor cells, interferon can also modulate tumor antigenicity.


Inhibition of mammary tumorigenesis in GR mice with 2-bromo-alpha-ergocryptine.

A high incidence of mammary tumors is found in multiparous GR mice during the 2nd and 3rd pregnancies and in nulliparous GR mice treated with estrone/progesterone. The purpose of this study was to determine if prolactin is a contributing hormone in the genesis of these neoplasms. In one series of experiments, 238 15-week-old nulliparous GR mice were treated with estrone (drinking water, 0.5 mg/liter) plus progesterone (30 mg progesterone pellet with cholesterol, implanted SC once monthly) for a period of 13 weeks. Half of these mice were injected SC once daily with 100 micrograms of the prolactin-suppressing drug 2-bromo-alpha-ergocryptine (CB-154) for the duration of hormone treatment, and the other half were injected SC once daily with 0.9% NaCl solution (controls). In another series of experiments, 87 pregnant GR mice were divided into two groups and injected SC once daily from day 7 to 21 of pregnancy with 0.9% NaCl solution (controls) or CB-154 (100 micrograms/mouse). In the first series, the numbers of mice with mammary tumors and total number of mammary tumors were: controls, 58/119 (49%) and 73; CB-154 treatment, 34/119 (29%) and 37, respectively. In the second series, the numbers were: controls, 39/44 (89%) and 73; CB-154 treatment, 24/43 (56%) and 43, respectively. In both studies, CB-154 treatment significantly (p less than 0.05-0.005) reduced the percentage of mice with mammary tumors and total number of mammary tumors. These results provide evidence that prolactin is a contributing hormone in the genesis of estrone/progesterone and pregnancy-induced mammary tumors in female GR mice.


Drug abuse, hopelessness, and suicidal behavior.

This study focused on assessing variables which may differentiate suicidal drug abusers from nonabusers. Data from a sample of drug abusing (n = 86) and nonabusing (n = 298) suicide attempters were subjected to a stepwise multiple regression analysis to identify factors related to suicidal intent. The analysis revealed that in our sample of suicide attempters, drug abuse status was not a significant contributor to the severity of suicidal intent. However, it was found that hopelessness accounted for a significant proportion of the variance of intent. The findings suggest that hopelessness among drug abusers, an important determinant of suicidal behavior, presents an important target for therapeutic intervention.


Role definition and confidentiality in the drug treatment process.

This national survey found that responses to confidentiality boundaries were determined by role definition. The extent to which confidentiality was viewed as a necessity depended upon the job that the individual held. Those individuals dealing with the drug abuser from an apprehension and corrections standpoint tended to see confidentiality in a limited sense, feeling that it pertained only to background material and medical records. Those in counseling positions saw confidentiality in much broader terms, in both its scope of protection and importance to the counseling situation.


Side effects in methadone patients: a survey of self-reported complaints.

Fifty-one patients in a methadone maintenance program completed a questionnaire containing 38 complaints upon admission and after 3 and 9 months in treatment. The questionnaire contained a graded scale of five possible responses from "no problem" to "a very bad problem." Only three complaints at 3 months and five complaints at 9 months showed an increase in the percentage of clients reporting them as a problem compared to before methadone matinenance (BMM). When analyzed by summed mean, only one complaint at 3 months and two at 9 months showed an increase in severity on the graded scale compared to BMM. However, when each patient's responses were analyzed as to whether problems showed no change in severity, were improved, or increased in severity comparing BMM and after 9 months of methadone, 11 of 38 complaints showed a significant number of patients reporting them as more severe.