Low-dose continuous intravenous insulin infusion in childhood diabetic ketoacidosis.

We studied 58 children with diabetic ketoacidosis using a random, prospective protocol, with insulin administered either as a low-dose continuous infusion or as high-dose intermittent subcutaneous injections. There were no statistically significant differences between admission pH and glucose determinations or the time to metabolic correction. The incidence of hypoglycemia and hypokalemia was higher in patients receiving subcutaneous insulin. Insulin levels in the low-dose patients were 85--160 microU/ml. The insulin required to achieve metabolic recovery was 1.6 U/kg in the low-dose group and 4.5 U/kg in the high-dose group (p less than 0.01). Glucose administered at a rate of 3 to 4 g er unit of insulin infused in the low-dose group maintained a serum glucose of 150 to 250 mg/dl. Our studies suggest that low-dose intravenous insulin therapy is safe, as effective as high-dose intermittent subcutaneous injections and avoids the risks of hypoglycemia and hypokalemia. Meticulous attention to individual patient care, however, must remain the most important single variable.


Carcinoma of the cervix: results of a hyperbaric oxygen trial associated with the use of the cathetron.

Since 1971, 82 patients with advanced carcinoma of the cervix have been included in a randomised clinical trial in association with the Working Party on Radiotherapy and Hyperbaric Oxygen of the Medical Research Council. External irradiation was given in 10 fractions by an unconventional schedule, either in air or HBO, and combined with three large fractions of intracavitary irradiation using the Cathetron. The results are acceptable overall, with 69% local control, 15% with tumour developing outside the treated volume and 40% survival at five years, but no improvement has been shown with HBO. Symptoms suggestive of some degree of late damage to the small bowel were present in 13% of patients, with a higher but not statistically significant, incidence in the HBO group. It is postulated that the schedule of radiotherapy used has allowed reoxygenation during treatment and that no further gain due to the use of HBO may be achieved. After a review of the results from other centres and taking into account the difficulties of treatment in HBO it is concluded that for advanced carcinoma of the cervix the addition of HBO to radiotherapy is not clinically worthwhile.


The radiological features of craniofacial neurofibromatosis.

Three cases of neurofibromatosis are reported showing a wide spectrum of roentgen abnormalities affecting the skull and facial bones. One case had macrocrania and multiple calvarial defects; enlargement of the sella turcica and middle cranial fossa was also present. All the three cases had orbital changes either in the form of enlargement, reduced anteroposterior width or loss of bony outlines with an appearance of emptiness. The other two cases showed predominantly facial involvement with hypoplasia of the mandibular body and ramus, abnormal coronoid process, zygomatic arch, hypoplastic maxilla, cystic mandible with abnormal dentition and absence of the osseous external auditory meatus. Intra-orbital calcification was present in one case. The radiological projections required to evaluate such cases are discussed. The 20 degrees occipito-mental view has been found extremely useful and is recommended.


Cardiac output response to extreme hemodilution with hemoglobin solutions of various P50 values.

Cardiovascular responses have been studied in baboons, after total exchange transfusion with hemoglobin solutions having various P50 values. At the end of the exchange transfusion, the hematocrit was 1.5%, the mean hemoglobin concentration was 4.4 g/dl, and the P50 varied between 12 and 26 mm Hg. Cardiac output did not change during the study, although heart rate increased, and stroke volume and MAP decreased. Hemoglobin concentration, per se, does not appear to be the critical stimulus for an increase in cardiac output with hemoglobin solution. In addition, the position of the hemoglobin-oxygen dissociation curve does not appear to influence these hemodynamic responses. The physiological response to anemia in the presence of hemoglobin solution appears different from that observed in the absence of plasma O2 carriers.


Cytological studies of heterochromatin function in the Drosophila melanogaster male: autosomal meiotic paring.

In Drosophila melanogaster it is now documented that the different satellite DNA sequences make up the majority of the centromeric heterochromatin of all chromosomes. The most popular hypothesis on this class of DNA is that satellite DNA itself is important to the pairing processes of chromosomes. Evidence in support of such a hypothesis is, however, circumstantial. This hypothesis has been evaluated by direct cytological examination of the meiotic behaviour of heterochromatically and/or euchromatically rear-ranged autosomes in the male. It was found that neither substantial deletions nor rearrangements of the autosomal heterochromatin cause any disruption of meiotic pairing. Autosomal pairing depends on homologs retaining sufficient euchromatic homology. This is the first clear demonstration that the highly repeated satellite DNA sequences in the heterochromatin of the second, third and fourth chromosomes are not important in meiotic pairing, but rather than some euchromatic homology in the autosome is essential to ensure a regular meiotic process. These results on the autosomes, when taken in conjunction with our previous studies on sex chromosome pairing, clearly indicate that satellite DNA is not crucial for male meiotic chromosome pairing of any member of the D. melanogaster genome.


Sexual and aggressive behaviour in social groups of talapoin monkeys.

In social groups not all monkeys are equal, in terms of either their behaviour or their endocrine status. When a dominant monkey is compared with one that is subordinate the level of sexual behaviour is high in the dominant and low in the subordinate monkey, while levels of aggression received follow an inverse pattern. Attention in terms of visual monitoring is primarily focused on the dominant animal even when overt aggression is extremely low. Cortisol and prolactin concentrations tend to be higher in subordinate monkeys while only the dominant male shows elevated testosterone levels during group interactions with attractive females. A question of some importance is whether these differences in endocrine status are a determinant of the differences in behaviour or whether they reflect the behaviour and, if the latter, to what purpose. Recent attempts to answer this problem have focused on the hypothalmo-pituitary axis in order to examine whether differences in behaviour between dominant and subordinate monkeys are reflected in differences in its responsiveness to endocrine changes.


The effects of neonatal exposure to testosterone on the development of behaviour in female marmoset monkeys.

Experimental investigations of sexual differentiation in primates have been mainly confined to the rhesus monkey, a highly polygamous species with marked anatomical and behavioural sexual dimorphism. The marmoset is a monogamous monkey which shows little anatomical or behavioural sexual dimorphism, and both sexes exhibit positive feedback in response to the administration of oestradiol. This monkey has a relatively short gestation period of 144 days and usually gives birth to dizygotic twins. These share a common placental circulation and hence develop as haematopoietic chimaeras. However, a female with a male co-twin is not adversely affected as a result of this and the freemartin condition does not occur. Since the newborn male experiences raised testosterone levels soon after birth it is possible that the 'critical period' for sexual marmosets were implanted with 25 mg of testosterone for 50 days after birth. After removal of the implants their genitalia remained partly masculinized and they initiated more masculine rough-and-tumble play than their controls. After puberty they exhibited a mixture of male and female sexual behaviour when presented with unfamiliar normal males and females during 15-minute behavioural trials. Four of the implanted females have also ovulated. Neonatal administration of testosterone therefore has had an organizing effect on female behaviour. Whether the marmoset is exceptional in this respect, or whether other primates which exhibit a male neonatal testosterone surge, such as man and the rhesus monkey, also undergo some postnatal behavioural differentation, remains to be seen.


[Animal experimental short and long-term study of a calcium hydroxide line].

Thirty-two cavities (class 5) out of total of 64 were coated either with the test substance Hydroxyline or with the control substance Dycal and closed with the standard compound Adaptic. Statistical analysis of seven criteria evaluated histologically (rating: 0-3) revealed no significant differences between the tested characteristics of the control substance Dycal and Hydroxyline in either the short-term or the long-term study.


The effect of estrogen on the tubal epithelium of immature ovariectomized rhesus monkey (Macaca mulatta).

The effect of 3 doses of estradiol dipropionate (EDP) on tubal epithelium of immature ovariectomized rhesus monkey (Macaca mulatta) was studied under both light and electron microscopy. EDP at a dose of 5 microgram/kg/day for 6 consecutive days changed differentiation of the epithelial cells into clear and dark cell-types; ciliogenesis, formation of some ciliary buds and even a few cilia were also induced in some clear cells throughout the tubal epithelium. Development of ciliated cells with fully formed ciliary apparatus was accelerated at 10 microgram/kg dosage. The secretory granules (SG) appeared at this dose in some nonciliated cells of the infundibular and ampullary but not the isthmic segments of the tube; some of the infundibular secretory cells, so formed, exhibited even a tendency to secrete. Nearly complete maturation of the tubal epithelium occurred at 20 microgram/kg dose; further signs of secretory activity appeared in all tubal segments. The results indicated that--(i) Nearly complete transformation of tubal epithelium of the immature animal into one of the adult type could be achieved by EDP at a dose not less than 20 microgram/kg under the present conditions. (ii) The response of undifferentiated cells to EDP differed depending upon the location of the epithelial cell within the tube and nature of the cell-type to be formed. (iii) The mode of tubal secretion in this infra-human species was probably apocrine.


Characteristics of elderly people admitted to hospital, Part III homes, and sheltered housing.

Approximately 100 consecutive admissions in Southampton to sheltered housing, to Part III homes, and to long-stay geriatric hospital beds in 1975 and 1976 were selected and data were collected by interview with patients and staff. There was a total of 299 admissions in the final sample. The sheltered housing group were younger and more often married than those admitted to Part III homes, who were more often married but only slightly younger than the new geriatric patients. The three groups were separated on dependency measures with almost no overlap between the sheltered housing and the other groups, but a little more evidence of overlap and interchange between Part III and hospital admissions. The patients in hospital whose dependency scores were more typical of Part III residents were almost all special cases and this was found to be true of other apparently misplaced individuals. Most of the sheltered housing admissions were suffering from heart, chest, and musculoskeletal complaints, while new Part III residents had more psychiatric disturbance; cerebrovascular and psychiatric problems occurred most often in the hospital group. The three groups of admissions form distinct categories and it is arguable that this is a concomitant of underprovision. This also shows that there is no great measure of misplacement on the basis of the current norm, although the suitability of this norm in sheltered housing is open to question.


Identification and characterization of a 19-S complex containing a 27 000-Mr protein in Artemia salina.

The cytoplasm of the cryptobiotic Artemia salina gastrula contains a large quantity of a unique 19-S complex. This particle is a specific aggregated form of a 27 000-Mr protein, having a molecular weight of 10(6) and an apparent buoyant density of 1.25 -- 1.26 g/cm3 in sucrose and 1.31 g/cm3 in CsCl. The relative quantity of this 19-S complex decreases significantly with respect to 80-S monoribosomes during the postgastrula development. Biochemical and immunological studies indicate that the 27 000-Mr protein is one of the RNA-binding proteins [Ovchinnikov et al., FEBS Lett. 88, 21 -- 26 (1978)] but is absent in the protein components associated with poly(A)-containing ribonucleoprotein complexes. The possibility is also suggested that the 27 000-Mr protein and Artemia elongation factor eEF-Ts might be related to each other on the basis of amino acid composition and immunological cross-reactivity.


The lipoxygenase of reticulocytes. Purification, characterization and biological dynamics of the lipoxygenase; its identity with the respiratory inhibitors of the reticulocyte.

A lipoxygenase has been purified from rabbit reticulocyte-rich anaemic blood cells. It possesses a molecular weight of 78 000 and an isoelectric point of 5.5 and contains 5% neutral sugars and two iron atoms per enzyme molecule. The lipoxygenase has proved to be identical with the inhibitors of respiratory proteins described formerly. The actions of the lipoxygenase on linoleic acid, phospholipids, mitochondrial and erythrocyte membranes and electron transfer particles were studied. A special feature of the reticulocyte lipoxygenase is the suicidal character of its action on lipids. With electron transfer particles the reticulocyte lipoxygenase causes a loss of acid-labile sulfur which accompanies respiratory inhibition; the strong respiratory inhibition is not exerted by soybean lipoxygenase. The reticulocyte lipoxygenase acts preferably on mitochondrial membranes as compared with cell membranes of the erythrocyte; erythrocyte cytosol moderates the action on mitochondrial membranes. Furthermore, the lipoxygenase reaction can concomitantly and irreversibly inactivate sulfhydryl enzymes as demonstrated with muscle glyceraldehyde-3-phosphate dehydrogenase. The occurrence of the lipoxygenase here described is restricted to reticulocytes; very low amounts were observed in bone marrow and no lipoxygenase was detectable in normal blood. During the course of an experimental anaemia the lipoxygenase is produced owing to superinduction in large amounts, which may persist for a long time since they escape inactivation. Preliminary evidence was obtained for the occurrence of other lipoxygenases in tissues of lung, spleen, kidney and also epithelial tumours.


Synthesis of non-globin proteins in rabbit-erythroid cells. Synthesis of a lipoxygenase in reticulocytes.

Peripheral rabbit reticulocytes synthesize at least 30 non-globin proteins. One of them is identified as a characteristic lipoxygenase on the basis of its molecular weight, its immunological properties and its behaviour on an ion-exchange column. The enzyme is not produced in bone marrow cells. The synthesis of the lipoxygenase in peripheral blood cells commences on the 3rd day of a bleeding anaemia, increases up to the 5th day and stays constant thereafter at least up to the 14th day. It is concluded that the appearence of the lipoxygenase, which plays a key role in the degradation of mitochondria in the course of maturation of reticulocytes to erythrocytes, is regulated at the translational level.


Methylation of basic proteins in ribosomes from wild-type and thiostrepton-resistant strains of Bacillus megaterium and their electrophoretic analysis.

Ribosomes, radioactively labelled in vivo with both [1-14C]methionine and [methyl-3H]methionine, have been isolated from both wild-type and thiostrepton-resistant strains of Bacillus megaterium and their constituent proteins separated by two-dimensional gel electrophoresis. Ribosomes from the wild-type strain possess one basic protein that is extensively methylated. In contrast no such protein can be detected in ribosomes from the thiostrepton-resistant strain.


Chemical evidence for a codon-induced allosteric change in tRNALys involving the 7-methylguanosine residue 46.

[32P]TRNALys, from Escherichia coli, was modified with kethoxal, in the presence and absence of the oligonucleotide codon (A)4. The presence of the codon resulted in a faster modification rate of the tRNA at three guanine sites which were identified by a diagonal fingerprint method. A large increase in the modification rate occurred at the 7-methylguanosine residue 46 (m7G-46) in the presence of the codon: weakly enhanced modification was observed at G-15 and G-57. It is concluded that the formation of a codon-anticodon complex induces, primarily, a conformational change involving disruption of the m7G-46 from the m7G-46 . G-22 . C-13 base triple. Subsequently, the guanines of G-15 and G-57, in the D and T loops, respectively, become slightly more reactive, suggesting a weak tendency for these two interacting arms to unfold. The results are interpreted in terms of an equilibrium between two main conformers, and a third minor one; the possible significance of these conformers in protein biosynthesis, is considered.


Regions of the lipopolysaccharide of Pseudomonas aeruginosa essential for antitumor and interferon-inducing activities.

Resistance against ascites tumor development and interferon-inducing activity were demonstrated in lipopolysaccharide derived from the protein-lipopolysaccharide complex obtained from an autolysate of Pseudomonas aeruginosa. Lipid A obtained from the lipopolysaccharide was sufficient to induce interferon in vitro but no antitumor activity was found if lipid A or the polysaccharide derived from lipopolysaccharide was injected into the animal. Chemical modification of the polysaccharide portion or deacylation of the lipopolysaccharide also diminished antitumor activity. In contrast, interferon was induced by these incomplete lipopolysaccharides. These results indicate that both the lipid A portion and covalently linked polysaccharide are necessary for the inhibition of ascites tumor development, whereas incomplete lipid A with amide-linked fatty acids is sufficient to induce interferon in vitro.


Purification of rat-liver microsomal UDP-glucuronyltransferase. Separation of two enzyme forms inducible by 3-methylcholanthrene or phenobarbital.

Glucuronidation reactions catalysed by rat liver microsomal UDP-glucuronyltransferase are differentially inducible by 3-methylcholanthrene and phenobarbital. To elucidate the molecular basis of this functional heterogeneity the enzyme was purified from livers of rats pretreated with the inducing agents. Using cholate solubilization, chromatography on Bio-Gel A-1.5m and on DEAE-cellulose in the presence of the nonionic detergent Brij 58, two enzyme forms could be separated. Both forms were subsequently purified to apparent homogeneity by affinity chromatography on UDP-hexanolamine Sepharose 4B, 3-Methylcholanthrene-inducible enzyme activity towards 1-naphthol, 4-nitrophenol, 3-hydroxybenzo(a)pyrene and N-hydroxy-2-naphthylamine copurified with one enzyme form (enzyme 1). In contrast phenobarbital-inducible enzyme activity towards morphine, chloramphenicol and 4-hydroxybiphenyl was associated with the other enzyme fraction (enzyme 2). Sodium dodecylsulfate/polyacrylamide gels showed similar molecular weights of 54000 for enzyme 1 and 56000 for enzyme 2. The results suggest the presence of at least two forms of UDP-glucuronyltransferase in rat liver. Factors affecting enzyme activity in purified and membrane-bound states are discussed.


Binding of thiostrepton to a complex of 23-S rRNA with ribosomal protein L11.

Thiostrepton binds with high affinity and with a 1 : 1 stoichiometry to a complex formed between Escherichia coli 23-S ribosomal RNA and ribosomal protein L11 of E. coli or the homologous protein BM-L11 of Bacillus megaterium. In the presence of T1 ribonuclease, protein BM-L11 and thiostrepton protect from degradation a fragment of E. coli 23-S RNA estimated to be about 50 nucleotides in length.


RNA synthesis in starved deciliated Tetrahymena pyriformis.

Tetrahymena pyriformis which has been starved for 20 h by incubation in buffer, and then deciliated, can regenerate its cilia in about 90 min while still in suspension in non-nutrient medium. The process of reciliation is accompanied by protein synthesis which begins a few minutes after deciliation and by synthesis of ribosomal and messenger RNAs during a period extending from about 1 h to about 3 h after deciliation. Although net synthesis of RNA remains at a very low level until 1 h after deciliation, a qualitative change in the translatable poly(A)-containing messenger RNA content of deciliated cells, and in particular, formation of beta-tubulin mRNA can be detected almost immediately after deciliation.


A lipopolysaccharide-binding cell-surface protein from Salmonella minnesota. Isolation, partial characterization and occurrence in different Enterobacteriaceae.

1. Protein extracts obtained from Salmonella minnesota Re mutant cells by treatment with EDTA/NaC1 solution contain a protein which exhibits high affinity to bacterial lipopolysaccharides. The isolation and partial characterization of this lipopolysaccharide-binding protein is described. 2. The protein was purified from EDTA extracts by a two-step procedure consisting of ion-exchange chromatography on CM-Sephadex and preparative polyacrylamide gel electrophoresis at pH 9.5. The yield of the total purification procedure was around 16%. 3. The resulting protein preparation was homogeneous on the basis of disc gel electrophoresis, dodecylsulfate gel electrophoresis, isoelectric focusing in polyacrylamide gel and immunoelectrophoresis. 4. The isoelectric point of the protein was found to be 10.3 at 4 degrees C. Its molecular weight determined by dodecylsulfate gel electrophoresis is 15000. Its amino acid composition is characterized by the absence of histidine and proline, a low content in tyrosine and high amounts of alanine, lysine, aspartic and glutamic acid residues, or their respective amides. 5. The lipopolysaccharide-protein association was shown to be mainly due to ionic interactions of the basic protein with negatively charged groups (probably phosphate and pyrophosphate groups) of the lipid A moiety. 6. Purified lipopolysaccharide-binding protein is immunogenic in rabbits, thus enabling the preparation of specific antiserum. 7. The protein is located at the surface of Salmonella minnesota Re mutant cells as revealed by antiserum absorption with total bacteria. Ferritin-labelling studies further demonstrated that it is evenly spread over the entire cell surface. 8. Comparative antiserum absorption studies using smooth and rough strains of Salmonella minnesota, Salmonella typhimurium, Escherichia coli, Klebsiella and Shigella revealed the presence of lipopolysaccharide-binding protein (or a serologically cross-reacting antigen) in most of the strains tested. From these results the protein can be considered as a common antigen of Enterobacteriaceae.


Purification and properties of nitrogenase from the cyanobacterium, Anabaena cylindrica.

The nitrogenase complex was isolated from nitrogen-starved cultures of Anabaema cylindrica. Sodium dithionite, photochemically reduced ferredoxin, and NADPH were found to be effective election donors to nitro genase in crude extracts whereas hydrogen and pyruvate were not. The Km for acetylene in vivo is ten-fold higher than the Km in vitro, whereas this pattern does not hold for the non-heterocystous cyanobacterium, Plectonema boryanum. This indicates that at least one mechanism of oxygen protection in vivo involves a gas diffusion barrier presented by the heterocyst cell wall. The Mo-Fe component was purified to homogeneity. Its molecular weight (220,000), subunit composition, isoelectric point (4.8), Mo, Fe, and S2- content (2, 20 and 20 mol/mol component), and amino acid composition indicate that this component has similar properties to Mo-Fe-containing components isolated from other bacterial sources. The isolated components from A. cylindrica were found to cross-react, to varying degrees, with components isolated from Azotobacter vinelandii, Rhodospirillum rubrum, and P. boryanum.


Characterization of long guanosine-free RNA sequences from the Dahlemense and U2 strains of tobacco mosaic virus.

Four naturally occurring strains of tobacco mosaic virus, U2, Dahlemense, CV4, and the bean form of tobacco mosaic virus, were tested for the existence of long T1 RNAase oligonucleotides analogous to the oligonucleotide omega found in the common or U1 strain of tobacco mosaic virus and which makes up the 5' non-coding region of the RNA molecule. U2 and Dahlemense RNA were each found to contain this type of long T1 RNAase oligonucleotide with chain lengths of 54 and 74--77 residues, respectively. The sequence of the two oligonucleotides was determined mostly by using 5'-32P-labelled material in vitro and rapid polyacrylamide gel sequencing techniques.


A clinical comparison of 2 h and 4 h bone scans obtained with 99Tc H.E.D.P.

A comparison of 2 h and 4 h bone scan images obtained with technetium labelled H.E.D.P. in ten patients demonstrated no increase in lesion detection rate between the 2 h and 4 h scans. The 2 h bone scans were of sufficient quality to permit identification of tumours in all cases.


A new unidirectional moving whole body scanner: comparative study of performances.

A new whole-body unidirectional moving scanner was built using a single large bar crystal, 12 photomultipliers on its top, and a delay line system to compute the X coordinate. Motion is required in only one direction on the Y-axis, and a special collimation is adapted in order to equal the X and Y performances of the detector. The performances of this detector (C.G.R. Scanicamera) (SC) were compared under the same conditions with those of a moving rectilinear scanner (R.S.) (Ohio Nuclear F 84 dual-head scanner, 12.5 cm crystal) and with an Anger gammacamera equipped with its whole body attachment (W.B.C.) Nuclear Chicago Pho Gamma III H.P.). The general impression is that this new whole-body unidirectional moving scanner is a very convenient device for whole body studies and can also be used for large scintigraphies.


Serum kinetics of doxycycline polyphosphate in dogs.

Serum kinetics of Doxycycline polyphosphate (DPP) have been studied in dogs after oral administration of 10 mg.kg-1 by measurement of total serum concentration (Ct) of tetracycline derivatives by a chemical assay and active concentration (Ca) by a microbiological method. Kinetics have been studied using a one compartment open model with absorption by oral route. DPP is rapidly absorbed, the peak serum level is reached three hours after absorption and slowly eliminated (elimination half-life = 12 hours). The main differences observed between Ct and Ca kinetics are in the values of the areas under the curves (AUC) and the peak serum level. The values obtained for these parameters for Ca kinetics were found to be 50% of those obtained for Ct, the volumes of distribution being in inverse proportion. These results are in a good agreement with the correlation and linear regression observed between Ca and Ct showing that 55% of total serum Doxycycline possesses immediate antibacterial activity. It is postulated that this difference between Ct and Ca kinetics is essentially a reflection of the ratios of bound and free drug. Similar results were obtained with the finished pharmaceutical form except for a 15% increase of AUC indicating improvement of the bioavailability of the drug.


Therapeutic effects of pindolol and nifedipine in patients with stable angina pectoris and asymptomatic resting ischemia.

A single blind randomized parallel study designed to assess the anti-anginal efficacy of pindolol and nifedipine was carried out in 42 ambulatory coronary patients with stable angina pectoris. Drug efficacy was assessed in terms of (a) pain, (b) frequency of anginal episodes, (c) nitroglycerin consumption, (d) exercise tolerance and (e) ST-segment changes. The effect of these drugs on asymptomatic resting myocardial ischemia was also assessed by means of 24-h dynamic electrocardiography (DCG). All patients were checked at weekly intervals. At the end of a 4-wk placebo period, the patients were randomly assigned either to the pindolol or nifedipine group. The treatment lasted for 45 days. During the placebo period, ischemic ECG changes and symptoms of coronary insufficiency were detected in all patients. Furthermore, 12 out of 42 patients had asymptomatic myocardial ischemia at rest. One patient from each group was dropped because of tolerance. At the end of the 45-day study, pindolol and nifedipine were equi-effective on spontaneous and effort-related angina. There were, however, some differences: increased tolerance to exercise appeared earlier with pindolol: the pindolol group showed a slightly reduced while the nifedipine group showed a slightly increased heart rate. Furthermore, nifedipine reduced or eliminated asymptomatic myocardial ischemia in 6 out of 7 patients while only 1 out of 5 improved in the pindolol group.


Pituitary hormones and the small bowel: effect of hypophysectomy on intestinal adaptation to small bowel resection in the rat.

The influence of pituitary hormones on intestinal adaptation to small bowel resection was studied by examining jejunal and ileal structure and function in control and in sham-operated rats, and in animals with 50% proximal or distal resection which were divided into three main groups: normally-fed, hypophysectomized. and pair-fed. The pituitary was removed 2 weeks before intestinal surgery and gut structure and function were studied 4 weeks later. The effectiveness of hypophysectomy was confirmed by histological examination of the aspirated pituitary, and by showing a significant subsequent reduction in weight of the testes and adrenals. Food intake and body weight fell significantly after removing the pituitary; intestinal surgery caused a transient further decrease in food intake. Measurements of intestinal villus height and crypt depth, indices of mucosal mass (mucosal wet weight, protein and DNA content/cm intestine), measurements of mucosal alpha-glucosidase activity, and in vivo galactose absorption/unit length of intestine all showed comparable results. In rats with an intact intestine, resection resulted in mucosal hyperplasia and increased segmental absorption. Following hypophysectomy, there was marked mucosal hypoplasia and hypofunction which seemed to be due largely to associated hypophagia since comparable changes were found in the pair-fed, sham-operated rats. However following pituitary removal, both distal jejunum and proximal ileum retained their capacity to regenerate though the magnitude of this adaptive change was much greater in the resected, pair-fed rats suggesting that hypophagia alone cannot explain the diminished adaptation to resection after hypophysectomy. By inference, pituitary hormones do influence the adaptive response to resection.


Impaired feedback control of fat induced gastric inhibitory polypeptide (GIP) secretion by insulin in obesity and glucose intolerance.

To investigate the role of endogenous insulin on the secretion of immunoreactive gastric inhibitory polypeptide (IR-GIP) the response of IR-GIP and immunoreactive insulin (IRI) to an oral fat load (100 g triglyceride) alone and during an intravenous glucose infusion (0.7 g/kg/h) was examined in normal weight and obese subjects. In normal weight subjects the fat induced integrated rise of IR-GIP was 112.7 +/- 9.4 ng/ml/120 min. When glucose and fat were given together this IR-GIP response was lowered to 46.2 +/- 2.9 ng/ml/120 min while the serum IRI response to i.v. glucose and the glucose tolerance were enhanced by fat ingestion. In obese subjects with normal glucose tolerance the GIP suppressing effect of i.v. glucose infusion was less marked than in controls. The integrated IR-GIP response to fat ingestion was 225.6 +/- 20.3 mg/ml/120 min and to fat plus glucose 152.6 +/- 14.8 ng/ml/120 min. In obese subjects with glucose intolerance i.v. glucose completely failed to lower the exaggerated secretion of IR-GIP following oral fat. Thus, a graded abnormality of the GIP response to glucose induced insulin release occurs in obesity with normal and pathological glucose tolerance. After reducing the ideal body weight of six obese subjects with glucose intolerance by hypocaloric diet for 3 weeks the exaggerated rise of IR-GIP after oral fat was reversed and the lowering effect of i.v. glucose on the IR-GIP response re-established.


Polymyalgia arteritica: a clinical review.

In a series of thirty-seven consecutive patients with polymyalgia arteritica, twenty-five had polymyalgia rheumatica and twelve had cranial arteritis. Some failed to respond promptly to low doses of prednisolone and it is recommended that the initial dose should be in the order of 40 mg daily. An ESR above 40 mm in the first hour was present in four patients 3 months after admission; three were found to have rheumatoid disease and one pulmonary tuberculosis. Symptomatic relapses occurred in fourteen patients on twenty-one occasions and all responded to an increase in the daily dose of maintenance prednisolone. Most occurred in the first year and were attributable to an excessively rapid reduction in steroid therapy. Relapses occurring in patients on a stable dose of prednisolone were commonly associated with the development of rheumatoid disease. In elderly patients who have relapsed, or who have had arteritic complications, life-long prednisolone therapy appears justifiable.


Inhibition of gastrin secretion by hypertonic solutions in patients with pernicious anaemia and duodenal ulcer.

Serum gastrin increased in patients with pernicious anaemia after a beef-meal, but decreased after an oral load of glucose, xylose or sodium chloride. 50 g of glucose and 25 or 75 g of xylose suppressed serum gastrin to approximately 40% of basal values at 60 min and were slightly more effective than 10 g of sodium chloride. There was no rise in beef-meal stimulated serum gastrin concentration in vagotomized patients and only a slight rise in two patients with duodenal ulcer when an oral dose of 10 g of sodium chloride was given together with the beef-meal. 25 g of xylose suppressed basal serum gastrin concentration significantly in six vagotomized patients. Nasal administration of small amounts of vasopressin decreased basal serum gastrin significantly in six vagotomized patients. Nasal administration of small amounts of vasopressin decreased basal serum gastrin significantly in all subjects examined. Further studies indicated, however, that vasopressin was only effective when pharmacological plasma concenten orally and intraduodenally were compared in six patients with pernicious anaemia. Serum gastrin concentration decreased approximately to the same extent in both experiments. It is concluded that the inhibitory effect of glucose on gastrin secretion most likely is mediated hormonally via osmo-receptors located in the small intestine.


Effect of hyperglycaemia-induced hyperosmolality on heart function in the dog.

Changes in myocardial water content, left ventricular diastolic stiffness, cardiac performance, coronary blood flow, myocardial contractile force, rate of change of myocardial force, and peak acceleration of the aortic volume flow were examined in twenty-five dogs during glucose-induced hyperosmolality before and after pancreatectomy, the latter with and without insulin treatment. Glucose-induced hyperosmolality accounted for myocardial dehydration, increased diastolic stiffness and consequent decrease of left ventricular performance only in the absence of insulin, while coronary blood flow, myocardial contractile force, rate of change of myocardial force and peak acceleration of the aortic volume flow increased independently from the presence or absence of insulin during the glucose-induced hyperosmolality. These findings suggest that the frequent development of heart failure in hyperosmolar diabetic coma could partly be explained by myocardial dehydration and by the consequent decrease in left ventricular compliance and performance.


Differential effects of fibroblast and leucocyte interferon in HBsAg positive chronic active hepatitis.

Six patients with hepatitis B surface antigen, hepatitis B 'e' antigen positive chronic active hepatitis, and elevated hepatitis B specific DNA polymerase activity were treated sequentially with fibroblast and leucocyte interferon. Fibroblast interferon induced a fall in serum transaminase activities in all patients, whereas a consistent decline in DNA polymerase activity was observed during leucocyte interferon administration only. After treatment one patient remained persistently DNA polymerase and hepatitis B 'e' antigen negative, whereas relapse to initial values occurred in others. Side effects included severe but reversible granulocytopenia, and chills responding to promethazine treatment. The differential biologies with their non-identity in in vitro studies.


Effects of weight reduction on squalene, methyl sterols and cholesterol and on their synthesis in human adipose tissue.

Quantitation of cholesterol and its precursors from human adipose tissue biopsies revealed very high squalene and moderately high methyl sterol concentrations. The squalene and cholesterol values were correlated with each other. Weight reduction in obese subjects following a jejuno-ileal bypass resulted in a significant but transient increase in adipose tissue cholesterol. The squalene concentration was also increased postoperatively, the maximum being reached about 6 months later than that of cholesterol as if the mobilization of squalene from shrunken adipocytes had been slow. Weight reduction with a 2--14 day total fast significantly reduced the adipocyte size but had no consistent effect on adipose tissue squalene, methyl sterol and cholesterol concentrations or on their adipocyte contents. Incubation of adipose tissue with labelled acetate and mevalonate revealed that the bulk of the labels in non-saponifiable lipids stayed in the large intermediate pools of methyl sterols and squalene in particular, fairly little being found in the cholesterol fraction itself. The total fast inhibited the incorporation of both 14C-acetate and 3H-mevalonate to squalene, methyl sterols and cholesterol, suggesting that cholesterol synthesis was inhibited before and after the mevalonate step.


Beneficial effects of colchicine in experimental nephrotoxic serum nephritis in the rat.

Glomerulonephritis was induced in rats by multiple injections of rabbit anti-rat kidney serum. Colchicine was administered daily for 4 months to nephrotoxic serum treated rats and untreated control animals. Nephritic rats receiving colchicine had significantly less proteinuria and less glomerular damage than unprotected nephritis animals. A possible role for colchicine in the early treatment of human glomerulonephritis is suggested.


Kinetics of escape from suppression of Ig heavy chain allotypes in multiheterozygous rabbits.

Three rabbits of genotype a1n81f73g74/a2n82f71g75 which had been injected at birth with anti-a l (VH) antiserum and which were previously shown to be suppressed for the paternal allotypes a 1, n81, f73 and g74 at 8 weeks of age, were monitored over a 2-year period for the concentration of suppressed and nonsuppressed allotypes in their sera. In all three suppressed animals, the f73 (C alpha) and g 74 (C alpha) allotypes were expressed again at a much greater rate than the a1 (VH) and n81 (C mu) allotypes. In one suppressed animal, the a l (VH) allotype was re-expressed at a much greater rate than the n81 (C mu) allotype and reflected primarily the reappearance of a l IgG. Thus, the escape from allotype suppression in this animal was in the order IgA, IgG, IgM which is the reverse of the order of appearance of these Ig classes during ontogeny. While the al(VH) and n81 (C mu) allotyes remained suppressed, the f73 (C alpha) and g74 (C alpha) allotypes were re-expressed to the same concentration as in the unsuppressed controls, and no compensatory decrease of the f71 and g75 allotypes occurred. During the re-expression of the f73 and g74 allotypes, the ratio of the concentrations of f73/g74 remained approximately constant.


Disodium cromoglycate: a novel gastric antiulcer agent?

The influence of oral pretreatment with disodium cromoglycate (2.5 or 5 mg/kg X 9 doses) on the 4-h gastric effects of i.p. injected reserpine (5 mg/kg) was examined in rats. Disodium cromoglycate markedly prevented reserpine-induced ulceration, mucosal mast cell degranulation and superficial mucosal microcirculatory changes in the glandular portion of the stomach wall. These interesting results points to the possibility that disodium cromoglycate may also have gastric antiulcer effects in man.


The afferents and projections of the ventroposterolateral thalamus in the monkey.

In seven monkeys (M. fascicularis), recordings were made from neurones in subnuclei VPLo and VPLc of the thalamus. The peripheral inputs to these cells from the forelimb were established by stimulating muscle, skin and joint nerves, and cutaneous receptive fields were examined by natural stimulation of the skin. The projection of the same cells to motor and sensory cortex was examined by stimulation of the cortex to demonstrate antidromic responses and by retrograde axonal transport of horseradish peroxidase injected into these regions of cortex. Of the 139 neurones which were driven by stimulation of peripheral nerves, 73 were located in VPLo. This suggests that there is a significant projection of forelimb afferents to VPLo in the monkey. Of the 73 neurones located in VPLo, 60 responsed to stimualtion of muscle or joint nerves. The projection to VPLo is therefore predominantly from deep receptors. Twenty-one of these 73 neurones had convergent inputs. The latencies of activation of units in VPLo were short (4--8 ms) and consistent with a lemniscal pathway via the dorsal column nuclei. Injection of horseradish peroxidase into the arm area of the motor cortex labelled cells in VPLo and not in VPLc. The neurones from which recordings were made in VPLo were located within the population of cells labelled with horseradish peroxidase after injections into the primary motor area. This suggests that this subnucleus is the thalamic relay for the sensory input from peripheral receptors to cells of the motor cortex.


[Brodmann's area 18 and area 19].

This article, written on the 60th anniversary of Korbinian Brodmann's death, discusses his schematic cytoarchitectonic chart of the cerebral cortex in relation to the brain sections from which it was derived and draws attention to the discrepancies between the two.


The sparing effect of dose-fractionation in adult Drosophila.

The sparing effect of dose-fractionation was observed in adult male and female Drosophila melanogaster; 24-, 48-, 72-, and 96-h-old female flies, in general, show a higher recovery (increase in life-span) following dose-fractionation as compared to the males of the respective age. Recovery in 72-h-old females is maximal (31% increase in life-span) as against only 12% increase in the life span of the males.


Anticonvulsant action of YG 19-256 in baboons with photosensitive epilepsy.

YG 19-256, 4-(1,3,4,9b-tetrahydro-5 methyl-2H-indeno[1,2-c]pyridine-2-yl)-2-butanone methane sulphonate, 1-3 mg/kg i.v., abolished or reduced photically-induced myoclonic responses for 1.5-6.5 h in baboons, Papio papio, without producing signs of acute neurological toxicity.


Enhancement by caffeine of sister-chromatid exchange frequency induced by antineoplastic agents in human lymphocytes.

The SCE frequency induced by Thiotepa and the effect of this antineoplastic drug in combination with caffeine have been studied in cultures of human peripheral blood. Caffeine was found to enchance SCE and breakage frequencies induced by Thiotepa in human lymphocytes.


The effect of protein-energy malnutrition on appositional bone growth in the rat.

During protein-energy malnutrition appositional bone growth in the seventh caudal vertebra of the rat slows and finally ceases. During rehabilitation appositional growth begins agains and attains a rate in excess of that of the controls. This may account for alterations in skeletal proportions resulting from malnutrition.


Prolactin response to TRH after intravenous cimetidine.

Cimetidine administered intravenously to six healthy volunteers caused a significant increase in plasma prolactin response to TRH. The meaning of these results and their relation with the physiological role of histamine H2-receptors in the control of prolactin secretion is discussed.


The interaction of ligands with enzymes. A starting point in drug design.

The problem of inhibiting a specific enzyme of a pathogen without inhibiting the corresponding enzyme of the host is one which has intrigued medicinal chemists for years. While it is easy to find potent inhibitors of purified enzymes transforming these inhibitors into effective drugs, it still is a very poorly understood business. This report discusses studies with two enzymes, papain and dihydrofolate reductase, and the nonspecific (phi and MR correlated) interaction of ligands with them. The QSAR which has been developed for the inhibition of dihydrofolate reductase by triazines is compared with the QSAR which has been reported for the same inhibitors acting against S. aureus.


[Studies on growth hormone secretion in starved rats under urethane anesthesia (author's transl)].

Adult male wistar rats averaging 200 g each were subjected to food removal for 1--6 days or fed ad libitum throughout (controls). Plasma GH levels and pituitary GH contents were measured by radioimmunoassay. The GH responses to intravenous injection of TRH (2.5 microgram/100 g B.W.), PGE1(5 microgram/100 g B.W.), LH-RH (1 microgram/100 g B.W.) and Chlorpromazine (CPZ, 100 microgram/100 g B.W.) were tested under urethane anesthesia. Circulating GH levels were significantly increased by prolonged starvation, while pituitary GH contents progressively decreased with increased periods of starvation. In addition, following the TRH administration, plasma GH levels increased in starved rats compared to the control rats. A similar effect was also observed with PGE1. In contrast, the administration of CPZ, which was reported to act at the hypothalamic level, failed to potentiate GH release in starved rats under urethane anesthesia. These observations suggest an increased susceptibility of starved rats to urethane anesthesia with the administration of TRH and PGE1 in the GH secretory mechanism. In addition, the fact that no further potentiation of GH release was observed by CPZ treatment may indicate an abnormality of the hypothalamic dopaminergic mechanism in starved animals.


Effect of hormones and related compounds on the multiplication of Tetrahymena.

The vertebrate hormone triiodothyronine, the commonly occurring animal and plant hormone serotonin, and the plant alkaloid gramine, chemically related to the latter, stimulated the multiplication of Tetrahymena. Neither epinephrine nor gibberellin had such an effect. These experimental observations support the previous suggestion that unicellular animals possess structures capable of responding to certain hormones, which do not seem to elicit specific responses of the unicellular animal, but rather act through the activation of certain general functions.


Combination of attenuated measles vaccine (Schwarz) with meningococcus A and A + C vaccine.

There is an obvious interest in a combined meningococcus-measles vaccine since the two diseases are widespread and serious in Third World countries among children under five years of age. The purpose of our study was to show the safety and effectiveness of such a combined preparation. The study covered 110 children between 8 months and 4 years of age who were followed systematically in a maternal child health center in the Paris area. Only 93 of them were checked before and after the immunization. The serologic titrations by the hemagglutination assay (IHA) for measles, and by radioimmunological assay (RIA) for meningococcus A and C showed that the Schwarz strain measles vaccine combined with meningococcus A or the association A+C does not interfere with the increase of A or C titers. 100% of the children showed a seroconversion equal to or less than 2 micrograms per ml, in the case of meningococcus A, as well as for C, regardless of age. Furthermore, 88% of the subjects showed a titer greater than or equal to 4 micrograms for the meningococcus A and 79% for C. On the other hand, meningococcus A or the association A+C seem to depress measles vaccine activity. Nevertheless, more than 80% of the children tested showed seroconversion when the measles vaccine was combined with meningococcus A, and only 69% when combined with meningococcus A and C.


The expanded program in immunization. Ghana's experience.

The expanded programme on immunization feasibility studies is currently running into its second year of operations. The objectives of the study are to test the possibility of increased coverage using both fixed centre and mobile field teams for the vaccination of children under the age of 2 years against measles, poliomyelitis, diphtheria, pertussis, tuberculosis and smallpox and also to test the immunological response to two doses of pertussis and two doses of oral polio. Reports so far indicate some success in the areas of training and manpower development as well as the development of the cold chain system which is considered to be the most important requirement for an efficient, expanded immunization programme. It goes without saying that the progress of the study has been marked by some technical, social and administrative constraints.


Tuberculosis in nonhuman primates as a threat to humans.

Nonhuman primates are used in many laboratories either as modest systems for studies of disease processes or as a source of these tissues for cell culture and vaccine production. Much too frequently, the health of these donor animals is taken for granted, although T.B. testing is one of the few procedures routinely performed. In spite of this screening, outbreaks of T.B. among various simian species are still sufficiently commonplace to make maintenance and use of these animals a continuing source of danger to the human population. Development of rampant fatal tuberculosis in established colony animals (chimpanzees, baboons, others) previously tested as tuberculin negative suggests the need for continuing monitoring as well as extreme caution in handling of these animals, especially at necropsy. Further, use of complete Freund's adjuvant or isoniazid either experimentally or therapeutically will obscure the interpretation of the skin test. Present lack of concern by many investigators for biohazards associated with use of nonhuman primates makes the problem of laboratory-associated infections a major source of concern. Positive conversion of animal handlers has occurred a sufficient number of times to make development of tuberculosis in a colony of animals a matter of more than academic interest.


Studies on insulin secreted by isolated islets of the monkey, Macaca radiata radiata.

The effects of various experimental conditions during the isolation of monkey islets by the collagenase method on the insulinogenic response of the isolated islets to glucose have been studied and compared with rat islets isolated under similar conditions. The monkey islets gave a normal response for at least 120 min. The results are compared with available studies on primate islets.


Prolactin response to TRH in diabetic ketoacidosis.

The prolactin response to 200 microgram thyrotropin-releasing hormone (TRH) IV was studied in seven patients with diabetic ketoacidosis, at the start of the treatment, and again, in the same patients, five days after recovery, when the diabetes was well controlled. Normal basal prolactin concentrations and prolactin responses to TRH were found in both situations. There was no correlation between basal prolactin concentrations, or magnitude of prolactin responses to TRH, and any of the metabolic variables measured. These findings do no suggest a role for prolactin in the development of diabetic ketoacidosis.


Radiologic abnormalities and autonomic neuropathology in the digestive tract of the ketonuric diabetic Chinese hamster.

Barium x-ray patterns of ketonuric diabetic Chinese hamsters displayed marked dilatation of the stomach, small and large intestine. Hypomotility was manifested by flocculation of barium in the small and large bowel. Impaired transit time was further characterized by prolonged emptying of the stomach (mean 570 min diabetics; 200 min controls) and delayed stool formation (mean 230 min diabetics; and 100 min controls) and passage (mean 457 min diabetics; 210 min controls). Ultrastructural analysis of Auerbach's myenteric plexuses of the small intestine indicated acute degeneration in certain distal, unmyelinated axons. Swelling, deposition of glycogen, aggregation of neurofilaments and dense accumulation of lamellar bodies were observed. The severity and frequency of barium flocculation, glycogen deposition, aggregation of neurofilaments and lamellar inclusion bodies in axons were directly related to duration of ketonuria. The data strongly suggest that autonomic neuropathology in the plexuses of Auerbach may be a critical factor underlying gastrointestinal dysfunction in the ketonuric diabetic Chinese hamster.


Cell interactions in the differentiation of a melanotic tumor in Drosophila.

The cellular events in the formation of melanotic tumors in the tu-W mutant larva of Drosophila melanogaster are described. The first step is the differentiation of spherical hemocytes to flattened cells, the lamellocyte variants. Subsequently, the surface of the caudal fat body undergoes changes to which the hemocytes respond by forming cellular capsules. The hemocytes utilize two mechanisms in this process: (1) phagocytosis of small particulate materials escaping from the adipose cells, (2) adhesion to form a multilayered wall of lamellocytes. Differentiating hemocytes in the vicinity of the tumor-forming site extrude membrane-bound vesicles that tend to adhere to the hemocyte surfaces. These vesicles are trapped between the lamellocytes as they pile in layers to form the capsule wall. It is suggested that the vesicles play a role in lamellocyte-to-lamellocyte adhesion during the initial stages of hemocyte aggregation at the tumor-forming site.


Effect of aluminium chloride on metabolism of 4-nitroquinoline 1-oxide.

Aluminium chloride was subcutaneously administered to mice and its effect on the activities of 4-nitroquinoline 1-oxide (4-NQO) reductase and 4-hydroxyaminoquinoline 1-oxide (4-HAQO) reductase, and the organ distribution of carcinogen(s) in mouse lung and liver were examined. Subcutaneous administration of aluminium chloride in mice results in significant elevation of 4-NQO reductase and 4-HAQO reductase activities in their lung and liver, compared with those of the control. Simultaneous subcutaneous administration of aluminium chloride with 4-nitroquinoline[5, 6, 7, 8, 9, 10-14C] 1-oxide (14C-4-NQO) and examination of radioactivity distribution in the lung and liver showed that the radioactivity per tissue, 0.5 and 1 hr after the administration, decreased in the lung but inversely increased in the liver. Radioactivity in the lung and liver 2 hr after the administration was not different from that of the control. Simultaneous subcutaneous administration of 14C-4-NQO and aluminium chloride resulted in decreased distribution of 4-NQO and 4-HAQO in the lung compared with that of the control, while the distribution of their metabolites, 4-aminoquinoline 1-oxide (4-AQO) and 4-hydroxyquinoline 1-oxide (4-OHQO), inversely increased. Distribution of 4-aminoquinoline (4-AQ) and 4-hydroxyquinoline (4-OHQ) in the lung was not different from that of the control. These results suggest that the rapid metabolic changes of carcinogenic 4-NQO and 4-HAQO to noncarcinogenic substance(s) and decrease in the concentration of carcinogenic substances in the lung by the subcutaneous administration of aluminium chloride constitutes one of the factors for the mechanism of the suppression of carcinogenesis by aluminium chloride.


Blastogenic potency of concanavalin-A-bound L1210 leukemic vaccine associated with its immunogenic activity.

Glutaraldehyde-treated L1210 murine leukemic cells induced immune resistance in mice when concanavalin-A (Con-A) was bound to their surface. They were not immunogenic when Con-A was separately inoculated, indicating requirement of vaccine-bound Con-A for enhancing immunogenic potency of the vaccine. Based on the finding that vaccine-bound Con-A induced in vitro blastogenesis of spleen cells 10 times as efficiently as unbound Con-A did, the association of blastogenic potency of Con-A-bound vaccine with its immunogenic activity was examined. The possibility of their association was supported by the finding that induction of immune resistance by vaccines was reduced when their blastogenic activities had been reduced by treatment of the vaccine with anti-Con-A antisera or by substituting succinyl-Con-A or other lectins for Con-A. Moreover, the fact that combined inoculations of Con-A-bound vaccine, assumed to be blastogenic to T cells, with anti-thymocyte sera, but not with cyclophosphamide or carrageenan, resulted in reduced production of resistant animals was also consistent with, but not proving, this possibility. Feasibility of this possibility was further supported by the finding that Con-A-bound vaccine did not induce immune resistance in animals that had been abrogated in blastogenic activity of spleen cells by prior administration of Con-A.


Effect of aluminium chloride on binding of 4-hydroxyamino-quinoline 1-oxide to nucleotides.

Effect of aluminium chloride on the binding of carcinogenic 4-hydroxyaminoquinoline 1-oxide (4-HAQO) with mouse lung DNA, RNA, and various homopolyribonucleotides was examined in vitro, in the presence of seryl-AMP. Mouse lung DNA, RNA, or homopolyribonucleotide [poly(A), poly(G), poly(I), poly(X), poly(C), or poly(U)] was pretreated with aluminium chloride in an ice bath and the binding with 4-HAQO was examined. Binding with DNA, RNA, poly(A), and poly(G) was markedly inhibited, and their binding rates were 46%, 56%, 53%, and 18% of that of the control, respectively. Binding with poly(C) and poly(U) was hardly different from that of the control. Consequently, effect of aluminium chloride in inhibiting the binding of 4-HAQO with mouse lung DNA and RNA is assumed to be due to the inhibition of its binding with guanine. Effect of various metals (Mg2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, and Fe3+) on the binding of 4-HAQO with mouse lung DNA was examined and it was found that aluminium chloride had the strongest inhibitory effect, followed by copper and zinc. Trivalent iron showed hardly any inhibition.


Effect of an elemental diet on body composition. A comparison with intravenous nutrition.

Measurements of changes in body fat, protein, and water were carried out on two comparable groups of 14 ill surgical patients each over 2-wk period during which one group received an elemental diet (nonprotein energy source was 67% carbohydrate and 33% fat) and the other a course of intravenous nutrition (nonprotein energy source was 100% carbohydrate). The patients fed with the elemental diet had no significant changes in body weight, fat, protein, water, or plasma proteins over the study period, and although the patients fed intravenously also had no changes in body protein or plasma proteins, there was an average gain of 3.2 kg of body weight. This weight gain was mainly extracellular water. It is concluded that the administration of the elemental diet by continuous infusion was comparable to intravenous nutrition in maintaining body protein in these very ill patients and had the advantage of being cheaper and easier to manage. The problem of extracellular water accumulation seen in the patients fed intravenously was not present in the patients who received the elemental diet.


Synthesis and degradation of proteins and DNA in Streptomyces aureofaciens.

The rate of protein synthesis in Streptomyces aureofaciens, measured by incorporation of U-14C-L-leucine into cells, fluctuated during the production phase in the range of 10-15% of the values determined in the phase of intensive growth. Tetracycline partially inhibited the protein synthesis during the growth phase only. The proteins synthesized between the 6th and 18th hour of growth, were 75% degraded by the 48th hour. The DNA synthesis, measured by means of incorporation of 2-14C-thymine into the mycelium, occurred predominantly during the first 24 h of cultivation. Similarly, DNA synthesized between the 6th and 12th hour of cultivation was degraded by 75% after 48 h. The turnover of culture proteins is thus caused largely by degradation of old cells and growth of new ones which are more resistant to tetracycline. The activity of alanine aminotransferase and aspartate aminotransferase increase substantially towards the end of fermentation.


Genetic mapping of the region c of the bacteriophage G101 (Pseudomonas aeruginosa).

Morphological mutants of the c type of the bacteriophage G101 (Pseudomonas aeruginosa) were isolated after mutagenesis with hydroxylamine. Complementation analysis of 27 c mutants showed that the c region is formed by at least two genes. Two types of c mutants were obtained. One of them (cI26) behaves analogously to a mutant in the gene controlling the synthesis of the repressor of phage lambda. The second type of the c mutants (cII1, cII18) specifies a gene having probably an auxiliary function in the "c" region. According to the low frequency of recombination between the genes cI26 and c II18 (1.37 recombination units), these genes responsible for lysogenization are localized in a short region of the chromosome.


Inhibition of germination of Bacillus cereus T spores by phenylglyoxal.

Phenylgloxal at a concentration of 0.6 mM inhibited germination of Bacillus cereus T spores as characterized by a decrease in absorbance, dipicolinic acid and loss in heat resistance in a chemically defined growth and sporulation medium. In a germination medium containing L-alanine and adenosine, phenylglyoxal inhibited decrease in absorbance and affected partial loss of viability. It is postulated that phenylglyoxal interacts with free amino groups of various enzymes or amino compounds present in the spore structure thereby causing the inhibition of germination.


Microorganisms in the rhizosphere of wheat colonized by the fungus Gaeumannomyces graminis var. tritici.

The population of microorganisms in wheat rhizosphere changed in the presence of the fungus Gaeumannomyces graminis var. tritici causing the take-all of wheat. In the majority of cases when the soil was artificially contaminated by the fungus, both the number of bacteria in the rhizosphere and the bacteria/fungi ratio temporarily increased. At the beginning bacteria growing in the presence of NH4+ predominated, later bacteria utilizing organic N-substances prevailed. Pseudomonas fluorescens and the related species colonized the rhizosphere and the soil to a greater extent in the presence of G. graminis. The wheat rhizosphere with G. graminis was found to contain a higher level of the slime-producing bacterium Agrobacterium spp.; this microorganism occurred on hyphal surfaces (in hyphosphere) of both G. graminis growing in soil and Mucor spp. Changes in microbial populations in the wheat rhizosphere during the first stage of colonization by G. graminis can be partly explained by a simultaneous rhizosphere colonization by microorganisms which accompany this fungus in soil. In the period of increase in the number of bacteria in rhizosphere a temporary stimulation of wheat growth was observed.


Long-term perspectives of thyroxine administration in neonatal rats.

Newborn pups were injected with normal saline (group A) and exogenous thyroxine (group B). Elevated T4 and decreased TSH levels from day 7 in group B continued until day 35. T4 and TSH were in normal range by day 42 and were similar to group A. Weight gain was significantly lower in group B. On day 45, half hourly injections (subcutaneous) of TRH were given to half of group A and group B each. Remaining halves were injected with saline. TSH response to TRH was significantly decreased in group B rats. Thus, neonatal hyperthyroidism results in (1) permanent decrease in pituitary reserve of TSH secretion and (2) a permanent imprinting regarding growth and thyroidal development and thus, neonatal period is critical for thyroidal development.


Amino acid sequences of antibody light chain variable regions of pedigreed rabbits: kappa light chain K49-501 (allotype b4 anti-streptococcal group A-variant polysaccharide antibody).

The amino acid sequence of positions 1--150 of a light chain, isolated from another monoclonal rabbit anti-streptococcal group A-variant polysaccharide antibody, was determined. The analysis was performed with 2 mumol of polypeptide chain, using a grossly modified Beckman 890B sequenator. This sequence stretch accounts for the whole variable region and a considerable part of the constant region at a total length of 218 amino acids. This allotype b4 light chain was isolated from a non-precipitating, end-group-specific antibody with a KD = 1.3 X 10(-5)M. This brings the present number of totally known rabbit VL sequences of antigen elicited antibodies to 21. A comparison of these 21 sequences reveals a building plan of ribbit VL homologous to that of human and murine VL regions. The observed variability does follow a pattern of linked amino acid substitutions, indicating that this information must be contained in the germ-line of the rabbit in the form of multiple VL region genes. This conclusion, however, does not rule out the occasional variant being due to somatic rearrangement. Finally, this comparison reveals that the joining peptide between positions 96--110 is also a separate entity in rabbit VL region sequences.


[The primary structure of the Bence-Jones protein Kue. The amino acid sequence of the variable part of a human L-chain of the kappa-type (author's transl)].

The complete primary structure of the variable region of Bence-Jones protein Kue was elucitated with the aid of a few tryptic peptides, as well as one chymotryptic and one BNPS-scatol fragment. As a consequence of the evident homologies to other proteins this protein belongs to subgroup k/I. Protein Kue has some amino acid exchanges in certain positions in common with other proteins, probably giving rise to a new sub-subgroup. The constant region shows no amino acid exchanges in comparison with other human kappa L-chains. With valine covering position 191, protein Kue should be grouped per definition as an allotype Km (3).


Selling mental health services to businesses: concepts and strategies.

In order to interest businesses in buying mental health services for their employees, professionals must be able to speak the businessman's language and market their product--mental health services. They must emphasize the cost-effectiveness of mental health care and explain how the business can benefit from including such services in the company's benefits package. The authors describe some concepts and strategies they found helpful when they ventured into the business community to "sell" the services of their community mental health center. They discuss such factors as the need to present a polished, professional image and to gear services to the needs of the particular employer and his employees.


How to evaluate health promotion.

Evaluation of health promotion programs' impact, rather than their outcome or process, currently is needed most.


The development, enhancement, and reversal of the secondary complications of diabetes mellitus.

Diabetic glomerulopathy continues as a major problem in the management of the patient with diabetes mellitus; however, evidence in man and in animals underlines the fact that good control of diabetes favorably alters the course of this complication. Islet transplantation in the diabetic rat returns plasma glucose and insulin levels to normal. In parallel mesangial matrix thickening, mesangial deposition of immunoglobulin and urinary excretion of albumin markedly improve following islet transplantation. Although amelioration of diabetes affects the course of glomerulopathy, other factors (most notably measures that increase glomerular capillary pressure) enhance the development of the diabetic renal lesions. Following uninephrectomy or clipping of a renal artery, the remaining (in the case of uninephrectomy) or unclipped diabetic kidney develops the morphologic and functional changes of diabetic nephropathy at a rate greater than in kidneys in an intact diabetic rat. The clipped kidney demonstrates diminished diabetic changes, suggesting a protective effect with decreased glomerular capillary pressures. In addition to measures improving the control of diabetes, procedures reducing factors accelerating diabetic complications may improve the prognosis in diabetic glomerulopathy.


Myocarditis with microabscess formation caused by Listeria monocytogenes associated with myocardial infarct.

Myocardial infarction complicated by bacterial infection is rare. The present case is an instance in which the infecting organism, Listeria monocytogenes, is also rare--an instance not previously reported. The clinical findings were fever without localized infection, severe atherosclerotic heart disease, a myocardial infarct of indeterminate age, and a left ventricular aneurysm. Additional electrocardiographic findings include left bundle branch block, intraventricular conduction defect, and multiple episodes of ventricular tachycardia, all of which may be associated with myocardial infarction and none of which is specific for suppurative myocarditis. Myocardial enzyme abnormalities were absent. Listeria monocytogenes was identified from blood cultures on the day following the patient's death. This case illustrates the difficulty in diagnosing suppurative myocarditis complicating myocardial infarction and the dire consequence of such infection. A review of the literature is included.


Chromosomal evolution in primates: tentative phylogeny from Microcebus murinus (Prosimian) to man.

The karyotypes of more than 60 species of Primates are studied and compared, with the use of almost all existing banding techniques. There is a very close analogy of chromosome banding between the Simians studied and man. The quantitative or qualitative variations detected all involve the heterochromatin. It is very likely that all the euchromatin (nonvariable R and Q bands) is identical in all the species. Approximately 70% of the bands are common to the Simians and to the Lemurs (Prosimians). In the remaining 30%, technical difficulties prevented a valuable comparison, but this does not exclude the possibility that a complete analogy may exist. Thus, it is very likely that chromosomal evolutions of the Simians, and probably of all the Primates, has occurred without duplication or deficiency of the euchromatin. Approximately 150 rearrangements could be identified and related to the human chromosomes. The types of rearrangement vary from one group (suborder, family, genus) to another. For instance, Robertsonian translocations are preponderant among the Lemuridae (44/57), but are nonexistent among the Pongidae. Chromosome fissions are very frequent amng the Cercopithecidae (10/23), but were not found elsewhere, and pericentric inversions are preponderant in the evolution of Pongidae and man (17/28). This suggest that the chromosomal evolution may be directed by the genic constitution (favouring the occurrence of a particular type of rearrangement, by enzymatic reaction), by the chromosomal morphology (the probability that Robertsonian translocation will be formed depends at least partially on the number of acrocentrics), and by the reproductive behaviour of the animals. Reconstitution of the sequence of the chromosomal rearrangements allowed us to propose a fairly precise genealogy of many Primates, giving the positions of the Catarrhines, the Platyrrhines, and the Prosimians. It was also possible to reconstruct the karyotypes of ancestors that died out several dozen million years ago. The possible role of chromosomal rearrangements in evolution is discussed. It appears necessary to consider different categories of rearrangements separately, depending on their behaviour. The 'nonfavoured' rearrangements, such as pericentric inversions, need to occur in an isolated small population for implanting, by an equivalent of genic derivation. The 'favoured' rearrangements, e.g., Robertsonian translocations, may occur and diffuse in panmictic populations, and accumulate. Their role of gametic barrier could be much more progressive. For discrimination between these two categories, it was necessary to differentiate the selective advantage or disadvantage of the rearrangement itself. It was not possible to show that chromosomal rearrangements play a direct role in modification of the phenotype by position effect. Comparison of the rearrangement that have occurred during evolution and those detected in the human population shows a strong correlation for some of them...


On the incidence of blood group O and Gm(-1) phenotypes in patients with malignant melanoma.

Fifteen polymorphic systems of the blood (ABO, MNSs, Rhesus, P, Kell, Duffy, Kidd, Hp, Gc, Gm, Inv, aP, PGM1, EsD, and 6-PGD) were examined in 191 unrelated male and female patients suffering from malignant melanoma. These polymorphic systems were compared with the corresponding phenotype and gene frequencies of controls from the same geographical area (Rhineland-Palatinate). The only associations discovered were the ABO and Gm polymorphisms: The incidence of O and Gm(-1) phenotypes in patients is obviously higher than in controls. These observations agree with the findings in other population samples from Germany and Bulgaria.


Progressive myoclonus epilepsy. A variant with probable X-linked inheritance.

The syndrome of myoclonus, epilepsy, and mental deficiency is observed in a number of distinct nosologic entities differing with respect to clinical course, (--) pathologic, and biochemical findings. Genetically, the heterogeneity within this group of disorders is shown by the occurrence of autosomal recessive and dominant forms with incomplete penetrance. In this paper we report on a sibship with at least four affected males suffering from progressive myoclonus epilepsy, ataxia, and mental deterioration. The syndrome is probably X-linked, as suggested by the maternal transmission and mild, variable symptoms in some female carriers. In a survey of the literature we have found another pedigree suggesting X-linked inheritance of this variant of progressive myoclonus epilepsy.


Linkage studies on the human Pi, Gm, GLO, and HLA genes.

Linkage data of the four gene markers Pi, Gm, GLO, and HLA exclude Gm and Pi gene assignment to the short arm of chromosome 6. The findings, however, do not disprove the following gene order: HLA--GLO--centromere--Gm--Pi.


Another family with purine neucleoside phosphorylase deficiency.

A brief genetic report is given on a family with a child affected by nucleoside phosphorylase deficiency. Our observations confirm the genetic heterogeneity of this enzyme deficiency which is inherited as a mendelian autosomal trait.


Mechanisms of clonal abortion tolerogenesis. II. Clonal behaviour of immature B cells following exposure to anti-mu chain antibody.

This paper uses B-lymphocyte cloning methods to quantify the effects of anti-mu chain antibody on immature and mature B cells. Nude mouse spleen lymphocytes were incubated with various concentrations of sheep anti-mouse mu chain antibody for times varying from 10 min to 24 h. They were then washed and plated in the agar B-cell colony formation assay. Five to six days later, control B cells had developed into colonies with a plating efficiency of about 5%. B cells from newborn mice pretreated with anti-mu yielded fewer colonies. Remarkably low concentrations sufficed to inhibit subsequent mitogenesis. For example, 3 microgram/ml acting for 1 h or 0.1 microgram/ml acting for 24 h gave greater than 50% inhibition. Adult B cells were about thirty-fold more resistant to negative signalling. Immature cells become more profoundly inhibited as anti-mu treatment was prolonged. Anti-Ia or anti-H2 antibodies, in the absence of complement, did not deliver a negative signal. Anti-mu pretreatment also reduced the capacity of immature B cells to form clones of anti-hapten antibody-forming cells in a liquid microculture system where the triggering stimulus was a T-cell independent antigen. Mature 'T-independent' B cells were not inhibited. Populations of hapten-specific B cells prepared by the hapten-gelatin method were investigated in the agar cloning system. Pretreatment of immature cells with anti-mu reduced their capacity to form colonies, this subpopulation of cells behaving like unfractionated B cells. Furthermore, hapten-HGG delivered a negative signal also. Mature hapten-specific cells or unfractionated immature spleen cells formed normal numbers of colonies following hapten-HGG treatment. Overall, the studies support the view that anti-mu antibody and hapten-HGG deliver strong negative signals to immature but not mature cells with appropriate receptors. The value of anti-mu as a model, universal tolerogen was supported. Fluorescence-activated cell sorter (FACS) analysis was performed to study the relationships between functional inhibition and Ig receptor modulation. We confirmed that the IgM receptors of immature B cells are more readily modulated by anti-mu antibody than those of mature cells. Furthermore, the receptor regeneration could be partially inhibited amongst immature but not mature B cells. There was not a close quantitative relationship between the degree of modulation and the degree of functional inhibition. The results did not support the view that irreversible receptor modulation as such was the cause of functional inhibition.


In vitro complement activation by rabbit lymphocytes and thymocytes in autologous serum.

The activation of C3, previously demonstrated to occur during the isolation of lymphocytes from rabbit blood, has been investigated further by in vitro exposure of blood and lymph node lymphocytes and thymocytes to autologous serum. Activated C3 deposited on the lymphoid cell-surface was detected by (i) anti-C3, (ii) immune adherence reaction, and (iii) blocking of receptors for C3. An affinity shown by guinea-pig erythrocytes for activated complement was also investigated. Using EGTA, which inhibits the classical complement pathway while leaving the alternative pathway unaffected, it was shown that either pathway may be activated by rabbit cells depending on the temperature of incubation. The classical pathway was triggered at 4 degrees, probably by the reaction of cold auto-antibodies with lymphoid cell-surface determinants. At 37 degrees, however, comlement activation followed the alternative pathway in a similar manner to that reported by other workers with human lymphoblastoid cell lines.


In vivo effects of antiserum to IgD on surface immunoglobulins, serum immunoglobulins and lymphocyte blastogenesis in rhesus monkeys.

The effects of injecting monkeys with goat antiserum to IgD, the IgG fraction of that antiserum or normal goat serum (NGS) were compared. The subcutaneous injection of 4 ml/kg of the whole antiserum resulted in decreased percentages of lymphocytes with surface IgD or IgM lasting from day 1 through day 7 post-injection followed by substantial recovery on day 10. Lymphocytes from these animals were stimulated as indicated by the increased incorporation of 3H-TdR by cells placed in culture on days 7-21 post-injection. The increased blastogenesis occurred in rosette-depleted (B cell) populations and did not occur in rosette-enriched (T cell) preparations. Hypergammaglobulinaemia and increased concentration of serum IgG were first detected on day 10 postinjection, maximal on day 14 and were in decline by day 18. Injection of 4 ml/kg NGS did not alter the percentages of lymphocytes with surface immunoglobulins, result in hypergammaglobulinaemia, or stimulate the degree of blastogenesis observed after anti-IgD. Injection of the IgG fraction of the antiserum resulted in decreased lymphocytes with surface immunoglobulins but did not stimulate hypergammaglobulinaemia or increase blastogenesis. Injection of one monkey with the IgG fraction of anti-IgD combined with NGS resulted in increased serum IgG and increased blastogenesis. Both antibody to IgD and multiple antigenic challenge appear to be required for these responses.


Delayed-type hypersensitivity and acquired cellular resistance in mice immunized with killed Listeria monocytogenes and adjuvants.

Delayed-type hypersensitivity (DH) and acquired cellular resistance (ARC) to Listeria monocytogenes in mice was studied following immunization with killed bacteria in combination with Freund's complete adjuvant or the adjuvant dimethyldioctadecylammonium bromide (DDA). Intracutaneous or intraperitoneal injections of killed listeria mixed with Freund's complete adjuvant did neither result in DH nor in ACR. Intracutaneous injections of killed listeria and DDA resulted in an antigen-dose dependent DH but not in ACR. Intraperitoneal injections of listeria and DDA, however, induced ACR but no DH. Optimal conditions for the induction of ACR were simultaneous intraperitoneal injection of 15 mg DDA/kg body weight and 10(7) or 10(8) listeria. The optimal interval between immunization and challenge was 7 days. No protection was found against challenge with a lethal dose of Salmonella enteritidis, suggesting that the protection is specific. Intraperitoneal injection of mice with DDA resulted in inhibition of phagosome-lysosome fusion in macrophages harvested 24 h later. Interference with macrophage activity is discussed as one of the possible mechanisms for the adjuvant effect of DDA.


The effect of soluble material from mouldy hay dust on the complement system.

The soluble material derived from the respirable fraction of mouldy hay dust has anti-complementary as well as enzyme activity. The anti-complementary activity resides in a heavy molecular weight fraction (approx. 800,000) and acts directly on C1 without combination with or alteration of IgG or IgM. The enzyme function has a lower molecular weight (approx. 30,000-38,000) and is related to papain in that IgG is split into two distinct components of similar molecular weight and with antigenic determinants the same as Fab and Fc pieces respectively. C1 activation leads to C3-9 depletion and on a per sample basis it is calculated that the soluble mouldy hay dust material is up to sixty-six times more active at C3-9 activation than the particulate material in mouldy hay dust. It is probable that the capacity to activate C1 resides in other dusts and may be a basis for non-immune histamine release in the lungs when such a dust is inhaled. It is also probable that non-specific skin reactions are related to C1 activation. The finding of an enzyme with papain-like activity is significant since the introduction of papain into the lungs of the experimental animal leads to emphysema and this has been described as a feature of farmer's lung.


The mechanism of T-cell mediated cytotoxicity. VII. Lysis of isolated cytoplasts and karyoplasts.

Isolated P815 karyoplasts are up to four times more susceptible to lysis by T cells than intact cells, suggesting that the target cells nucleus or a nuclear associated structure may be particularly sensitive to cell-mediated cytotoxicity. Cytoplasts showed variable susceptibility. The morphological changes seen by time-lapse cinematography show that the first change seen with intact cells is a burst of zeiosis (membrane blebbing), whereas neither cytoplasts nor karyoplasts exhibit zeiosis. These observations suggest that zeiosis results from changes in the cytoskeletal system. This is discussed in relation to the possibility that T cells kill target cells by causing physical damage to a critical organelle inside the cell rather than to the membrane itself.


Receptors for activated C3 on thymus-dependent (T) lymphocytes of normal guinea-pigs.

In a survey of lymphocyte subpopulations in normal guinea-pig blood, lymph node, spleen, thymus and peritoneal cavity, a considerable overlap was observed between the percentages of C3-receptor bearing lymphocytes (CRL) and of thymus-dependent (T) cells in lymph nodes. Simultaneous rosette-formation reactions with sheep erythrocytes carrying rabbit complement (EAC) and papain-treated rabbit erythrocytes (a T-cell marker) revealed that 20--50% of the lymph node CRL were T lymphocytes. These experiments and others on cell suspensions depleted of Ig-bearing (B) lymphocytes showed that between 8 and 36% of lymph node T cells have complement receptors. The frequency of T-CRL in other lymphoid tissues was lower, representing between 0 and 8% of the T-cell population. The reaction of T-CRL and EAC was not inhibited by EDTA which is known to inhibit the C3 receptor activity on macrophages.


Neisseria meningitidis bacteremia in association with deficiency of the sixth component of complement.

The serum of a 26-year-old black man with a recent episode of meningococcemia complicated by meningitis and arthritis was found to lack hemolytic complement activity. The sixth component of complement was not detected by functional or immunochemical assays whereas other components were normal by hemolytic assay. His fresh acute-phase serum lacked complement-mediated bactericidal activity against the homologous strain of Neisseria meningitidis, but the addition of fresh normal serum or purified C6 restored bactericidal activity as well as hemolytic activity. The absence of C6 activity could not be accounted for on the basis of an inhibitor. Opsonization and chemotaxis functioned normally. Histocompatibility typing of family members did not demonstrate evidence for genetic linkage of C6 deficiency with the major histocompatibility loci. This report represents the first published case of C6 deficiency associated with bacteremic Neisseria infections in which antimeningococcal bactericidal antibodies have been definitively demonstrated against the homologous strain in the acute phase of the illness.


Suppressive effect of bacterial endotoxin on the expression of cell-mediated anti-Listeria immunity.

Intravenous injection of bacterial endotoxin into mice at any time during ongoing infection with Listeria monocytogenes resulted in a markedly increased multiplication of this organism in the liver and spleen. Experiments designed to investigate the basis of this infection-enhancing effect revealed that endotoxin was also capable of inhibiting the expression of adoptive T-cell-mediated anti-Listeria immunity if given to normal recipient mice up to 48 h before they were infused with protective T-cells. On the other hand, endotoxin had only a marginal effect on the expression of adoptive immunity if given to donor mice before their spleen cells were harvested for adoptive transfer. Taken together, these results indicate that endotoxin probably interferes with the antibacterial function of macrophages rather than with mediator lymphocytes. The additional finding that the infection-enhancing action of endotoxin could be greatly reduced by making mice "tolerant" to endotoxin suggests that the acquisition of tolerance to this effect of endotoxin may be an important adaptive mechanism in acquired resistance to infection with gram-negative bacteria.


Correlation between genetic regulation of antibody responsiveness and protective immunity induced by Plasmodium berghei vaccination.

High (H) and low (L) antibody responder lines of mice were produced by two independent bidirectional selective breedings for quantitative antibody responsiveness to heterologous erythrocytes (selection I and selection II). In both selections the antibody response to P. berghei antigens was 8- to 10-fold higher in H than in L lines. The character "high response" presents an incomplete dominance o- 18% in selection I and 67% in selection II. In selection II the variance analysis indicates that at least three independent loci intervene in the regulation of responsiveness to P. berghei antigens. The innate resistance and the protective efficacy of vaccination against P. berghei infection induced by parasitized erythrocytes was measured in H and L lines and in the interline hybrids F1, BcH, and BcL of selections I and II. No very significant difference was observed in the innate resistance to P. berghei infection between H and L mice of both selections. Vaccination induced a very efficient protection in the two H lines (94 and 95% survival), whereas only a weak protection was induced in the two L lines (16 and 31% survival); the degree of protection is intermediate in interline hybrids F1, BcH, and BcL. In both selections a good linear correlation was demonstrated between the level of vaccination-induced antibody and the degree of resistance measured as percentage of survival. The present results indicate that the vaccination-induced P. berghei immunity is essentially due to the antibody response, whereas the bactericidal activity of macrophages and the cell-mediated immunity do not play a determinant role.


Production of exoenzyme S during Pseudomonas aeruginosa infections of burned mice.

Antisera which distinguished between Pseudomonas aeruginosa exoenzyme S and toxin A neutralized the adenosine diphosphate ribosyl transferase activity of the homologous, but not the heterologous, enzyme. Skin extracts and sera from burned mice infected with the exoenzyme S-producing strain P. aeruginosa 388 contained adenosine diphosphate ribosyl transferase activity that was not found in skin extracts or sera from uninfected mice. On the basis of immunological reactivity and enzymatic properties, the adenosine diphosphate ribosyl transferase activity present in skin extracts and sera from P. aeruginosa 388-infected mice was identified as exoenzyme S. Active elongation factor 2 levels in tissues from strain 388-infected mice were normal at 24 h postinfection, indicating that strain 388 does not produce detectable amounts of toxin A in vivo. An unexpected finding in this investigation was the presence of exoenzyme S-inactivating activity in the sera from some nonimmunized animals.


Humoral response to experimental petriellidiosis.

The humoral antibody response elicited by experimental infection with Petriellidium boydii and Monosporium apiospermum was studied. The variables of fungus strain, route of inoculation, and concentration of inoculum were examined. Viable spores from three strains of P. boydii and from three strains of M. apiospermum were inoculated intravenously into mice. Serum specimens were tested for antibody by the microtiter indirect hemagglutination assay. At 4 weeks after infection, the percentage of positive specimens among survivortically related either to the incidence of positive specimens or to the magnitude of the humoral response. Mice inoculated by either the subcutaneous or the intramuscular route with viable or killed spores from M. apiospermum 813 developed antibody. The mean antibody titer was greater in those animals receiving viable spores, and the magnitude of the humoral response was dose dependent. Animals inoculated intravenously with comparable inocula of the same strain developed similar levels of antibody. However, cultural studies of infected mice showed chronic infection only after intravenous inoculation. The kidney was the organ most consistently involved.


Release of soluble peptidoglycan from growing gonococci: hexaminidase and amidase activities.

Peptidoglycan (PG) turnover in exponentially growing Neisseria gonorrhoeae RD5 type 4 was accompanied by release of soluble PG fragments into the medium. Turnover of the D-[14C]glucosamine-labeled glycan moiety and of the meso-[3H]diaminopimelic acid (DAP)-labeled peptide region occurred at similar rates (ca. 35% per generation). Turnover of D-[14C]alanine-labeled sites within the peptide side chain of PG occurred at roughly twice this rate; no turnover of L-[3H]proline-labeled protein was detected. Gel filtration of supernatants of cultures grown in the presence of labeled DAP, glucosamine, and D-alanine as described above and paper chromatography of hydrolyzed peak fractions revealed four major types of soluble PG. Two of these contained both peptide and glycan moieties and appeared to represent forms of disaccharide peptide monomers and dimers. The other two were (i) a 3H-labeled product lacking 14C and (ii) a 14C-containing product lacking 3H, which were similar in size to that expected for free tetrapeptides and free disaccharides, respectively. Together the appearance of these PG fragments and the concurrent turnover of glycan and peptide regions indicate that both glycan splitting and amidase PG hydrolase activities are involved in the turnover of PG in growing gonococci. If released during gonococcal infections, similar soluble PG fragments might influence the consequences of host-gonococcus interactions.


Bound immunoglobulin and foreign antigen in lungs of sudden infant death syndrome victims.

Lung sections from 33 infants who died suddenly and unexpectedly and were diagnosed by medical examiners as sudden infant death syndrome (SIDS) gave evidence of bound immunoglobulin G (IgG) when examined by direct fluorescent antibody technique. Ten tissues from appropriate control infants were negative. Specimens containing IgG exhibited no IgA or IgE, but three contained IgM. Sixty-one percent of lung sections with IgG contained either K or lambda antigens; the remainder contained both. The indirect fluorescent antibody technique gave similar results. Blood sera of some individuals in the study which were tested all contained both K and lambda antigens. Fluorescent-labeled immunoglobulin from one SIDS victim stained 7 of 17 SIDS lung sections tested, including his own. Labeled immunoglobulin from three mothers of SIDS victims exhibited differential selectivity in reaction with antigen in lungs of a group of 18 SIDS infants. They did not react with 10 control infant tissues. Various labeled adult sera, cord sera, and serum from an apneic child did not react with the various lungs of SIDS victims in the study.


Experimental bacterial keratitis in neutropenic guinea pigs: polymorphonuclear leukocytes in corneal host defense.

Quantitative techniques were used to determine the relative concentrations of viable bacteria and polymorphonuclear leukocytes (PMNs) in the corneas of neutropenic and non-neutropenic guinea pigs with experimental bacterial keratitis induced with three strains of Pseudomonas aeruginosa. Neutropenia was produced by whole-body X-irradiation 1 week before infection. Significantly greater numbers of bacteria were present in the cornea of neutropenic animals 48 h after infection than were present in the corneas of non-neutropenic animals. The same was true 24 and 48 h after infecting animals with Staphylococcus aureus. Examination of histological sections showed that fewer PMNs were present in the corneas of infected neutropenic animals than in the corneas of infected non-neutropenic animals. Radiolabeling of PMNs confirmed a significant reduction in PMN concentration in the corneas of infected neutropenic animals. Tears and the corneal epithelium appear to be the most important elements protecting the cornea against local invasion by bacteria. However, once bacterial keratitis is established, PMNs play a role in limiting bacterial multiplication.


In vivo conjugal transfer of R plasmids in Neisseria gonorrhoeae.

In vivo R plasmid transfer between two Neisseria gonorrhoeae strains was detected in the absence of antibiotic pressure.


Nephelometric activity as a criterion of adequate antisera for use in immunofluorescence.

We have characterized monospecific sheep antisera to human IgG, IgA and IgM using Ouchterlony double diffusion, immunoelectrophoresis, quantitative precipitation and nephelometric activity. The antisera were conjugated at high and low F/P ratios, absorbed and subsequently evaluated in both direct and indirect immunofluorescence. Antisera which exhibited excellent reactivity in double diffusion, IEP and quantitative precipitation but gave a poor nephelometric response (Ab dilution greater than 1/25 gave no measurable response in the Technicon Fluoronephelometer) showed a marked decreased effectiveness in both direct and indirect fluorescence. Antisera which exhibited a strong nephelometric response were invariably excellent in double diffusion, IEP and quantitative precipitation and gave strong positive fluorescence at reasonable dilutions in both direct and indirect fluorescence. We suggest nephelometry prior to conjugation is the method of choice in screening antisera usable in immunofluorescence.