[Proteeae enzymes that participate in the amino acid metabolism of food products]. Biosynthesis of enzymes, catalyzing amino acid conversion in food products, and deposition of end products of protein metabolism is a current problem for hygiene-indicatory microorganisms. Results are reported of a study of decarboxylase and aminotransferase activities of a large number of Proteus strains. It was found that aminotransferases are produced by all members of this group of microorganisms, despite the specific differences in their quantitative characteristics. The composition of the different protein-containing food substrata exerts emphatic influence on the induction of these enzymes. The results of study of decarboxylase activity also point to some specific differences, applicable in the differential diagnosis. The inferences summarize the importance of the whole Proteus group as hygiene-indicatory microorganisms, producing enzymes of essential importance for the quality and biologic value of food products.


[Effect of a deficiency of carbon, nitrogen, phosphorus and magnesium in the growth medium on the mechanical properties of Escherichia coli cell walls]. Values of modulus of elasticity of cell walls and strength level of cells Escherichia coli cultivated in the carbon, nitrogen and phosphorus deficient media or incubated in the magnesium-free medium were determined. Elastic modulus of cells grown in the magnesium-free medium was by two order of magnitude lower than that of the control cells. Elastic modulus of cells cultivated in the nitrogen and carbon deficient media was by one and two orders of magnitude lower than in the control cells whereas strength level was by 1.15 and 1.39 times higher, respectively. Elastic modulus of cells grown in the phosphorus deficient medium remained undetermined and strength level of those cells proved to be the lowest (0.9 of the control).


[Clinico-radiological comparisons in autoimmune thyroiditis]. The author observed 293 patients suffering from autoimmune thyroiditis (Hasimoto's thyroiditis--in 236). Four symptom complexes of the disease were distinguished: typical chronic autoimmune thyroidits in euthyroidal condition, chronic autoimmune thyroiditis with thyrotoxicosis, chronic autoimmune thyroiditis with hypothyroidism, relapsing autoimmune thyroiditis. Radioindication and scanning of the thyroid gland with radioactive iodine-131 was conducted preoperatively in 74 patients and at various postoperative periods in 26 patients. Radioisotopic methods were of importance in the comprehensive clinical examination of patients suffering from autoimmune thyroiditis. By means of these methods diagnosis of autoimmune thyroiditis was confirmed in 6.7% of patients. All the patients with autoimmune thyroiditis were operated on. Resection of the peritracheal segments of the thyroid gland with the isthmus extirpation was performed. During the postoperative period the patients required prolonged dispensary observation and treatment with immunodepressors and thyroid hormones.


Circular dichroism and magnetic circular dichroism of nitrogenase proteins. Circular dichroism (CD) and magnetic circular dichroism (MCD) spectra of nitrogenase components (MoFe protein and Fe protein) from Azotobacter vinelandii (Av) and Klebsiella pneumoniae (Kp) have been obtained in the near infrared-visible-near ultraviolet spectral region. Previously, visible CD was reported to be absent or barely detectable in nitrogenase proteins; MCD spectra have not been reported. The chiroptical spectra can be measured in solution at room temperature, an advantage relative to spectroscopic methods requiring cryogenic sample temperatures. Absorption spectra were also obtained. The CD and MCD are markedly more structured, and thus interpretively more useful, than the corresponding absorption spectra. The dithionite-reduced MoFe proteins (Av1, Kp1) have nearly identical CD and MCD, demonstrating identical numbers and types of metal centers in similar protein environments. The CD and MCD cannot be explained solely in terms of contributions from known 4-Fe or 2-Fe clusters; the near-infrared MCD is inconsistent with the presence of known 4-Fe clusters. CD and MCD spectra of Lauth's violet-oxidized Kp1 are also reported. The reduced Fe proteins (Av2, Kp2) have similar CD and MCD, again indicating significant conservation of chromophore environment. The spectra clearly demonstrate the presence of a reduced bacterial ferredoxin-like (C(3-)) 4-Fe cluster. No obvious evidence of additional chromophores is observed. CD, MCD, and absorption spectra of Av1-oxidized Av2 are reported. The absorption spectrum shows the expected shoulder near 390 nm. The CD and MCD are characteristic of a C(2-) 4-Fe cluster; in particular, the diagnostic near-infrared MCD peak is observed at approximately 8300 cm(-1). The CD of Av2 oxidized in the presence and absence of MgATP are radically different, providing the first direct evidence for MgATP interaction with Fe protein in this oxidation state.


Initiation of general recombination catalyzed in vitro by the recA protein of Escherichia coli. Homogeneous recA protein catalyzes the hybridization of single-stranded DNA to homologous regions in duplex DNA. The products are D-loops, which are formed with equal efficiency in linear and supercoiled molecules. This assimilation reaction can be separated into two partial reactions. In the first, recA protein binds to duplex DNA and produces a reA protein-DNA complex. The binding shows a sigmoidal dependence on recA protein concentration, requires ATP, GTP or the gamma-thio analog of ATP, and Mg2+, but does not require hydrolysis of the nucleoside triphosphate. In the second reaction, single-stranded regions of the recA protein-ATP-duplex DNA intermediate hybridize with free complementary single strands to produce D-loop structures. This reaction is coupled to ATP hydrolysis and is analogous to the renaturation of single-stranded DNA catalyzed by the recA protein [Weinstrock, G.M., McEntee, K. & Lehman, I.R. (1979) Proc. Natl. Acad. Sci. USA 76, 126-130]. Hydrolysis of ATP appears to be required in these reactions for dissociation of recA protein from the DNA.


lac repressor changes conformation upon binding to poly[dA-T)]. N-(Iodoacetylaminoethyl)-1-naphthylamine-5-sulfonate reacts with Escherichia coli lac repressor to selectively label cysteine-140 with the fluorescent N-(acetylaminoethyl)-1-naphthylamine-5-sulfonate group. The fluorescence intensity of this label decreases by 20% when labeled repressor associates with poly[d(A-T)]. Fifteen base pairs of poly[d(A-T)] per repressor tetramer are required to complete this decrease. Stopped-flow experiments have shown that the repressor undergoes at least two conformational changes as it binds to poly[d(A-T)], with half-lives of 5.0 +/- 1.2 msec and 3.5 +/- 1.0 sex. Quite likely, these conformational changes serve to strengthen the interaction of repressor with DNA.


Insertion mutant of bacteriophage f1 sensitive to EcoRI. The nucleotide sequence A-A-T-T was inserted into the intergenic region of the f1 genome at a site cleaved by Hae III (cleavage sequence (G-G-C-C). The resultant viable phage mutant (R199) contains a single site sensitive to the restriction endonuclease EcoRI (cleavage sequence G-A-A-T-T-C). This phage is sensitive to EcoRI restriction and modification in vivo and in vitro. Its potential for use as a cloning vector has been tested by construction in vitro of an f1/pBR322 chimeric phage. The four bases inserted into wild-type f1 to generate the R199 mutant came from a small restriction fragment obtained by digesting plasmid pBR322 with EcoRI and HindIII. The use of this linker prepared from a biological substrate is an example of a technique for constructing restriction enzyme sites in vitro. It is presented as an alternative to the use of synthetic linkers and should be generally applicable.


Transcription of Ti plasmid-derived sequences in three octopine-type crown gall tumor lines. Total RNA isolated from three octopine-type crown gall lines contains sequences homologous to specific regions of the tumor-inducing (Ti) plasmid of Agrobacterium tumefaciens strain 15955. A comparison of transcripts in these three tumor lines suggests that tumor cells transcribe various sequences within a sector of plasmid DNA of 13 x 10(6) daltons and that transcription may not be uniform across the plasmid derived sequences (T-DNA). Transcription of T-DNA by octopine-type tumors occurs at four major sites. The levels of transcription occurring at three of these sites appear to vary considerably among the three tumor lines investigated. Part of this variability may reflect differences in the organization and copy number of T-DNA. One of the transcription sites maps within a region of DNA with common sequence homology with all Ti plasmids. Varying amounts of transcript homologous to this region of T-DNA are present in all three tumor lines. It is suggested that transcription of these conserved sequences in the plant may have significance regarding the mechanism of tumorigenesis.


Immunocytochemical localization of alpha-actinin in intestinal epithelial cells. alpha-Actinin was localized in chicken intestinal epithelial cells by immunofluorescence and immunoferritin labeling of thin frozen sections. Most of the label of the brush border was confined to the terminal web area. The label there was concentrated mainly along the "roots" of the microvilli core microfilaments and in the vicinity of the zonula adherens. In the latter structure, the narrow electron-dense zones adjacent to the cell membranes, however, were not significantly labeled. This suggests that alpha-actinin does not mediate directly the association of the transverse terminal web microfilaments to the membrane at the zonula adherens. Sparse ferritin labeling was found near the tight junction, whereas the staining associated with the spot desmosome was negligible. The microvilli were not significantly labeled by either immunofluorescence or immunoferritin staining unless the sections were previously treated with detergent. Moreover, alpha-actinin (or a structurally related protein) was not detected in preparations of purified microvillar vesicles, suggesting the possibility that the alpha-actinin staining in the microvilli may be an artificial due to its translocation by the detergent from the terminal web onto the microvilli. The possible roles of alpha-actinin in the organization and function of the brush border are discussed.


Physical map of chromosomal nitrogen fixation (nif) genes of Klebsiella pneumoniae. We describe a method for the rapid determination of the physical location of mutations caused by insertion of transposable elements. We used this method to construct a detailed physical map of the nitrogen fixation (nif) gene cluster of Klebsiella pneumoniae and to correlate it with the genetic map. Total cellular DNA was isolated from individual strains, each carrying an insertion in 1 of 15 different nif genes. The DNA was digested with a restriction endonuclease, fractionated by agarose gel electrophoresis, denatured, and blotted onto nitrocellulose filter paper. The DNA on the filters was hybridized with (32)P-labeled DNA fragments derived from amplifiable plasmids carrying cloned nif DNA fragments from K. pneumoniae. Altered hybridization patterns caused by insertions into nif genes allowed us to map nif mutations with respect to the previously mapped cleavage sites for various restriction endonucleases. We have used the same method to map the end points of nif deletions. Using this procedure, we assigned physical locations on the K. pneumoniae chromosome to 86 nif insertion mutations and 13 nif deletion end points. This mapping procedure provides a convenient alternative to deletion mapping as a definitive method for mapping insertion mutations within a gene or for ordering genes within a gene cluster. This procedure will be especially useful for mapping mutations conferring phenotypes that are difficult to monitor and for mapping mutations in bacterial species in which techniques for conducting deletion mapping have not been devised.


Endogenous oncornaviral antigen in the bursa of Fabricius of 15B X 7(2) chickens. Oncornaviral antigen was detected in the bursal epithelium and in a subpopulation of bursal follicular cells of 15B X 72 chickens. This antigen is present in the bursal epithelium at 11 days of embryogenesis and persists there for at least 3 weeks after hatching. The absence of detectable antigen in the intestinal epithelium contiguous to the bursal epithelium indicates that the accumulation of viral antigen is a specific property of the bursal epithelium. The observation of C-type particles in the intraepithelial spaces suggests that the viral antigen in synthesized and assembled into virions by the bursal epithelial cells. In embryonic bursas, viral antigen-positve cells radiate from the surface epithelium toward the central region of the follicles. In bursas from post-hatch chickens, viral antigen-positive cells, including intrafollicular epithelial cells and cells resembling lymphocytes, are confined to the medullary region of the follicles.


Immunochemical characterization of surface antigens of TerC, a teratocarcinoma-derived cell line. Rabbit and mouse antisera prepared against teratocarcinoma cells precipitate both glycoproteins and glycolipids from detergent extracts of radiolabeled cells. Extracts of immunoprecipitates with chloroform/methanol, 2:1 (vol/vol) have been resolved on thin-layer gels into multiple peaks. There are more species seen in extracts of teratocarcinoma cells than in extracts of the crossreacting cultured cell line, cl 1d. The teratocarcinoma antigens may be extracted out of chloroform/methanol into buffered saline. Incubation in these secondary extracts converts unreactive cells (lymphocytes to cells reactive with antisera against teratocarcinoma. Furthermore, the coated cells absorb at least 80% of the activity of antisera against teratocarcinoma targets.


Hybrid resistance to parental bone marrow transplantation: adaptive modification of hemopoietic stem cell in a nonsyngeneic environment. Defective growth of parental bone marrow in an F1 hybrid is associated with delay of the exponential growth phase of injected hemopoietic stem cells rather than with their rejection. This is demonstrated both by parental hemopoietic stem cell kinetics in the irradiated hybrid and by the increase in the number of spleen colonies with time after hemopoietic cell injection. After passage through an F1 hybrid the parental hemopoietic stem cells acquire ability for better growth in the same F1 host. This phenomenon, which we designated "adaptive modification of hemopoietic stem cells," is associated with the appearance, on their surface, of histocompatibility molecules carrying H-2 determinants of the recipient. Treatment of the modified cells with antiserum against the second parental strain abrogates the state of adaptive modification.


Enkephalin-containing amacrine cells in the avian retina: immunohistochemical localization. The distribution of enkephalin-like immunoreactivity within the avian retina was studied by immunofluorescence and immunoperoxidase techniques with antiserum to [Met5]enkephalin and [Leu5]enkephalin. Formaldehyde-fixed retinae were sectioned and incubated in antiserum to either [Met5]- or [Leu5]enkephalin. Specificity to the antiserum was established by absorption of the antiserum with synthetic [Met5]- or [Leu5]enkephalin at 1 mM. Positive immunohistochemical staining for enkephalin was observed in the somata of amacrine cells and their processes within the inner plexiform layer. A large number of enkephalin-containing amacrine cells were distributed throughout the retina, and their density appeared to be greatest within central retinal regions. The majority of labeled amacrine cells were about 7.5 micrometers in diameter although, occasionally, amacrine cells were observed that were 12--15 micrometers in diameter. Amacrine cells had a cell-to-cell spacing of approximately 40 micrometers within central retinal regions. Labeled processes of the amacrine cells were observed to project into the inner plexiform layer where they arborized as a fine plexus, within laminae 1, 3--5 of the inner plexiform layer. These observations demonstrate the existence of opioid peptides in seemingly select populations of amacrine cells within the retina. The localization of enkephalin-like immunoreactivity within the retina suggests that opioid peptides play a specific and unique functional role in retinal processing.


EEG profile studies of clozapine in volunteers and psychiatric patients. Among the newer psychoactive compounds, clozapine is classified by some authors as an antipsychotic compound, but it exhibits differences in pharmacology and clinical effects that clearly distinguish it from established antipsychotic compounds. It represents an anomaly in the EEG classification scheme as well. In normal volunteers and in psychotic patients, it elicits EEG effects that are more like those of sedative thymoleptic antidepressants than the established antipsychotic compounds. It is probable that the antipsychotic activity reported by some observers reflected the sedative qualities of the compound and not a prototypic antipsychotic activity. Further testing in other psychiatric populations, particularly patients with depressive illnesses, is warranted.


Staphylococcal and streptococcal infections of the skin. Acute pyogenic infections of the skin, caused by hemolytic streptococci and S. aureus, account for the vast majority of bacterial infections of the skin seen in ambulatory practice. In preschool children the principal manifestation is pyoderma, which is usually caused by Group A Streptococcus. In this age group pyoderma regularly responds to systemic penicillin therapy plus adjunctive local care to the lesions. However, in older age groups, the ability to distinguish streptococcal from staphylococcal skin infections on the basis of clinical features alone is poor, and penicillin treatment failures are more common. Safe, effective antibiotics that are effective against both staphylococci and streptococci are readily available. For this reason penicillinase-resistant semisynthtic penicillins and or erythromycin can be used to treat acute pyogenic skin infections in older age groups.


Diagnostic virology in clinical practice. Viral illnesses are among the most common clinical problems encountered in medicine. Some have important epidemiologic implications and some are preventable by immunization, improved sanitation or other means. Recently, drugs have been developed which show promise for specific prophylaxis or treatment. It is thus increasingly important that physicians in practice be acquainted with methods of identification of common viral illnesses so they can intervene with appropriate counsel, preventive measures or treatment for their own patients. Physicians should also consider the larger epidemiologic implications of many viral illnesses and cooperate with local, state and national efforts to accurately determine the number of patients involved and the severity of their illnesses. It is only with this sort of information that an estimate of medical, social and economic impact of the common viral diseases can be made, so that attention will be given to development of better prevention and methods of control.


Sensory pleasure.

Sensory pleasure. In response to a stimulus, a sensation is tridimensional: qualitative, quantitative, and affective. The affective part of sensation, pleasure or displeasure, depends on the qualities of the stimulus. Within a narrow range of intensity, chemical, thermal, and mechanical stimuli are able to arouse pleasure. In addition, pleasure depends on the internal state of the subject. This is easily observed in the case of temperature: pleasure is aroused by a warm stimulus in a hypothermic subject and by a cold stimulus in a hyperthermic subject. This property of a given stimulus to arouse pleasure or displeasure according to the internal state of the subject is termed alliethesia. Alliesthesia is also produced by chemical and mechanical stimuli. Acquired preferences or aversions for alimentary stimuli represent a case of alliesthesia. In the same way, the capacity of any indifferent stimulus to become rewarding, or punishing, by association with some reward or punishment, is also a case of alliethesia. In all cases, pleasure is a sign of a stimulus useful to the subject; displeasure a sign of danger. Usefulness and danger are judged by the central nervous system with reference to homeostasis and the set point of the implied regulation. Pleasure and displeasure thus appear to motivate useful behaviors.


Milestones and rates of growth in the development of biology. An attempt has been made to examine the exponetial rate of increase of the great discoveries, the "milestones," in the rise of biology from the beginning of the seventeenth century, and particularly in the rise of genetics from the beginning of the twentieth century. The biological sciences in general, during the three centuries named, exhibit a doubling of the number of great discoveries in each fifty years. Genetics, in the twentieth century, has risen much faster. Its doubling time for the most significant discoveries has been about twenty-two and a half years. Either of these rates is of course far slower than the exponential rise in the total output of biological science, the number of scientists, or the cost of science, which have been generally reported to double about every ten years or less. It follows that, as time passes, and until these exponetial rates become considerably altered, a relationship of diminishing returns is quite evident. As time passes, even though the most significant discoveries continue to increase exponetially, it takes a greater total output, a greater number of (assisting?) scientists, and greater amounts of money to yield a set quantity of major new findings. The rapid rise of the life sciences cannot continue its present course into the twenty-first century without meeting ineluctable limits to expansion. It may be argued that as in other human spheres of activity, so too in natural science there are limits to growth which we are rapidly approaching. From the predictable asymptote only unpredictable breakthroughs might deliver us.


[Use of an immunoenzymatic test in the serological diagnostics of toxoplasmosis (author's transl)]. Four hundred and thirty four human sera have been tested for antitoxoplasma antibodies using an immunoenzymatic test on slides. A corpuscolar antigen, a peroxidase-labelled antiglobulin and a modified peroxidase stain have been employed. Results are compared with those obtained by indrect immuno-fluorescence and passive haemoagglutination; a good corrispondence between immunoenzymatic test and indirect immunofluorescence is found.


[Quantitative alterations of the immunoglobuline classes and the presence of autoantibodies in liver diseases (author's transl)]. The AA., after the literature revision concerning the autoantibodies in the autoimmune diseases, have examined the cases of acute and chronic hepatitis happened in the period 1972-1976. After a short observation of used methodologies the AA. have connected the presence of autoantibodies (FN, SM, AM) with the rate of immunoglobulins in single groups of liver diseases, divided in acute hepatitis, chronic persistent hepatitis, chronic active hepatitis, liver cirrhosis (cryptogenetic and alcoholic). The results are that while the immunoglobulins fractions increase, although in different manner, in every pattern of liver disease studied, instead, there are no typical changes of single immunoglobulins rate in the groups with autoantibodies. Statistically it is not possible to assert that single antibodies belong to immunoglobulins determinate class. Finally it had been impossible to demonstrate sex and age influence on the immunoglobulins increase in the groups of liver disease with autoantibodies.


Ultrasonography of the brachiocephalic arteries. Sixteen patients with various lesions involving the brachiocephalic arteries were studied ultrasonographically. The examination was very useful in diagnosing aneurysms of the peripheral arteries and in differentiating an aneurysm from other causes of palpable pulsatile masses, such as a tortuous artery and tumor beneath an artery. The ultrasound technique used for evaluation of these lesions is described.


Changing radiologic technology education: evolution or revolution? I. Past and present. The radiologic technology profession, now over fifty years old, is still in a dynamic state. It has moved forward from commercially-sponsored, on-the-job training in the early years to the formal educational programs that are now the standard. The first part of a two-part article reviews the past and present educational accomplishments, defines some current educational methods, and provokes the reader to look at the profession in terms of what educational standards are needed for the future and determine how and when they should be achieved.


A method for administration of prolonged intravenous infusion of prostacyclin (PGI2) to unanesthetized rats. Prostacyclin is short acting and chemically unstable. To study sustained effects in an intact animal, prolonged intravenous infusion may be required. The compound has adequate stability for 24 hr in pH 10.0 carbonate buffer at 0 degrees. A "displacement syringe" is described wherein the prostacyclin solution is stored in a rubber bag inside the barrel of a 5 ml syringe. This device is placed in an ice bath. A syringe pump drives water into the barrel displacing an equal volume of solution out of the bag. Chronic venous cannules, saddles, and flow-through swivels are used as for drug self-administration studies. A simple, inexpensive rack for use with conventional individual hanging cages is also described.


The cardiovascular pharmacology of prostacyclin (PGI2) in the rat. Physiological roles have been suggested for prostacyclin in the cardiovascular system. Prostacyclin was administered by intravenous infusion to unanesthetized rats. Over a 24 hr period, 0.32 mg/kg/day caused only flushing of the ears. Larger doses (0.56 and 1 mg/kg/day) caused hypothermia, behavioral depression, and swelling of the paws. Cumulative dose-response curves for its depressor action were determined in both unanesthetized and anesthetized, vagotomized, ganglion-blocked rats. In unanesthetized rats, the threshold dose was about 0.1 ug/kg/min. Respiratory depression precluded doses larger than 1 ug/kg/min. In anesthetized rats, the threshold dose was about 0.001 ug/kg/min, and the maximally effective dose was about 0.1 micrograms/kg/min. At 0.032 ug/kg/min, blood pressure first fell and then rose slightly. This compensatory rise did not occur in nephrectomized rats, suggesting renin release as the mechanism. Intravenous infusion of 0.1 but not 0.01 ug/kg/min in unanesthetized rats doubled plasma renin activity. In saline-loaded unanesthetized rats, urine volume and urinary sodium excretion were decreased by 0.1 ug/kg/min of prostacyclin.


Effects of prostacyclin on the canine isolated basilar artery. Prostacyclin (PGI2) produced a biphasic response in canine isolated basilar arteries. In low doses (1 X 10(-8)M-1 X 10(-7)M) PGI2 caused a slight but consistent relaxation of resting muscle tone. In low concentrations (1 X 10(-8)M-1 X 10(-6)M) PGI2 antagonized muscle contractions caused by serotonin or prostaglandin (PG) F2 alpha. This relaxant effect with low doses of PGI2 on the isolated cerebral artery contrasts with findings obtained with other PGs and supports the hypothesis that PGI2 is a mediator of vasodilatation. However, in 1 X 10(-5)M concentrations PGI2 contracted the arterial muscle and did not antagonize contractions induced by serotonin or PGF2 alpha.


The prostaglandins system and insulin release. Studies with the isolated perfused rat pancreas. Using the isolated perfused rat pancreas PGE2 (1 MUM and 10 muM) had no effect on basal or glucose (10 and 20 mM)-induced insulin release (IR). PGF2 alpha stimulated basal IR at 1 muM and inhibited IR at 10 muM. The glucose-induced IR was unaffected by this PG. Furosemide (5 and 10 mM) led to a monophastic IR at low glucose (glu) and to a potentiation of IR at high glu. Only high indomethacin (Indo) (50 microgram/ml) inhibited glu-induced IR. The stimulatory effect of furosemide on IR could not be inhibited by indomethacin. However mepacrine (0.1 mM) abolished the furosemide effect. Also glu-induced IR was inhibited by mepacrine. Acetylsalicylic acid (30 mg/100 ml) had no significant influence on glu-induced IR. These findings provide evidence that phospholipase activation rather than increased PG synthesis might primarily be involved in the secretory process of insulin.


Prostaglandins and myogenic control of tension in lower esophageal sphincter in vitro. Active tension is produced by the lower esophageal sphincter (LES) of North American opossum in vitro by a myogenic mechanism. Strips of LES, but not those from the esophageal body, contracted to prostaglandin (PG)F2 alpha, stable expoxymethano derivatives of PGH2 and to thromboxane B2. Stable endoperoxides were more than 500 times more potent than PGF2 alpha. PGI2 and 6-keto PGF1 alpha were weak relaxants of LES strips. LES strips transformed arachidonic acid into contractile substances. This transformation was prevented by agents which interfere with PG synthesis by inhibiting cyclo-oxygenase [indomethacin (IDM), 5,8,11,14-eicosatetraynoic acid (ETA) or thromboxane synthetase [imidazole]. Tranylcypromine 500 microgram/ml also inhibited contractions to arachidonic acid. These agents also reduced muscle tone, so that endogenous PG formation may contribute to active tension in the LES. ETA and IDM increased tone before inhibiting it, and this effect was prevented by prior treatment with ETA or imidazole. There may also be an endogenous PG which inhibits LES tone. The possibility that this may be PGI2 is discussed.


Modification of a mathematical model for survival curves in photobiology. A modification of the Haynes' mathematical model (1966) can be suggested as a result of bacterial UV-survival experiments carried out. A new equation is proposed: lnS = Fi(x), + Fr(x), wherein x is the radiation dose, Fi(x) = -- kox describes how radiation damage is produced on the cell and Fr(x) = (krec + kc)x + Re(x) describes how repair systems act. ko is the relative inactivation efficiency of radiation on each cell. krec is the recombination recovery system efficiency. kc gives the additional repair increasing per cell when excision and recombination systems act simultaneously. Re(x) = a(1-e-bs) describes solely the excision repair process. The asymptote of non-exponential curves intercepts the survival fraction axis on the ordinate so (extrapolated point). In the modified model a=lnSo instead of a=So (Haynes' model).


Pilot study on adjuvant chemotherapy and hormonal therapy for irradiated inoperable breast cancer. A pilot study of adjuvant chemotherapy and hormonal therapy for inoperable breast cancer was performed. The patients were known to have a bad prognosis because of occult generalized disease. At the time of first treatment, the patients selected showed no signs of systemic disease. Local control of the breast and regional lymph nodes was achieved by radiotherapy. Adjuvant therapy consisted of alternating chemotherapy and tomoxifen. Adriamycin was dropped from the treatment schedule after 1 year because of enchanced radiation side-effects. Meanwhile the radiotherapy schedule was changed. A questionable control group was formed by patients radiated in the same period who failed to meet the entry criteria for various reasons. At presents, patients in the treated group show a better relapse-free survival than patients in the control group. The differences is statistically significant for premenopausal women. There is no significant difference in the overall survival between the treated group and the control group after an average follow-up of 2 years. After 2 years, the pilot study was closed. A randomized controlled clinical trial was started. In one group of this trial intensive chemotherapy is the first treatment employed.


[Improvement of the conditions of rat liver preservation by concomitant perfusion of the liver and kidney]. One of the factors limiting the duration of rat liver storage is the excessive accumulation of catabolites in the perfusion medium. In view of obtaining of an efficient depuration the authors have introduced a new circuit allowing for the concomittant perfusion of the liver and of the kidneys. The excretion effort of the kidneys is assessed by the estimation of urea nitrogen in the perfusion medium and in the urine collected over the entire duration of the experiment. The results have confirmed the good function of the system which provides possibilities for improved storage conditions of rat liver.


Randomized trial with Poly A-Poly U as adjuvant therapy complementing surgery in patients with breast cancer: in vitro study of cellular immunity. The immunologic reactivity of patients with initially operable breast cancer was measured by the leukocyte migration inhibition test using autologous tumor extract (T), autologous serum (S), and a combination of both (T + S). These patients formed part of a randomized clinical trial comparing, on the one hand, conventional treatment and, on the other, conventional treatment complemented by injections of poly A-poly U. A sequential study was carried out on 159 patients, testing them 7 days, 2 months, 4 months, and 1 year after the operation. Statistical comparisons revealed no significant difference in the reaction of the two groups. In addition, no significant differences were found between those with lymph node involvement and those without. Radiotherapy given to those with lymph node involvement did not significantly change their reactions. We were able to show that the percentage of patients with a positive leukocyte migration inhibition test (LMIT) increases regularly and significantly with time. This study confirmed the presence in some autologous serum of a synergistic factor (SS factor) which increased the inhibition of migration of leukocytes by autologous tumor extract. This factor was found in 18 patients, equally divided between both therapeutic groups. In the group with SS factor, the percentage with lymph node involvement appeared greater (83% compared with 68% among those patients who had no SS factor), and the incidence of metastases was also increased (44% compared with 21%). This factor seemed to indicate a bad prognosis. However, there was a difference in the results between the two therapeutic groups in patients with the synergistic factor. Of nine patients undergoing conventional treatment, six had devleoped metastases, whereas only two out of the nine patients who also poly A-poly U developed metastases. The same trend was observed in the whole trial population.


Levamisole: as adjuvant to cyclic chemotherapy in breast cancer. The addition of levamisole, administered in adjunctive manner between the cycles of conventional high dose chemotherapy in patients with hormone resistant end state breast cancer substantially improved the survival of treated patients. Analysis of this double-blind study in 60 such patients suggests that improvement in remission status and survival is related to better tolerability of such cytotoxic therapy as regards both specific and nonspecific cytotoxicity. This improved tolerability enabled patients to receive higher doses of cytotoxic drugs over a shorter time period resulting in an improved remission rate and ultimate survival.


Adjuvant therapy with levamisole in resectable lung cancer. In view of the discouraging results that have been obtained so far with the use of cytotoxic chemotherapy as an adjunct to surgery, a double-blind placebo-controlled evaluation of the adjuvant use of levamisole was conducted in 211 resectable lung cancer patients, following these patients for 2 years after their operation. Levamisole (or the placebo) was given for 3 days every 2 weeks and the dose level ranged 1.1--3.8 mg/kg per day (a fixed dose of 3 x 50 mg was given to all patients). It appeared that recurrences and carcinomatous deaths had occurred significantly less often in patients who had received a high dose (i.e., 2.1--3,8 mg/kg: patients weighing 70 kg or less) but not in the patients who received a lower dose. Patients who had more advanced cancers at the time of surgery seemed to have profited more from the treatment, but the results did not seem to depend upon the histologic type of the tumor or on the immune status of the patients as estimated from the skin test reactivity at the start. There was also suggestive evidence that levamisole may be more effective in preventing hematogenous dissemination than in inhibiting recurrences in the lung or the mediastinal tissues. Levamisole, if dosed adequately, appears to be a very suitable adjuvant treatment in resectable lung cancer patients as judged from its efficacy and its lack of troublesome side-effects.


Adjuvant trial of levamisole in patients with squamous cancer of the head and neck: a preliminary report. A preliminary report is made of a randomized double-blind study comparing levamisole with placebo as surgical adjuvant treatment of patients with squamous cancer of the head and neck. The study groups were comparable according to the prognostic factors of type (primary or recurrent), site (oral cavity, pharynx, larynx), and stage of disease and were also similar in pretreatment immune function and in radiation exposure. Of 65 evaluable patients, 31 were treated with levamisole and 34 received placebo. Although there was no difference in the distribution of the time to recurrence of the overall treatment group, there was a difference of borderline significance in favor of levamisole in the primary disease patients (P less than 0.006). Further analysis of subgroups in the primary disease category showed decreased recurrence rates in patients receiving levamisole who had cancer of the oral cavity P less than 0.01 or who had stage II disease, P less than 0.02. Considering site and stage simultaneously, the only significant difference was in stage II patients with oral cancer. The above results, though encouraging, must be viewed with caution due to small sample sizes and relatively short follow-up of most patients.


[Various considerations in the treatment of amebic liver abscess]. From 1974 to 1976 Acute Amoebic Hepatic Abscess treatment was viewed retrospectively with a random double blind prospective study administering metronidazol emetine, or a combination of both to three groups of 20 patients per group. The retrospective study of 1974 underlines the then predominant tendency toward a surgical management with a higher mortality (p less than 0.002). In 1976 medical treatment patients increased with a corresponding diminution of mortality (p less than 0.001). The prospective study showed no statistically significant response difference to the pharmacologic treatment variations. Here only 1.6% of patients underwent surgery and 1/3 of them received puncture drainage due to medical treatment failure. We conclude that non complicated acute amoebic liver abscess treatment should be medical, preferably with only one antiamoebic drug.


[Treatment of hepatorenal syndrome with dopamine and bromocriptine]. Two cirrhotic patients with hepatorenal syndrome were treated with Dopamine hydrochloride and Bromocriptine, a Dopamine agonist. Dopamine hydrochloride was given at a dosis of 0.30 to 0.90 mg/min. and Bromocriptine 15 mg/day. Although a transient raise of urinary output was observed in one patient, both patients died six to ten days later with an urinary output of less than 100 ml/day. Dopamine and Bromocriptine combined are of poor therapeutic value in hepatorenal syndrome.


[10 years after the death of Professor Mihai Ciucă (18 July 1883--20 Feb 1969). Mihai Ciucă and the study of bacteriophage, recorded in his working notebooks]. The work records of professor Mihai Ciucă (found in the archives of the Department of Microbiology) give us an insight into his scientific thoughts and practical activity. These documents speak of his dedication to the problem of the bacteriophage started in Jules Bordet's laboratory of the Pasteur Institute in Brussels, in 1920 and continued until 1969, the year in which he died. Since the discovery of the phenomenon of lysogeny, called the Bordet-Ciucă phenomenon, the professor initiated a wide range of research themes on the bacteriophage, guiding and promoting the work of a great number of specialists in the National Center, founded in 1949.


[Iron and infection. I. Iron and "nutritional immunity". The leukocytic endogenous mediator]. With reference to the studies carried out in the Center of Hematology, Bucharest, the authors review recent publications concerning the correlation between iron metabolism and infection, and emphasize the importance of iron deficiency within the framework of nutrition-infection-immunity relationship, and the role of iron in antinfectious defence. Among the metabolic responses of the host organism to infection is the early redistribution of essential oligoelements, known as "nutritional immunity", which is discussed in detail. Data refering to the leukocytic endogenous mediator are given.


[Passive hemagglutination test in the serodiagnosis of syphilis]. Passive haemagglutination test with pathogenic Treponema pallidum antigen in the serodiagnosis of syphilis, carried out on 752 sera (518 syphilitic patients and 234 subjects without evidence of syphilis) showed a greater general sensitivity as compared the cardiolipin tests and complement fixation test with Reiter protein antigen, and lower, to immunofluorescence (FTA--ABS). Its specificity is relatively lower than that of the cardiolopin and treponemal tests. Associated with the cardiolipin test it may be preferably used for the detection of syphilis, and moreover, passive haemagglutination may confirm the diagnosis in case of weak positive results with the FTA--ABS test. The latter is, however, essential for problem cases.


[Immunity aspects in syphilis].

[Immunity aspects in syphilis]. Until lately, the host-parasite relationship in syphilis registered a certain latency because of the difficult approach to the problem and especially because of the enthusiasm caused by the possible eradication of the disease by penicillin. As these expectations were not confirmed, attention was again focussed on study by modern means of the biology of pathogenic treponema, its antigenic properties, possibility of in vitro cultivation and certain humoral and cellular immune aspects that govern the evolution of the disease and, probable, the acquiring of specific immunity. The attempts made for obtaining a live vaccine, attenuated by irradiation and experimented in animals, appear to foreshadow the possible use of this vaccine in the near future in man.


[Studies of oral microbiogenesis. II. Significance of staphylocci present in periodontal lesions, pulp gangrene and in the alveolus after tooth extraction]. A study was carried out on the properties and significance of staphylococci isolated from the alveoli after dental extraction (12 strains), from parodontal pus (19 strains) and pulpar gangrene (15 strains). By their frequency, staphylococci of the Staphylococcus aureus have an etiologic significance in pulpar gangrene. Of particular importance for the diagnosis and epidemiology was the predominance of lysotype 80 among the staphylococci isolated from pulpar gangrene and lysotype 77 in healthy carriers. In 2 of 11 patients the coexistence of the same lysotype was found in the pulpar gangrene and nasal secretion.


[Embryogeny of facial, mastication, tongue, palate and neck muscles (author's transl)]. The mesenchymal origin muscular tissues entailing some difficulties in the knowledge of certain muscles embryogeny, two methods are therefore applied: the comparison of the ontogenesis data with those of comparative anatomy and the use as a guide of the functional motor unit with which the muscle combines. In resorting to these methods necessary precautions are precisely defined. The origins of the concerned muscles are, at first, situated among those of the whole musculature subjected to will, which are of two types "somitic" and "branchial". The realities lying under these two misleading terms are analysed. Then the usual data on each of the muscular groups embryogeny reviewed and compared, if necessary, with recent works. For the facial muscles a confusion results from the use of the term platysma both in comparative anatomy and in embryology, in pursuance of transposition, exact on that particular point, of the philogenic development of these muscles in ontogenesis. The development of these muscles comes in the scope of the extensive general character of the superficial hyoïd arch derivatives, and their topographic and functional particularities should be brought together with the disposition of the facial nerve nucleus and its arising fibres. Among the muscles in action in the mastication, a link appears between their precise role in this function and their embryogeny. For the neck muscles, the spinal nerve systematisation and the variations of the sterno-mastoïd muscle in mammals agree in assigning to this muscle an entire somitic origin lying exactly at the junction with the so-called branchial muscles. The somitic origin of the tongue muscles and the sharing between the somitic and branchial origins of those of the soft palate bring to light the place in the organism of these two anatomic structures. Then, the conjunction of muscles proceeding thus from two origins in these anatomic structures carries a particular signification in man by reason of the language.


[Dental problems before irradiation (author's transl)]. Before antitumoral facial irradiation, those teeth that cannot be conserved for a sufficiently long post-irradiation period of at least two years should be extracted. Teeth that are less affected, in patients given palliative treatment and in whom the prognosis is better, can be conserved. The conserved teeth are protected from destruction by the application of a fluoride gel. Dental reconstruction is ensured by the conventional methods, including the fixed prosthesis. The arches can be restored with atraumatic fixed prostheses but prudence is required. If extraction is necessary, a strict procedure must be employed and sufficient antibiotic treatment prescribed.


[Functional rehabilitation of irradiated maxillary bones (author's transl)]. The teeth should be conserved before radiotherapy: --in patients with good buccodental hygiene the teeth are conserved and fluoride treatment instituted,--when hygiene is only moderate, the mandibular teeth outside of the treated area are left in place and fluoride treatment is also attempted. The crowns are conserved, and an attempt is even made in some cases to apply them, as for example on the canines.--when hygiene is inexistant, all the teeth are extracted. Following radiotherapy, the authors will restore a prosthesis two months after irradiation in long-standing edentulons patients, and after 6 months for patients who have recently become edentulons. They sometimes recommend conservative treatment and a fixed prosthesis when the social context is favourable.


[Surgical treatment of orostoma after oral cavity irradiation (author's transl)]. Surgery treatment of orostoma raises the problem of when operation is indicated and more particularly at what period it should be performed. The imperatives defined have to be respected, and a distant flap, such as a deltopectoral flap, has to used immediately in order to hope for the best results, though the possibility of a recurrence has to be kept in mind.


[Twenty years follow-up of a case of extensive osteoradionecrosis (author's transl)]. A patient was found to have the first signs of a fibrous dysplasia of the left maxilla 50 years ago. At that time it was thought to be a maxillary sarcoma and was treated by irradiation on two occasions. The authors first saw the patient 20 years ago when he presented for treatment of an extensive degenerated osteoradionecrosis due to the previous irradiation therapy. Excision and reconstructive treatment caused many medical, psychological, and surgical problems. A part from the interest aroused by the numerous surgical repair procedures carried out, the essentially iatrogenic nature of the lesion and its effect on the life of this unfortunate patient convinced the authors of the need for publishing this rather sad history.


[Bone reconstruction after resection of the mandible for osteoradionecrosis (author's transl)]. Resection of the sections of the mandibular affected by osteoradionecrosis has completely modified the progression and prognosis of this affection by ensuring that the patient does not have to suffer long periods of pain and suppuration, constantly observed when medical treatment is used alone. Unfortunately, these resections are usually extensive and are themselves responsible for functional and esthetic sequelae supported with difficulty by some patients, especially in the case of bilateral or mandibular arch resections. All efforts must be made, therefore, to limit the consequences, and with this in mind it is possible: -- to perform an uninterrupted resection limited to the alveolar area involved, in early cases of mandibular osteoradionecrosis; -- to reconstitute mandibular continuity with a bone graft in more advanced stages; -- to improve the esthetic appearance with skin and subcutaneous grafts whenever this is necessary. Good results can only be obtained if certain anatomical conditions exist and if surgical precautions are adapted to each case.


Concanvalin-A-binding proteins on the surface of human malignant and normal lymphocytes. The concanavalin-A-binding cell surface glycoproteins from normal and certain leukaemic human lymphocytes were radiolabelled and then solubilized with detergent, isolated by affinity chromatography on Con A insolubilized on agarose beads, and subsequently analysed by SDS-polyacrylamide gel electrophoresis. Leukaemic T cells from patients with Sezary syndrome were found to express major concanavalin-A-binding glycoproteins on their outer surface similar to those of normal T lymphocytes. Leukaemic B cells from patients with chronic lymphocytic leukaemia expressed Con-A-binding proteins similar to those of B-cell lines. HLA antigens were predominant among the major Con-A-binding proteins on the surface of the normal and the malignant T cells studied. Human Ia-like antigens, HLA antigens, and the cell surface immunoglobulins IgD and IgM represented the major Con-A-binding proteins on the B cells studied. beta 2-microglobulin was found associated with HLA antigens on both leukaemic and non-leukaemic T and B cells. The presence of additional Con-A-binding proteins expressed on the surface of the different cell types studied is discussed along with some physical characteristics of the human Ia-like antigens isolated.


Characteristics of individual polymorphonuclear leucocyte motility obtained with a new opto-electronic method. An opto-electronic device has been used for a quantitative assessment of the motility of individual polymorphonuclear leucocytes (PMNL) adhering to a glass cover slip. One of the oculars in a phase contrast microscope is provided with a mini-array of 32 x 32 light-sensitive elements. These are connected to an electronic unit, capable of recording the number of light-intensity changes on each element and of visualizing the path of a cell on an oscilloscope screen, as a pattern of dots. The results clearly show that individual PMNL respond differently to environmental conditions; for instance, (i) raising the temperature increased the motility of cells to a maximum at around 39 degrees C and lowering the temperature from 42 degrees C restored their peak motility, (ii) protein was required at attachment depending on the temperature at attachment, (iii) endotoxin-activated normal human serum affected more drastically cells with a low initial motility and cytochalasin B more adversely influenced cells with a high initial motility, (iv) phagocytosis of yeast cells reduced the percentage of motile cells, which was more pronounced if the PMNL were washed before the motility measurement. The average motility of the PMNL was also diminished, although individual PMNL retained normal activity after ingestion of one or more yeast cells.


Lymphocyte subpopulations in man: relationship between four subpopulations identified by membrane markers. The interrelationship between four subpopulations of human lymphocytes was studied in eight normal persons. Double marking and fractionation experiments established that lymphocytes with receptors for AET-treated sheep erythrocytes constitute a population complementary to cells that carry surface membrane immunoglobulins as they are identified by polyvalent rabbit anti-human immunoglobulin; the latter includes nearly all cells with complement receptors. Two functionally different receptors for antigen-bound IgG are identified by their binding avidity for rabbit-antibody-sensitized ox erythrocytes, defining populations of lymphocytes with high-avidity and low-avidity receptors, indicating two valuable differentiation markers.


Lymphocyte subpopulations in man: characterization of human killer cells against allogeneic targets sensitized with HLA antibodies. Human killer cells mediating antibody-dependent cytotoxicity against allogeneic lymphoblasts presensitized with HLA antibodies have been studied by rosette fractionation experiments. Enriched and/or depleted cell suspensions have been tested in dose-response studies. Two different populations can act as killer cells. The major cytotoxic capacity is retained among T cells with high-avidity Fc receptors, whereas a minor cytotoxic capacity was found among non-T cells with high-avidity Fc receptors. These two populations have different dose-response curves, indicating different effector mechanisms.


Immunoelectron-microscopic localization of immunoglobulin A and secretory component in jejunal mucosa from children with coeliac disease. Using peroxidase-labelled antibodies, the ultrastructural localization of IgA and secretory component (SC) was investigated in duodeno-jejunal biopsies from six children with coeliac disease and compared with that observed in non-coelic mucosa. In normal intestinal mucosa this study confirmed the presence of IgA in the rough endoplasmic reticulum and the perinuclear space of numerous subepithelial plasma cells and one the lateral cell membranes of villous and especially crypt epithelial cells. SC was only detected in the epithelium and principally in crypt epithelium where it was identified in endoplasmic reticulum, Golgi saccules, perinuclear spaces and on lateral cell membranes. These findings support the suggestion that SC is synthesized mainly in crypt epithelium and acts as a receptor on epithelial cell membranes for dimeric IgA. In untreated coeliac patients, SC was observed at the same sites, but SC staining was reduced in damaged surface epithelial cells. The number of IgA immunocytes was increased and heavy deposits of IgA were found on basement membranes. In post-treatment biopsies, no abnormality was apparent. After re-exposure to gluten, depositions of IgA on basement membranes were the only early change. The unaltered distribution of SC and IgA in crypt epithelium strongly suggests that the epithelial transport mechanism of secretory IgA is normal in coeliac disease.


Peanut agglutinin. IV. A tool for studying human mononuclear cell differentiation. Peanut agglutinin (PNA) has previously been shown to be a 'marker' for early T subpopulations in mice. We have investigated whether it could also be used in the study of human mononuclear cells. 50--60% of human thymocytes have binding sites for PNA. When separated on a discontinuous Ficoll gradient, the PNA-positive thymocytes are found preferentially in the layers corresponding to the immunoincompetent cells. In the peripheral blood only 5% of the mononuclear cells are PNA-positive and we have shown that these cells are monocytes. In tonsils 13% of PNA+ cells are found and they are mostly lymphocytes. Thus, PNA is a marker for some T cell subsets present in the thymus and tonsils.


IgM-rheumatoid factors cross-reactive with IgG and a cell nuclear antigen: apparent 'masking' in original serum. Fourteen out of fifteen IgM-rheumatoid factor (IgM-RF) preparations isolated from high-titred seropositive rheumatoid sera by affinity chromatography on immobilized human IgG have been shown to cross-react with a cell nuclear antigen, as manifest by positive immunofluorescent anti-nuclear antibody (ANA) staining on rat liver and kidney tissue sections. The cross-reacting ANA activity within isolated IgM-RF preparations was inhibitable by both human and rabbit IgG, as well as by isolated rat liver chromatin, and could be isolated from seropositive ANA-negative sera. It would appear that this cross-reacting ANA activity can be masked in the original seropositive serum and may often require purification of RF from serum for its manifestation.


Correlation between serum immunoglobulin concentrations and smooth-muscle antibodies in acute viral hepatitis. Smooth-muscle antibodies (SMA) were investigated by the indirect immunofluorescence method and serum immunoglobulin (Ig) concentrations measured by radial immunodiffusion in 15 patients with hepatitis B antigen (HBAg)-positive and 20 patients with HBAg-negative acute hepatitis. In both types of hepatitis the serum IgM and IgG concentrations were significantly higher than in 55 controls, while the IgA levels were the same in patients and controls. IgM-SMA in titres of 10--80 occurred in 11 (55%) patients with HBAg-negative acute hepatitis, and this was significantly higher than in controls (P = 10(-8), whereas IgM-SMA were found in only 2 (13%) patients with HBAg-positive acute hepatitis. IgG-SMA occurred in 3 (15%) HBAg-negative and in 4 (27%) HBAg-positive patients. In HBAg-negative hepatitis the serum IgM concentrations were significantly higher in IgM-SMA-positive (mean: 439 mg/dl) than in IgM-SMA-negative (mean: 216 mg/dl) cases (P = 0.028). It was not possible to demonstrate a similar rleationship in HBAg-positive acute hepatitis. No correlation between the occurrence of IgG-SMA and the IgG levels could be demonstrated in acute hepatitis. It is assumed that IgM-SMA may account for a minor part of the elevated IgM levels in HBAg-negative acute hepatitis, but the reason for formation of SMA in acute viral hepatitis is not known.


An outbreak of skin infections caused by group A beta-hemolytic streptococci probably originating from wild moose. An outbreak of about 20 recorded cases of impetiginous skin infections occurred during the moose (Alces alces) hunting season in October and November 1976 in persons having been in contact with moose from Hailuoto Island, Northern Finland. Samples for bacteriological studies werre obtained from 4 patients, and beta-hemolytic streptococci group A were isolated from all. The strains were biochemically identical. Epidemiological data strongly support a moose origin of the streptococci, even though none were isolated from the animals.


Anaerobic infection of the liver and biliary tract in experimental common duct occlusion. The pathogenicity of single anaerobic, single aerobic, and mixed anaerobic and aerobic bacterial inocula was studied in 3 groups of 12 rabbits with biliary tract obstruction. B. fragilis, ss. fragilis and E. coli serotype 01:K1:H7 were used. The investigation was made 7 days after bacterial inoculation and included bacteriological studies of the liver and bile as well as studies of liver function and morphology of the liver and biliary tract. Inoculation of 10(5)--10(6) E. coli did not cause biliary tract infection, liver abscesses or death. Inoculation of 10(9) B. fragilis caused biliary tract infection in 83 per cent and liver abscesses in 17 per cent of the animals inoculated, without any mortality. Combined inoculation with B. fragilis and E. coli in reduced doses significantly increased mortality (42 per cent) and frequency of liver abscesses in surviving animals (86 per cent). All abscesses, however, yielded pure culture of B. fragilis only. 84 per cent of the animals inoculated with B. fragilis alone or with B. fragilis in combination with E. coli developed biliary tract infection with B. fragilis, the bile yielding from 10(7)--)0(9) B. fragilis per ml, gall bladder bile yielding significantly higher bacterial counts than common duct bile. E. coli was never recovered from bile in surviving animals but from both bile and blood in animals not surviving the experimental period.


Are anaerobic pleuropulmonary infections uncommon or commonly undetected in Britain? Despite marked and increasing awareness of the clinical significance of pathogenic anaerobes, the role of anaerobes in pleuropulmonary infections is still largely unrecognised in Britain. A considerable literature testifies that this is not so in America. The reasons for this paradox are explored. British anaerobic methodology is briefly reviewed, with special reference to the range of recognised respiratory pathogens and the anaerobes that can be cultured in simple anaerobic jars. The limitations of sampling and transport procedures are considered. Differences in approach are discussed. The technological problems of the isolation and culture of "difficult" pathogenic anaerobes have been largely solved at the laboratory level; effective approaches to sampling and transit of specimens require more positive consideration and the results might influence our choice of specific antimicrobial therapy. If these points are taken and an increased awareness of the role of the anaerobes in certain pathological conditions of the lower respiratory tract is generated, we might hope either to produce a meaningful parallel to the experience of our American colleagues--or to structure a more valid defence to explain our lack of experience of these infections in the lower respiratory tract.


Anaerobic infections of the female genital tract. The anaerobic flora of the cervix undergoes cyclic change during menstruation and pregnancy. The etiopathogenesis of anaerobic infections of the female genital tract is described. The in vitro susceptibility of the cervical microflora to various antibiotics presented and treatment of anaerobic infections of the female genital tract briefly is discussed.


Acute appendicitis and Bacteroides fragilis. Bacteria belonging to the Bacteroides fragilis group (B. fragilis, B. ovatus, B. vulgatus, B. distasonis, B. thetaiotaomicron and B. uniformis) were cultured in quantities of less than or equal to 10(5) c.f.u./ml from the excised appendix from 30 patients. Twenty-two patients (group I) had an acute purulent appendicitis (three with perforation), four were classified as slightly inflamed cases (group 2) and four had a normal appendix (group 3). The B. fragilis group of bacteria dominated among the anaerobic isolates, but Bifidobacteria, Fusobacteri, Clostridium perfringens, Lactobacilli, Leptotrichia and Veillonella, in decreasing order, were isolated as well. Among isolates of aerobic bacteria, E. coli was most frequently isolated (26/30 patients). No other genus was isolated from more than four of the appendices. Serological investigations of the humoral antibody response to polysaccharide antigens from four of the Bacteroides species showed that a doubling of the titer, or more, in paired serum samples could be observed as follows: against B. fragilis 6/22 patients (group 1), 3/8 patients (groups 2 and 3). The corresponding figures for B. ovatus were 11/22 and 2/8, B. vulgatus 3/22 and 0/8 and B. distasonis 4/22 and 0/8. Sera from two patients with ruptured appendix, and B. fragilis cultivated, showed the highest titer increases against the B. fragilis antigen. The data from the bacteriological and immunological investigations make us conclude that (i) the B. fragilis group of bacteria is the most common anaerobic group of bacteria isolated from normal and diseased appendices, (ii) the mere isolation of B. fragilis, encapsulated or not, does not imply an etiological role in appendicitis since there was no obvious difference in titer increases against B. fragilis in sera from patients with or without an inflamed appendix, and (iii) high, and significant, titer increases against B. fragilis are seen in sera from patients with ruptured appendix.


Is beta-receptor blockade of value in continence training of children? The relaxation of the outlet region of the bladder is subserved by beta-adrenergic receptors. It is conceivable, therefore, that inhibition of beta-adrenergic function should be of value as part of a continence training program in patients with neurogenic bladders. This hypothesis was tested in a series of thirteen children with spinal lesions. A double-blind, cross-over study of alprenolol versus placebo was performed during conventional continence training. The number of "dry periods", however did not differ during the alprenolol and placebo periods. One reason for the lack of clinical effect may be that the drug simultaneously blocked the beta receptors in the corpusfundus of the bladder, thereby decreasing the volume capacity.


[Intact function of a transplanted kidney 3 years after organ transplantation with primary oxalosis]. The case is presented of a 42-year-old patient with type I primary hyperoxaluria. Following failure of a first kidney allotransplant due to recurrence of oxalosis after an episode of anuria, a second graft is functioning perfectly 3 years after transplant. The literature is reviewed and possible supportive therapies are discussed.


[Centuries-old community involvement of South African physicians]. Involvement in community affairs is an honoured tradition among South African medical practitioners. The so-called old doctor belonged to an era when dedication to the arts, botany, zoology and nature in general was often combined with the practice of medicine. They were colourful individuals and their names are worth remembering in this eventful year.


[The development of occupational health in South Africa]. Industrial development in South Africa started after the discovery of diamonds and gold towards the end of the last century. Two world wars gave impetus to an industrial revolution which is still continuing. Experience with good occupational health services on the mines was not fully applied to industries, and the Erasmus Commission of Inquiry (1975) found many shortcomings. It is hoped that 1979, the Health Year, will bring a new deal for good health in our industries.


Health legislation--a historical review. The historical developments which led to the eventual promulgation of the Health Act of 1977 are enumerated. Mention is made of the parts played by the secretaries for health and the various commissions and committees in the evolutionary progress of the Act. The future pattern of responsibility for health services by three levels of government are suggested.


Antibiotic-resistant Serratia marcescens infection in a hospital. Over a 12-month period, 74 isolates of Serratia marcescens were obtained from various sources at Tygerberg Hospital. The majority of these isolates were from catheterized patients with urinary tract infections, and were non-pigmented and resistant to all antibiotics tested, excepting amikacin and neomycin. All isolates transferred resistance to tobramycin, gentamicin and tetracycline by conjugation to Escherichia coli recipients as separate markers at low frequency. A non-self-transmissible plasmid conferring resistance to kanamycin, ampicillin and gentamicin was mobilized from Serratia species to E. coli, and became fully self-transmissible in subsequent matings.


Anton Chekhov (1860-1904). Writer, physician and tuberculosis patient. Chekhov chose writing as a career after a childhood of hardship and poverty. Tuberculosis manifested soon after medical graduation and caused his death at the age of 44. Essentially a short story writer, he used simplicity and impressionism to portray sympathetically the psychology of the common man. Similarly his plays, popular today, written in a light and ethereal style, while static, have an inner psychological evolution. The best example is The Cherry Orchard.


Constant positive airway pressure. A review. Constant positive airway pressure (CPAP) represents a major advance in the treatment of hypoxaemia. By increasing the functional residual capacity (FRC), airway closure and airway resistance are minimized. Ventilation and perfusion are more evenly matched so that gas exchange is made more efficient. In addition, the lung remains on a favourable portion of the compliance curve so that the work of breathing is reduced. The increased oxygenation is achieved at the lowest possible inspired oxygen concentration (FiO2) to minimize oxygen toxocity. A unified approach to the terms used, as well as their abbreviations, is presented.


Factors affecting coping of adolescents and infants on a reverse isolation unit. This paper describes factors that affect the coping processes of adolescents with aplastic anemia and infants with severe combined immuno-deficiency disease treated on a reverse isolation unit. The adolescents demonstrated a rich diversity of coping styles depending on the interaction of a variety of factors. Special stresses to other family members, such as the reactions of the child donor, are also highlighted. For the infants, the dyadic relationship with the mothering figure, the feelings of the family about the fact of genetic transmission, and the impact of isolation on the infant's development are identified as important psychosocial variables in the infant's adjustment. A multidimensional perspective such as that provided within a systems framework, which encourages an appreciation of the interactive diversity of all factors, is presented as the most useful approach to interventions.


Split thickness skin grafting of the plantar surface of the foot after wide excision of neoplasms of the skin. Results of our studies show split thickness skin grafts are an effective cover for plantar surface defects resulting from tumor excision. Long term follow-up studies of these patients revealed no graft failures. The ease with which split thickness skin grafts can be performed makes it the treatment of choice for reconstruction of areas of excison of neoplasms of the skin on the plantar surface of the foot.


A simple geometric flap for the closure of skin defects. The Limberg flap is a useful method of closing defects anywhere on the body which are too large for simple closure but where skin grafting is not desirable. It is an easy flap to perform, and it is reliable and safe to use. It must not, however, be used indiscriminately or by rote. Care must be taken in planning both the excision and the flap so that the points which must move farthest are placed where the skin is maximally extensible. With such planning, accurate and precise designing and careful surgical technique, the Limberg flap can be used successfully to solve a number of otherwise extremely difficult problems.


Physiological and metabolic correlations in human sepsis. Invited commentary. The septic response in man appears to be a disease in which the infecting agent induces a state of disordered metabolic control in the host. The abnormal regulation of metabolic pathways causes a diversion of substrate utilization toward gluconeogenesis and ketone body formation and a reduction in oxidative energy-producing metabolism. This state of metabolic insufficiency is reflected in the pattern of cardiorespiratory, vascular, and physiological compensation. The precise magnitude of the resultant physiological compensation and its rate and direction of change can be quantified by the use of physiological state trajectories which also reflect the magnitude of underlying metabolic derrangements. The prognostic and therapeutic implications of these changes are discussed.


Selective lymphoid irradiation. I. An approach to transplantation. The kinetics, distribution, and radiobiologic effects of palladium (Pd)-109-hematoporphyrin were determined in the rat. In addition, we studied the effect on rat heart allograft survival of Pd-109-hematoporphyrin, with and without antilymphocyte serum (ALS). A single sublethal dose of Pd-109-hematoporphyrin (up to 36 muCi/kg) resulted in the following: predominant concentration in lymphoid tissue and proximal bone marrow, complete central and proximal bone marrow ablation with preservation of distal bone marrow, massive depletion of lymphocytes from lymph nodes and spleen, an 80% reduction in peripheral blood lymphocytes which was completed by the addition of ALS, full recovery of lymphoid tissue and blood cellularity within 60 days of administration of radionuclide, and a 100% animal survival rate. This method of selective lymphoid irradiation (SLI) prolongs indefinitely Fisher cardiac allografts in Lewis recipients and significantly prolongs cardiac allograft survival across major histocompatibility barries (ACI to Lewis or to Fisher). Specific tolerance to donor strains was demonstrated by the acceptance of Fisher skin by Lewis recipients carrying 150-day-old Fisher hearts. Third party (ACI) skin allografts were rapidly rejected by the same animals. Further studies of SLI in larger animals are required to determine the optimal safe dose of SLI in man.


The blood-ocular barriers.

The blood-ocular barriers. The introduction of the concept of blood-ocular barriers in the ophthalmic literature is briefly reviewed. Two main blood-ocular barriers are proposed: the blood-aqueous barrier and the blood-retinal barrier. The blood-aqueous barrier is formed by an epithelial barrier located in the nonpigmented layer of the ciliary epithelium and in the posterior iridial epithelium, and by the endothelium of the iridial vessels. Both these layers have tight junctions of the "leaky" type. The pereability of the blood-aqueous barrier shows a significant degree of pressure-dependent diffusion associated with transport activity, resembling the standing gradient osmotic flow model. The blood-retinal barrier is located at two levels, forming an outer barrier in the retinal pigment epithelium and an inner barrier in the endothelial membrane of the retinal vessels. Both these membranes have tight junctions of the "nonleaky" type. The permeability of the blood-retinal barrier resembles cellular permeability in general, diffusion being directly related to the predominant roles of lipid solubility and transport mechanisms. Finally, the clinical significance of the blood-ocular barrier is analyzed. The metabolism of cornea and lens and the regulation of intraocular fluids are directly influenced by the blood-aqueous barrier. Similarly, an alteration of the blood-retinal barrier appears to play an important role in the development of vascular retinopathies, pigment epitheliopathies, and retinal edema.


The founding and early years of the Massachusetts Eye and Ear Infirmary. The Massachusetts Eye and Ear Infirmary, one of America's first such institutions, was founded on October 1, 1824, and incorporated on February 23, 1827, by Edward Reynolds, John Jeffries, and a group of charity-minded Bostonians. The Boston men looked, as did the founders of other early U.S. eye infirmaries, to John Cunningham Saunders' London Eye Infirmary for guidance. During its first years the Massachusetts Eye and Ear Infirmary knew economic insecurity, but once it earned in the Boston community the reputation of being a worthy charity, its fiscal affairs ceased to be a pressing problem, and it went on to know a growth worthy of the motives of its founders.


The effects of glucagon on protein metabolism in normal man. Plasma glucagon rises after major injury and could act to increase gluconeogenesis and ureagenesis in the post-traumatic state. This study documents the effect of prolonged glucagon infusion on ureagenesis and nitrogen excretion, as well as possible sources of the increased ureagenesis, in normal man. Four healthy men fasted for 6 days during intravenous infusion of glucose (750 gmday), establishing a steady state of minimal ureagenesis. Glucagon (1 mg/day) then was added to the infusion for 5 days. Glucose alone was given for the final 2 days. Forearm muscle flux of metabolites was determined by standard arterial-deep venous sampling and capacitance plethysmography. Glucagon concentration was suppressed during glucose infusion (11 +/- 13 pg/ml) and rose to levels seen in subjects with major trauma during glucagon infusion (669 +/- 138 pg/ml). Glucose infusion stabilized urine nitrogen excretion at 1.54 +/- 0.42 gm of N/sq m/day. Nitrogen excretion increased to 2.40 +/- 0.53 gm of N/sq m/day with glucagon infusion, with urea accounting for the increased excretion. Excretion of 3-methylhistidine was unchanged. Plasma amino acid concentration was strikingly reduced on the first day of glucagon infusion, where it stabilized. Forearm flux showed a slight net release of amino acid nitrogen during glucose infusion. Addition of glucagon to the glucose infusion resulted in a net uptake of nitrogen by forearm skeletal muscle. These evidences strong suggest that glucagon infusion in normal man increases ureagenesis, not only at the expense of the free amino acid pool, but by the hydrolysis of visceral protein as well, with muscle protein being maintained.


Improved renal allograft survival with selected HLA antigen matching. We examined the influence of the three most frequent linkage disequilibrium antigen combinations, HLA 1-8, 2-12, and 3-7, on renal allograft survival. We reviewed the results of 214 first transplants to recipients sharing exactly two HLA-A or -B antigens with the donor, excluding failures caused by hyperacute rejection or technical factors. Actuarial graft survival for matches having HLA 1-8, 2-12 or 3-7 was compared with all other two-antigen matches within the group. Improved graft survival, occurred with HLA 1-8 matches (85% and 80% at 2 and 5 years, respectively) and with HLA 2-12 matches (80% at both 2 and 5 years), compared to all other two-antigen matches (71% and 58% at 2 and 5 years, respectively). Allografts matched for HLA 3-7 had poorer graft survival (44% at both 2 and 5 years). We compared nondiabetic and diabetic recipients and found similar improved graft survival with HLA 1-8 or 2-12 matches in nondiabetic recipients. There was no difference, however, in graft survival in diabetic recipients with HLA 1-8 or 2-12 matches, as compared to other two-antigen matches. We conclude that HLA antigen matches of 1-8 or 2-12 between donor and recipient have demonstrated improved graft survival in nondiabetic recipients, while HLA 3-7 matches have poorer survival, as compared to other two-antigen matches. Thus, unlike single antigen serotyping, selected HLA antigen matching appears to afford superior graft survival.


A double blind single dose comparison between two analgesics, rimazolium and acetylsalicylic acid in oral surgery outpatients. The relief of pain after extraction of a mandibular third molar by two analgesics, rimazolium and acetylsalicylic acid (ASA) was studied in three groups of patients, who received either of these analgesics or a placebo. A questionnaire and careful instructions on its use were given to the patients. ASA had a better effect than both rimazolium and placebo. The results are discussed with regard to differences between analgesics with or without anti-inflammatory properties.


Environmental cancer: on the causes of the main human cancers. A brief review is given of the causes of the main human cancers. We distinguish occupationally-incurred cancer, which arises in individuals exposed at work to varied carcinogenic chemicals and which yielded cancer at a site depending on the nautre of the carcinogen. In the context of the total incidence of cancer in the United States, occupational cancer assumes a minor quantitative role. Nonetheless, provided proper plant design and hygienic measures are developed, these cancers are totally preventable. Most of the remaining human cancers in the United States such as cancer of the respiratory tract, the digestive tract including stomach and large bowel, and in the endocrine-sensitive organs like breast, prostate, ovary, and endometrium are related to our lifestyle, namely smoking of cigarettes, and diet. The mechanism whereby lifestyle translates to certain of these diseases is presented, and recommendations for prevention are made. Considering the increasing cost of health care, it is noted that prevention is not only ethically best, but economically sound.


Thrombosis: a study of coagulation parameters and mechanisms during allograft rejection. Thrombosis of the microvasculature has been recognized at the end product of organ rejection, but the exact biological pathway through which this occurs has not been clarified. Normal, factor VII deficient and heterozygous hemophilic (factor VIII) dogs were grouped to study the intrinsic and extrinsic clotting and platelet mechanisms during unmodified renal allograft rejection. The observed alterations of the hemostatic mechanisms are related to the changes observed in the microvasculature. Six groups of donor-recipient animals were studied: Group I -autografts (control); Group II - normal to normal allografts with bilateral nephrectomy; Group III - heterozygotes for factor VIII deficiency; Group IV - normal to normal allografts with unilateral nephrectomy; Group V - normal to factor VII deficiency without nephrectomy; and Group VI - normal to normal allografts with unilateral nephrectomy and dipyridamole. Each engrafted animal was followed pre- and posttransplantation for change in the blood clotting factors, fibrin split products, platelets, white blood cells, renal function and microvasculature. The animals with factor VII deficiency rejected in a similar fashion as the control animals. The group with impaired factor VIII synthesis and platelet function had longer survival times. These data suggest that the intrinsic clotting pathway and platelets are the primary mechanism through which thrombosis occurs secondary to immune injury.


[The blood supply of the single tooth and its functional change caused by prosthetic therapy]. The author presents two functional diagnostic procedures for determining the blood supply to the individual tooth. Due to its methodical and instrumental prerequisites, it is not likely that intravital angiography will be developed into a procedure suited for stomatological practice. On the contrary, the nuclear-medical method for determining the microcirculation will become practice-relevant after technical improvement.


[Possibilities and limits in the early diagnosis of peridontal insufficiency]. Up to now, the early detection and the discriminating evaluation of periodontal insufficiency are not feasible due to the variety of conditions provoking a pathological response of the tissues. In general, the defence may be regarded as sufficient. Exceptions to this rule are periodontal changes existent already in adolescence and therapy-resistant gingivitides in which endogenous causal factors obviously predominate. A disproportion of tooth mobility to bone reduction and a tendency to abscess-formation, tooth migrations and recurrences after periodontal therapy are indicative of insufficiency. The development of a progressive course is to be compared with the breakdown of the barrier of defence. The reduction or elimination of provoking and conditioning factors prior to prosthetic therapy is considered to be the way to maintain the "stability" of the periodontal tissues.


[Demonstration of gingival and mucosal findings]. As the conventional diagnostic methods are largely dependent upon the subjective power of judgment, despite the good recognizability of the mucosa which lines the oral cavity, the present day possibilities of extended diagnostics are discussed and commented upon. Neither the ultrasonic diagnostic methods for determining the thickness of the mucosa, nor the cytologic and histologic methods may be considered practice-relevant. But it is of interest that the specialized, lining and masticatory mucosae show specific reactions. The masticatory mucosa which comprises also the rests of the gingiva propria, is as well individually determined, which explains the different responses to mechanical, chemical and bacterial-toxic stimuli. A choice of clinical examples serves to demonstrate that such empirical values may be useful in clinical diagnostics and, thus, that they are of great importance in preparation of prosthetic-therapeutic measures.


[Temporomandibular joint an insufficient dentition]. The disease of the orofacial organ is predominantly a dysfunction, the parts of the organ affecting one another reciprocally. All changes in the dentition disturb the balance and may produce occlusal disorders. For this reason, it is recommendable to initiate the prosthetic treatment of the incomplete dentition as early and properly as possible. Temporary biteguard splints (fig. 3) have proved a success.


[The use of composites (with referenceto their technological and clinical properties)]. In the present paper the authors report of the pulp tolerance, marginal adaptation, abrasive behaviour and discolouration of composites. Starting from these properties, they deal with indications, cavity preparation, pulp protection, enamel etching, processing and finishing. Finally, the composites are evaluated with reference to recent findings.


[The cleansing phase of periodontal therapy]. Having substantiated the need for treatment and having explained the treatment plan, the author describes the contents of the hygienizing phase of periodontal therapy. Now as before, great importance is attached to tooth-cleaning. The Charter technique is recommended for the periodontally diseased dentition. Mineralized deposits on teeth may be removed by means of hand instruments or ultrasonics. Various modifications of balneotherapy are indicated for all diseases of the tooth-supporting structures. The mechanotherapy supports the stomatological efforts towards oral health rehabilitation and prevents recurrences.


Quantitative studies on the tissue distribution of Ia and SD antigens in the DA and Lewis rat strains. The tissue distribution of major histocompatibility complex (MHC) antigens in the DA and Lewis (LEW) strains was studied using LEW anti-DA and DA anti-LEW alloantisera. Quantitative absorption analyses were used with quantitative binding assays for SD and Ia antigens. Initial screening showed that the LEW anti-DA serum contained significant amounts of antibodies against both Ia and SD antigens. On the other hand, the DA anti-LEW serum seemed to be directed almost entirely against Ia antigens, and it was not possible to set up assays for SD antigens in the LEW strain. The most surprising finding was the presence of large amounts of Ia antigen on the kidneys of both the DA and LEW strains, one kidney containing as much Ia antigen as half a spleen. Kidney also contained large amounts of SD antigen. Liver had large amounts of SD, but very little Ia. Heart had only small amounts of both SD and Ia. The relevance of these findings to transplantation of the kidney, liver, and heart are discussed. The other tissues studied were brain, spleen, lymph node, thoracic duct lymphocytes, bone marrow, thymus, RBC, and platelets. The most interesting findings were the presence of relatively large amounts of SD antigens on DA RBC, and small amounts of Ia on the thymus and bone marrow.


The lymphatic drainage of the rat prostate and its status as an immunologically privileged site. Recent suggestions that the rat prostate is an alymphatic, immunologically privileged site stimulated further investigation of its status using a variety of techniques. Fixation of certain organs by vascular perfusion of glutaraldehyde followed by plastic embedding avoids the distortion and stromal reorganization that often obscures evidence of lymphatic vessels in conventional histological preparations. When applied to the rat prostate, this technique revealed small lymphatic vessels at irregular intervals throughout the sparse stroma. Ink injected into the prostate drained from the organ into iliac lymph nodes within 3 to 4 hr. Enlargement of iliac lymph nodes within 1 week after injection of parental strain lymphoid cells into the prostate of F1 rats confirmed the drainage pattern. Ink and lymphoid cell injections into the bladder wall yielded comparable results, although ink reached iliac nodes sooner than it did in prostate injections. Immunological privilege was investigated by determining survival of skin allografts implanted in the prostate. Skin-into-prostate grafts bearing either major or minor histocompatibility antigens were rejected within a few days of similar orthotopic grafts. The inability of the rat prostate to allow significantly prolonged allograft survival as well as its demonstrated lymphatic drainage argues against an immunologically privileged status.


Influence of matching for HLA-DR antigens on skin graft survival. HLA-DR typing results of 47 skin transplant donor-recipient pairs were analysed. HLA-A, B, and C typing and mixed lymphocyte culture (MLC) testing was also included in this study. Skin transplants exchanged between HLA-A-, B-, and DR-identical, MLC-negative donor-recipient pairs had the longest graft survival (mean survival time, 17 days), whereas skin grafts exchanged between completely nonidentical donor-recipient combinations had the shortest survival (mean survival time, 10 days). Because of the correlation between identity for the DR antigens and the low or nonreactivity in the MLC test, identity for DR will predict a better skin graft survival than nonidentity. It was concluded that the best match between donor and recipient of a graft, using only serological techniques, is one where there is identity for HLA-A, B, and DR.


In vivo activity of an H-2 alloantiserum purified by affinity chromatography on transplantation antigens. Transplantation antigens were isolated from murine tissue by solubilization with NP-40 and purification on a lentil lectin-Sepharose column. The glycoproteins eluted from the lectin column were coupled to CNBr-activated Sepharose to prepare a specific immunoadsorbent. Intact histocompatibility antigens were demonstrated on the carrier particles in a cytotoxic inhibition assay with specific antiserum and spleen lymphocytes. Adsorption and subsequent elution of alloantiserum directed against the coupled antigens yielded a 30-fold purified product. The presence of both active K and I region products on the column was demonstrated by the in vivo activities of the alloantibodies eluted from the coupled molecules. Both acute rejection, a function of H-2K antibodies, and passive enhancement, a function of Ia antibodies, could be induced by administration of the eluate to recipients of skin allografts. These in vivo results show that the adsorbent can be used for preparative purposes.


Effect of splenectomy alone and in combination with antilymphocyte serum on renal allograft rejection in the rat. The effect of splenectomy alone and in combination with suboptimal doses of antilymphocyte serum (ALS) have been studied in the relatively weak (DA X Lewis)F1 to DA and the strong DA to Lewis renal allograft models. In the F1 to DA model, splenectomy alone produced a slight but significant prolongation of graft survival and in combination with a suboptimal dose of ALS gave excellent suppression of rejection. In the strong DA to Lewis model, splenectomy alone had no effect on graft survival and there were no additive effects with suboptimal doses of ALS. However, splenectomy alone produced a striking suppression of the lymphocytotoxic response to the kidney grafts in this combination. To elucidate the mechansim whereby splenectomy weakens the immune response, (DA X Lewis)F1 to DNA renal allografts were performed with the renal vein anastomosed to the recipient's portal vein. This procedure had no effect on graft survival.


Rat mutant (NZNU) showing "nude" characteristics. A new rat mutant (nznu) is described which shows characteristics similar to those of the nude mouse. The mutant is an autosomal recessive. Homozygotes are essentially hairless (except for stunted vibriassae) and show deficient thymus gland development. Under conventional breeding conditions the mutants are difficult to raise and few survive weaning. The absence of functional thymus-derived lymphocytes in the nude rat is implied by (1) acceptance of histoincompatible skin grafts, (2) lack of response to the T cell mitogens phytohaemagglutinin and concanvalin A, and (3) absence of cells sensitive to alloantiserum directed against rat thymus-derived lymphocytes. Although total blood leukocytes from the nude rat were within the normal range, differential counting of leukocytes showed a 4-fold elevation of neutrophils and a 2.5-fold reduction of lymphocytes, compared with normal rats. Phenotypically normal heterozygotes gave values intermediate between nude and normal rats.


Orthotopic bone transplantation in mice. I. Technique and assessment of healing. A technique for orthotopic bone transplantation in mice has been developed. A section of recipient tibia was removed and replaced by a similar section from the donor animal. The graft was held in place by internal fixation. Bone healing was assessed clinically, histologically, radiologically, and by torsion testing. The most objective measurements of bone healing were the maximum torque and the energy absorbed by the bone to failure, which were derived from torsion testing. The degree of bone healing in donor-recipient combinations differing at H-2, non-H-2, or H-Y antigens was compared to the degree of healing in syngeneic controls. The incidence of nonunion was significantly increased in the H-2-disparate group. Furthermore, the extent of bone healing as measured by torsion testing was significantly reduced in both the H-2-and the H-Y-disparate groups. Thus, in the strain combinations tested, the order of importance of the genetic disparities influencing allogeneic bone grafts was H-2 greater than H-Y greater than non-H-2. The impaired healing of allogeneic bone grafts was probably immunologically mediated, as suggested by the observation that recipients of bone allografts rejected subsequent skin allografts in an accelerated manner.


Orthotopic bone transplantation in mice. II. Studies of the alloantibody response. The alloantibody response of mice receiving cortical bone allografts was investigated. Such grafts were highly immunogenic, resulting in antibody responses at least as strong as those to skin allografts in the same combinations. The duration of the response to a single bone allograft was very prolonged (greater than 10 months). The antibody response was shown to be directed against H-2K, H-2D, Ia, and at least two non-H-2 antigens. Although the great majority of the parenchymal cells of the graft were dead, the immunogenicity of the graft required living cells, since bone that had previously been frozen and thawed was nonimmunogenic. By retransplanting bone allografts to a second recipient it was possible to demonstrate that the grafts remained immunogenic for at least 4 weeks after transplantation, indicating that the living immunogenic cells survived in the recipient for at least 4 weeks. Such cells may be certain cells of the cortical bone itself, or else residual bone marrow elements which adhere to the endosteal surface of the bone. The observation that a small subpopulation of living cells can provoke strong immune responses against a wide variety of antigens may have implications for understanding the immunogenicity of other types of allografts.


[Factors affecting the course of DNA acid hydrolysis in carrying out the Feulgen reaction]. Literature data concerning acid hydrolysis of DNA during the Feulgen procedure are reviewed, with emphasis being made on the dependence of Schiff-apurinic acid binding on the fixation technique, the temperature of hydrolysis and acid concentration, the rate of extraction of depolymerized DNA fragments, the nucleotide composition of DNA, the chromatin state, and on the composition of nucleoprotein. Some practical considerations for optimization of the Feulgen procedure for a precise quantitative determination of DNA amount are given.


[Quantitative cytochemical study of the RNA in tumor cells. II. The characteristics of the cell populatoins]. The quantity of DNA and RNA in tymocytes of AKR mice has been determined by Methylen blue staining. Cell populations of normal and tumor animals were divided into two groups with equal content of DNA to measure RNA content in either of them. The tumor cells had up to 380% RNA, if the normal content be taken for 100%. Dynamics of RNA modifications in cells of normal tymocytes corresponded to the increasing DNA quantity. The RNA quantity in tumor cells increased in the beginning of S-phase.


[Cytofluorimetric study of the content of glycogen and its fractions in rat liver cells in the course of the 1st week of postnatal ontogeny]. A cytofluorometric study of the total glycogen and its fractions in rat liver cells using the fluorescent PAS reaction was made during 1--7 days of the postnatal development. It was established that glycogen content was small on the first two days of development. The glycogen content increases only on the third day after birth. The glycogen of the rat liver cells during a first week of the postnatal development is different from that detected in adult liver cells in two aspects: in 3 day old hepatocytes soluble and stable glycogen fractions are equal, while in adult rat liver cells the former makes 80--90%; during the first week of the postnatal development, the stable fraction of rat liver cell is more labile, while in the adult rat liver the soluble fraction of glycogen is more labiles.