Fine structure and mechanics of the anterior border of the primate iris: a scanning and transmission electron microscope study. The morphology of the anterior border of the primate iris has been examined by transmission and scanning electron microscopy. The results confirm that the anterior iris is composed of heavily pigmented melanocytes, fibroblasts, and a loosely arranged network of collagen fibres. The melanocytes are slender, elongate structures, which show some branching in the peripheral iris. They run parallel to the surface and are filled with spindle-shaped pigment granules which are oriented in the long axis of the cell. In the miotic state, the peripheral iris melanocytes form a dense, interlacing network. As the pupillary margin is approached, the angles between intersecting melanocytes diminish; the melanocytes appear to be parallel and in close contact with one another.During mydriasis, the peripheral iris melanocytes are compressed and pupillary components are found to intersect at angles greater than 90%. The superficial fibroblasts are flattened cells, closely applied to the underlying melanocyte processes and in the mydriatic iris form a resonably continous monolayer over the anterior iris surface. Iris pores are present, exposing the underlying melanocytes and stromal collagen. During miosis, the surface fibroblasts become attenuated and the pores increase in size and number. This paper demonstrates the value of the scanning electron microscope in presenting an accurate three dimensional model of the iris.


Provoked iris ischaemia in the rabbit: A fluorescien angiographic study. We studied experimental anterior segment ischaemia in rabbits by fluorescein angiography of the iris. Nine rabbits were subjected to diathermy occlusion of one or both long posterior ciliary arteries or to disinsertion and reattachment of up to 4 rectus muscles. Occlusion of one LPCA or up to 3 recti had only a minor ischaemic effect on the iris vessels. Occlusion of both LPCAs produced necrosis of the anterior segment or ischaemia of the iris detectable by angiography. Disinsertion of 4 recti produced small patches of transient ischaemia in those areas of the iris most distal from the LPCAs. When further surgery is planned after retinal detachment cyclodiathermy or strabismus operations, fluorescein angiography is a  useful indicator of the vascular status of the iris and hence of the possibility of necrosis of the anterior segment.


Therapy of experimental herpetic keratitis with IDU and fluorescent light: A negative study. In vitro studies by workers in basic fields of biology have shown that halogenated DNA-base analogs are capable of sensitizing the DNA of various infectious agents in such a way that exposure to fluorescent light results in lethal damage to the DNA. In the present studies we treated experimental herpetic keratitis in rabbits with fluorescent light after using topical iododeoxyuridine (IDU) as a photosensitizing agent. So far as it clinical course was concerned, there was no significant difference between the disease treated with both IDU and light, and the disease treated with IDU alone. This was true in both the standard experimental disease and in the disease made more severe by prelimiary subconjunctival injection of corticosteroid.


A disposable vitrectomy instrument: the vitrophage. We describe a new, light weight, disposable vitrectomy instrument (vitrophage), which utilizes an oscillating principle for cutting. It is convenient and effective.


Photographic assessment of the optic disc. Increasing the sensitivity of methods of examining the visual field may merely increase subjective errors already inherent in this test. The optic disc can be examined quite objectively and subtle changes are best assessed by photography. A method, evolved through trial and error, is outlined for obtaining high quality colour transparencies and Polaroid Land Prints of the optic disc for follow up. Routine disc photography should be an important part of a glaucoma record.


Production of methionine-excreting mutants of Streptomyces fradiae. Methionine-excreting mutant strains of Streptomyces fradiae ATCC 10745, producedby exposure to N-methyl-N'-nitro-N-nitrosoguanidine, were selected on the basisof ethionine-resistance and ability to support the growth of an auxotroph which requiredmethionine or methionine precursors. When acid hydrolysates of dehydrated liquid cultures were analyzed for amino acid content, one of the mutants had produced 268% more methionine that the parental strain. To obtain an accurate analysis of methionine content, it was necessary to determine the amount of diaminopimelic acid which had been synthesized. This compound appeared in eluates during column chromatography at about the same time as methionine, and its presence increased apparent methionine concentrations by 25 to40%.


Basis for the susceptibility of several algae to microbial decomposition. Partially purified cellulase and a cellulase-containing polygalacturonase but notlysozyme extensively degraded the walls of Chlamydomonas reinhardtii and Ulothrix fimbrata and converted intact cells of the algae to spheroplasts. A streptomycete cellulase cochromatographed with the enzyme system releasing glucose from walls of these organisms, and this preparation also converted the algal cells to spheroplasts. The dominant constituent in the walls was carbohydrate, and glucose and small quantities of galacturonic acid but no amino sugars were present in acid hydrolysates of the walls. Glucose accounted for essentially all of the material solobilized by the cellulase preparation. Lysozyme acted on Cylindrospermum sp. walls, and it, but not the otherenzymes, converted some of the Cylindrospermum sp. cells to spheroplasts. Streptomycete enzymes lysing Micrococcus lysodeikticus cochromatographed with the proteins releasing reducing sugars from Cylindrospermum sp. walls, and components in the active fraction converted cells of this alga into spheroplasts. X-ray diffraction revealed that the walls of C. reinhardtii and U. fimbrata but not those of Cylindrospermum sp. contained cellulose. The data suggest that the susceptibility of the first twospecies to microbial degradation in natural ecosystems results from an attack on the cellulose in their walls, and the susceptibility of the third is linked with the microbial production of a lysozyme.


Evidence for the existence of endotoxic activity in three strains of Moraxella. The phenol extraction technique was used to obtain material with endotoxic activityfrom three strains of Moraxella. This material was subjected to partial purification. Biological activity was determined by inoculation of the extracts into the skinof rabbits, and noting the resultant skin reactions. Although containing some cellular contaminants such as nucleic acid from the extraction procedure, the endotin preparations showed biological activity in the microgram range. Killed but unextracted cellsalso elicited skil reactions when injected intradermally into the rabbit. A partial analysis of the biochemical components of the endotoxin revealed that these three strains contain endotoxin whose composition is similar in several respects to that of the endotoxins of the neisseriae and  some of the enteric bacteria.


Deep-sea bacteria: growth and utilization of n-hexadecane at in situ temperature and pressure. A mixed culture of bacteria was obtained from the sediment-water inferface of a core sample taken off the coast of Florida at a depth of 4940m. The mixed culture wasfound capable of utilizing n-hexadecane as a sole carbon source for growth at the insitu temperature (4C) and pressure (500atm). The rate of utilization under deep-ocean conditions was found to be much slower than the rate observed at ambient pressure(1 atm) and low temperature (4C).


Differentiation of Arthrobacter soil isolates and named strains from other bacteria by reations on dye-containing media. Twenty-five gram-negative and 62 gram-positive bacterial cultures, of which 37 werearthrobacters, were tested, using a multipoint inoculation device, for responses on varying concentrations of 35 dyes. Both selective (growth vs. no growth) and differential (dye absorption) responses were obtained. It was possible to differentiate the arthrobacters from the other gram-positive bacteria tested as well as to distinguish separately each Arthrobacter-named strain. The results indicated that dyes have a greater potential for use in selective and differential media than has been presently realized; and the possibility of using dye-reactions as features in taxonomic schemes to differentiate rapidly many of the common genera of soil bacteria is discussed.


[Rubella virus. I. Morphology and structural proteins]. Degradation of purified rubella virus by heat treatment (37, 45, or 56 degrees C) revealed the following structures. The viral envelope, a modified cellular membrane, bears spherical subunits, 5-6 nm in diameter, hexamers, or pentamers. Two glycoproteins, VP-2 (50 000 daltons) and VP-3 (63 000 daltons), are associated with the envelope. The nucleocapsid if formed by the condensation of the viral ribonucleic acid on acentral structure 10 nm in diameter. Only one protein, VP-1 (35 000 daltons) is present in the nucleocapsid. Similarity between rubella virus and Togaviruses is discussed.


Amino acid requirements of staphylococci isolated from human skin. Amino acid requirements and auxotrophic reversion properties were determined for 823 Staphylococcus strains isolated from natural populations on human skin. Ten species of Staphylococcus exhibited distinct amino acid requirement patterns. Proline, arginine, and valine were the most frequently required amino acids for the genus Staphylococcus.


Villous adenoma of the cecum.

Villous adenoma of the cecum. Villous adenoma of the cecum developed in a 49-year-old man; the diagnosis was confirmed at operation. The pathologic and radiologic features of villous tumour in this location differ from those of tumours situated in the sigmoid colon and rectum. Signs and symptoms are vague; bleeding per rectum may not occur. Right hemicolectomy is recommended because of the high malignant potential of this tumour.


Impedance phlebography: accuracy of diagnosis in deep vein thrombosis. In an evaluation of the diagnostic accuracy of impedance phlebography for the diagnosis of deep vein thrombosis, 51 limbs in 32 patients were examined simultaneously by impedance phlebography and by venography. The impendance diagnosis and accurate in 47 limbs, erroneous in 2 and inconclusive in 2; the overall accuracy was 92%. Simultaneous clinical diagnosis yielded an accuracy of 53%. The method requires full cooperation by the patient and meticulous attention to the details of the test by the physician or technician performing the examination.


Correlation between hemodynamic changes and the presence, size, and site of myocardial infarction. Values for eight measured and calculated hemodynamic variables were recorded in 12 dogs before and after experimental anterior myocardial infarction. Changes were noted in stroke work and stroke power only; the changes in stroke work and stroke power were closely correlated with the presence of the infarct, whereas the changes in the other six dynamic variables were unpredictable and uncorrelated. The degree of correlation between the stroke work and power, and the size and site of the infarction, however, suggested that none of the eight variables would be an adequate indicator of all three characteristics of the infarction.


Squamous cell carcinomas of the skin of the pinna. Among 52 patients with squamous cell carcinoma of the skin of the pinna seen consecutively between 1952 and 1973, a single course of treatment failed to control the disease in 10 (19%). This failure rate is higher than that usually reported for squamous cell carcinomas of the skin in general (2 to 6%), and appears to be in conflict with the belief that squamous cell carcinomas of the skin of the pinna rarely metastasize. It appears that other factors than neglect are responsible for this discrepancy. In this series it was not possible to judge the relative efficacy of one mode of treatment over another.


Serum ferritin, cobalt excretion and body iron status. Serum ferritin concentration was measured by immunoradiometric assay in 64 subjects. It was closely related to the size of body iron stores measured by hemosiderin content of bone marrow in all subjects and by the deferoxamine test in 10 patients with iron overload. Urinary cobalt excretion, an indirect measure of iron absorption, was inversely related to hemosiderin content of bone marrow in 34 patients aged 18 to 72 with or without liver disease, but this relation did not hold in a group of 20 student volunteers aged 17 to 30, indicating that the test is unreliable in young people. A strong inverse correlation was demonstrated between values for cobalt excretion and serum ferritin in the 34 patients and between those for iron absorption and serum ferritin in the 20 students. Serum ferritin concentration appears to reflect accurately the iron status of the healthy individual but high values in liver disease must be interpreted with caution.


Appendicitis in pregnancy.

Appendicitis in pregnancy. Over a 9-year period at one hospital 25 appendectomies were performed during pregnancy. In 20 cases the appendix was acutely inflamed. All mothers survived. Two women aborted and two went into premature labour. One of the premature infants survived. The fetal loss associated with acute appendicitis was 15%. Early diagnosis and operation is essential.


Dogs and intestinal parasites: a public health problem. The stools of 239 stray dogs were examined for intestinal parasites. Of the helminths found, Toxocara canis (43.5%), tapeworms (25.5%), Ascaris species (21.3%) and hookworms (12.5%) were the commonest. Of the protozoans found, Isospora species and Entamoeba coli were the most prevalent. An unusual feature of the present study was the finding of Ascaris species. The importance of the high prevalence of intestinal parasites in dogs, the close contact of humans with dogs' excreta and the possible role of this environmental pollution in the spread of human disease are discussed.


Mucocutaneous lymph node syndrome in Canada. Two Edmonton children recently had a disease seemingly new to North America but a common problem in young children in Japan in the last few years. Named "mucocutaneous lymph node syndrome", it is an acute febrile condition with massive focal cervical lymphadenopathy, conjunctivitis and indurative edema of the hands and feet progressing to desquamation. It may have an infectious basis and therefore may become common in Canada.


The heterogeneity of Streptococcus viridans: therapeutic considerations in infective endocarditis. A 24-year-old woman with Marfan's syndrome and mitral regurgitation had clinical features suggestive of infective endocarditis. The causative organism was Streptococcus viridans. Initial therapy with penicillin G, in a dose that should have been bactericidal and hence curative according to the results of the initial quantitative antimicrobial studies, became inadequate. The strain of S. viridans displayed considerable variation in both growth properties and antimicrobial sensitivity during the course of therapy. In addition, a different strain of S. viridans was cultured 1 month after treatment had begun. It is therefore important to repeat cultures and antimicrobial sensitivity testing during treatment of infective endocarditis.


Effect of treadmill exercise testing on serum enzymes and the resting electrocardiogram. Fifty-three adult male patients with chest pain underwent treadmill exercise stress testing according to the Bruce protocol. The resting 12-lead electrocardiogram (ECG) and serum concentrations of glutamic oxaloacetic transaminase, lactic dehydrogenase creatine phosphokinase and alpha-hydroxybutyrate dehydrogenase were evaluated before, and at 1 and 20 hours after exercise. Twenty-eight subjects (53 percent) had a normal test result, 10 (19 percent) had ischemic ST -segment changes and anginal pain, and 15 (28 percent) were considered to have equivocal results because of an abnormal baseline ECG or the concurrent administration of cardioactive medication. In contrast to earlier reports, no significant changes in the serum enzyme values were seen in any of the three groups orin any individual subject, nor were ECG changes detected after recovery from exercise. The diagnostic evaluation of the exercise ECG must depend upon the demonstration of ischemic ST -segment changes and not upon changes in concentrations of serum enzymes.


Treatment of persistent knee effusions with intra-articular radioactive gold. Patients with a total of 112 chronic knee effusions unresponsive to the usual conservative methods of therapy were treated with intra-articular injections of radioactive gold and followed from 6 months to 5 years. Most patients in the study had rheumatoid arthritis but others had ankylosing spondylitis, psoriatic arthritis, intermittent hydrathrosis and undiagnosed synovitis. After 6 months 81% showed improvement. This figure diminished to approximately 70% at 1 and 2 years, 60% at 3 and 4 years and 50% at 5 years. The mose beneficial results were seen in patients with intermittent hydrarthrosis. Twelve patients with a synovial cyst and/or rupture improved. Patients with thin synovia and anatomic stage I or II disease did best, but those with stage III disease also did well. After the injection 33% of the patients had a reactive synovitis. A variable amount of radioactive material escaped from the knee to the regional lymph nodes and general circulation.


Cost of primary health care services in the emergency department and the family physician's office. An attempt has been made to determine the true cost of providing primary health care for nontraumatic conditions in the emergency departments of two hospitals in Ontario and in the offices of family physicians. A total of 1117 patients presenting with 1 of 10 common symptom/sign complexes at the emergency departments or the offices of 15 participating family physicians were studies with regard to number of visits made, type of assessment by the physician, investigations undertaken, management, therapy and outcome of the illness. Costs were calculated from the charges that would be made against the provincial health services insurance plan and from the system of hospital financing in effect in the province. The average true cost per illness episode of this type of care was $14.63 in hospital A, $14.20 in hospital B and $15.90 in the family physician's office.


An unusual case of recurrent left atrial myxoma. In a patient who had a calcified left atrial myxoma resected, recurrence developed 31 months later. Although complete radical resection of the recurrent tumour presented a special problem, the patient survived the second operation. The tumour recurred again and the patient had two episodes of cerebral embolism 1 1/2 and 2 years later, respectively, and died 3 1/2 years after the second operation. The erythrocyte sedimentation rate correlated with the size of the tumor, and the recurrent tumour seemed to grow more rapidly than the primary tumour. Experience with this case and a review of the nine reported cases of recurrent left atrial myxoma suggest that a radical approach is necessary at the primary operation.


Fetal monitoring during maternal cardiac surgery with cardiopulmonary bypass. Fetal cardiac activity was monitored with an external ultrasound transducer in two patients with clinical class III heart disease due to severe mitral stenosis complicated by pulmonary hypertension, undergoing open heart surgery with cardiopulmonary bypass in the 2nd trimester of pregnancy. Fetal distress was detected in one patient, who had mitral valvuloplasty, and was corrected by increasing the rate of blood flow, and the other patient had a mitral valve replacement but no fetal distress was noted. The postoperative course of both mothers and fetuses was uneventful.


Language behaviour and child psychotherapy. The dichotomy between non-verbal or play therapy for the younger and verbal psychotherapy for the older child is questionable in view of the fact that lexical representation begins in the second year of life. It is equally doubtful whether, in the absence of certain communications expressed in verbal symbols, any type of interaction between therapist and child may be called psychotherapy. Language, in varying forms of syntactical and semantic complexity, constitutes the matrix which connects and makes coherent all interactive processes in psychotherapy. This paper attempts to relate some notions of language development to current concepts of child psychotherapy. Linguistic growth is characterized by a fixed gross developmental schedule as well as a specific and universal sequence of acquisition. For the preschooler, still lacking a flexible grammer and syntax to express intricate relationships of perceived events, the value of "interpretations" is doubted; simple statements concerning expression of affect are seen as a rudimentary psychotherapeutic intervention. For the latency child the play situation, with its familiar concrete activity, fuels the child's linguistic competence. Not the play itself but the resulting language becomes the major element of psychotherapy. In late childhood distancing devices and role playing may correct the sociolinguistic asymmetry (adult-child) which inhibits verbal behaviour.


Hyperkinesis and maternal smoking.

Hyperkinesis and maternal smoking. Mothers of methylphenidate-sensitive hyperkinetic children reported smoking two to three times as many cigarettes as the mothers of dyslexic and normal controls; the reported cigarette consumptions of the fathers showed no significant differences. These findings are consistent with the hypothesis that smoking during pregnancy is an important cause of the hyperkinetic syndrome.


Mental health problems associated with the only child. This study was undertaken to provide an evaluation of the mental health problems associated with the only child and a basis for further studies of singletons. Data were obtained from the recores of the Mental Health Clinic, London Psychiatric Hospital, of 115 only children and 115 non-only children between 5 and 15 years of age. The results showed that the only child did not differ significantly from his non-only peer in intelligence, school progress, referral reasons and the majority of mental health disturbances, but a significant difference was found in his increased submissiveness, greater number of repeat visits to clinic, and in the overprotective attitude of his parents. Aggressive behaviour was more frequently observed in the control group, which also had a significantly higher proportion of rejecting mothers. Suggestions for further research in this area are made.


A case of manic-depressive illness in childhood. A case of manic-depressive illness in a boy of 14 is presented and discussed. The illness began at the age of 12, before the onset of puberty, and conformed with most of the criteria set out by Anthony and Scott for the diagnosis of manic depressive illness in childhood. Some of the literature on bi-polar affective illness in childhood is reviewed and the case is discussed.


[Evaluation of care in child psychiatry. Results of an exploratory study]. The growing awareness of the importance of evaluating patient care has inspired a psychiatric team at Sainte-Justine Hospital to contact some cases closed during 1971. The population was divided into three groups: the Treated group; Drop-Out "B" (after 1 or 2 sessions); Drop-Out "A" (after a single phone call). A different type of questionnaire was sent to the members of each of these groups. Analysis of the results shows, among other things, that there is a 36 percent drop-out rate ("A" and "B"); that the patients' understanding of the treatment process appears to be of great importance in the treated group; and there is a positive correlation between this and patient improvement. The diagnosis does not appear to be a significant variable in either the Treated Group or the Drop-Out "B" Group. It appears that dropping out is related to the way the cases were handled, particularly in the Drop-Out "A" Group. The results of this study underline the importance of listening to the recipients of our serveces and being easily available to them. It is only after their needs are fully understood that the necessary and pertinent changes can be introduced.


Length of interbirth intervals in female psychiatric patients and controls. Length of 121 interbirth intervals for 77 multiparous female psychiatric patients was contrasted with the length of 605 interbirth intervals for 385 matched population-control women to test a clinical observation that female psychiatric patients often have long intervals between consecutive reproductions. No significant difference was found between all patients versus all controls or between any patient diagnostic group versus controls in studying the length of only those intervals including or subsequent to the first psychiatric hospitalization. Intervals during which this hospitalization occurred were significantly longer for all patients combined, for schizophrenic-like-psychotics, and for psychopaths, each as compared with its parity-matched control group. The clinical observation was not generally supported by the current data.


Synthesis of 2-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-D-mannose, and its interaction with D-mannose-specific lectins. Condensation of 3, 4:5, 6-di-O-isopropylidene-D-mannose dimethyl acetal with 2-methyl-(3, 4, 6-tri-O-acetyl-1, 2-dideoxy-alpha-D-glucopyrano)-[2', 1':4, 5]-2- oxazoline in the presence of a catalytic amount of p-toluenesulfonic acid afforded crystalline 2-O-(2-acetamido-3, 4, 6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl)-3, 4:5, 6-di-O-isopropylidene-D-mannose dimethyl acetal (3) in 25 percent yield. Catalytic deacetylation of 3 with sodium methoxide, followed by hydrolysis with dilute sulfuric acid, gave 2-O-(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)-D-mannose (4). Treatment of 3 with boiling 0.5 percent methanolic hydrogen chloride under reflux gave methyl 2-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-alpha-D-mannopyranoside (5) and methyl 2-o-2-acetamido-2-deoxy-beta-D-glucopyranosyl)-alpha-D-mannofuranoside (6). The inhibitoryactivities of 4, 5, and 6 against the hemagglutinating and mitogenic activities of Lens culinaris and Pisum sativum lectins and concanavalin A were assayed. From the results of these hapten inhibition studies, subtle differences of specificity between these D-mannose-specific lectins were confirmed.


Binding studies on a mouse-myeloma immunoglobulin A having specificity for beta-D-(1 yields 6)-linked D-galactopyranosyl residues. The free energies of binding between immunoglobulin A J539 (Fab') and methyl 6-O-acetyl beta-D-galactopyranoside (1) and 6-O-beta-D-galactopyranosyl-1, 2:3, 4-di-O-isopropylidene-alpha-D-galactopyranose (2) have been measured. The values found suggest that bulky substitution on O'-6 or O-1, O-2, O-3, and O-4 in the hapten 6-O-beta-D-galactopyranosyl-D-galactose (3) does not interfere with effective binding of that ligand and the immunoglobulin. This conclusion supports the postulations that (a) the ligand 3 binds only on one side of the molecule, and (b) the combining site of the immunoglobulin J539 appears to be located on an exposed surface area.


[Synthesis of 2-acetamido-2-deoxy-6-0-(alpha-D-glucopyranosyl)-alpha-D-galactopyranose and its p-aminophenyl-alpha-glycoside]. Benzyl 2-acetamido-3, 4-di-O-acetyl-2-deoxy-alpha-D-galactopyranoside was condensed with 2, 3, 4-tri-O-benzyl-6-O-p-nitrobenzoyl-alpha-D-glucopyranosyl bromide or with 2, 3, 4-tri-O-benzyl-6-O-p-methoxybenzoyl-alpha-D-glucopyranosyl bromide in benzene at 50 degrees in the presence of pyridine, to give benzyl 2-acetamido-3, 4-di-O-acetyl-2-deoxy-6-O-[2, 3, 4-tri-O-benzyl-6-O-p-nitro(or methoxy)benzoyl]-alpha-D galactopyranoside in excellent yield. The title disaccharide was obtained in crystalline form after deacylation and catalytic hydrogenation. It proved identical with a disaccharide isolated from Salmonella johannesburg 5.58 (40) converted by phage phi 1 (40). In order to bind this disaccharide covalently onto various proteins, p-aminophenyl 2-acetamido-2-deoxy-6-O-(alpha-D-glucopyranosyl)-alpha-D-galactopyranoside has been obtained in an analogous way, starting from p-nitrophenyl 2-acetamido-3, 4-di-O-acetyl-2-deoxy-alpha-D-galactopyranoside.


Immunochemical and chemical investigations of the structure of glycoprotein fragments obtained from epiglycanin, a glycoprotein at the surface of the TA3-Ha cancer cell. The structures of the carbohydrate chains present in fragments of a large-molecular-weight glycoprotein, epiglycanin, cleaved from the surface of viable TA3-Ha murine mammary carcinoma ascites cells and purified by gel filtration, were studied by immunochemical and chemical methods. Inhibitory activities for neuraminidase-treated and untreated glycoprotein material in the hemagglutination of NN-specific human erythrocytes by eight purified lectins were determined. Excellent inhibition was obtained in the Bauhinia purpurea, Arachis hypogaea, Iberis amara, and Wistaria floribunda systems, and weak inhibition against the Ricinus communis and Glycine max lectins. No activity against hemagglutination by the Phaseolus vulgaris and Phaseolus limensis lectins was observed. These results, when compared with those obtained by periodate oxidation, alkaline borohydride reduction, and partial methylation, suggest the possible presence of six different carbohydrate chains of 1 to 5 components in length, having as terminal groups N-acetylneuraminic acid, galactose, and 2-acetamido-2-deoxygalactose. All chains are attached to a single polypeptide chain by O-glycosyl bonds involving a 2-acetamido-2-deoxygalactose residue and a serine or threonine residue. It is suggested that the native molecule of epiglycanin of molecular weight 500,000 contains more than 500 carbohydrate chains attached to a single polypeptide chain of similar to 1,300 amino acid units.


The synthesis of 3, 6-di-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-D-galactose, a branched trisaccharide reported as a hydrolysis product of blood-group substances. Protected disaccharides were the only products that could be isolated after condensation of 3, 4, 6-tri-O-acetyl-2-deoxy-2-diphenoxyphosphoramido-alpha-D-glucopyranosyl bromide or 2-acetamido-3, 4, 6-tri-O-acetyl-2-deoxy-alpha-D-glucopyranosyl chloride with benzyl 2, 4-di-O-benzyl-beta-D-galactopyranoside. On the other hand, reaction of 2-methyl-(3, 4, 6-tri-O-acetyl-1, 2-dideoxy-alpha-D-glucopyrano)-[2', 1': 4, 5]-2-oxazoline (6 moles) with the same galactopyranoside (1 mole) gave benzyl 3, 6-di-O-(2-acetamido-3, 4, 6-tri-O-acetyl-beta-D-glucopyranosyl)-2, 4-di-O-benzyl-beta-D-galactopyranoside, which was converted, by alkaline methanolysis followed by hydrogenolysis, to the title compound. This appears identical with an oligosaccharide previously obtained through degredation of a blood-group A glycoprotein from hog gastric mucin.


Identification of a 2, 3-diamino-2, 3-dideoxyhexose in the lipid A component of lipopolysaccharides of Rhodopseudomonas viridis and Rhodopseudomonas palustris. A hitherto unknown amino sugar (Compound A), detected in acid hydrolyzates of lipopolysaccharides of Rhodopseudomonas viridis and Rhodopseudomonas palustris, is present in the Lipid A component but not in the O-specific part of the lipopolysaccharides. 2-Amino-2-deoxy-D-glucose is lacking in the purified Lipid A of both strains. Compound A, characterized by a very high migration in paper electrophoresis was obtained in a pure state by ion-exchange chromatography and shown by m.s. of the alditol acetate to be a 2, 3-diamino-2, 3-dideoxyhexose. G.l.c. and periodate oxidation excluded all possible stereoisomers with the exception of 2, 3-diamino-2, 3-dideoxyglucose and 2, 3-diamino-2, 3-dideoxydose. G.l.c. of the alditol acetates of Compound A and of the glucose derivative suggests that Compound A is 2, 3-diamino-2, 3-dideoxyglucose. The significance of the occurrence of this new aminodeoxy sugar in the Lipid A component of Rhodopseudomonas viridis and Rhodopseudomonas palustris O-antigens for the biological properties of the respective lipopolysaccharides and for the taxonomy of the Rhodospirillaceae family is discussed.


The isolation and characterization of rat sublingual mucus-glycoprotein. A purified glycoprotein, designated RSL-major, was isolated from the rat sublingual gland by means of the procedure of Tettamanti and Pigman. It was found to be homogeneous by analytical ultracentrifugation, to have a mol. wt. of 2-2 times 10-6, and to contain 81 percent (W/W) of carbohydrate, which consists mainly of sialic acid, 2-acetamido-2-deocy-D-glucose, 2-acetamido-2-deocy-D-galactose, and D-galactose in the molar ratio of 1.4:1.4:1.0:1.5; small amounts of fucose and mannose [1.2 and 2.8 percent (W/W), respectively] were also present. The sialic acid residues were resistant to the action of V. cholerae neuraminidase. This resistance was completely abolished by removal of the O-acetyl groups contained in the sialic acid. The sialic acid in RSL-major appeared to be a mixture of N-acetyl-4-O-acetyl- and N-acetyl-4, 7(8)-di-O-acetylneuraminic acids. The carbohydrate to protein attachment of RSL-major was shown, by alkaline beta-elimination reaction, to consist of an O-glycosyl linkage between 2-acetamido-2-deoxy-D-galactosyl residues in the oligosaccharide chains and seryl and threonyl residues in the protein core. The average oligosaccharide, contained in RSL-major, was postulated to be a heptasaccharide. A second material, designated RSL-minor, and also isolated from the ratsublingual gland, was obtained as a mixture of glycoprotein(s) and hydroxylapatite gel, and was not purified further.


The influence of genetic resistance on CFU growth kinetics in spleen and femur. An impaired colony formation of C57BL marrow cells transplanted into F1 (C57BL TIMES CBA) mice was observed. In accordance with the literature this phenomenon has been designated as "genetic resistance". Studies to elucidate the mechanism of the genetic resistance demonstrated that the multiplication phase of the CFU growth curve started in the semi-isogeneic combination about 48 hr later than in the isogeneic combination. In the spleen this resulted in a lower "dip". For the spleen as well as for the femur similar CFU doubling times were found during the multiplication phase when both transplantation combinations were compared. Furthermore the percentage of CFU in S-phase (assessed with the 3-H-TdR suicide technique) during the first days after transplantation were similar in both combinations. When the spleen was removed 5-6 months before irradiation and bone marrow transplantation was performed the growth curve of parental CFU in the femur was identical with the growth curve of isogeneic CFU (no delay was observed). These results are discussed and a few theories explaining the observations are proposed.


A comparison of computer methods for the analysis of fraction labelled mitoses curves. Computer methods developed by the authors for analysis of fraction labelled mitoses curves (FLM curves) have been compared. Four test examples were used in the study; the first example was the synthesis of a FLM curve with fixed parameters and the others involved fitting actual data. Experimental FLM curves showing various degrees of damping were used in the curve fitting tests. In each test example the comparison was based on the assumptions of exponential growth, a growth fraction of unity and no cell loss. In three of the test examples good agreement between the methods was observed but in one example some important discrepancies arose in the analysis of a heavily damped FLM curve.


Inhibitory effects of mitogens on adenoidal lymphocytes in vitro. Cultures of human adenoidal lymphocytes exposed briefly to either phytohemagglutinin (PHA), Staphylococcus filtrate (Staph-F), concanavalin-A (Con-A), or pokeweed mitogen (PWM) incorporate increased amounts of thymidine earlier than replicate cultures exposed continuously to the mitogens. These effects can begin in the first 24 hr of culture and are seen maximally between 36 and 72 hr. Once a blastogenic response is established, PHA or PWM can diminish that response. Inhibition with PWM requires that the initial stimulation was with this mitogen, while PHA can inhibit blastogenesis to both PHA and PWM-stimulated cells. Because these mitogens can have a paradoxical effect on adenoidal lymphocytes, being capable of both initiating and inhibiting DNA synthesis, this phenomena should be kept in mind when such systems are utilized for the evaluation of antigens and drug effects.


Changes in intestinal cell kinetics in the small intestine of lactating mice. The enlargement of the small intestine of mice during lactation is due, at least in part, to hyperplasia in the mucosal crypts and villi. The number of cells per crypt increases by 130% and the cell production rate by 63% after 15 days of lactation. These parameters were measured from crypt squashes and sections using both double-label and PLM techniques. Neither the numbers of crypts and villi in the small intestine nor the turnover time of post-mitotic cells on the villi changed. A number of factors appear to act in concert during lactation to trigger this increase in epithelial cell number in the small intestine. The experiments reported suggest a role for the increased quantity of food consumed by the lactating animal, for changing hormonal levels, and for the increased demands placed on the body by milk production.


Colony-forming ability of bone marrow cells of W anaemic mice on macrophage layer formed in peritoneal cavity of mice. The colony-forming ability of haematopoietic cells of W anaemic mice was examined on the macrophage layer formed in the peritoneal cavity of mice. Bone marrow cells of W anaemic mice formed a considerable number of colonies on the macrophage layer, notwithstanding they did not form any colonies in the spleen of the same recipients. As the colony-forming ability of the bone marrow cells was not reduced by the incubation with 3-H-thymidine, most of the cells which formed colonies on the macrophage layer seemed to stay in  G0 state. The interrelationship between the spleen colony-forming cells, the macrophage-layer colony-forming cells, and in vitro colony-forming cells was discussed.


Fission of crypts in the small intestine of the irradiated mouse. Following 1600 R of X-rays there was a reduction in the number of crypts in the small intestine of the mouse by 77% as measured 5 days later. However, by 21 days the number had increased steadily to levels approaching normal. The number of villi did not change following irradiation. The mechanism of increase in crypt number was by budding and fission of repopulated crypts which had become larger than normal. Some aspects of crypt organization are discussed.


Lymphocyte populations in mouse bone marrow: quantitative kinetic studies in young, pubertal and adult C3H mice. Continuous 3-H-thymidine infusion was used to characterize two kinetic subpopulations of small lymphocytes in mouse bone marrow during normal growth and development. Young (4 wk), pubertal (8 wk) and mature (16 wk) C3H mice were infused subcutaneously with 3-H-thymidine for periods up to 10 days. Femoral marrow was then examined in radioautographic smears. During the first 3 days the proportion of marrow small lymphocytes labelled by 3-H-thymidine showed a rapid exponential increase to 93%, 81%, and 72% in 4 wk, 8 wk and 16 wk mice respectively. The rate of appearance of labelled small lymphocytes then declined markedly but remained higher in younger than in older animals. The labelling curves were found to represent the summation of two exponential curves from which the proportions and renewal rate of corresponding cell populations were calculated. Most marrow small lymphocytes comprised a rapidly renewing population but in mice of increasing age the relative incidence of these cells fell (93-3% at 4 wk; 88-0% at 8 wk; 78-5% at 16 wk) and their half-renewal time (T1/2) lengthened (14 hr at 4 wk; 18 hr at 8 wk; 24 hr at 16 wk). The remaining small lymphocytes were slowly renewing with mean T1/2 OF 4, 7 and 14 days in 4, 8 AND 16 wk mice, RESPECTIVELY. Some heavily labelled small lymphocytes persisted in the marrow up to 10 wk after fourteen daily 3-H-thymidine injections in 10-12 wk mice. The numbers of rapidly renewing cells decreased from 604 times 10-3 to 228 times 10-3 per mm-3 of marrow from 4 wk to 16 wk, respectively, while slowly renewing cells increased from 44 times 10-3 to 61 times 10-3 per mm-3. The total number of nucleated marrow cells per femur increased from 4 wk to 16 wk but the rapidly renewing small lymphocytes per femur fell in numbers by 36% and in renewal rate by 63%. The results demonstrate a selective change in bone marrow small lymphocytes with age; rapidly renewing cells decline in number and renewal rate while the number of slowly renewing cells increases. The concept of bone marrow as a primary lymphoid organ is discussed.


Messenger ribonucleoprotein complexes isolated with oligo(dT)-cellulose chromatography from kidney polysomes. As an initial step towards understanding the role of mRNP complexes in translational regulation during compensatory renal hypertrophy, characteristics of polysome-associated mRNP isolated by affinity chromatography were studied. Renal mRNP contained 15-30 percent of the counts after a 1 hr pulse with -3H-orotic acid; it sedimented mainly between 10S and 100S and had a buoyant density of 1.42-1.44 g/cm-3. RNA derived from the mRNP sedimented between 5S and 40S on sucrose density gradients, with the greatest radioactivity in the region of 15S. After labeling with -3H-adenine for 1 hr, up to 17 percent of the radioactivity present in the mRNP-associated RNA was resistant to digestion by pancreatic and T1 ribonucleases. The mRNP protein moiety contained six polypeptides with molecular weights 69,000, 75,000, 80,000, 100,000, 109,000, and 118,000 daltons, which were undetected in the material not binding to oligo(dT)-cellulose.


Synthesis of all the gene products of the reovirus genome in vivo and in vitro. Sixteen virus-specific polypeptides have been resolved in reovirus-infected mouse L cells by using SDS-polyacrylamide slab gel electrophoresis and autoradiography. Of these, ten have been designated as primary products of the genome by the following criteria: they are present in lysates of infected cells labeled for a short time; they co-migrate on SDS-polyacrylamide slab gels with polypeptides synthesized in cell-free-extracts of wheat germ in response to purified viral mRNA; and their molecular weights correspond to the values expected if all ten reovirus mRNA species are monocistronic. Reovirus mRNA species lack 3' poly(A) but are translated into proteins of the expected size. The pattern of synthesis of the primary gene products observed in vitro mimicks that observed in reovirus-infected cells suggesting that the structure of the mRNA may profoundly influence its translation. The results further indicate that there is little, if any, exclusively regulatory information in the reovirus genome since both in vivo and in vitro, transcripts of the ten genome segments direct the synthesis of ten polypeptides that presumably correspond to the primary gene products. The expression of the reovirus genome thus appears to be complete.


Units of transcription and translation: sequence components of heterogeneous nuclear RNA and messenger RNA. Defining the units in which the eucaryotic genome is transcribed and translated is central to any analysis of eucaryotic gene expression. The relationship between heterogeneous nuclear RNA and messenger RNA raises the question of whether the primary transcript may be more complex than the sequence which is translated; as I concluded last month in the first part of this review, kinetic analyses of these two RNA populations provide some suggestive indications but cannot prove whether the nuclear population includes messenger precursors that are much longer than mature cytoplasmic messengers (Lewin, 1975). Here I discuss recent analyses of the sequence components present in hnRNA and mRNA and how they may be related to each other and to the organization of the genome.


Quantitative analysis of DNA content in the salivary gland chromosomes of Chironomus thummi at larval and prepupal stages. Relative DNA content during the polytenization of the salivary gland nuclei of Chironomus thummi was measured by cytophotometric and cytofluorometric methods. To estimate the degree of polyteny, the DNA content was calculated in hemocyte and spermatocyte nuclei. Chromosome polytenization is associated with 10 to 12 replication rounds. There are 4-5 replication rounds in 1st instar, 2-3 rounds in 2nd instar; 3rd and 4th instars have 1-2 rounds each. From early postembryonic development, larvae already have salivary gland nuclei representing two polyteny classes (2-3 - 2-4C); A similar heterogeneity is retained in all instars. The approximate DNA content is 0.51-0.58 picogram per diploid set.


Synthesis of oviduct nuclear and chromatin proteins during steroid induced differentiation. Synthesis of nuclear histones and nonhistones was studied in chick oviduct during stimulation with estrogen and progesterone. In estrogen primed chicks, as compared to progesterone primed chicks, oviduct nonhistones are enriched in polypeptides of 50,000 daltons and larger. A secondary stimulation with the steroids increases the amino acid incorporation into histones and nonhistones two to six fold. Injection with estrogen induces preferential labelling of nonhistone polypeptides at 50,000 to 60,000 daltons independent of the kind of primary stimulation. A secondary injection with progesterone increases the amounts of highly labelled polypeptides with a molecular weight of over 70,000 daltons.


DNA and RNA content of Chironomus thummi polytene chromosomes determined by micro column gel filtration. A new microtechnique was used to determine the nucleic acid content of Chironomus polytene chromosomes. The method based on UV-microspectrophotometric measurement of alkali digested chromosome samples before and after gel filtration through Sephadex microcolumns permits the simultaneous estimation of DNA as well as RNA amount of single chromosomes and nucleoli. The DNA and RNA content of C. thummi salivary gland chromosomes I-III carrying a large number of puffs (but no nucleoli or Balbiani rings) corresponds roughly to their relative lengths. Chromosomes of the most frequent polyteny level (class B; probably 8192 C) contain 418 (Chromosome I), 372 (II), and 307 times 10-12 g DNA (III) and 116, 120 and 69 times 10-12 g RNA, respectively. The 4th chromosome, which carries the nucleolus and two Balbiani rings, contains about 150 times 10-12 g DNA and 328 times 10-12 g RNA. As the result of one of the last replication steps both DNA and RNA content of chromosomes I-III becomes duplicated whereas nucleolar RNA content is increased to a smaller extent.


Transient cytoplasmic bridges among the cells of developing cerebellum: a possible mode of induction for cell differentiation. In the developing cerebellum of neonate rats, membrane fusions and cytoplasmic bridges were observed between the pre-existing Purkinje cells and the migratory and differentiating granule cells. These ultrastructural specializations of the apposing membranes were seen to be transient in nature, and represented a developmental phenomenon. On the basis of literature available on this type of direct cell-to-cell interaction it is suggested that such transient cytoplasmic bridges may provide induction for differentiation from the pre-existing Purkinje cells to the undifferentiated cells.


In vitro reaction of beta-propiolactone and gamma-butyrolactone with glutathione and cysteine. The in vitro reaction of the carcinogenic beta-propiolactone (BPL) and the non-carcinogenic gamma-butyrolactone (GBL) with glutathione (GSH) and cysteine (CySH) was examined spectrophotometrically. The characteristic absorbance of thioesters in the region of 233 nm appeared when BPL and GSH reacted but not when BPL and CySH reacted or when GBL was mixed with GSH or CySH. The absorbance disappeared when hydroxylamine was added. The results are in striking contrast to the notion that all carcinogenic lactones alkylate nucleophiles and that all inactive lactones acylate nucleophiles. The reaction between BPL and GSH produced about equal quantities of thioester and thioether, which could be separated chromatographically.


Effect of aflatoxins on oxidative phosphorylation by rat liver mitochondria. The in vitro effect of aflatoxins M1, B1 and G1 on oxidative phosphorylation by rat liver mitochondria with succinate as substrate has been studied. All these toxins inhibit the electron transport chain at a 1-10-4 M concentration and the site of inhibition is between cytochrome b and cytochrome c or c1. Aflatoxin M1 (AFM1) uncouples oxidative phosphorylation at a concentration of 1-10-6 M and reduces the ADP:O ratio, whereas aflatoxin B1 (AFB1) at 1-10-6 M concentration uncouples oxidative phosphorulation but does not affect the ADP:O ratio. At a concentration of 1-10-5 M, AFB1 also decreases the ADP:O ratio along with the uncoupling of oxidative phosphorylation. Aflatoxin G1 (AFG1) acts as an uncoupler at a relatively higher concentration of 1-10-4 M. Preincubation of mitochondria with these aflatoxins resulted in inhibition of respiration and uncoupling of rat liver mitochondria.


Decreased synthesis of hepatic satellite DNA in pyrrolizidine alkaloidosis of the sheep. the proportion of heavy satellite in the DNA isolated from the livers of sheep suffering from experimental pyrrolizidine alkaloidosis is significantly lower (3.5%) than that found in the DNA from lovers of normal sheep (12%). Dehydroheliotridine, the major unbound, relatively stable metabolite of lasiocarpine and heliotrine, the alkaloids used in the study, was found to inhibit selectively the semiconservative replication of the satellite DNA in cultures of ovine kidney cells. It is suggested that the inhibition of the synthesis of satellite DNA may be related to an attack by the metabolite on the pericentromeric region where the majority of the satellite sequences are located.


Rate-limiting steps in drug metabolism by microsomes from CCl-4-cirrhotic rat liver. Comparative studies have been conducted of the activity of microsomal mixed-function oxidases from livers of normal, precirrhotic and cirrhotic rats linked with the metabolism of type-I (aminopyrine, hexobarbital), type-II (aniline, metyrapone) and "modified type-II" (corticosterone) substrates. The following factors were investigated: the possible role of cytochrome P-450 content, the state of the "substrate-binding protein" of this enzyme, the degree of affinity of this hemoprotein for both type-I and type-II substrates and finally, the activity of the enzymes of the microsomal electron-transport chain (both in the absence and in the presence of type-I substrate) -- as rate-limiting reactions, "tight spots" in the biotransformation of drugs in experimental microsomes. It was found that the hydroxylation activity for type-II and "modified type-II" substrates during the entire period of liver cirrhosis development is determined by the cytochrome P-450 content and the amplitude of maximal spectral changes observed in the presence of excess substrate. Type-I substrate metabolism, however, is limited in the precirrhotic phase by the state of the "substrate-binding protein" contained in P-450 as well as by the NADPH-cytochrome P-450 reductase activity. On the other hand, the N-demethylating activity in CCl-4-cirrhotic liver microsomes does not depend on either the concentration of P-450, on the amplitude of the maximal spectral changes or on the Ks value. The rate-limiting step in this case is the rate of reduction of the P-450-substrate complex by NADPH.


Alterations in the metabolism of fats and phosphatides in rat liver induced by halide ions. The effects of halide ions on several pathways of lipid metabolism have been investigated in rat liver slices. Through the use of carboxyl-14-C-labeled acetate and palmitate and U-14-C-labeled glycine, striking differences were found when the effects of the four halide ions on the labeling of the lipids were compared. Both fluoride and iodide dpressed [14-C]acetate incorporation into phosphatide and triglyceride fractions. The effects of the halide ions on the labeling from the effects observed when [14-C]acetate was the precursor of the lipid molecule. In contrast with the phospholipid fractions, the level of radioactivity from [14-C]palmitate incorporated into the triglycerides was lower with fluoride than with chloride. The incorporation of [14-C]glycine into the phospholipids was also greatly depressed by fluoride. The effects of halide ions on acetoacetate formation, on 14-CO2 production and on the acetylcoenzyme A synthetase of rat liver were also investigated. Decreasing [I-14-C]-acetate conversion to acetoacetate iodide had an opposite effect on 14-CO2 production from the same labeled substrate. The effects of the four halide ions and the differences observed with the three labeled substrates on several pathways related to lipid metabolism are discussed.


The inhibition of glyceradehyde-3-phosphate dehydrogenase by benz(a)anthracene and its derivatives after exposure to laboratory lighting. Colloidal dispersions of polycyclic aromatic hydrocarbons were found to inhibit glyceraldehyde-3-phosphate dehydrogenase (GPDH) and lactic acid dehydrogenase (LDH) after a short exposure of the incubation medium to laboratory lighting. The activation effect was observed with substituted 7-methyl derivatives of 12-methylbenz(a)anthracene also. One minute exposure of 7-methoxymethyl-12-methylbenz(a)anthracene (MeO-DMBA) to light was sufficient to produce a measurable amount of GPDH inhibition. The rate of enzyme inhibition was related to the pH of the dispersion. A small but significant effect of light on the inhibition of the enzymes by K-region epoxides was seen. Protein binding of the epoxides was not well correlated with the inhibition. The light effect was oxygen-dependent and was related to the hydrocarbon concentration. The active form decayed over a period of more than 25 days. The necessity for protecting reactions involving hydrocarbons and their derivatives from light is emphasized.


Localization in the cell cycle of the antimitotic action of the pyrrolizidine alkaloid, lasiocarpine and of its metabolite, dehydroheliotridine. The antimitotic action of the pyrrolizidine alkaloid lasiocarpine on rat liver parenchyma was investigated using as the experimental model the wave of mitosis produced in liver by a single dose of thioacetamide. A single low dose of lasiocarpine administered two weeks before the thioacetamide, almost completely inhibited the mitotic wave without inhibiting to the same extent the preceding wave of DNA synthesis. By the use of selective inhibitors and radioisotope labelling, the location of the mitotic block was found to be either in the latter half of the DNA synthetic phase, S, or early in G2, the post-synthetic phase. The mitotic wave was similarly inhibited by pretreatment of the rats with a single injection of dehydroheliotridine, a pyrrolic metabolite of heliotridine-based pyrrolizidine alkaloids.


The occurrence of multiple forms of cytochrome P-450 in hepatic microsomes from untreated rats and mice. The hepatic microsomes of rat and mice were subfractionated by the procedure of Dallner. When a 1.3 M sucrose lower layer was used for the two-step discontinuous gradient, no differences in spectral characteristics were noted between subfractions, though the smooth fractions (SER) had higher oxidative activity towards the substrates tested. When lower layers of 1.05, 1.1 or 1.15 M sucrose were used, and the SER isolated contained cytochdrome P-450 with significantly different spectral characteristics from that of the rough fraction (RER). The SER cytochrome P-450 had a wavelength maximum in the carbon-monoxide reduced difference spectrum that was significantly lower (ca. 1.0 nm) than that in the RER. In addition, the type I:CO-reduced spectral ratio of these fractions is significantly elevated. These data indicate that liver microsomes from untreated rats and mice contain more than one cytochrome P-450 and that of these cytochromes may be located in different parts of the endoplasmic reticulum.


ORD and CD studies of saturated glycerides. A convenient method for transforming 3-acyl-sn-glycerols into 1-acyl-2,3-diacyl'-sn-glycerols, antipodes of 1,2-diacyl'=3-acyl-sn-glycerols, of relatively high optical purity, via the 1,2-dimesyl-3-acyl-sn-glycerols has been worked out. ORD and CD curves of optically active triglycerides and also some mono- and diglycerides have been studied in detail. The curo 200 nm or below. A Cotton effect from the n yeilds  ets* transtition of the ester chromophore was observed at 215-220 nm, which was negative for triglyceritical rotations could be observed in triglycerides with very small differences in chain length, such as 1,2-dilauroyl-3-myristoyl-sn-glycerol.


PMR analysis of unsaturated triglycerides using shift reagents. The addition of Pr(fod)3 i.e. tris(1,1,1,2,2,3,3-heptafluoro-,7-dimethyl 1-4,6-octanedionato) praseodymium, to trilinolein has been found to induce a difference in the chemical shifts of the absorptions from the acids on the alpha- and beta positions. At 220 MHz this was observed up to 18 carbon atoms along the chain. Decoupling of the alkenyl protons at 100 MHz enabled the absorptions from the skipped methylene groups to be used to determine the position of linoleate and linolenante chains in triglycerides.


Acomparative study of two methods of urine preservation. In preparation for the conduct of biochemical experiments in the Skylab Orbital Workshop a study was performed on the stability of various chemical constituents in urine in 2 different techniques for preservation and storage. Urine samples were either vacuum dried or frozen and maintained in storage at minus 20 degrees for periods of up to 10 weeks. The urinary constituents studied included aldosterone, antidiuretic hormone, epinephrine, norepinephrine, urea, nitrogen, creatine, hydroxyproline, 17-hydroxycorticosteroids, calcium, sodium potassium, chloride, magnesium and phosphate. Some degradation of urinary compounds was observed after both treatments. The rate and variability of destruction following the vacuum drying treatment, however, was greater than for freezing. It was concluded that only the freezing treatment could be used to preserve with predictable loss the urinary samples which would be returned to earth following the conclusion of each Skylab flight.


[Quality control of testosterone and digoxin radioimmunoassays and cortisol competitive protein binding assay by the reference sample method]. The inclusion of a minimum of 2 reference samples in the radioimmunoassay of testesterone and digoxin, and the competitive protein binding assay of cortisol served as a simple and practical index of overall assay performance. Statistical parameters, the mean plus or minus 2 standard deviation limits as well as the % coefficient of variation were determined at 3 clinically significant values for these samples. While a 50% intercept served mainly to indicate standard curve sensitivity, quality control sera provided a valid assessment of annay precision.


A simulation model for determination of the economic production rate of the auto analyzer system. 1. The problem is considered of determining the appropriate rate of operation of an Auto Analyzer System. A computer model is presented which simulates the operation of the system, so as to describe the frequency of such events as repeated samples. 2. Estimates may be obtained of average total running costs, incorporating those of consumables and technician time and the rate which minimises the average cost, subject to stated test quality constraints, may then be calculated.


A micro method for direct determination of ionic fluoride in body fluids with the hanging drop fluoride electrode. A simple method for direct determination of ionic fluoride in 5 mul samples of body fluids with the hanging drop fluoride electrode, using sodium acetate buffer (pH 4.8) is described. The hanging drop electrode should prove useful in experimental investigations employing small laboratory animals and in clinical laboratories.


The glycoprotein content of meconium.

The glycoprotein content of meconium. Meconium pooled according to blood group activity has been studied. It was found to consists largely of glycoproteins. Two glycoprotein fractions have been isolated, one of which consisted of mucous-type glycoproteins and the other of "mannose-containing" glycoproteins.


Estimation of serum uric acid by high performance liquid chromatography with electrochemical detection. A precise method for serum uric acid is described based on direct electrochemical oxidation in the eluate from high performance liquid chromatography. The detection limit for uric acid was found to be approximately 1 pg and accurate measurements were possible at the 100 pg level. Detailed procedures are outlined for 0.5 ml and 25 mul serum samples, the relative standard deviations being 1.7% and 1.8%, respectively, for a 6.2 ml/dl serum pool. Samples were normally deproteinized, however, the analysis can be carried out by injection of 2 mul of serum diluted 10-fold with distilled water. The proposed micro method is highly selective and eliminates the need for the enzyme preparation and/or nonspecific colorimetric reagents in common use.


N-EPSILON-(CARBOXYMETHYL)LYSINE, A CONSTITUENT OF HUMAN URINE. An unknown urinary amino acid, present in small amounts in many children with various diseases, has been isolated and identified as N-Epsilon-(carboxymethyl)lysine. The identity of this compound was confirmed by synthesis. Its chromatographical characteristics are described. The compound also occurred in the urine of prematurely born infants. Even in healthy adults trace amounts could be detected. In a few patients strikingly higher excretions were observed, up to 67 mg/g creatinine, as determined by cation-exchange column chromatography. No clear correlation with a distinct clinical picture could be established. Speculations are given about the origin of the compound.


A new cocktail for liquid scintillation counting of aqueous radioimmunoassay-samples. The aim of this investigation was to find a scintillation mixture for counting up to 1 ml of plasma. We succeeded in obtaining a mixture of xylene/Triton X-100/mono- and di-butylphosphate, and called it Plasmasol. The properties were ideal for radioimmunoassays of steroids.  Good dissolving properties, high counting efficiency, absence of chemiluminescence and a good stability and reproducibility with respect to the disintegrations per minute were achieved. The cost was only 25% of the commercially available ready-to-use liquid scintillation mixtures, with which a comparison was made.


Activation by pyridoxal 5-phosphate of aspartate transaminase in serum of patients with heart and liver disease. When aspartate transaminase activity in serum is increased, pyridoxal 5-phosphate addition produces more pronounced activation of post-myocardial infarct sera than of sera from patients with chronic liver disease. Possible explanations for this are considered. Routine pre-incubation of sera with pyridoxal phosphate prior to aspartate transaminase determination is recommended.


Analysis of heat inactivation curves of alkaline phosphatase isoenzymes in serum. The course of the decline in alkaline phosphatase activity during exposureof serum samples to a temperature of 56 degree C can be resolved into two phases. These represent the exponential decay of an enzyme component with an average half-inactivation time of 112 seconds and of a second component with an average half-inactivation time of 456 seconds. The more rapid fall is due to inactivation of bone alkaline phosphatase and the slower to inactivation of liver and, when present, intestinal phosphatases. The half-inactivation times of the different enzyme species show considerable variation from one serum sample to another. The implications of this variation for methods of estimating the relative proportions of alkaline phosphatase isoenzymes by selective inactivation procedures are discussed.


The separation and characterization of liver plasma membrane fragments circulating in the blood of patients with cholestasis. Investigations on the high molecular weight isozyme of alkaline phosphatase (R type of AP), which is typically found in the serum of patients with cholestasis, have revealed that AP of the R type corresponds to the conventional liver AP which is attached to vesicular material. The isolation of these vesicles by Sepharose gel filtration is described. Several features were found to be characteristic for these vesicles: 1. The presence of the following enzymes known to be membrane bound: alkaline phosphatase (AP), 5FEET-NUCLEOTIDASE, L-leucyl-beta-naphthylamidase (LAP), and gamma-glutamyl transpeptidase (gamma-GT). 2. The absence of the following enzymes known not to be present on cell membranes: glutamic pyruvic transaminase (SGPT), glutamic oxalacetic transaminase (SGOT), lactate dehydrogenase (LDH), and acid phosphatase. 3. The typical ultrastructural appearance and the cytochemical visualization of alkaline phosphatase and 5feet-nucleotidase. It is concluded that the vesicles correspond to fragments of the liver cell membranes that appear and continue to circulate in the blood of patients with cholestasis.


Incidence and some properties of an electrophoretically slow form of alkaline phosphatase in sera of patients with diseases of the intestine. A zone of alkaline phosphatase activity migrating at about 40 percent of the rate of liver phosphatase in gel electrophoresis has been detected in sera from 2 out of 22 cases of ulcerative colitis and 1 out of 32 cases of Crohn's disease, but in no other specimen from 33 patients with other diseases of the digestive tract. This rare form of alkaline phosphatase was unlike small-intestinal alkaline phosphatase in several properties. Its appearance in association with diseases of the colon suggests that the rare isoenzyme may originate in that organ. However, the slowly migrating alkaline phosphatase was equally prominent in serum specimens taken before and after operation in one patient who underwent a pan-proctocolectomy for the alleviation of uncontrollable ulcerative colitis.


Effect of essential oil of onion (allyl propyl disulphide) on blood glucose, free fatty acid and insulin levels of normal subjects. The administration of allyl propyl disulphide (APDS), a volatile substance contained in onion, to six normal volunteers after a 12 hour fast caused a significant fall in the blood glucose levels and a significant rise in the serum insulin levels during the subsequent 4 hours. It is argued that this effect is due to an insulin sparing action. The expected rise of serum free fatty acid levels after fasting did not occur after APDS administration and this effect is probably related to the simultaneous rise in the insulin levels.


Semi-automated radioimmunoassays for total serum thyroxine and triiodothyronine. Single stage semi-automated radioimmunoassays for total serum thyroxine (T4) and triiodothyronine (T3) are described which employ an automatic pipetting station, automatic gamma counter, and a programmable calculator with paper tape reader and printing facility. Both assays require only a small volume of unextracted serum, and are specific and sensitive. Their sample capacity, precision, speed, and cost are comparable with the measurement of serum protein-bound iodine. Both assays therefore have significant advantages over previous methods for the assessment of thyroid function in the diagnostic laboratory. A Simple method of automating the calculation of results is described, which is applicable to any radioimmunoassay in which the standard curve is approximately linear on a plot of the free/bound fraction against the antigen concentration. In addition, a general method is reported which reveals the relative contributions of intrinsic, systematic, and random error to radioimmunoassay precision.


Carcinoembryonic antigen (CEA) of human tissue extracts: partial characterization of two variants separated by affinity chromatography on concanavalin A. The carcinoembryonic antigen (CEA) of normal and pathological tissue extracts was separated into two variants, Concanavalin A reactive (CEAr) and non-reactive CEA (CEAn) by affinity chromatography on Con A Sepharose columns. CEAr was the quantitatively predominant variant. CEAn varied in concentration between 0.2 and 6 percent of the total CEA activity. The affinity of CEAn for anti-CEA antibodies was significantly lower than that of CEAr. Pooled extracts of primary adenocarcinomas of the colon contained CEAn in the lowest concentration and with the least affinity for antibodies. It is suggested that a deficiency and/or steric blocking of alpha-D-mannopyranosyl residues in CEAn reduce the affinities for both antibodies and Con A.


Variations in human metabolism of methaqualone given in therapeutic doses and in overdose cases studied by gas chromatography-mass spectrometry. The individual variations in human metabolism of methaqualone were studied after oral administration of therapeutic doses. The effect of antabuse on the drug metabolism as well as metabolites in some autopsy cases were also studied. The metabolites were identified using the GC-MS computer technique, and the relative amounts of the indicated metabolites were calculated from the sum of the peak heights in the gas chromatogram. The results show that the individual variations were small in the cases of therapeutic doses and that antabuse did not interact with the metabolism of methaqualone. Large amounts of one single metabolite 2-methyl-3-[phenyl(2'-methyl-4-hydroxy)]-4(3H)-quinazolinone was found in the bile from the two autopsy cases where the bile was also collected.


Empirical relations as interference correctives in multichannel analyzers. Interference from turbidity and bilirubin on 20 serum constituents have been examined on the AutoChemist multichannel analytical system. Empirical relations are presented which correct for these effects on tests such as acid phosphatase, alkaline phosphatase, bilirubin, chloride, cholesterol, creatinine, iron, lactate dehydrogenase, phosphate and uric acid. The interference correctives are routinely applied to patient specimens by aid of the computer attached to the system.


Improved fibrin plate method for fibrinolytic activity measurements: use of bentonite precipitation and agar solidification. A modification of the fibrin plate method to assure sterility and fibrin stability is described. Bovine fibrinogen is precipitated with bentonite to remove the plasminogen and agar is added to assure stability. Storage of the plates up to 7-10 days has resulted in no bacterial growth. This rapid, sensitive method is useful in the isolation of plasminogen or its activators by chromatographic separation.


Resistance to Levamisole (R12456) in heat-stable alkaline phosphatases. The inhibitory effect of Levamisole (R12456) on human alkaline phosphatases has been studied. At a concentration of 0.1 mM it is possible to differentiate the source of the enzyme. Enzyme activity relatively resistant to Levamisole (less than 20 percent loss) is present in serum with the Regan isoenzyme, in placental extracts, in the intestinal "B" preparation and in heat-stable alkaline phosphatases "unmasked" after treatment at high ionic strength.


Urinary organic acid analysis in non-ketotic hyperglycinemia: non-specific occurrence of free benzoic acid, due to a beta-streptococcus infection. The presence of free benzoic acid in the urine of a patient with non-ketotic hyperglycinemia was demonstrated to be due to a urinary tract infection with beta-streptococci (group B), and was eliminated by treatment with Penicillin G. In addition, the continuous excretion of p-hydroxyphenylacetic acid was observed. The patient was also found to excrete small and variable amounts of tiglic acid during the period of observation. Except for benzoic acid, large excesses of any specific organic acid were not observed.


The diagnostic value of certain alkaline phosphatase isoenzyme patterns in human serum, fractions obtained by polyacrylamide disc electrophoresis. Over 2500 pathological sera were analysed to determine alkaline phosphatase (EC 3.1.3.1) isoenzyme levels. 3% of these sera showed two or more narrow isoenzyme bands with a lower electrophoretic mobility on polyacrylamide than that of the intestine type of alkaline phosphatase and higher than that of the bile type of alkaline phosphatase (the extra-bands group). This latter group showed significantly more intestine-tupe alkaline phosphatase than a control group of 240 sera lacking extra serum bands. Significantly more of the individuals in the extra-bands group belonged to blood group O or B than did individuals of the control group. This relationship with blood groups suggests that the presence of the extra bands is genetically determined. It is concluded that the presence of these extra bands is not a specific indication for a particular disease or malignant process. The serum of seven patients showed an unusually strong alkaline phosphatase band with a relative mobility amounting to about one-third of that of the liver-type band (2nd fraction group). Specificity for a particular disease could not be established in this group either. In four patients the serum showed an alkaline phosphatase band with an electrophoretic mobility greater than that of the liver-tupe band (6th fraction group). All of these patients had liver metastases of a primary adenocarcinoma localized in the pancreas or stomach. After the demonstration of this fraction in ther serum, the course became progessively worse.


Nothing dehydrogenase reaction as an artefact in serum isoenzyme analyses. A nonspecific staining occurs in serum in isoenzyme methods based on tetrazolium staining reactions. The artefact is pronounced when a large application volume, a prolonged incubation time, distinctly alkaline conditions, or excess of phenazine methosulphate is used. Only phenazine methosulphate and a tetrazolium stain are required for the appearance. Inhibition studies and histochemical staining reactions give evidence that protein-bound sulphydryl groups are responsible for the artefact in serum.


Electrophoretic analysis of the major polypeptides of human erythrocyte membranes prepared by low and high osmolarity haemolysis. Human erythrocyte membranes were prepared in three ways: washing in hypotonic Tris buffer, pH 7.6, by lysis in isotonic Tris buffer pH 7.6 after incubation at 37 degrees C for 2 hours and by ultrasonication in an isotonic medium, pH 7.6. Analysis of the major polypeptides of the erythrocyte membranes by  sodium dodecylsulphate polyacrylamide gel electrophoresis revealed a selective depletion of a major polypeptide representing glyceraldehyde-3-phosphate dehydrogenase in the membranes prepared by high osmolarity lysis. The pattern of seperation of the remaining polypeptides was identical in the 3 different membrane preparations.


Serum protein changes in coal workers' pneumoconiosis. Differences from the normal were found in the serum proteins of coal workers suffering from pneumoconiosis which were similar to those in subjects suffereing from bronchitis, cancer and rheumatoid arthritis. The differences consisted of decreased albumin and increased globulin contents, and decreased sulphydryl contents, and decreased sulphydryl contents in both albumin and globulin proteins. These differences caused a reduction in the number of protein sulphydryl groups in serum. In pnemoconiotic coal workers the amount of idsulphide-linked cysteine in albumin increased above the normal, the increase tending to depend on the severity of the pneumoconiosis. Apart from this correlation the above differences could not be used to diagnose the class of pneumoconiosis.


Assessment of a new enzyme reaction rate analyser, the Vitatron AKES. We have assessed the function of the Vitatron AKES (Automatic Kinetic Enzyme System) in terms of three enzymes, alpha-hydroxybutyrate dehydrogenase, alanine transaminase and asparate transaminase, and have compared the results with our existing techniques. Overall a good precision and correlation with routine laboratory methods was found. The machine is entirely automatic in operation and is economical in its use of sample and reagents.


Relation of steatosis to cirrhosis.

Relation of steatosis to cirrhosis. Steatosis of the liver is a harmless symptom of disturbed lipid metabolism but not a disease. The cause of the steatosis, and not the fat accumulation by itself, produces cirrhosis. There is no evidence so far in man that cirrhosis may be caused by nutritional deficiencies alone. Even cirrhosis after small bowel bypass procedures seems to be result from metabolic rather than nutritional disturbances.


Physical and mental defect of chromosomal origin in four individuals of the same family. Trisomy for the short arm of 9. A family with the reciprocal translocation t(9;22)(q13;q11) segregating in genetically balanced and unbalanced form is identified. The clinical features of four members with trisomy for the short arm of 9, and the proximal part of the long arm of 9, are described in detail. Features in common are summarized and compared with developmental abnormality observed in other examples of trisomy for the short arm of 9. An attempt is made to delineate further the clinical features commonly seen in trisomy for the short arm of 9.


The unique green phenomenon and colour vision. The mode of inheritance of the Unique Green phenomenon is investigated by a new technique. This involves a spectrometer which generates the stimulus in such a manner that the exact position that is neither blue-green nor yellow-green can be compared with neighbouring positions in the spectrum. This technique is used in conjunction with the single field techniques of Waaler to confrim the mode in inheritance he has suggested: that it is an effect carried on the X chromosome. The placing of the Unique Green point in the spectrum is shown to correlate with the mid-matching point in the blue-yellow axis on the Pickford Nicolson Anomaloscope. It is concluded that there may be a highly photolabile visual pigment present, which absorbs maximally at about the yellow region of the spectrum,


Dominant mesomelic dwarfism of the hypoplastic tibia, radius type. A new type of mesomelic dwarfism in two male siblings and their father is presented. The responsible mutant gene manifests itself phenotypically as a severe dysostosis of the tibia with shortening, bowing and pseudarthrosis and as a mild dysostosis of the radius. The fibulae and ulnae are secondarily affected, but the rest of the skeleton is normal. The disorder has an autosomal dominant mode of inheritance. It can be differentiated rather easily from the already known forms of mesomelic dwarfism.


Friedreich's ataxia in Western Norway.

Friedreich's ataxia in Western Norway. Friedreich's ataxia (FA) was investigated in Western Norway, an area comprising several isolated communities and with a population of 725,000 as at 1 January 1968. The prevalence of FA was estimated to be 1/100,000 in this population. An autosomal recessive mode of transmission appeared likely in all instances. The gene frequency was only 7-9.10 minus 5, but the consanguinity rate was high in the families observed. The mutation rate was relatively high at 1-6.10 minus 5. The clinical features displayed by the 10 examined patients agreed well with those observed by other investigators. Spinal and cerebellar ataxia dominated the clinical picture. In most cases signs of peripheral neuropathy were also observed. Epilepsy was seen in some cases, and also dementia. Unspecific neuropathy, defined according to a scoring system may represent disease manifestation in FA heterozygotes.


Materno-fetal ABO incompatibility as a cause of spontaneous abortion. In a series of 288 spontaneous abortions occurring during the first 16 weeks of gestation, simultaneous karyotyping and ABO blood grouping of 555 of the parents were carried out. In 74 of the 288 chromosome-analyzed abortuses, the ABO blood group of the fetus was determined by the immuno-fluorescence technique and the mixed cell agglutinating reaction in fetal tissue. The results of the blood grouping were compared with the ABO blood group frequencies of 8818 blood donors from the same area. Among abortuses with normal karyotype, a significantly higher frequency of ABO incompatibility was found between mother and fetus (p smaller than 0.005) and also between mother and father (P smaller than 0.01) in comparison with abortuses with abnormal karyotype. Furthermore, the ABO blood group frequencies of the karyotypically normal fetuses deviated significantly from those of fetuses with abnormal karyotypes (P smaller than 0.001). No significant difference was found when the total ABO frequencies of the abortuses and of their parents were compared with the frequencies in the control group. It is concluded that the ABO incompatibility between mother and fetus is likely to be a cause of early spontaneous abortions, but almost exclusively in chromosomally normal abortuses. In the present series of cases, the maximum fraction of abortions caused by materno-fetal ABO incompatibility is estimated to be 18%.


Trisomy 9p in a patient with a de novo 9/15 translocation. Mental retardation, facial dysmorphism, hypertelorism, antimongoloid eye slants, epicanthus, globular nose, malformed ears, bone abnormalities, one flexion crease on 5th finger, simian crease, and speech difficulties with delayed expressivity were found in a girl with trisomy of the short arm of chromosome 9. The 9p+ syndrome was due to a sporadic translocation of the short arm of chromosome 9 onto the short arm of chromosome 15.


Focal dermal hypoplasia symdrome in a male. Focal dermal hypoplasia (Goltz syndrome) is characterized by a pathognomonic abnormality of the skin in association with other congenital defects. There are only seven males among the 52 reported cases. We report the eighth case in a male and evaluate the possible genetic origin of the syndrome. A critical review of the literature provides no evidence for the previously accepted single gene mode of inheritance.


Two cases of 8p trisomy in one sibship.

Two cases of 8p trisomy in one sibship. Two cases of 8p trisomy in one sibship are presented. The father was a balanced carrier of a translocation rcp (8;13) (p11; q34). Case 1 was a 2-year -old boy with multiple minor anomalies and severe mental retardation. Giemsa banding studies revealed that he was trisomic for the greater part of 8p (8p11 yields pter). When his mother became pregnant again, amniocentesis was carried out in the 17th week of gestation. The fetus (Case 2) was shown to have the same 8p trisomy as Case 1. The pregnancy was terminated in the 22nd week. An autopsy revealed no major anomalies. Clinical features of cases with 8 and 8p trisomy are reviewed briefly.


Influence of calcium infusion on calcitonin and parathyroid hormone concentrations in normal and hemodialyzed subjects. Plasma calcitonin and parathyroid hormone concentrations were compared before and after calcium infusion in both hemodialyzed patients and control subjects. Levels of both hormones were significantly higher in patients with chronic renal failure. In the uremic group, calcium infusion inhibited parathyroid hormone secretion but did not affect calcitonin. In the control group, calcium infusion stimulated calcitonin secretion but had no effect on parathyroid hormone.


Plasma angiotensin II, renin, renin-substrate and aldosterone concentrations in acute renal failure in man. Plasma concentrations of angiotensin II, renin, renin-substrate and aldosterone were measured in cases of acute renal failure. Angiotensin II, and renin levels were abnormally high on at least one occasion in nearly all patients. Mean angiotensin II and renin levels were highest in the first ten days of the disease. There was a highly significant positive correlation between concurrent estimations of renin and angiotensin II. Renin-substrate was also frequently elevated, but the correlations with renin and angiotensin II were not statistically significant. Despite the frequently marked elevation of plasma angiotensin II, only 2 of 17 measurements of plasma aldosterone were abnormally high. There was no significant relationship between aldosterone and plasma concentrations of angiotensin II, renin, sodium or potassium. The data are discussed in relation to current hypotheses implicating renin and angiotensin in the pathogenesis of acute circulatory renal failure.


Histidines and renal function.

Histidines and renal function. The results of endogenous renal clearances of 3-methylhistidine and histidine in twelve patients with normal and decreased renal functions are reported. Differences in the renal handling of the amino acids have been established. 3-methylhistidine showed a hyperbolic relationship between serum concentration and inulin clearance: histidine a linear relationship. The percentage tubular reabsorption of 3-methylhistidine was found to be about half that of histidine. The possible use of the measurement of serum 3-methylhistidine concentration as an index of renal insufficiency is discussed.


Plasma concentration and urinary excretion of guanidine derivatives in normal subjects and patients with renal failure. (1)Plasma and urinary levels of methylguanidine, guanidinosuccinic acid and guanidinoacetic acid were measured in normal subjects and in patients with renal failure. (2)Urinary excretion of methylguanidinosuccinic acid was increased in renal failure. Plasma guanidinosuccinic acid concentration was increased and was significantly correlated with the plasma urea concentration. The plasma concentration of methylguanidine was not consistently elevated probably because of an adaptive increase in renal tubular excretion. The excretion of guanidinoacetic acid was decreased in renal failure and plasma concentration remained low. (3) All three guanidines were removed by haemodialysis and their plasma concentrations, although not normal, were much lower in regularly dialysed subjects. (4) Guanidinosuccinic acid and methylguanidine appear to provide alternative pathways for the excretion of nitrogen in patients with renal failure. In advanced uraemia the plasma concentration of methylguanidine and guanidinosuccinic acid may reach levels which have been associated with toxic effects. However, their importance in relation to other uraemic toxins remains difficult to assess.


Pressure-flow relationships in the peripheral circulation of the dog with practolol. 1. The influence of practolol (a proposed beta1-adrenoreceptor antagonist) upon the pressure-flow relationships in the peripheral circulation was studied in eight anaesthetized dogs during right heart by-pass procedures. 2. Practool (1 mg/kg) produced a significant increase in the resistance to venous return which resulted in a significant fall in venous return. 3. There was no significant change in arterial resistance. 4. This study suggests that practolol should not be classified as an exclusive cardioselective beta-adrenoreceptor antagonist.


The role of trochanteric osteotomy in total hip replacement. In a study of 225 hip replacements, 126 had trochanteric osteotomy and 99 did not. Trochanteric osteotomy was found to be invaluable in approaching the difficult, previously operated hip. Even though 81 hips without trochanteric osteotomy had no complications directly related to the operative technique, 19 had significant operative problems. Hips with fixed flexion or external rotation contractures preoperatively presented technical difficulties and postoperative problems avoidable only by trochanteric osteotomy. Complications are encountered with and without osteotomy and various indications for osteotomizing the greater trochanter through a lateral approach to the hip are reviewed on the basis of experience with 184 patients with an average age of 61 years.


Pugh nail fixation of displaced femoral neck fractures. A long term follow-up. Of 695 intracapsular hip fractures with known end results, 80 per cent occurred in women whose average age was 71 years; of 101 consecutive undisplaced intracapsular fractures reported up to 1959, 81 were treated by internal fixation and 20 nonoperatively and all united but 11 per cent developed necrosis. From 1937 to 1959, displaced intracapsular fractures at St. Luke's Hospital were generally treated by closed reduction and Smith-Petersen nail fixation. From 1948 to 1952, 22 per cent of these fractures failed to unite, but from 1952 to 1959, 44 per cent failed to unite. Many of the failures were due to the Smith-Petersen nail backing out. These poor results inspired another device which might provide better fixation and prompted the use of the telescoping Pugh nail. From 1955 to 1971, the telescoping Pugh nail was used in 256 displaced intracapsular fractures with known end results. Ninety per cent united, and avascular necrosis was seen in 17 per cent of the united fractures. Since many of the patients with avascular necrosis has no pain, they were considered satisfactory results. Subtracting these 17 per cent of 256 patients with displaced intracapsular fractures of the femoral neck may be evaluated as examples of satisfactory results with the Pugh nail.


The use of wire mesh in total hip replacement surgery. Metal mesh is helpful in relation to two complications of total hip replacement; namely, migration of the trochanter and fatigue fracture of the medial wall of the acetabulum. Mesh is applied over the greater trochanter in instances when the trochanter is excessively porotic and would crush as the wires are tightened. It is used to "recapture" the trochanter or trochanteric fragments if migration has occurred. The wires are then brought through the mesh and tied over the mesh, thus distributing the load widely across the porotic trochanter. The problem of a thin medial acetabular wall is dealt with by medially embedding a hemisphere of metal mesh in the methacrylate creating the effect of reinforced concrete. This increases the physical properties of the methacrylate and helps to distribute the load to the public, ischial and iliac portions of the socket. Potentially this approach will be useful in treating fatigue fractures of the medial acetabular wall after total hip replacement. Thirteen patients treated using chrome cobalt metal mesh in association with total hip replacement are presented.


Shear strength of self-curing acrylic cement. The average shearing strength of surgical Simplex P bone cement has been experimentally evaluated and found to be 5,762 plus or minus 180 psi. The average shearing strength for compact bone is about 10,000 psi. Therefore surgical Simplex P does not resist shear forces as well as compact bone and should not be used as a substitute for bone whenever possible. The inclusion of 10 per cent barium sulfate U.S.P. for radiographic purposes does not adversely affect the shear strength of the cement. This amount of barium is the same percentage by weight as that found in radiopaque Simplex P in clinical usage today. Varying the loading rate between 0.005 and 0.5 in/min slightly affected the magnitude of the shear force at failure. A comparison of the effect of short term curing times on the magnitude of the shear force at failure reveals that surgical Simplex P strengthens with time. The curing periods varied from 2 to 168 hours.


Biomechanical considerations of multiple-component hip prostheses. Analysis of three failures of the Lippman transfixation hip prosthesis. Three cases are presented and analyzed in which a Lippman Transfixion Hip Prosthesis had to be replaced because of the discomfort of the patient. In each case, there was evidence of wear between the head of the prosthesis and the flange. The different wear patterns indicated problems which exist in the alignment of component parts of the prosthesis. In each case there was low grade sepsis to which the debris may have contributed. Because of phagocytosis, amount of debris accumulation was difficult to evaluate. The factors which appear to have contributed to the amount of debris accumulation were: the length of time the prosthesis had been used; the degree of alignment and amount of debris which may be formed and is phagocytized; the degree of manufacturing control. The design of this prosthesis incorporated mechanical problems which are generally undesirable because of: the eventual deformation of the end of the pivot rod or hole in the head of the prosthesis: progressive loosening of the movement due to this and inherent malalignment; the difficulty in fabrication, assembly and installation of the prosthesis because of the multiplicity of parts; the difficulty in maintaining adequate control of surface finishes.


Congenital absence of lumbar articular facets. Report of two cases. X-ray evidence of an absent lumbar facet is usually considered to be indicative of the presence of an osteolytic bone lesion but on rate occasions may be due to a congenital anomaly. Two cases of the congenital absence of a lumbar superior articular facet suggest that this anomaly is not symptom-producing, and in one case was discovered incidentally in a patient without back pain yet led to the performance of a major surgical diagnostic operation. While, rare, a greater awareness of this condition, as clearly defined in the literature on the subject, might occasionally eliminate the need for a similar surgical procedure.


Surgery of the shoulder in rheumatoid arthritis. A report of nineteen patients. Surgery of the shoulder has been neglected in the treatment of rheumatoid arthritis. Nineteen patients are reported to demonstrate that if conservative management fails, surgical treatment is indicated and worthwhile.


Femoral neuropathy as a complication of heparin anticoagulation therapy. Femoral nerve compression by retroperitoneal hematoma is an uncommon but significant complication of Heparin anticoagulation. The orthopedic surgeon today, utilizing anticoagulation more frequently than ever, must be ever mindful of the early warning signs and symptoms of this syndrome.


Fracture of the axis arch. "Hangman's fracture" of the cervical spine. Fifteen patients with fracture of the axis arch ("Hangman's Fracture" of the cervical spine) reviewed with regard to the clinical features, mechanism of injury and management, present a relatively high rate of cord involvement (11 patients) and injuries around the jaw (5 patients). All of the injuries occurred in civilian accidents. The jaw injuries suggest the inclusion of an extension-distraction force. Treatment was conservative in all patients, even in those with severe displacement. Union generally occurred in about 3 months. The only complaint in those patients with union in the displaced position, was limitation of lateral rotation of the head.


A review of the Bristow operation for recurrent anterior shoulder dislocation in athletes. Twenty-four recurrent dislocating shoulders, in patients ranging from 15 to 26 years, were evaluated after surgical treatment using the Bristow procedure. The operative procedure is discussed in detail recommending the use of an A-O malleolar compression screw, because of ease in insertion, to fix the caroacoid process to the anterior scapular neck. The Bristow procedure as described is an effective operation for achieving shoulder stability while maintaining nearly a complete range of motion in most cases. There was one case of recurrent dislocation after surgery which is described in detail. Six of 24 shoulders demonstrated some loss of external rotation, with the maximum being only 10 degrees. Five of 9 patients had some difficulty in throwing when the dominant extremity was treated. This did not appear to be related to any possible decrease in external rotation.


Report on compound dislocation of the elbow with entrapment of the brachial artery. Entrapment of the brachial artery within a compound dislocated elbow joint seems not to have been reported previously. Brachial artery rupture is the usual vascular injury associated with a compound elbow dislocation. A review of the surgical literature suggests that wide spectrum of disability may follow interruption of brachial artery flow at the elbow. While most patients experience no immediate or late ischemic symptoms because of the rich collateral network about the elbow, intermittent claudication or gangrene of the hand is possible and has been well-documented in the literature. To assure adequate circulation to the hand and prevent potential complications, reanastomosis or venous graft replacement of the damaged arterial segment is recommended at the time of traumatic disruption of the brachial artery.


Restoration of elbow flexion by a new operative technique. In order to treat some of the awkward and unusual problems and to avoid some of the complications associated with paralytic elbows, the distal part of the flexor carpi ulnaris is detached and the muscle is freed up to its neurovascular bundle. The tendon is turned upon itself, its distal end is passed through a subcutaneous tunnel to the upper arm, and fixed to the humerus by staples. A posterior splint is applied for a period of 6 weeks followed by supervised graduated active elbow flexion exercises.


Osteoid-osteoma of the radius. Report of a case. This case is a report of a 9-year-old boy with an osteoid osteoma in the distal radius, an unusual location. The tumor was remarkably large in size, and pain unrelieved by aspirin. Osteoid-osteomatat have been described in just about every bone in the skeleton. Lower extremity involvement is more frequent than upper in all series and incidence is much higher in males than in females. Pain is the major complaint, both night and day. The response to aspirin is variable. The diseases is most frequently encountered in the second decade of life.