The stability of osteosyntheses bridging defects. Segmental defects of 2 cm in the femoral midshaft of dogs were bridged with either single, double or a single plate and cortical bone graft. The massive bone transplant was fixed with screws opposite the plate in order to diminish harmful bending loads. The biomechanical behavior was tested under continuous increasing axial stress. The combined osteosynthesis of internal plate and contralateral cortical bone graft fixation increased the stability in the defect region significantly (see Figs. 3 and 4). The results of our tests are discussed with respect to the basic problem that the biological behavior of transplanted cortical bone depends mainly on absolute stability in the transplanted area. We think--although the transplantation of autologous cancellous bone should be favoured--the transplantation of massive bone grafts still has its indications under well defined conditions particularly when good mechanical stability is present.


[Symptoms and therapy of spontaneous osteonecrosis of the medial femoral condyle in elder patients (author's transl)]. The author reports on symptoms, therapy and results of a follow-up of 17 patients with the rare disease of osteonecrosis of the medial femoral condyle. The therapy depends on the extend of the necrosis, the axis of the leg and the results of scintigraphy or scintimetry and arthrography or arthroscopy. Small necroses can be treated conservatively, but in case of a genu varum a valgus-osteotomie should be performed. Bigger necroses are bored or bolted combined with a valgus-osteotomie, if necessary. Extensive osteonecroses can only be treated by partial endoprosthesis or autologue bone-cartilage-transplantation.


Mass lesion of the breast after augmentation mammoplasty. Examination of the breast after augmentation mammoplasty may be relatively easy, but the evaluation of a mass lesion presents particular possibilities and problems. Closed compression capsulotomy occasionally results in rupture of the gel prosthesis, and when silicone contacts the surrounding breast tissue, a firm granuloma can result. A patient after augmentation mammoplasty had a mass lesion of the breast following trauma. At operation, the gel prosthesis was found to have ruptured and resulted in a silicone granuloma. A history of closed compression capsulotomy or trauma is important in the preoperative evaluation of such patients, and both the surgeon and the patient should be prepared to procede with replacement of the implant at the time of biopsy.


Vascular substances that modulate blood-to-vessel interactions. The vessel wall contains powerful inhibitors of thrombogenesis. One substance, a proteoglycan, is a strong anticoagulant but has only a limited effect on platelet aggregation. It prolongs the thrombin clotting time and partial thromboplastin time, but only blocks platelet aggregation induced by thrombin. Another vessel wall constituent, a prostaglandin derivative (prostacyclin), is a potent inhibitor of platelet aggregation. It antagonizes platelet aggregation induced by a variety of agents including adenosine diphosphate, collagen, arachidonic acid and thrombin; however, its only effect on coagulation is through the inhibition of platelet factor-3 release. Proteoglycans and prostacyclin comlement each other's antithrombotic activities, and together serve to limit the hemostatic response of blood to vessel wall injury. Vessels devoid of the intima continue to produce prostacyclin. Prostacyclin produced by these vessels is probably more important than that produced by vessels with the intima in the prevention of thrombus deposition.


[Morphofunctional characteristics of the pancreas in the progeny from females with experimental hypothyroidism]. Histophysiological pancreatic indices were studied in 1-, 21- and 30-day-old offsprings of white non-lineal female rats that were given antithyreoid drug mercasolil in the dose 3 mg/kg of body weight during pregnancy and lactation. Chemical inhibition of maternal thyreoid function results in decreasing weight index of the offspring's pancreas, in decreasing section area of the terminal secretory parts, in narrowing the homogenous zone of exocrine pancreocytes, in decreasing the portion occupied by the endocrine part on the section area, as well as in decreasing the index of B/A cells ratio of pancreatic islands and of nuclear volume of basophilic insulocytes. It is possible to conclude from the data obtained that maternal hypothyreosis produced by mercasolil unfavourably affects the process of structural and functional setting and the status of the pancreas in the offspring.


[Structural organization of the juxtaglomerular complex of the kidney and its changes in the modelling of renovascular hypertension]. While studying a normal juxtaglomerular complex (JGC) under light optic and electron microscope, histotopographic dependence in distribution of its components in the renal cortical substance was stated. In normal periglomerular cells, processes of synthesis and excretion of renine granules are taking place that is demonstrated by the presence of young maturing, mature forms and subsequent excretion of their contents. In 157 rats during the development of experimental renovascular hypertension, correlation of the JGC of various classes of granularity was increasing towards the latter. Hyperfunction of the periglomerular cells is dynamically performed transferring from the accumulative type into the secretory one; this is proved by both changing in granularity index and correlation in stages of granule formation and excretion of their contents. Juxtavascular cells (Goormaghtigh's cells) and mesangiocytes are the reserve for renine production. Cellular reaction of macula densa is manifested in metaplasia of epitheliocytes of the distal part of the nephron, in increasing index of macula densa and in ultrastructural changes.


External septorhinoplasty.

External septorhinoplasty. One of the disadvantages of the usual endonasal technique of rhinoplasty is the poor surveyability of the surgical field. By joining the left and right marginal incision via a transverse columellar incision and elevating the skin of the columella and the dorsum nasi, the infrastructure of the nose can be exposed. The good exposition results in a meticulous surgery of the nasal dorsum, precise correction of the triangular cartilages, good access to the septum and more a-curate augmentation procedures of the prespinal area, columella or nasal dorsum. This "external" approach is more or less a synthesis of the subcutaneous endonasal method and surgery under visual control, with the only sacrifice of a small scar which has marked advantages on the other hand. The results of the external approach to septorhinoplasty in 30 patients with cosmetic and functional complaints are discussed. No complications attributable to the method were seen. Especially for difficult cases as revisional operations, congenital nasal deformities and multiple traumatic damaged noses the external approach appears to be very useful.


[Nystagmometry and biocybernetics (author's transl)]. Nystagmus can be predicted or simulated by means of mathematical models. If the simulation seems to be successful the parameters of the model may be used for an adequate description of the nystagmic response. Considering the biocybernetics of the vestibulo-oculomotor system a minimal extent of computer-nystagmometry is determined. The efficient application of this method requires the knowledge of standard values for the involved parameters. These values have been determined for tests with sinusoidal rotatory stimulation. Age dependent nominal values can be computed and are compared with actual results. The differences are divided by the standard deviation; values less than 2 are supposed to be normal. Thus a first step of automatic assessment of the vestibular system's function becomes possible.


The vascular mantles of labyrinthine bone; a comparative anatomical study. The vascular mantles of the endochondral layer of labyrinthine bone in dog (Canis f. intermedius Woldrich) and monkey (Pithecus fascicularis Raffl.) were examined by means of light and transmission electron microscopy and compared to those in man. A three-dimensional reconstruction of vessels and their vascular mantles is demonstrated. It is shown that these mantles only cover parts of the vessel. Using polarized light one can find vascular mantles containing lamellar fragments. By means of transmission electron microscopy a canalization of perivascular mantle matrix can be demonstrated. The ultrastructure of cells in mantle zones shows that these cells are osteoblasts, osteocytes, and osteoclasts. Signs of osteocytolysis are found. The importance of oxygenation via canalization of the vascular mantle matrix is discussed as well as the importance of lacking biomechanical stress in endochondral layer as to their influence on formation of vascular mantles. According to the "embryologic character" of endochondral layer an analogy between incomplete osteons which are to be found in developing woven bone and vascular mantles is considered.


Living related renal transplantation: experience in 22 cases. Twenty-two living related renal transplant operations have been performed at Prince Henry's Hospital over the last seven years. Donors have been accepted for nephrectomy only after exhaustive examination of their health and serach for renal disease. The one and three year graft survival rates have been 85% and 64% respectively. Only two recipients have died, and recipient morbidity has been low. Donors have not suffered any serious complication from nephrectomy. It is concluded that living related renal transplantation has many advantages over cadaveric renal transplantation and is a relatively safe procedure for the donor, provided that rigid criteria are used in donor selection.


Transplant renal artery stenosis.

Transplant renal artery stenosis. Renal artery stenosis occurred in 13.5% of 229 consecutive cadaver renal transplants performed at the Royal Melbourne Hospital over an eight and a half year period. Clinical and laboratory indices which suggested the diagnosis were examined. The presence and severity of hypertension were of little predictive value, while deterioration of renal function for which other causes had been excluded and the histological appearance of renal biopsy speciments were valuable in suggesting the diagnosis. A selective approach in both investigation and attempted surgical repair is recommended.


Cancer following renal transplantation.

Cancer following renal transplantation. Ninety-nine (21%) of 471 patients who survived with functioning grafts for at least six months following renal transplantation developed cancer. Of these 76 (77%) had skin malignancy, 29 (29%) had malignancy affecting other organs, and six had cancer of both skin and other organs. In patients with skin cancer squamous cell carcinoma (SCC) was three times as frequent as basal cell carcinoma (BCC). SCC tended to be multiple, recurrent and aggressive. Seven (12%) patients with SCC developed metastases of whom five died. Cancers other than skin included reticulum cell sarcoma (9), acute leukaemia (2) and cancers involving the gastrointestinal (5), genitourinary (11) and respiratory (2) systems. Incidence of cancer in patients surviving beyond one, five and nine years after operation was 98/428 (23%), 70/179 (39%) and 20/45 (44%) respectively. In 31 patients who died more than five years after transplantation cancer was the major cause in eight (26%). For the types of cancers recorded estimates show allograft recipients to be at increased risk when compared with the age-matched Australian population by factors which varied from 300 times for reticulum cell sarcoma to 1.8 times for invasive carcinoma of the cervix. The full extent of the threat of cancer in immune suppressed transplant recipients remains to be determined.


Gastrointestinal complications following renal transplantation. Gastrointestinal complications occurred in 19 of 290 recipients (6.6%) of the 325 cadaveric renal allografts undertaken between September 1969 and December 1978. The mortality was 42.1%. Upper gastrointestinal complications, principally haemorrhage, occurred in 12 patients (4.1%), 11 of whom were males, usually within four months of transplantation, and often associated with acute rejection and its treatment. Surgery was required in five patients. The overall mortality was 16.7%. Colonic complications occurred in five patients (1.7%), four of whom died, the absence of specific signs having led to a significant delay in diagnosis. One patient died from abdominal vascular disease, and one from carcinoma of the gallbladder. To decrease the high morbidity and mortality, both medical and appropriate surgical prophylaxis for peptic ulceration and diverticular disease are necessary, as is an awareness of the transplant recipient's propensity to develop a gastrointestinal complication at any time, up to years after transplantation. Early recognition and treatment of such complications are essential.


Lymphocele after renal transplantation.

Lymphocele after renal transplantation. Lymphoceles occurred in 25 of 115 patients after renal transplantation in the Oxford Unit. Signs of obstruction or pressure were produced in 16 of these 25 patients (15%), while nine were detected on a routine ultrasound scan. The 16 symptomatic lymphoceles were treated successfully by aspiration or surgical fenestration into the peritoneal cavity . Of the possible causes examined, diathermy and division of iliac lymphatics seemed to be the most likely reason for this high incidence. Since a technique of ligating or clipping the iliac lymphatics has been adopted, no lymphoceles have occurred in the subsequent 70 transplants.


Further experience with an external ureterovesical anastomosis in renal transplantation. Review of the results of the use of an external ureterovesical anastomosis in 266 renal transplantations showed that urinary fistulae occurred in 34 patients (12.8%), and ureteric obstruction in six (2.3%). The fistulae were due to technical failure of the anastomosis in 13 patients, to distal ureteric necrosis in 13, to total ureteric necrosis in six, and to other causes in two. Fistula management was successful in 26 cases (76.5%), but multiple operations were often necessary and wound complications frequent (41.2%). The continuing high incidence of urological complications following ureterovesical anastomosis has resulted in increasing use of ureteroneocystostomy as the primary form of urinary reconstruction after transplantation in this unit.


A vascular surgeon's approach to renal transplantation. The blood vessels and blood supply are of first importance in organ transplantation, and the use of established vascular surgical principles and techniques can simplify renal grafting and reduce its risks and complications. This paper describes a vascular surgeon's approach to the problems of donor nephrectomy, kidney insertion, and the avoidance and management of complications, based on the surgical experience in the Royal Melbourne Hospital of some 350 transplants.


Purse string placement for staple anastomosis using the end-to-end anastomosis stapling instrument. There may be technical difficulties in the use of recommended clamp for the insertion of the purse-string suture during the construction of an end-to-end staple anastomosis. Hand sewing the purse string eliminates some of the problems, but unless the suture is positioned within a few millimetres of the cut edge of the bowel, ischaemic tissue may be included in the staple line. In dogs, this leads to anastomotic dehiscence. The anastomosis may, however, be protected by excising the ischaemic tissue and reinforcing the staple line with sutures. An "over and over" purse-string technique is now preferred to minimize the risk of this occurring.


A comparison of flushing fluids for initial perfusion of kidneys for transplantation. Four solutions for initial flushing of kidneys prior to transplantation were tested under conditions designed to resemble those of clinical cadaveric donor renal transplantation. The experimental model was the dog subjected to bilateral nephrectomy with renal autograft. Kidney grafts were subjected to 15 minutes' anoxia in vivo, 30 minutes' warm ischaemia at 37 degrees C ex vivo, and two hours' cold ischaemia before reimplantation. The four solutions used were Collins (C3), Perfudex (P), hyperosmolar citrate (HC), and a solution of bovine albumin containing dog red blood cells (BBA). Effects of the flushing fluids were compared by parameters relating to dog survival, renal function, and serum enzyme levels. With all parameters studied the best results occurred in HC perfused kidneys. Results with BBA perfusion were marginally worse, while C3 perfused kidneys were again inferior. P perfused kidneys clearly did least well. The results support the use of HC for clinical application.


Effect of transdermally administered scopolamine in preventing motion sickness. The efficacy of transdermally administered scopolamine was compared with the efficacy of oral dimenhydrinate and placebo therapy in the prevention of motion-induced mausea in a vertical oscillator; medications were administered on a double-blind cross-over basis, with the order of treatments counterbalanced. Thirty-five subjects known to be susceptible to the stimulus were utilized. A placebo effect reduced the motion sickness incidence (MSI) from 100% to 59%. Administration of dimenhydrinate reduced the MSI to 32%, and use of the transdermal therapeutic system scopolamine (TTS-scopolamine) further reduced the MSI TO 16%. TTS-scopolamine afforded 73% protection against motion-induced nausea, compared to 46% protection with dimenhydrinate. The TTS-scopolamine is designed to remain in the body for 72 hours, providing advantages over intramuscular or oral administration of scopolamine, which include reduced daily dosage, and an effective alternate to the gastrointestinal tract for administrating medication at times of gastrointestinal distress.


Characterization of a picornavirus isolated from broiler chicks. The rectal content of an apparently normal 1-week-old broiler chick yielded an unclassified cytopathogenic virus with cytopathic effects of the round type. It was identified as a picornavirus from the following: ribonucleic acid in the viral core; virus growth in the cytoplasm; a particle about 30 nm in diameter; resistance to ethyl ether, chloroform, trypsin, and acid; relative heat-lability; and partial stabilization to molar magnesium chloride. The virus was stable under freezing and thawing, and sonication. It was distinguished from avian encephalomyelitis virus by the neutralization test.


Prophylactic and therapeutic activity of Rofenaid-40A in an experimental Escherichia coli airsac infection in chickens. Rofenaid at a 0.02% dose level in feed was effective prophylactically and therapeutically against an experimentally induced Escherichia coli airsac infection in chickens. The activity of Rofenaid compared very favorably with that of the approved dose level of NF-180. Furthermore, the prophylactic use of Rofenaid did not interfere with the therapeutic efficacy of NF-180.


Candidiasis in cockatiel nestlings and mucormycosis in a pigeon. Deaths of cockatiel nestlings caused by Candida albicans, and of a pigeon caused by air-sac infection with Absidia corymbifera, are described. Lesions in the cockatiels were pseudomembranes and ulcers in the mouth, esophagus, and crop. In the pigeon the air sacs were thickened and contained a grayish gelatinous exudate.


Purification of the membrane-bound hydrogenase of Escherichia coli. The membrane-bound hydrogenase (EC class 1.12) of aerobically grown Escherichia coli cells was solubilized by treatment with deoxycholate and pancreatin. The enzyme was further purified to electrophoretic homogeneity by chromoatographic methods, including hydrophobic-interaction chromatography, with a yield of 10% as judged by activity and an overall purification of 2140-fold. The hydrogenase was a dimer of identical subunits with a mol.wt. of 113,000 and contained 12 iron and 12 acid-labile sulphur atoms per molecule. The epsilon 400 was 49,000M-1 . cm-1. The hydrogenase catalysed both H2 evolution and H2 uptake with a variety of artificial electron carriers, but would not interact with flavodoxin, ferredoxin or nicotinamide and flavin nucleotides. We were unable to identify any physiological electron carrier for the hydrogenase. With Methyl Viologen as the electron carrier, the pH optimum for H2 evolution and H2 uptake was 6.5 and 8.5 respectively. The enzyme was stable for long periods at neutral pH, low temperatures and under anaerobic conditions. The half-life of the hydrogenase under air at room temperature was about 12 h, but it could be stabilized by Methyl Viologen and Benzyl Viologen, both of which are electron carriers for the enzyme, and by bovine serum albumin. The hydrogenase was strongly inhibited by carbon monoxide (Ki = 1870Pa), heavy-metal salts and high concentrations of buffers, but was resistant to inhibition by thiol-blocking and metal-complexing reagents. These aerobically grown E. coli cells lacked formate hydrogenlyase activity and cytochrome c552.


The exchange of histidine C-2 protons in superoxide dismutases. A novel method for assigning histidine-metal ligands in proteins. The rates of exchange of the C-2 protons of histidine residues in copper-zinc superoxide dismutase are substantially decreased by metal ion binding. This observation was used to distinguish between ligand and non ligand histidine residues in bovine and yeast copper-zinc superoxide dismutases; the effect was shown to depend only on metal ion co-ordination and not as a consequence of concomitant changes in protein structure. Selective deuteration of the zinc-only proteins at pH (uncorrected pH-meter reading) 8.2 and 50 degrees C resulted in the distinction between copper and zinc ligand resonances in the 1H n.m.r. spectrum of the enzymes. This method is proposed as a generally applicable technique for identifying histidine residues as ligands in metalloproteins.


Comparison of glyoxalase I purified from yeast (Saccharomyces cerevisiae) with the enzyme from mammalian sources. Glyoxalase I from yeast (Saccharomyces cerevisiae) purified by affinity chromatography on S-hexylglutathione-Sepharose 6B was characterized and compared with the enzyme from rat liver, pig erythrocytes and human erythrocytes. The molecular weight of glyoxalase I from yeast was, like the enzyme from Rhodospirillum rubrum and Escherichia coli, significantly less (approx. 32000) than that of the enzyme from mammals (approx. 46000). The yeast enzyme is a monomer, whereas the mammalian enzymes are composed of two very similar or identical subunits. The enzymes contain 1Zn atom per subunit. The isoelectric points (at 4 degrees C) for the yeast and mammalian enzymes are at pH7.0 and 4.8 respectively; tryptic-peptide ;maps' display corresponding dissimilarities in structure. These and some additional data indicate that the microbial and the mammalian enzymes may have separate evolutionary origins. The similarities demonstrated in mechanistic and kinetic properties, on the other hand, indicate convergent evolution. The k(cat.) and K(m) values for the yeast enzyme were both higher than those for the enzyme from the mammalian sources with the hemimercaptal adduct of methylglyoxal or phenylglyoxal as the varied substrate and free glutathione at a constant and physiological concentration (2mm). Glyoxalase I from all sources investigated had a k(cat.)/K(m) value near 10(7)s(-1).m(-1), which is close to the theoretical diffusion-controlled rate of enzyme-substrate association. The initial-velocity data show non-Michaelian rate saturation and apparent non-linear inhibition by free glutathione for both yeast and mammalian enzyme. This rate behaviour may have physiological importance, since it counteracts the effects of fluctuations in total glutathione concentrations on the glyoxalase I-dependent metabolism of 2-oxoaldehydes.


Purification and properties of Klebsiella aerogenes D-arabitol dehydrogenase. An Escherichia coli K12 strain was constructed that synthesized elevated quantities of Klebsiella aerogenes D-arabitol dehydrogenase; the enzyme accounted for about 5% of the soluble protein in this strain. Some 280 mg of enzyme was purified from 180 g of cell paste. The purified enzyme was active as a monomer of 46,000 mol.wt. The amino acid composition and kinetic constants of the enzyme for D-arabitol and D-mannitol are reported. The apparent Km for D-mannitol was more than 3-fold that for D-arabitol, whereas the maximum velocities with both substrates were indistinguishable. The enzyme purified from the E. coli K12 construct was indistinguishable by the criteria of molecular weight, electrophoretic mobility in native polyacrylamide gel and D-mannitol/D-arabitol activity ratio from D-arabitol dehydrogenase synthesized in wild-type K. aerogenes. Purified D-arabitol dehydrogenase showed no immunological cross-reaction with K. aerogenes ribitol dehydrogenase. During electrophoresis in native polyacrylamide gels, oxidation by persulphate catalysed the formation of inactive polymeric forms of the enzyme. Dithiothreitol and pre-electrophoresis protected against this polymerization.


Impairment of the catalytic activity of Escherichia coli ribonucleic acid polymerase by a unique reaction of 4-chloro-7-nitrobenzofurazan. Escherichia coli RNA polymerase loses 55-65% of its catalytic activity on reaction with Nbf-Cl (4-choro-7-nitrobenzofurazan). This partial inactivation was shown to be the result of specific impairment of RNA-chain elongation, since initiation of RNA chains was not altered after treatment with Nbf-Cl. The site of reaction was shown to be a unique thiol on the beta-subunit. This thiol is not accessible to reaction with 5,5'-dithiobis-(2-nitrobenzoic acid). No protection of the enzyme against reaction with Nbf-Cl could be obtained with the inhibitor rifamycin nor with calf thymus DNA, GTP or 1,10-phenanthroline, indicating that the unique thiol is probably not within the active site. The specific impairment of RNA-chain elongation thus appears to be the result of a local conformational change which leaves chain initiation unimpaired. Changes observed in the tryptophan fluorescence spectrum of the enzyme or reaction with Nbf-Cl are consistent with formation of a Meisenheimer complex of the reagent with a nucleophilic group on the enzyme near the reactive thiol. It is proposed that formation of such a complex and a subsequent conformational change renders this thiol unusually susceptible to reaction with Nbf-Cl.


The anion-transport protein of the human erythrocyte membrane. Studies on fragments produced by pepsin digestion. We have studied the fragmentation by pepsin in 1 M-acetic acid of the erythrocyte anion-transport protein in erythrocyte membranes. The location of the fragments obtained was determined by radioiodinating the protein with the use of lactoperoxidase, and identifying the labelled peptides obtained in peptide "maps" of thermolysin digests of the fragments. Three of the fragments were found to be related overlapping products, and shared a common C-terminus. The major site of pepsin cleavage leading to the C-termini of these fragments was shown to be close to the major site of extracellular cleavage of the protein by proteinases active at a neutral pH. Another two fragments were isolated and shown to be derived from the C-terminal portion of the protein. No well-defined large radioactive fragments of the protein were solubilized from the membrane by pepsin in 1 M-acetic acid, the bulk of the radioactivity attributable to the anion transport protein being recovered in very small fragments that could not be resolved by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Our results suggest that the polypeptide chain of the anion-transport protein emerges at the extracellular face of the membrane 8000-13000 daltons on the N-terminal side of the major site of extracellular cleavage of the protein by proteinases that are active at a neutral pH.


Synthesis of cytoplasmic membrane during growth and division of Escherichia coli. Dispersive behaviour of respiratory nitrate reductase. We have used the penicillin selection method of Autissier & Kepes [(1972) Biochimie 54, 93--101] to study the segregation of membrane-bound respiratory nitrate reductase (EC 1.9.6.1) in Escherichia coli for the three generations after cessation of nitrate reductase synthesis caused by withdrawal of nitrate from the growth medium. We also included a physical separation procedure that permitted direct assay for nitrate reductase activity among all fractions produced by the penicillin selection method. We conclude that the segregation of nitrate reductase after cell division is dispersive, and not semi-conservative as proposed by Autissier & Kepes (1972).


Tissue and subcellular distribution of the lectin from Datura stramonium (thorn apple). Plants of Datura stramonium (thorn-apple) were dissected into their component tissues and examined for the presence of the Datura lectin. This lectin was easily detected in seeds and in various parts of the flowers of adult plants. Traces were also found in green (emerged) cotyledons and roots of seedlings. The specific lectin activity in seeds contained within the fruits increased as the seeds matured. Mature seeds were homogenized in sucrose and separated by differential centrifugation into four fractions, three of which were clearly of distinct composition. Most of the lectin activity sedimented with the low-speed (cell-wall/protein-body) pellet, but a similar specific activity was recovered from the other fractions. However, if EDTA was included in the homogenization medium, three or four times more lectin activity was recovered in the soluble fraction. Immunofluorescent staining of formaldehyde-fixed sections showed that the lectin was localized in the cytoplasm, with little associated with cell walls. The possible relevance of these results to the function of the lectin in plant cells is discussed.


The reaction of cytochrome omicron in Escherichia coli with oxygen. Low-temperature kinetic and spectral studies. 1. The reactions of cytochrome omicron in intact cells of aerobically grown Escherichia coli with O2 and CO have been studied at low temperature. 2. Flash photolysis of CO-liganded cells in the presence of O2 and at temperatures between -79 and -102 degrees C results in the oxidation of kinetically heterogeneous beta-type cytochromes (including cytochrome omicron), but not of cytochrome d. 3. The reaction of reduced cytochrome omicron with O2 involves O2 binding to give intermediate(s) with spectral characteristics similar to that of the reduced oxidase-CO complex. Observation in the alpha-region suggests that unexplained ligand dissociation accompanies the initial O2 binding. 4. At temperatures below -98 degrees C, an 'end point' in the reaction is reached; further reaction and oxidation of cytochrome omicron occurs on raising the temperature. 5. There is a linear relationship between the rate of formation of the oxygen compound and the O2 concentration up to 0.5 mM. The second-order constant for its formation (k+1) is 0.91 M-1.S-1 at -101 degrees C. The reaction is not readily reversible, the value of k-1 being 1.4 X 10(-5) S-1 and the kd 1.5 X 10(-5) M. 6. The energy of activation for this reaction at low temperatures is 29.9kJ (7.1 kcal)/mol. 7. The reaction with O2 is distinguished from that with CO by the markedly lower velocity and high photolytic reversibility of the latter. 8. Comparisons are drawn between the intermediate(s) in the O2 reaction of cytochrome omicron in E. coli and those identified in other bacteria and in the reaction of cytochrome aa3 with O2.


Two forms of 'malic' enzyme with different regulatory properties in Trypanosoma cruzi. 1. Cell-free extracts from culture epimastigotes of Trypanosoma cruzi contained two forms of NADP+-linked 'malic' enzyme (EC 1.1.1.40), I and II, with the same molecular weight but different electrophoretic mobilities and kinetic and regulatory properties. 2. The apparent Km for L-malate was lower for 'malic' enzyme I, with hyperbolic kinetics, whereas the kinetic pattern for 'malic' enzyme II was slightly sigmoidal (h 1.4). The kinetics for NADPH were hyperbolic for 'malic' enzyme I, and very complex for 'malic' enzyme II, suggesting both positive and negative co-operativity. 3. 'Malic' enzyme II was markedly inhibited by adenine nucleotides; AMP was the the most effective, at least in the presence of an excess of MnCl2. 'Malic' enzyme I was much less affected by the nucleotides. Both enzyme forms were inhibited by oxaloacetate, competitively towards L-malate, but the apparent Ki for 'malic' enzyme I (9 microM) was 10-fold lower than the value for 'malic' enzyme II. 'Malic' enzyme II, but not 'malic' enzyme I, was activated by L-aspartate and succinate (apparent Ka of 0.12 and 0.5 mM respectively); the activators caused a decrease in the apparent Km for L-malate and, to a lesser extent, in the apparent Km for NADP+. L-Aspartate, but not succinate, increased the apparent Vmax. 4. The inhibition by AMP suggests regulation by energy charge, with the L-malate-decarboxylation reaction catalysed by 'malic' enzyme II fulfilling a biosynthetic role. The inhibition by oxaloacetate and the activation by succinate are probably involved in the regulation of the 'partial aerobic fermentation' of glucose which yields succinate as final product. The activation by L-aspartate would facilitate the catabolism of this amino acid, when present in excess in the growth medium.


Benzene from bacterial cleavage of the carbon-phosphorus bond of phenylphosphonates. An organism, identified as a strain of Klebsiella pneumoniae, was proved by direct assay to utilize ionic methyl phenylphosphonate as sole phosphorus source. One product from C-P-bond cleavage was identified as benzene by combined g.l.c.-mass spectrometry. The molar yield of benzene from the phosphonate was 89%.


A comparative study of methyldopa and labetalol in the treatment of hypertension. 1 Twenty patients with essential hypertension completed a double-blind, dose-tritrated, cross-over comparison of methyldopa and labetalol. 2 Average lying BPs (systolic/diastolic) were reduced by 28/15 mmHg with methyldopa and by 23/15 mmHg with labetalol. 3 Average standing BPs (systolic/diastolic) were reduced by 29/14 mmHg with methyldopa and by 29/15 mmHg with labetalol. 4 Both lying and standing heart rates were reduced with labetalol. 5 It is concluded that the antihypertensive properties of labetalol and methyldopa are similar but that larger patient populations are needed to study the relative incidence of subjective adverse effects.


A multicentre open trial of labetalol in New Zealand. 1 In a multicentre open trial, labetalol was given to 128 patients in ten centres. Forty-three patients had not previously received antihypertensive therapy; the remainder (85 patients) had been on antihypertensive therapy with either unsatisfactory BP control or troublesome side-effects. 2 Thirty-two patients were withdrawn from the trial in the first 6 months of therapy, 24 (19% of the total) because of side-effects. 3 Control of BP was generally satisfactory or considerably improved. Other drugs (usually a diuretic) had to be added in 23 patients. 4 There was an abnormality of liver function in one patient; otherwise there were no biochemical or haematological problems.


Carcinoembryonic antigen in endoscopic brush specimens from benign and malignant gastric lesions. The measurement of carcinoembryonic antigen (CEA) in serum and endoscopic brush specimens was evaluated for the differential diagnosis of malignant and nonmalignant gastric disease. Brush specimens were studied from 33 patients with gastric cancer and 36 patients with benign gastric lesions or apparently normal gastric mucosa. Demonstrable CEA immunoreactivity was found by radioimmunoassay in brush specimens from 24/33 cancer patients (73%) and from 23/36 patients with benign lesions (64%). Patients with CEA+ tissue in the immunoperoxidase test had somewhat higher CEA concentrations in the brush specimens than cases with CEA- biopsy tissue, although overlap was considerable. Thirty-five per cent of cancer patients had both a positive tissue CEA reaction and a CEA/DNA ratio greater than 10 ng/micrograms, whilst patients with benign lesions had only 15% of positives by these criteria (0.01 greater than P greater than 0.001). The serum CEA concentration was above the upper normal level of 5 ng/ml in 2/39 patients, both of whom had gastric cancer. The CEA immunoreactive material from benign and malignant lesions eluted in gel filtration on Sephadex G-200 in the same volume as CEA purified from liver metastases of cancer of the colon, showing that a glycoprotein sharing immunological and physicochemical properties with CEA is present both in malignant and nonmalignant lesions of the gastric mucosa, and that there is considerable overlapping in the amount of CEA. The estimation of CEA in gastric-brush specimens is therefore of limited value in the differential diagnosis of benign and malignant gastric lesions.


Non-excretory multiple myeloma.

Non-excretory multiple myeloma. The clinical and laboratory features in five patients with non-excretory myeloma are described including plasma cell immunofluorescence and, in two cases, ultrastructure. Findings are compared with those in similar patients previously reported, and those in excretory disease. Clinical, haematological and biochemical features were similar to those found in excretory myeloma, showing differences only in relation to the absence of serum or urinary monoclonal immunoglobin. Cellular cytological and ultrastructural features allowed no differentiation from excretory cells. Within this non-excretory group distinction between secretory and non-secretory myeloma cells is possible on the basis of immunofluorescence. Differing patterns of intermittent excretion occurred in three of these patients.


Prostaglandins as inhibitors of human platelet aggregation. The potencies of prostaglandins (PG) I2, PGD2 and PGE1 as inhibitors of human platelet aggregation induced by threshold concentrations of four aggregating agents were determined in platelet-rich plasma from normal individuals who had not ingested aspirin. The order of activity against ADP, adrenaline and collagen was always PGI2 greater than PGD2 greater than PGE1. However, PGD2 and PGE1 were almost equipotent with PGI2 when tested against arachidonic acid (AA). The threshold inhibitory effects of PGD2, PGE1 and PGI2 could be over come by increasing the concentrations of the aggregating agents AA, collagen or ADP. Adrenaline was found to be different from the other aggregating agents. It could overcome inhibition of platelet aggregation by PGD2 but could not overcome inhibition by PGI2 or PGE1. These facts support the hypothesis that platelet receptors for PGI2 and PGE1 are similar to each other and different from the receptor(s) for PGD2. PRP obtained from normal subjects after the ingestion of aspirin exhibited only one wave of aggregation in response to ADP, adrenaline or collagen, PGI2, PGD2 and PGE1 were all powerful inhibitors of this single wave of aggregation. The inhibitory activity of all three prostaglandins at threshold concentrations was overcome by increasing the concentration of ADP or collagen but not by increasing the concentration of adrenaline.


Circulating levels of pregnancy specific beta 1 glycoprotein in pregnancies complicated by diabetes mellitus. Circulating levels of SP1 were measured in 20 insulin dependent diabetic women during the third trimester of pregnancy. With one exception, SP1 levels were between the 80 per cent confidence limits of the normal range. The exception was a patient who was delivered of a normal infant at 37 weeks but had consistently low levels of SP1 from 32 weeks until delivery, suggesting a specific defect in SP1 synthesis.


A prospective, controlled trial of six forms of hormone replacement therapy given to postmenopausal women. This study was undertaken to investigate the effect of various forms of hormone replacement therapy (HRT) upon postmenopausal women while controlling as many variables as possible. It was felt that the age, duration of amenorrhoea and the general health of the patients should be as comparable as possible and that each patient should provide her own pretherapy and post-therapy control data. In addition, it was felt that any placebo effect should be investigated and the patients were therefore randomly allocated to placebo tablets or one of six available forms of HRT. The age/sex registers of two large general practices were scrutinized and all women between 49 and 54 years of age were asked to cooperate; for a variety of reasons only 56 women were suitable and willing to take part in the project, yielding 8 women for each of the seven possible therapy groups. Blood samples were taken at 7-day intervals three times before therapy was given and the mean of the three values was used as the control value. The women returned on day 21 of each subsequent therapy cycle for six consecutive months and finally three months after discontinuing therapy. From the data the following broad conclusions can be drawn: (i) some women have classic symptoms of hot flushes and sweating despite high endogenous oestrogen concentrations; (ii) vaginal cytology is a relatively poor indicator of endogenous oestrogen status; (iii) while follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations are reduced on HRT neither is decreased to anywhere near premenopausal values while prolactin is unaffected; (iv) plasma cholesterol levels are reduced on HRT, the pulse rate is slower and both systolic and diastolic blood pressure are reduced to a small but significant extent; (v) there is no adverse effect upon blood clotting; and (vi) most women experience significant or complete relief of symptoms on all forms of HRT as do some women taking a placebo. The combined preparations containing an oestrogen and progestogen produced vaginal bleeding in only 80 per cent of the women. Thus protection by regular endometrical shedding may not be afforded to all women. As vaginal bleeding is unacceptable to most women if they can achieve the same symptomatic relief without inducing menstruation, it is suggested that women have a low dose oestrogen preparation prescribed cyclically for 6 to 12 months. If therapy is to be maintained for a longer time, uterine curretage should be undertaken at regular intervals to exclude the possibility of endometrial carcinoma developing.


Control of glaucoma by reduced dosage guanethidine-adrenaline formulation. The effect of formulations of guanethidine and adrenaline of different composition has been tested in rabbits and in patients with glaucoma. The concentrations of guanethidine and adrenaline used for the rabbits were 5.0% and 1.0%; 2.5% and 0.5%; 1.0% and 0.2%; 0.5% and 0.1%. All except the lowest combination were equally effective in the magnitude of the decrease in intraocular pressure brought about and in their duration of activity. Two formulations containing guanethidine and adrenaline at concentrations of 3.0% and 0.5% and 1.0% and 0.2% respectively (formulated as Ganda drops by Smith and Nephew Pharmaceuticals Ltd) were tested in a blind, cross-over, short-term clinical trial on 20 patients. The drops containing the lower concentration of drugs were as effective as those of higher concentration. These results lead us to believe that most patients who respond to this treatment could be put on a reduced dosage regimen, which should result in a decreased incidence and severity of side effects.


The effect of transcendental meditation on iconic memory. Three experiments investigated the effects of transcendental meditation (TM) on iconic memory. The task involved reporting of digits shown tachistoscopically, using Sperling's partial-report technique. Experiment 1 was a pilot study involving a meditation group and a nonmeditation gropu. All subjects were run in a pretest/treatment/posttest design. During the treatment phase the meditation group practiced TM for a 20-minute period and the nonmeditation group relaxed with eyes closed. The results showed that the treatment increased performance in meditators, but not in nonmeditators. In this experiment important controls such as individual administration of the task, extrinsic rewards, subject pacing, and adequate practice were lacking. Experiment 2 was a replication of the first, with these controls added. The results no longer showed a superiority for the meditation treatment. In fact, the meditation group performed worse on each day of running. Experiment 3 was a replication of Experiment 1, to assess whether the meditation effect of Experiment 1 was due to (a) differential increased attention of the meditators (minimized in subject-paced Experiment 2), (b) a gain early in learning for the meditators that was eliminated due to practice in Experiment 2, or (c) a lack of proper control procedures in Experiment 1. The performance of the meditators was, again, significantly lower. This research illustrates the importance of careful control when investigating the effects of meditation on behavior. It also suggests that the effects of meditation may depend on which hemisphere is dominant in performing the task.


Frontal electromyographic feedback. Stress attenuation and generalization. This study evaluated the effects of one session of frontal electromyographic (EMG) feedback on (1) frontal EMG, (2) frontal EMG response to stress, (3) cardiovascular variables, and (4) cardiovascular responses to stress. Eighteen male and female undergraduate volunteers received either frontal EMG feedback or a relaxation instructions control procedure and were then exposed to a fear stimulus (visualization of a feared situation) and a post-stress adaptation period while several cardiovascular measures were monitored. In comparison to the control group, frontal EMG feedback significantly reduced resting levels of frontal EMG and frontal EMG response to stress but had no significant effect on cardiovascular measures. The results of this study suggest that one session of frontal EMG feedback may attenuate response to stress but, within the paradigm utilized, may be confined to the specific muscle groups monitored. Additional areas of needed research were noted including individual differences in generalization, the effects of EMG feedback from multiple sites sequentially and concomitantly, and the generalized effects from symptom-specific sites.


Temperature biofeedback and relaxation training in the treatment of migraine headaches. One-year follow-up. In a previous controlled group outcome study, a comparison of temperature biofeedback with progressive relaxation indicated that relaxation training was more effective in reducing migraine headache activity at the end of treatment. However, follow-up data obtained at 1, 2, and 3 months after the completion of treatment showed no difference between the two groups on any dependent measure. In the current study, 18 of 26 subjects who completed treatment in the original investigation collected headache data and completed a headache questionnaire 1 year subsequent to the conclusion of treatment in order to evaluate the long-term effectiveness of the two treatments. The results indicated that gains achieved in the reduction of headaches during both treatments were maintained at a 1-year follow-up. With the exception of medication consumption (for which relaxation training led to better long-term results) the 1-year follow-up data reveal no differential efficacy for temperature biofeedback or progressive relaxation in treating migraine headaches.


Effect of luteinizing hormone-releasing hormone on plasma testosterone in immature and adult male rabbits. 1 microgram/100 g body weight of synthetic luteinizing hormone-releasing hormone (LHRH) was administered to immature (25, 35 and 55 days of age) and adult (180 days) male rabbits. Testosterone was measured by radioimmunoassay in plasma samples taken just before and 30 min after LHRH injection. At all stages studied, LHRH significantly increased plasma testosterone. Expressed as a percent of over basal levels, the plasma testosterone was increased by 2,695% at 25 days, 3,955% at 35 days, 6,032% at 55 days and 3,766% at 180 days. Expressed in absolute amounts, the plasma testosterone levels showed an increase of 520 pg/ml at 25 days, 604 pg/ml at 35 days, 1,189 pg/ml at 55 days and 7,596 pg/ml at 180 days. The exact interpretation of the data was difficult since it is dependent on the mode of expression used. Nevertheless, the results support the observation that the hypophyso-testicular axis is functional in immature rabbits.


A qualitative discrepancy between censored data rank tests. Two popular censored data rank tests were used to compare cancer incidence rates between dogs receiving bone marrow transplantation and control dogs. The logrank test gave a significance level of 0.01. In contrast, Gehan's generalized Wilcoxon test gave a significance level of 0.76. The statistics are displayed in a manner that shows how such contrasting significance levels can arise. The Gehan statistic is shown to be subject to a serious criticism that does not apply to other Wilcoxon generalizations. Further insight into the data is obtained using a time-dependent logrank test and the proportional hazards regression model.


The cachexia of cancer.

The cachexia of cancer. This review examines the contributions made by anorexia, loss of taste, malabsorption and disturbances of intermediary metabolism to the cachexia of cancer. Methods of nutritional assessment are outlined and mention is made of the usefulness of nutritional support as an adjunct to anti-cancer therapies.


Prolongation of murine skin allografts across a major histocompatibility locus using supernatants from con-A activated spleen cells. Supernatants from Concanavalin A-activated mouse spleen cell cultures have been found to prolong skin graft survival across the H-2 locus in the mouse. There exist in these supernatants non-specific factors synthesized by suppressor T cells which have been activated by sub-optimal concentrations of Concanavalin A in vitro. The possible nature of these factors is discussed.


Colony-stimulating factor production and secretion following renal transplantation. Colony-Stimulating Factor (CSF) production by peripheral blood leukocytes of renal transplant recipients was assayed using semisolid agar culture. Patients with stable graft function had a normal ability to produce CSF and they reacted with an increase of CSF release following bacterial infection, while active viral infections impaired the process. A marked decrease of CSF production was detectable in kidney graft recipients undergoing acute rejection, a phenomenon sometimes reversible by bolus prednisolone administration. Less characteristic patterns of CSF secretion in urine were found in these patients.


A selected bibliography of biomedical and environmental applications of stable isotopes. V-2H, 13C, 15N, 18O and 34 S, 1977-1978. The first biennial updated compilation, for the period 1977-1978, of selected references to the use of 2H, 13C, 15N, 18 O and 34S in biochemical, pharmacological, clinical and environmental applications is presented. Author and subject indices for this information are compiled to enable the reader to make further use of these references.


[Microtubules and mitosis].

[Microtubules and mitosis]. The mitotic chromosome movements are discussed in relation with recent studies on tubulins, their assembly and disassembly, and the associated proteins. The role of contractile proteins in the mitotic spindle is considered, and also that of the calcium regulating protein (CDR) which has been demonstrated recently in the mitotic spindle. The study of more "primitive" mitoses underlines the differences between polar and chromosomal MT. The linear growth of the first, and the sliding movements of MT from opposing poles, explain the growth in length of the mitotic figure and the separation of chromosomes. The complex relations between various types of MT and the possibility of biochemical varieties of tubulins, are discussed.


[The action of antimitotics and the cell cycle]. Cell kinetics, which for a long time could only be worked out at the level of mitosis, has now at its disposal a set of technics which make it possible to label cells which replicate their DNA, to appraise the DNA content of individual cells and to synchronise cell populations. First of all, the meaning and the scope of results obtained by cell kinetics technics in the study of the action mechanism of antimitotic substances are discussed. The main results obtained are exposed, pointing to the complexity of the mechanisms concerned. A more detailed discussion of some personal results concerning the action of anti-inflammatory substances, of protein inhibitors and of hydroyure allows to underline the difficulties met with and the importance of the choice of an adequate methodology.


[The plasma membrane glycoconjugates of normal and transformed cells (author's transl)]. After having reviewed the importance of glycoconjugates in the organisation of the cell membrane and the multiple roles played by these membrane constituants, the disorders characteristics of malignant transformation are described : First, the changes affecting cellular properties (diminution of cellular adhesivity, abolition of the control of cell growth, disturbance of membrane permeability...) and second, the modifications concerning the glycoconjugates of the cell surface in the course of malignant transformation : alterations affecting membrane glycolipids and glycoproteins. It appears that certain modifications of glycannic structures of membrane glycoproteins, for whatever cell type and transforming agent, seem at the moment to constitute the only abnormality permanently associated with the tumorigenicity of malignant cells.


Do schizophrenics use linguistic rules in speech recall? Varying degrees of organization of verbal material were presented to determine their use in sentence reproduction by acute and chronic schizophrenic subjects, a psychiatric (alcoholic) control group, and a healthy control group. The material consisted of six-word sentences presented over earphones, with background noise of differing intensity. The main result was that schizophrenics use verbal organization as effectively as healthy and psychiatric controls when reproducing the sentences. The noise distraction influenced performance of all groups similarly. Results suggest that performance of schizophrenics is facilitated by structured material (semantic and syntactic organization). The results do not suggest that either the linguistic repertoire or the application of linguistic rules is specifically affected in schizophrenia. The flatter performance slope of schizophrenics with increasing contexual constraints, found by some researchers, is explained by the unspecific effect of task difficulty.


Collaborative United Kingdom-Australasian study of cancer in patients treated with immunosuppressive drugs. A collaborative study including centres in the United Kingdom, Australia, and New Zealand was instituted in 1970 to determine the incidence of cancer in patients treated for at least three months with azathioprine, cyclophosphamide, or chlorambucil. Follow-up of 3823 renal transplant recipients showed an almost 60-fold increase of non-Hodgkin's lymphoma together with an excess of squamous-cell skin cancer and mesenchymal tumours. A series of 1349 patients without transplants showed an excess of the same tumours, though to a less extent. These preliminary findings provide no clear evidence that immunosuppressive drugs produce the increased risk of most of the common cancers that might be expected from the simplest interpretation of impaired "immunosurveillance."


Effects of indomethacin on postural hypotension in Parkinsonism. A study was conducted to evaluate the effect of indomethacin on orthostatic hypotension in Parkinsonism. Twelve elderly patients participated and the drug was given in two-ways--as an intravenous infusion of 50 mg over 30 minutes and by mouth 50 mg thrice daily for six days. Results were assessed by measuring the degree of hypotension on standing, response to the cold pressor test, and forearm blood flow (by strain-gauge plethysmography). Indomethacin significantly reduced the fall in blood pressure on standing (P less than 0:001) and lessened or reversed orthostatic symptoms. Furthermore, there was an enhanced response to the cold pressor test and a reduction in forearm blood flow. These findings suggest that indomethacin has a positive effect on systemic vascular resistance.


Optimum concentration of dissolved oxygen for the survival of virulent Treponema pallidum under conditions of low oxidation-reduction potential. A maintenance medium with a low oxidation-reduction (redox) potential, when gently bubbled with 5% oxygen in nitrogen or with air for various periods of time, gave a range of dissolved oxygen concentrations between 1.6 and 5.8 micrograms/l. Virulent Treponema pallidum (Nichols strain) inoculated into these media were assayed 24 and 48 hours later for motility and virulence and were compared with samples taken at zero time. Virulent T. pallidum survived best in the presence of 2.4 micrograms/l dissolved oxygen over a 48-hour period, which corresponded to a gaseous mixture of 3% oxygen in nitrogen. Higher concentrations of oxygen did not give significantly different results from anaerobic conditions over this period. Thus, until it can be grown in vitro, T. pallidum would appear to be a microaerophilic bacterium.


Susceptibility of rabbits to Treponema pallidum after infection with Mycobacterium bovis. Rabbits stimulated with Mycobacterium bovis (strain BCG) one month before challenge with Treponema pallidum (Nichols) did not show any modification in their development of syphilitic lesions. A second infection with BCG given at the same time and at the same intradermal site as the T. pallidum challenge also failed to protect the rabbits against syphilis. Thus the non-specific activation of cell-mediated immunity by BCG does not appear to protect rabbits against T. pallidum infection even when both activation and challenge take place in the dermis. The role of the macrophage in syphilis remains obscure.


Limited protection of rabbits against infection with Treponema pallidum by immune rabbit sera. After intradermal infection of rabbits with 3 x 10(6) Treponema pallidum (Melbourne 1 strain) samples of serum were taken at one, two, three, four, and six months after infection. Normal rabbits were passively immunised with these sera, challenged with intradermal doses (10(4), 10(3), 10(2), 10) of T. pallidum, and the latent periods of infection, lesion diameters, and the number of inoculation sites developing into lesions were observed. The sera taken at three, four, and six months reduced the number of intradermal inoculation sites that developed into syphilitic lesions after challenge with 10 T. pallidum. These same three sera also increased the latent period of infection after challenge with 10(4) T. pallidum. The transfer of 50 ml of immune serum per rabbit over a nine-day period before challenge had very little effect on the course of the challenge infection. Only a low level of immunity in rabbits to this strain of T. pallidum appears to be mediated by immune serum but this small degree of protection did increase with time after infection. Enhanced growth of T. pallidum in the serum-recipient rabbits did not occur, thus suggesting that none of the sera was immunosuppressive.


Topography of cerebellar corticonuclear fibers of the albino rat. Vermis of anterior and posterior lobes. The distribution of cerebellar corticonuclear fibers of the vermis of anterior and posterior lobes was determined for the albino rat using the Fink and Heimer method. Efferent fibers from vermal cortex terminate in the ipsilateral medial cerebellar nucleus (NM) in an organized circumferential manner. Rostral lobules (I--III) project to rostroventral and rostrocentral NM, more central lobules (IV, V, VI) project to rostrodorsal, dorsocentral and caudodorsal areas of the nucleus respectively, while caudal lobules (VII, VIII, IX) send fibers into caudal and ventrocaudal NM. No evidence was seen to corroborate the contention that individual lobules of the vermis may project essentially throughout the rostrocaudal extent of the nucleus. Although species differences are apparent the arrangement of terminal fields in the NM for vermal cortex of rats is similar to that reported for other mammals. Degenerated fibers from medial aspects of each lesion primarily enter the NM while those coursing into the juxtarestiform body originate from more lateral portions of the cortical injury. This suggests that the arrangement of cortical zones in rat is fundamentally similar to that described in other mammals.


Comparison of minocycline and ampicillin in gonococcal urethritis. A prospective, randomised, single-blind trial was carried out to compare the efficacy and tolerability of minocycline and ampicillin in the treatment of gonorrhoea in men. One hundred and twenty men were treated with minocycline 300 mg and 121 men with ampicillin 2 g and probenecid 1 g. Cure rates were similar in both groups of patients. There were few side effects. Of 135 strains of Neisseria gonorrhoeae tested to different concentrations of minocycline and penicillin, two were resistant to penicillin (minimum inhibitory concentration (MIC) greater than or equal to 0.1 microgram/ml) and seven to minocycline (MIC greater than 1.0 microgram/ml). The incidence of PGU was 31% in those patients treated with minocycline and 34% in those treated with ampicillin plus probenecid, the difference not being statistically significant. PGU occurred more often after treatment with minocycline than in previous studies.


Anaesthesia and the respiratory system.

Anaesthesia and the respiratory system. Pulmonary gas exchange is disturbed during general anaesthesia; both oxygenation and elimination of carbon dioxide are impaired. The shape of the chest wall alters after induction of anaesthesia-paralysis in recumbent subjects, and its motion during inspiration is also altered. The mechanical properties of lung and chest wall are also affected and FRC may be reduced. Inspired gas distribution changes after induction of anaesthesia-paralysis with mechanical ventilation of the lungs. Distribution of pulmonary blood flow is altered in subjects in the sitting and right lateral decubitus positions, but the distribution is not adjusted to the altered distribution of inspired gas. This results in an increased mismatching of ventilation to perfusion, with development of lung regions that have low and high ventilation-to-perfusion ratios. Some lung regions with low ventilation-to-perfusion ratios develop into right-to-left shunt on breathing 100 per cent oxygen. The following sequence of events probably occurs after induction of anaesthesia-paralysis. The initial effect of anaesthesia seems to be on the shape and motion of the chest wall. This may alter the mechanical properties of both the chest wall and the lung. Intrapulmonary gas distribution is altered secondarily. Pulmonary bloodflow distribution, which is primarily determined by gravity, does not seem to adjust to the altered distribution of inspired gas. Hence, an increased mismatching of ventilation to perfusion develops. This includes the development of lung regions with low ventilation-to-perfusion ratios. These regions may progress into right-to-left shung during 100 per cent oxygen breathing. The low ventilation-to-perfusion regions and the shunt may both impair oxygenation. The development of lung regions with high ventilation-to-perfusion ratios after induction of anaesthesia-paralysis contributes to the inefficient elimination of carbon dioxide.


The mutagenic activity of 61 agents as determined by the micronucleus, Salmonella, and sperm abnormality assays. A comparison of two rapid and inexpensive in vivo mammalian assays and the Ames Salmonella assay is presented for 61 agents; Acetylsalicylic acid; Acriflavine; Actinomycin D; 2(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2); Aflatoxin B1; 2-aminofluorene; Aminopterin; Aroclor 1254; Ascorbic acid; Azathioprine; Benzo(a)pyrene; 5-Bromo-2'-deoxyuridine; Busulphan, Butylated hydroxytoluene; Cadmium chloride; Caffeine; Calcium cyclamate; Chloral hydrate; Chloromycetin succinate; Codeine phosphate, Colchicine; Cycloheximide; Cyclophosphamide; DDT; 2,4-Diaminoanisole; Dibutylnitrosamine; 9, 10 Dimethyl-1,2-benzanthracene; 1,1-Dimethylhydrazine; Dimethylnitrosamine; Epinephrine; Ethyl methane sulphonate (EMS); 2-formylamino-4-(5-nitro-2-furyl)thiazole (FANFT); 2-(2-formylhydrazino)-4-(5-nitro-2-furyl)thiazole (FNT); Glucose, Griseofulvin; Hycanthone methane sulphonate; Hydroxyurea; 5-Iodo-2'-deoxyuridine; Lead acetate; Mechlorethamine; 3-Methylcholanthrene; Methyl mercury acetate; Methyl methane sulfonate (MMS); N-methyl-N-nitro-N'-nitrosoguanidine; Mitomycin C; Monosodium glutamate; 1-Naphthalamine; 2-Naphthalamine; Nitrofurazone; 4-Nitro-O-phenylene diamine; 4-Nitro-quinoline-1-oxide (4-NQO); Phenobarbitone; Procarbazine; Quinacrine dihydrochloride; Radiation (gamma-rays); Sodium chloride; Triethylene thiophosphoramide; Trimethyl phosphate; Tris(2-methyl-1-arizidinyl) phosphine oxide; Urethan; Vinblastine. The results support the concept of multiple assays for mutagenicity and show that some combinations of assays are superior to others.


Effects of suprachiasmatic nucleus lesions on hypothalamic LH-releasing hormone (LHRH) content and gonadotropin secretion in the ovariectomized (OVX) female rat. Suprachiasmatic nucleus lesions in OVX rats blocked progesterone-induced gonadotropin surges without affecting tonic levels of these hormones or the expression of estrogen negative feedback. In addition, these lesions resulted in a decrease in LHRH content of tissue rostral and caudal to the lesion. These results suggest that the effect of suprachiasmatic nucleus lesions on phasic gonadotropin secretion may be due to the interruption of LHRH input to the median eminence from rostral centers known to be important in this event.


Noradrenergic innervation patterns in three regions of medial cortex: an immunofluorescence characterization. A homologous antiserum directed against rat dopamine beta-hydroxylase (DBH was used for the immunohistofluorescent visualization of the noradrenergic (NA) innervation of medial cortex in the albino rat. Three cytoarchitectonic divisions of the medial cortex were studied: prelimbic (PL), anterior cingulate (AC), and granular retrosplenial (RSg). Each division of medial cortex possesses a characteristic and distinct pattern and density of NA fibers. The branching patterns and density of the fibers in PL cortex are similar to those of lateral cortex. AC cortex has the lowest density of NA innervation found in the neocortex; there is minimal arborization in layer I, and a very low density of fibers in layers II and III. In contrast RSg is the most densely innervated region, and NA fibers arborize extensively throughout all layers. The dopaminergic (DA) fibers in medial cortex were studied with glyoxylic acid-induced histofluorescence following midbrain lesions of the dorsal noradrenergic bundle (DNB). A laminar complementarity exists in AC cortex such that the DA fibers terminate in layers I-III, while the NA fibers are largely confined to the deep layers. The distinctive patterns of termination of coeruleocortical fibers indicate that in different cortical areas NA axons contact different elements of neuronal circuitry and that there is some degree of specificity in the distribution of NA terminals within the cortex.


The influence of the PO1A1 mutation upon recombination in Escherichia coli K12. Genetic recombination in Escherichia coli is a highly regulated process involving multiple gene products. We have investigated the role of DNA polymerase I in this process by studying the effect of the po1A1 mutation upon DNA transfer and conjugation in otherwise isogenic suppressor-free strains of E. coli K-12. It was found that the po1A1 mutation greatly reduces recombination in Hfr crosses (a factor of 20 in Pol+ x Po1A1 crosses and more than a factor of 100 in Po1A1 X Po1A1 crosses). However, since the po1A1 mutation reduces the strains capacity to act as a recipient for an F-prime and the analysis of recombination transfer gradients revealed no differences between Po1+ and Po1- strains, it is concluded that DNA polymerase I probably affects the transfer and/or stability of donor DNA rather than the recombinational process itself.


Mixed bacteriophage infection of Escherichia coli: exclusion of superinfecting T4 by T7. Escherichia coli was infected with T7, then with T4. When the time between the addition of the tow phages was 5 or more minutes, T4 was excluded and most of the infective centres yielded T7 progeny. The DNA of excluded T4 was injected, but it did not replicate nor was it degraded extensively. Transcription of this T4 DNA was largely inhibited, and the transcripts produced were not translated. A variety of T7 amber mutants was examined for the capacity to exclude T4. Amongst the early T7 genes, only the product of gene 1, the T7 RNA polymerase, was essential for T4 exclusion. None of the late genes examined was essential for exclusion.


Changes in electrophoretic mobility and lytic enzyme activity associated with development of flocculating ability in Saccharomyces cerevisiae. Cells from stationary-phase cultures of two strains of Saccharomyces cerevisiae (3 and 20) failed to flocculate when grown in a complex or a chemically defined medium, while those of two other strains (11 and 13) flocculated when grown in either medium. Strain 30 flocculated when grown in complex but not defined medium and harvested from stationary-phase cultures. pH-electrophoretic mobility measurements on all five strains showed that mobility attributable to carboxyl groups usually increased as cultures progressed from the exponential to the stationary phase, while that caused by phosphate groups tended to decline. Acquisition of flocculating ability was accompanied in strains 11 and 30 by a slight increase in amidase activity, and greater increases compared with nonflocculent populations in activities of leucine aminopeptidase. alpha-mannosidase, and proteinase C. Activities of proteinases A and B showed no correlation with acquisition of flocculating ability.


Adherence of bacteria to leaves.

Adherence of bacteria to leaves. Members of seven genra of bacteria, pathogens and nonpathogens of plants, adhered to young leaves when leaves were suspended in cell suspensions for 10 min. With Pseudomonas lachrymans, the adherence rate (cells applied vs. cells adhering) to host (cucumber) and nonhost (chrysanthemum) leaves was a straight-line, log-log function, as was the adherence of Escherichia coli and Serratia marcescens to cucumber leaves. Adhering cells of these three bacteria were washed with water from cucumber leaves at a straight-line, log-log rate. Adhered cells of P. lachrymans were most commonly found near veins on cucumber leaves. There appeared to be a polymeric surface layer on this bacterium on the cucumber leaf when leaves bearing bacteria were stained with ruthenium red and viewed in thin section.


A new gene involved in expression of fructose-1,6-diphosphate aldolase activity in Escherichia coli. A new gene, fdaB, has been mapped by transduction and partial diploid analyses and located adjacent to argA at 59.9 min on the Escherichia coli recalibrated linkage map. This gene is involved in expression of fructose-1,6-diphosphate aldolase activity and indirectly in ribosomal RNA synthesis. The temperature-sensitive mutant strain AA-157, containing the defective gene product of of fdaB, accumulates high concentrations of fructose 1,6-diphosphate at the nonpermissive temperature.


Cutaneous immunofluorescent microscopy: a practical diagnostic technique. Cutaneous immunofluorescent microscopy is a relatively new technique for the diagnosis of cutaneous disorders. Its application has been well established in vesiculobullous and connective tissue disorders. With the development of a transport medium for skin biopsy specimens it has become a practical diagnostic technique. In 1974 a laboratory for immunofluorescent microscopy was established in Vancouver and, on the basis of its experience, the indications for, and results of, immunofluorescent studies are reviewed.


Malformations and the Manx syndrome in cats. Breeding experiments were conducted on cats with congenital taillessness, to test the dissemination pattern of taillessness in their offspring. Clinical evaluation, radiographic analysis of the vertebral column and histological studies of the digestive tract and central nervous tissue were conducted to determine the association of malformations of these systems in cats born with different degrees of taillessness noted in the rumpy and stumpy cats. The mode of transmission of the tailless (Manx) condition assumed to be through an autosomal dominant factor (M) was confirmed by this investigation. It is hypothesized that the problems associated with the tailless condition such as spina bifida, urinary and faecal incontinence and locomotor disturbances of the pelvic limbs may all be related to a disturbance affecting the development of the central nervous system in the early embryonic life.


Chemoimmunotherapy (DTIC and Corynebacterium parvum) as adjuvant treatment in malignant melanoma. Sixty-one patients with stage I or II (lymph node involvement) malignant melanoma were prospectively randomized into a control group receiving surgical treatment only (consisting of wide excision of primary and regional node dissection) and a group receiving the same surgical treatment plus adjuvant therapy with DTIC and Corynebacterium parvum. Followup times ranged from 1 1/2 to 4 years. Among the 29 patients in the surgical control group, there were five hematogenous recurrences and one regional recurrence and four patients have died. Among the 32 patients in the treatment group, there were 13 hematogenous recurrences and two regional recurrences and ten patients have died. However, the control group had six patients with involved lymph nodes while the treatment group had 15 patients in this category. It appears that although the combination of DTIC and C. parvum was well-tolerated, it did not reduce the recurrence and mortality rates.


Polyestradiol phosphate: a preliminary evaluation of its effect on breast carcinoma. The effect of polyestradiol phosphate (Estradurin), a long-acting estrogen preparation given im, was assessed in 24 elderly postmenopausal patients with stage II or III primary or recurrent breast carcinoma. Although the drug has been available for many years, there has been no report in the literature of its use in treating breast carcinoma. The results of this study show that a total of 17 of 24 (70.8%) patients had evidence of tumor regression lasting a minimum of 3 months, while in 14 (58.3%) patients regression was maintained for greater than or equal to 6 months. Seven patients had complete (100%) tumor regression. Side effects were almost nonexistent and the agent has been shown to be effective, with good patient acceptability and guaranteed administration. It could be considered as an alternative to oral estrogen therapy where patient compliance is poor and gastrointestinal side effects are severe enough that patients often request a change of treatment.


Phase II-III chemotherapy studies in advanced gastric cancer. Eastern Cooperative Oncology Group. In this study, 139 eligible and evaluable patients with advanced gastric cancer, measurable disease, and no prior chemotherapy were randomized between treatment with Adriamycin alone, 5-fluorouracil (5-FU) plus mitomycin C, and 5-FU plus methyl-CCNU. Objective responses were seen in eight of 37 patients (22%) receiving Adriamycin, in 17 of 53 (32%) receiving 5-FU plus mitomycin C, and in 12 of 49 (24%) receiving 5-FU plus methyl-CCNU. Median durations of response were 4, 3 1/2, and 8 1/2 months, respectively. Sixty-one patients were treated after previous failure to other chemotherapy regimens. Response rates were seen in seven of 47 patients (15%) receiving Adriamycin, in two of nine receiving 5-FU plus mitomycin C, and in one of five receiving 5-FU plus methyl-CCNU. Complete responses were observed more frequently with Adriamycin and with 5-FU plus methyl-CCNU than with 5-FU plus mitomycin C. Although 5-FU plus methyl-CCNU had a slight advantage in interval to disease progression, this was not statistically significant. Median survival for all previously untreated patients was slightly greater than 17 weeks, and there was no meaningful or significant survival difference between the three treatment groups.


Phase II-III chemotherapy studies in advanced gastric cancer. The Gastrointestinal Tumor Study Group. In this multi-institutional study of advanced gastric cancer, 141 eligible and evaluable patients were treated with either (a) Adriamycin alone, (b) a combination of 5-fluorouracil, Adriamycin, and methyl-CCNU (FAMe), or (c) a combination of 5-fluorouracil, mitomycin C, and cytosine arabinoside (FMC). In patients with measurable disease and no prior chemotherapy, objective responses were seen in four of 17 patients (24%) receiving Adriamycin alone, in seven of 15 (47%) receiving FAMe, and in three of 18 (17%) receiving FMC. In previously treated patients with measurable disease, objective responses were seen in three of 17 patients (18%) receiving Adriamycin alone and in one of 11 (9%) receiving FMC. In previously untreated patients with both measurable and nonmeasurable disease, FAMe showed a significant advantage over both Adriamycin alone and FMC with regard to interval to disease progression and survival. In comparing Adriamycin alone with FMC in previously treated patients, intervals to disease progression and survival were essentially identical.


Treatment of advanced gastric carcinoma with 5-fluorouracil: a randomized comparison of two routes of delivery. Fifty-seven patients with advanced gastric carcinoma were randomized to receive 15 mg/kg/week of 5-fluorouracil by either the iv or oral route. Toxic effects of treatment included nausea and vomiting (40% with the oral route versus 35% with the iv route) and myelosuppression, with a wbc count of less than 4000/mm3 (28% with the oral route versus 32% with the iv route). The frequency of partial response was 12% (three of 25 patients) for the oral route and 16% (five of 32 patients) for the iv route. Only two of 36 patients with liver metastases responded. No advantage was seen for the oral versus the iv route of 5-fluorouracil in the treatment of advanced gastric carcinoma.


The substrate specificity of yeast hexokinase: reaction with D-arabinose oxime. By chromatography, electrophoresis, n.m.r. spectroscopy, and spectrophotometric assay, it has been shown that D-arabinose oxime acts as a weak substrate for yeast hexokinase. The enzyme-catalysed phosphorylation of the oxime, which exists as a mixture of E (80%) and Z (20%) acyclic forms in solution at equilibrium, is proposed to proceed via the transient formation of a furanoid species. Weak substrate-activity was also observed with 4-deoxy-D-xylo-hexose, but not with 5-deoxy-D-xylohexose. The relation of these and previous results concerning the carbohydrate-substrate specificity of yeast hexokinase in solution to X-ray crystallographic studies is discussed.


Cis-dichlorodiammineplatinum(II) alone and combined with DTIC for treatment of disseminated malignant melanoma. Twenty-one patients with disseminated malignant melanoma were treated with cis-dichlorodiammine-platinum(II) (cis-DDP): ten with cis-DDP alone at a dose of 20 mg/m2 iv x 4 days every 4 weeks and 11 with cis-DDP at a dose of 15 mg/m2 iv x 4 days combined with DTIC at a dose of 200 mg/m2 iv x 5 days every 4 weeks. Two of 21 patients (10%) showed a partial response to therapy. There were no complete responses and no apparent increases in length of survival for responders compared to nonresponders. One drug-related death occurred. Otherwise, drug toxicity was acceptable and appeared to be diminished by iv hydration and prolonged administration. In this study, cis-DDP was not effective for treatment of disseminated malignant melanoma.


cis-Dichlorodiammineplatinum(II) and DTIC in malignant melanoma. Twenty-nine patients with advanced malignant melanoma were randomized to receive DTIC at a dose of 200 mg/m2 iv on Days 1-5 and cis-dichlorodiammine-platinum(II) at a dose of 40 mg/m2 iv on Days 1 and 4, repeated every 4 weeks (group A), or the same drugs plus procarbazine at a dose of 75 mg/m2 orally daily on Days 1-8 and vincristine at a dose of 1.4 mg/m2 iv on Day 1 (group B). These drugs were generally well-tolerated, but five of 16 patients in group A and six of 13 patients in group B required dose modification for either hematologic or renal toxicity. There were six objective responses among 16 patients in group A including one complete regression, while there were two objective responses among 13 patients in group B.


Phase I study of iv administration of methanol extraction residue of Bacillus Calmette-Guérin. Four weekly iv doses, ranging from 10 to 640 microgram/m2, of the methanol extraction residue of bacillus Calmette-Guérin (MER) were given to 22 patients with advanced cancer in an effort to determine a maximum tolerated dose. Fever and chills for 24-48 hours were common at doses greater than 80 microgram/m2 but were prolonged for 3 days to 9 weeks at 640 microgram/m2. While moderate decreases in pulmonary vital capacity were seen at all dose levels, diffusing capacity decreased consistently only at higher doses. However, no roentgenographic changes suggestive of multiple lung granulomas were observed, such as were produced in dogs and mice by iv administration of MER. Autopsy failed to reveal granulomas in three patients. There were no objective tumor responses, nor were consistent changes observed in blood counts or skin tests to recall antigens. MER can be given iv with acceptable acute toxicity in doses up to 640 microgram/m2, at which point fever may be unduly prolonged. Patients given MER iv must be followed carefully for the development of interstitial pneumonitis.


Treatment of metastatic pancreatic and gastric adenocarcinomas with 5-fluorouracil, adriamycin, and mitomycin C (FAM). Twenty-six patients with metastatic pancreatic or gastric adenocarcinoma were treated with 5-fluorouracil, Adriamycin, and mitomycin C. One complete and five partial responses were observed among 15 patients with pancreatic adenocarcinoma (40% response rate) and six partial responses were observed among 11 patients with gastric adenocarcinoma (55% response rate). Responders had a significantly longer survival than nonresponders in both groups.


Cis-dichlorodiammineplatinum(II) in metastatic soft tissue sarcomas. cis-Dichlorodiammineplatinum(II) was given to 13 patients with metastatic sarcomas following failure in two previous chemotherapy protocols. Two of these patients had complete regression which lasted 6 months in one patient and is still present after 8 months in the other. One patient had a greater than 50% regression which lasted 5 months. Three patients had disease stabilization for 2 months each. cis-Dichlorodiammineplatinum(II), as a single agent, was well-tolerated with no significant renal or auditory toxicity.


Preliminary report on the clinical use of human leukocyte interferon in neuroblastoma. The effectiveness of human leukocyte interferon (IF) injections on a female patient, 21 years old, with stage IV neuroblastoma was observed. IF (30 X 10(4) units) injected every second day intratumorally or around the tumor tissue rapidly reduced the tumor size. However, systemic administration of 300 x 10(4) units of IF by im injection showed no beneficial effects. Our results suggest that a high IF level in tumor tissue may be necessary to bring about tumor reduction.


Gonadotroph-rich cell lines derived from pituitary clonal cells (2A8) grafted under the kidney capsule. Gonadotroph-rich cell lines were established from multipotential pituitary clonal cells (2A8) which were implanted under kidney capsule of hypophysectomized female rats. These cell lines secrete gonadotrophins (FSH and LH) continuously over two months after establishment; LHRH stimulated the secretion of hormones into the culture medium. Many of the cells reacted immunohistochemically to antiserum to FSH or LH, while a small number reacted to antiserum to prolactin or TSH. They did not contain normal secretory granules such as those of gonadotrophs in vivo.


Demonstration of a somatostatin-like activity in retinal cells of the rat. A somatostatin-like substance is demonstrated by light microscopic immunohistochemistry (PAP-method) in perikarya and cell processes of the retina of adult and infant rats. These perikarya are identified according to their size, arrangement and distribution. Each of the first two neuronal orders (receptors, bipolar cells, ganglionic cells) of the visual pathway can be associated with retinal cells reacting positively with anti-somatostatin. In the adult rat, perikarya and processes of (i) horizontal cells, (ii) amacrine cells and (iii) large neurons in the ganglionic layer are specifically labeled. The staining of middle-sized and small ganglion cells is probably caused by the close attachment of labeled fibers to non-reacting cells. Postnatally, the immunoreactive elements develop in parallel to the differentiation of the corresponding retinal layers. It is discussed whether the three types of retinal cells containing a somatostatin-like substance provide an inhibitory system to each of the two orders of retinal neurons.


Synaptic ring images after silver impregnation. In view of the contradictory results obtained from a number of studies on the nature of ring images found after neurofibrillar silver impregnation, this question was reinvestigated at the ultrastructural level in the lateral geniculate nucleus of the monkey. The ring images found here are produced by silver deposits on ring-shaped accumulations of neurofilaments in the afferent synapses of retinal origin. Tubular impregnation of axons was not found to be a factor in the genesis of ring images.


Immunocytochemical identification of hyperglycemic hormone-producing cells in the eyestalk of Carcinus maenas. Antiserum raised in rabbits against extracts of sinus glands from Carcinus annd shown by several criteria to contain antibodies directed against the neurosecretory hyperglycemic hormone was used to locate the hormone-producing perikarya in the optic ganglia. By means of the double antibody fluorescence technique, selective staining of the large neurosecretory perikarya of the medulla terminalis ganglionic X-organ (MTGXO) and their axons is obtained. The axon endings of the sinus gland are also stained. None of the other groups of neurosecretory cells in the eyestalk shows fluorescence. Preabsorption of the antiserum with pure hyperglycemic hormone abolishes the fluorescence.


In vitro response of chloroquine-resistant Plasmodium falciparum to mefloquine. The present study was conducted to evaluate the application of the in vitro microtechnique system in determining the response of chloroquine-resistant Plasmodium falciparum to mefloquine.Using isolates of P. falciparum from Boa Vista, Brazil, and Villavicencio, Colombia, mefloquine was more than 7.7, 7.1, 7.1, and 6.4 times more effective than chloroquine in vitro at the ED(90), ED(95), ED(99), and ED(99.9) levels, respectively.


[Ecology of a cutaneous leishmaniasis focus in the Thies region (Senegal, western Africa). I. Recall of the cutaneous leishmaniasis status in Senegal and presentation of the studied area]. Opening an epidemiological survey of a focus of cutaneous leishmaniasis in the Thies region (Senegal), the authors present a short historical report on the disease situation in the country. They then describe the ecological characters of the studied area.


m-AMSA and PALA: two new agents in cancer chemotherapy. 4'-(9-Acridinylamino)methanesulfon-m-anisidide (m-AMSA) and N-(phosphonacetyl)-L-aspartate (PALA) are two new anticancer agents that have been recently introduced into clinical investigation. This review summarizes the preclinical information that has accumulated with these compounds as well as the very preliminary data presently available from early clinical trials. This information indicates the promising potential of m-AMSA and PALA in the treatment of cancer.


[Interaction between Salmonella and Schistosomes. Scanning electron microscopy study]. In our attempts to elucidate the pathogenesis of prolonged Salmonella bacteremia in patients with Schistosoma mansoni or Schistosoma haematobium infection, we have utilised MEB. Our results are significant. They show an association exists between Bilharziasis and Salmonellosis.


Immunochemical determination of human apolipoprotein B by laser nephelometry. The Hyland laser nephelometer PDQ system for the assay of apolipoprotein B (apo-B) in human serum is described. Within and between-batch precision, accuracy and reliability are discussed. This instrument represents an important development in the immunochemical assay of apo-B, and the speed, precision, and convenience of the methodology make such a system attractive. Quantitation of apo-B was assessed in normal and hyperlipaemic subjects. Comparisons were made with two other specific and sensitive immunological methods for quantifying apo-B: enzymeimmunoassay (EIA) and rocket immunoelectrophoresis (RIE). Results obtained by the three methods correlated very well.


Sequential chemotherapy and circadian rhythm in human solid tumours. A randomised trial. Sixty-three patients were randomised into two groups each receiving the same 40-h sequential chemotherapy regimen (methotrexate or 5-FU, followed by vinblastine and cyclophosphamide). In the group receiving infusions of chemotherapeutic agents at times taking into account the circadian rhythm of tumoral proliferation, the antitumoral effectiveness appeared significantly better with respect to both tumoral regressions (85% contrasting with 58% in the other group) and the duration of response and survival.


Confirmation of an influence of the inherited Lp(a) variation on serum insulin and glucose levels. Previously reported analyses on three different series of people suggested that fasting serum insulin levels are lower in males with (high levels of) serum Lp(a) lipoprotein (Lp(a+)) than in males without detectable Lp(a) lipoprotein (Lp(a-)). The same was observed during an oral glucose tolerance test. Also, blood glucose concentrations tended to be lower in males with high levels of Lp(a) lipoprotein than in those in whose serum no Lp(a) lipoprotein could be detected. In this paper, we present data which appear to confirm the previously reported results. A significant correlation was found between the fasting triglyceride level and the sum of insulin values determined during the oral glucose tolerance test in healthy Lp(a-) but not in Lp(a+) individuals. The present data, together with those previously reported on an effect of the Lp(a) locus on serum lipid levels and on propensity to contract coronary heart disease, indicate that the genetically determined Lp(a) lipoprotein may be of considerable clinical importance.


Antenatal diagnosis in three pregnancies at risk for mannosidosis. Three pregnancies were monitored in two families at risk for mannosidosis, alpha mannosidase and alpha fucosidase were determined on extracts from white blood cells of several members of these families, on fibroblast cell lines from the index cases and on uncultured and cultured amniotic cells of the foetuses. Two foetuses were diagnosed as affected and one as being free from the disease. The conclusions were confirmed on the affected foetuses after interruption of the pregnancy. The noticeable residual activity of alpha mannosidase found in some fibroblasts and cultured amniotic cells required complementary investigations (heat lability and dependency of substrate concentration) to reach a reliable diagnosis. Invesitgation of uncultured amniotic cells may give useful additional information.


A rapid and simple sandwich-method used for chromosome analysis from small fetal and adult biopsy specimens. A new Sandwich-Method is described which uses aborted material and yields a high frequency of metaphases. Chromosome studies may be performed after 7--8 days without subculturing. It is possible to freeze the original tissue for later cell culture.


Studies of migration inhibition tests in penicillin hypersensitivity. The release of the migration inhibition factors, leucocyte inhibitory factor (LIF) and macrophage migration inhibition factor (MIF) from stimulated peripheral blood lymphocytes has been compared in patients with immediate (IgE-mediated) penicillin allergy and in patients with delayed hypersensitivity to tuberculin PPD. It has been shown that in these two groups of subjects, a comparable specific proliferative response can occur following stimulation with the appropriate drug (benzylpenicillin) or antigen (PPD). By cell fractionation studies, the proliferation was found to occur in the isolated T cell population in both subject groups. However, the lymphocyte response to benzylpenicillin was rarely associated with the release of LIF or MIF, in contrast to the situation in tuberculin sensitivity where a concomitant release of LIF and MIF was found. In about one third of penicillin allergic subjects, culture supernatants from specifically stimulated lymphocyte cultures induced migration inhibition in the indirect leucocyte migration test, but the inhibitory activity apparently resulted from the presence of penicillin-specific antibody and not from LIF.


Lymphocyte cytotoxicity to autologous hepatocytes in HBsAg-negative chronic active hepatitis. In a micrototoxicity assay, lymphocytes from ten out of sixteen patients with HBsAg-negative chronic active hepatitis have been shown to be cytotoxic to autologous hepatocytes isolated from percutaneous liver biopsies. This cytoxicity was demonstrable in all six untreated patients but in only four out of ten receiving immunosuppressive treatment, the presence of cytotoxicity showing a significant association with the activity of the disease assessed histologically. The addition of excess purified lipoprotein (LSP), derrived from the hepatocyte plasma membrane, blocked the reaction in all cytotoxic cases, indicating that LSP was the major target antigen. Enriched fractions of T cells were cytotoxic in only one case, whereas non-T cell fractions were cytotoxic in the other ten cases investigated in this way. For optimum T cell cytotoxicity, effector and target cells must share histocompatibility determinants and the results of this study using an autologous system show conclusively that the lymphocyte cytotoxicity found in HBsAg-negative chronic active hepatitis is mediated by a non-T cell population.


A simple, rapid micro-latex fixation test. A micro-latex fixation test (LFT) for the determination of rheumatoid factor (RF) is presented. Its advantages compared to similar tests are greater precision, simplicity, increased sensitivity, lower cost, reproducibility and adaptibility to large-scale testing. Micro-LFT titres are presented from a wide range of sample populations. The majority of normal samples show measureable titres whereas rheumatoid patients show high titres. A large sampling of pre- and post-transplant sera from kidney patients was studied and the micro-LFT titres were in the range of normal persons. The transplant sera were tested for lymphocytotoxic antibodies and no correlation was observed with the micro-LFT titres.


Sperm autoantibodies as a consequence of vasectomy. II. Long-term follow-up studies. Thirty-four out of fifty-two vasectomized men studied previously were studied again about 5 years after vasectomy for sperm-agglutinating and sperm-immoblizing antibodies, and for antibodies to human protamine. Only one man lost his already weak antibody activity, whilst one out of eight men, negative at 1 year, appeared to be positive at 5 years. Slightly higher titres in one of the three sperm antibody tests were found in the sera of about 30% of the men. Only in three (9%) was there a rise of two or more steps in more than one technique. Agglutinins and immobilizins were shown to be strongly correlated, as was the case with antibodies to human protamine and head-to-head agglutinins. Seminal plasma sperm agglutinins were detected in the samples of only four (out of thirty) men, in low titres. Circulating immune complexes tested with various techniques were only found in a few sera and not consistently. This prolonged study shows that sperm autoantibodies formed within 1 year after vasectomy are persistent. Their role in remaining infertility after reanastomosis requires further study.


Antibodies directed against renal collecting ducts in sera of human renal allograft recipients. Anatibodies directed against the plasma membrane of renal collecting ducts were found in the sera of two out of 101 renal allograft recipients. The sera also reacted with the epithelium of the renal pelvis, the ureter, the ductus deferens, the skin, the oesophagus, the trachea and the bile ducts of random individuals, indicating that the antibodies were directed against a widespread epithelial antigen. The antibody activity against these structures was removed by absorption of the sera with homogenized renal medullary tissue; absorption with plasma proteins, erythrocytes, spleen leucocytes or platelets did not influence the antibody titers. In the two patients with circulating antibodies, the graft function was unremarkable eight and fifteen months after transplantation, respectively. From this study we conclude that circulating epithelial antibodies directed against the collecting ducts of the graft are of little or no clinical importance.