Comparison of techniques for measuring the local and systemic responses to tuberculin in cattle. Thermography of tuberculin skin reactions in cattle sensitized with Mycobacterium avium, Mycobacterium bovis, or Mycobacterium paratuberculosis was rapid and sensitive, but was not as specifically related to the homologous sensitization as was increased skin thickness at 48 and 72 hours. Systemic temperature responses were more completely monitored by radiotelemetry of intraperitoneally located temperature transmitters than by rectal thermometry, but the temperatures indicated by the 2 methods were nearly identical. The intraperitoneal transmitters showed that the systemic responses consisted of 1, 2, or 3 temperature peaks, and in 1 animal which had previously been exposed to a heterologous tuberculin, a hypothermic response developed. The systemic temperature responses were more specifically related to homologous sensitization than were dermal responses, but were more cumbersome to measure.


Development and evaluation of an enzyme-labeled antibody test for the rapid detection of hog cholera antibodies. A rapid enzyme-labeled antibody (ELA) microtechnique for the screening of swine for hog cholera antibodies was developed and evaluated with a blind study, using a 640-sample hog cholera serum bank. The total time to run a group of 22 samples was approximately 1 hour. The ELA test results correlated greater than 99% with hog cholera serum-neutralization test results on the same serums. Test results also indicated that the ELA test shares with the hog cholera serum-neutralization test the problem of cross reactions between the antibodies of hog cholera and bovine viral diarrhea.


Comparison of the effects of continuous negative external chest pressure and positive end-expiratory pressure on cardiac index in dogs. Continuous negative external chest pressure was used to increase the functional residual capacity in 6 dogs, and the effects were compared with the effects of increasing functional residual capacity using positive end-expiratory pressure. Cardiac index and mixed venous O2 stauration each decreased from control values during positive end-expiratory pressure, but did not decrease with continuous negative external chest pressure. Continuous negative external chest pressure may provide an alternative to positive end-expiratory pressure for increasing the functional residual capacity of patients in whom the latter causes unacceptable decreases in venous return and cardiac output.


Bronchial effects of aerosolized delta 9-tetrahydrocannabinol in healthy and asthmatic subjects. Effects on airway dynamics, heart rate, and the central nervous system of various doses of delta9-tetrahydrocannabinol administered in a random, double blind fashion using a Freon-propelled, metered-dose nebulizer were evaluated in 11 healthy men and 5 asthmatic subjects. Effects of aerosolized delta9-tetrahydrocannabinol were compared with aerosolized placebo and isoproterenol and with 20 mg of oral and smoked delta9-tetrahydrocannabinol. In the normal subjects, after 5 to 20 mg of aerosolized delta9-tetrahydrocannabinol, specific airway conductance increased immediately, reached a maximum (33 to 41 per cent increase) after 1 to 2 hours, and remained significantly greater than placebo values for 2 to 3 hours. The bronchodilator effect of aerosolized delta9-tetrahydrocannabinol was less than that of isoproterenol after 5 min, but significantly greater than that of isoproterenol after 1 to 3 hours. The magnitude of bronchodilatation after all doses of aerosolized delta9-tetrahydrocannabinol was comparable, but 5 mg of delta9-tetrahydrocannabinol caused a significantly smaller increase in heart rate and level of intoxication than the 20-mg dose. Smoked delta9-tetrahydrocannabinol produced greater cardiac and intoxicating effects than either aerosolized or oral delta9-tetrahydrocannabinol. Side effects of aerosolized delta9-tetrahydrocannabinol included slight cough and/or chest discomfort in 3 of the 11 normal subjects. Aerosolized delta9-tetrahydrocannabinol caused significant bronchodilatation in 3 of 5 asthmatic subjects, but caused moderate to severe bronchoconstriction associated with cough and chest discomfort in the other 2. These findings indicate that aerosolized delat9-tetrahydrocannabinol, although capable of causing significant bronchodilatation with minimal systemic side effects, has a local irritating effect on the airways, which may make it unsuitable for therapeutic use.


Prevention and treatment of tracheal injuries in children. Endotracheal intubation and tracheostomy, both procedures used to treat life-threatening respiratory problems, may in themselves produce internal tracheal or laryngeal injury and subsequent airway obstruction. A knowledge of the anatomy of the larynx and trachea in children and the proper techniques and equipment which are available for infants and small children is mandatory if complications are to be prevented. It is essential that all physicians who deal with respiratory problems in children be aware of the differences between children and adults and knowledgeable of special techniques and equipment necessary for children.


Granulocyte adherence changes induced by hemodialysis, endotoxin, epinephrine, and glucocorticoids. Granulocyte adherence was studied in several situations of altered granulycyte kinetics. During the transient granulocytopenia of hemodialysis, adherence increased to 481.7% of baseline by 15 min and was normal by 60 min. One hour after endotoxin administration, adherence was 160.5% of control as granulocyte counts fell to 21.4%; conversely, the 24-h postdose granulocytosis was associated with a 43.0% decrease in adherence. Epinephrine produced a 25.8% decrease in adhereence, with demargination granulocytosis 146.1% of control period. Alternate-day prednisone administration inhibited adhereence by 38.9% on the "on" day, concomitant with prolonged granulocyte intravascular half-life, but adherence returned to normal on the "off" day when intravascular half-life is normal. In each situation, a plasma factor not present in serum was responsible for the modified adherence; if these factors produce the sameadherence changes in vivo, they may be responsible for the alterations noted in granulocyte kinetics.


Pulmonary effects of radiation therapy.

Pulmonary effects of radiation therapy. The cellular effects of irradiating the lungs are rleated to the histologic and clinical sequelae. The occurrence and severity of damage rare semiquantitatively related to the volume of lung irradiated, and the dose rate of irradiation. The clinical syndrome occurs in up to about 10% of patients and consists of an acute transient phase, radiation pneumonitis, usually occurring 6 to 12 weeks after radiation therapy. This is followed by clinical remission except in the most severe cases and gradula radiologic progression to the stage of radiation fibrosis over the next 6 to 12 months. Concommittant chemotherapy, repeat courses of radiation, and steroid wihtdrawal are exacerbating factors. Characteristic changes in pulmonary function and radiographic appearance are described, and management is reviewed.


Efficacy of intermittent colchicine therapy in familial Mediterranean fever. Nine patients with familial Mediterranean fever (FMF) were admitted to a controlled, double-blind trial to determine if there are patients with this disease who are able to abort their acute episodes of pain and fever with short courses of colchicine taken at the onset of attacks. Five patients completed their treatment assignments, and colchicine was significantly effective in aborting the attacks of three but was ineffective in two. The remaining four patients could not be assessed because of insufficient numbers of courses. During the 10 months of the trial, 28 courses of colchicine and 31 of placebo were taken during the early stages of FMF attacks. Twenty-one (75%) colchicine courses were followed by attacks considered to have been aborted, compared to only three (10%) placebo courses. This trial shows that patients can recognize the prodrome of their FMF attacks and that some patients can consistently abort their attacks with short courses of colchicine taken at the very onset of symptoms.


Methotrexate.

Methotrexate. The folic acid antagonists, aminopterin and then methotrexate, have been the primary systemically administered drugs for the treatment of severe psoriasis for 25 years. Methotrexate was finally approved by the FDA 5 years ago and was recently estimated to be used for approximately 25,000 psoriatic patients annually. With the small but chronic doses used for psoriasis, methotrexate has been relatively safe, except for a limited occurrence of significant hepatotoxicity. The good to excellent results obtained in most patients must, therefore, be weighted against the small risk of liver damage. Methotrexate has also been used with some effectiveness in several other dermatologic conditions, including mycosis fungoides, dermatomyositis, pityriasis rubra pilaris, and others, although they are not yet FDA-approved indications. The recent successful introduction of photochemotherapy (psoralen and ultraviolet light) for moderate and severely affected psoriatics will probably lead to a substantial decrease in the number of patients requiring methotrexate.


The pathogenesis of podagra.

The pathogenesis of podagra. Precipitation of crystals from solution is a relatively simple phenomenon that should be explained by changes in concentration, temperature, pH, or other local factors. Which of these factors determines the preferential precipitation of urate crystals at the base of the big toe? Podagra correlates with degenerative joint disease of the toe, often follows abuse of the feet, and classically occurs in the middle of the night. These characteristics suggest that crystals may form in resolving synovial effusions. The urate concentration must transiently rise in such an effusion because water will leave the joint space twice as fast as urate. If the local concentration surpasses the solubility of urate, crystals will form that may than induce acute podagra.


Effects of dimethyl sulfoxide on ocular inflammation. The anti-inflammatory properties of topical ocular dimethyl sulfoxide (DMSO) were investigated using a standard experimental model of an acute inflammatory ocular inflammation. Ninety percent and 100% DMSO aggravated the inflammatory response, 50% to 70% DMSO had similar responses as the control eye; however, 30% DMSO had definite anti-inflammatory properties. Dexamethasone 0.1% was superior to 30% DMSO as an anti-inflammatory agent. From this study it is evident that high concentrations of DMSO are irritating to the inflammatory ocular model used while lower concentrations have anti-inflammatory properties. The two side effects of skin irritation at the site of application and breath odor may be the subjective influence that leads certain patients to report a beneficial effect of DMSO treatment in ocular inflammation.


Digital flexor tendon repair and return of function. It is widely accepted that all divided tendons other than the digital flexors, when sutured and with appropriate postoperative treatment, heal well and that a good return of function can be expected. Clinical and experimental evidence is presented. which indicates that digital flexor tendons also have the ability to heal well, with a good return of function, if suitably treated. The results of repair of 275 divided digital flexor tendons in man are presented.


Malleus fixed (ossified) to the tegmen tympani in an ancient skeleton in Israel. A right malleus fixed to the roof of the tympanic cavity in a 1,600-year-old skull is described. The possible etiolgy of this condition is examined and the literature concerning recent and paleopathology of the middle ear ossicles is reviewed.


Clinical evaluation of a hemagglutination method for microsomal and thyroglobulin antibodies in autoimmune thyroid disease. A simple and reproducible hemagglutination technique for detecting microsomal and thyroglobulin antibodies has been evaluated in normal subjects and in patients with thyroid disease. Microsomal antibodies were detected in 89 percent of all patients with autoimmune thyroid disease and in 97 percent of patients with biopsy proven Hashimoto's thyroiditis. In contrast, thyroglobulin antibodies were present in only 55 percent of patients with biopsy proven Hashimoto's thyroiditis and in 44 percent of all patients with suspected autoimmune thyroid disease. It is suggested, therefore, that measurement of microsomal antibodies by a simple hemagglutination techniques be carried out in all patients with suspected thyroid disorders.


Inhibition of multiplication of Mycobacterium leprae by polyinosinic-polycytidylic acid. Contrary to the results of an earlier study in which polyinosinic-polycytidylic acid [poly(I:C)] administered intraperitoneally to mice had no effect on multiplication of Mycobacterium leprae in the mouse footpad, the local administration of poly(I:C) every 12 h for 15 doses during logarithmic multiplication was found both to inhibit bacterial multiplication and to produce high tissue levels of interferon (IF). Local administration of poly(I) alone inhibited multiplication of M. leprae to almost as great a degree without at the same time producing a measurable IF titer in the footpad tissues. Mouse IF and "mock" IF both inhibited bacterial multiplication to the same degree, but administration of only the former resulted in a measurable IF titer. Polyadenylic-polyuridylic acid administered locally neither inhibited multiplication nor induced IF; fetal calf serum, administered in the same concentration as found in the preparations of IF and mock IF, was modestly inhibitory, without inducing IF. Thus, the local administration of poly(I:C) appears to have inhibited multiplication of M. leprae independently of IF induction.


Temperature-sensitive R plasmid obtained from naturally isolated drug-resistant Vibrio cholerae (biotype El Tor). A temperature-sensitive fi(-) R plasmid, pJY1, which confers resistance to chloramphenicol, streptomycin, and sulfonamide, was found in a drug-resistant strain of Vibrio cholerae (biotype El Tor) isolated in the Philippines in 1973. The R plasmid is temperature sensitive for transferability but not for stability in the hosts. pJY1 is stably maintained either in V. cholerae or in Escherichia coli at a range of culture temperatures from 27 to 42 degrees C. Compatibility tests with reference R plasmids revealed that pJY1 belongs to the J group. Growth of V. cholerae carrying pJY1 is poor on TCBS (thiosulfate-citrate-bile-sucrose) selective plates when the microbe is subcultured in nutrient broth at temperatures higher than 37 degrees C.


L-Glyceraldehude 3-phosphate, a bactericidal agent. At a concentration of 2.5 mM, dl-glyceraldehyde 3-phosphate has a bactericidal effect upon Escherichia coli. The glycerol 3-phosphate transport system is required for the entry of the biologically active l-enantiomer. l-Glyceraldehyde must be phosphorylated by the cell to exert its full effect upon growth. The addition of dl-glyceraldehyde 3-phosphate to a culture of E. coli caused no preferential inhibition of the accumulation of deoxyribonucleic acid, ribonucleic acid, or phosphoglycerides, although protein accumulation was less affected. Studies with mutant strains ruled out catabolic glycerol 3-phosphate dehydrogenase, anabolic nicotinamide adenine dinucleotide (phosphate):sn-glycerol 3-phosphate oxidoreductase, and fructose 1,6-diphosphate aldolase as the primary sites of action. l-Glyceraldehyde 3-phosphate is a competitive inhibitor of sn-glycerol 3-phosphate in the reactions catalyzed by acyl coenzyme A:sn-glycerol 3-phosphate acyltransferase (K(i) of 1.8 mM) and cytidine 5'-diphosphate-diglyceride:sn-glycerol 3-phosphate phosphatidyltransferase (K(i) of 2.7 mM). A K(m) mutant for the former enzyme was susceptible to the inhibitor. l-Glyceraldehyde 3-phosphate does not affect acyl coenzyme A:lysophosphatidate acyltransferase activity. In vivo, phosphatidylethanolamine and phosphatidylglycerol accumulation are inhibited to the same extent by the addition of dl-glyceraldehyde 3-phosphate to a culture of E. coli.


Nalidixic acid-induced protein alterations in Escherichia coli. The effect of nalidixic acid on pulse-labeled protein patterns was analyzed by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis. The drug was found to alter protein patterns in a drug-sensitive strain but not in the isogenic drug-resistant strain of Escherichia coli. The drug-induced alteration of protein patterns was demonstrated by the appearance of some and the disappearance of other pulse-labeled peptides elicited by the drug.


Bactericidal effects of combinations of ampicillin with anti-R-plasmid compounds on Salmonella typhimurium R1+. Salmonella typhimurium R1(+), resistant to 2,500 mug of ampicillin per ml, was rapidly killed by combinations of 60 mug of ampicillin per ml with quinacrine (4 x 10(-4) M), ethidium bromide (10(-4) M), tilorone (10(-4) M), or Nitroakridin 3582 (5 x 10(-6) M).


Therapy of murine aspergillosis with amphotericin B in combination with rifampin of 5-fluorocytosine. Suboptimal doses of amphotericin B in combination with either rifampin or 5-fluorocytosine were better than single-drug therapy in the treatment of disseminated Aspergillus fumigatus infection in mice. Despite the increased effectiveness of combination therapy, none of the therapeutic regimens we used completely eradicated infections in the mice when evaluated by mycological culture, even in long-term survivors.


Lysis if enterobacteria by cefoxitin, cefuroxime, and cephalothin. Cefoxitin, cefuroxime, and cephalothin were added to dense populations of beta-lactamase-producing enterobacteria, and the subsequent turbidity changes were monitored continuously. Viable counts and antibiotic assays were made at intervals after the addition of antibiotic, and the morphological appearances of the organisms were observed. Cephalothin caused lysis of most of the organisms tested, but even at high concentrations, after a few hours the antibiotic was destroyed and the organisms recommenced logarithmic growth. Cefoxitin produced lysis of all the strains of Escherichia coli and Klebsiella species tested, with supression of regrowth. With cephalothin and cefoxitin the viable counts after the addition of antibiotic correlated with the turbidity measurements. Cefuroxime infrequently caused lysis that suppressed multiplication, and the organisms became long and filamentous while the turbidity readings increased; the viable counts did not correlate with the turbidity measurements. Cefuroxime and cefoxitin were not destroyed by the beta-lactamases of any of the strains of enterobacteria that were studied.


Bioassay method for polyene antibiotics based on the measurement of rubidium efflux from rubidium-loaded yeast cells. A bioassay method for the polyene antibiotics nystatin and amphotericin B is proposed based on the measurement of the efflux of rubidium ions from a rubidium-loaded yeast culture challenged with the antibiotics. For this purpose a major proportion of the intracellular K(+) ions in a Saccharomyces cerevisiae culture has been substituted by Rb(+) ions. The rubidium leakage is measured by atomic absorption spectrophotometry, and a straight-line, dose-response correlation has been obtained for both antibiotics.


Cefoxitin activity against multiply antibiotic-resistance Klebsiella pneumoniae in vitro. Due to the emergence of cephalothin- and gentamicin-resistant Klebsiella pneumoniae at this institution, we investigated the in vitro activity of two new cephalosporin compounds-cefoxitin and cefamandole. Whereas both drugs were active against cephalothin- and gentamicin-susceptible isolates of Klebsiella, only cefoxitin exhibited significant activity against cephalothin- and gentamicin-resistant isolates. Seventeen of 20 (85%) of the cephalothin- and gentamicin-resistant isolates were inhibited by </=12.5 mug of cefoxitin per ml. The minimum bactericidal concentration in broth of representative isolates equaled the agar dilution minimum inhibitory concentration. Kirby-Bauer disk susceptibility testing correlated well with the agar dilution minimum inhibitory concentration. Cephalothin and cefamandole resistance of isolates could be correlated with antibiotic degradation by beta-lactamase. Cephalothin and cefamandole evoked only a transient decrease in viable bacterial cell count with rapid inactivation of antibiotics, and full regrowth of the organisms. Cefoxitin, on the other hand, was quite effective in vitro against multiply resistant Klebsiella. No beta-lactamase degradation of cefoxitin was detected. Growth curves with antibiotics indicated rapid killing of cephalothin- and gentamicin-resistant isolates by cefoxitin.


Coliforms from hides and meat.

Coliforms from hides and meat. Coliform tests were performed on 85 hide and 75 meat samples. IMViC reactions were determined on isolates from positive confirmed and fecal tests, and strains other than Escherichia coli were identified. Strains typed as Aerobacter aerogenes types I and II were identified as Enterobacter cloacae (51.4%), Klebsiella pneumoniae (21.5%), Enterobacter aerogenes (15%), and Enterobacter liquefaciens, Serratia, and unidentified coliforms (12.1%). K. pneumoniae appeared to be responsible for less than 1% positive fecal tests.


Comparison of microbial counts on beef carcasses by using the moist-swab contact method and secondary tissue removal technique. When a tissue removal rinse technique was compared to the moist-swab contact method, significantly greater numbers of bacteria were recovered from beef carcasses, especially when the flora exceeded log10 4.5/6.45 cm2. Secondary treatment of the removed surface tissue by blending resulted in a significantly greater number of bacteria being recovered than when the same sample was swabbed and/or rinsed. Data indicate that blending of the carcass surface tissue provides a more representative value of the true microbial flora.


Comparison of methods for the isolation of Salmonella from imported frog legs. Four methods of sample preparation were compared for their relative efficiency in recovering Salmonella from imported frog legs. No significant difference (P greater than 0.10) was observed in the efficiency of submersion, blending, and stomaching methods, but rinsing recovered significantly fewer (P less than 0.01) Salmonella-positive frog legs than the other three methods. No significant difference (P less than 0.25) was observed in the number of positive frog legs recovered by selenite cystine or tetrathionate broth. Salmonella-Shigella agar, when streaked from either of these broths, gave significantly fewer (P less than 0.01) Salmonella-positive frog legs than brilliant green, bismuth sulfite, xylose lysine deoxycholate, and Hektoen-enteric agars. Use selective agars, resulted in detection of an additional 11 and 6 Salmonella-positive frog legs, respectively. A variety of serotypes, mostly uncommon, was recovered. One Salmonella serotype (6,14,24:r,i:e,n,z15), possessing a heretofore unreported antigenic formula, was isolated.


Cutaneous manifestations of Wegener granulomatosis. In a series of 19 patients (15 male and 4 female) who had Wegener granulomatosis with specific cutaneous histopathologic findings, the skin was only involved at onset in two. Four distinct histologic subgroups were defined as follows: necrotizing vasculitis (11 patients); necrotizing palisading granuloma (Churg-Strauss lesion) 2 patients); granulomatous vasculitis (2 patients); and lymphomatoid granulomatosis (4 patients). The 11 patients with necrotizing vasculitis had purpuric and hemorrhagic lesions, and the presence of vesicles and ulceration correlated with the severity of onset and extent of disease. The remaining eight patients had papular and nodular lesions. The patients with necrotizing vasculitis and lymphomatoid granulomatosis had a worse prognosis that did those with a predominant granulomatous reaction.


Influence of folic acid on birthweight and growth of the erythroblastotic infant. I. Birthweight. The birthweights of 100 infants with erythroblastosis were carefully matched as to sex, gestational age, and parity with the birthweights of 200 control infants born during the same period. At all gestational ages the average birthweight of the affected infants was below that of the controls, the average reduction being 227 g. The more severely affected infants tended to be at a lower centile for birthweight than were the mildly affected ones. The relationships between maternal serum folate, cord blood serum folate, and centile for birthweight among affected infants were also studied. There was a strong correlation between low maternal serum folate and the incidence of small-for-dates babies among the affected infants. There was also a strong correlation between maternal and cord blood serum folate values. There was a lack of correlation between maternal serum folate and cord blood haemoglobin. It is concluded that infants with erythroblastosis are lighter than controls and that the reason for this may be a shortage of folic acid available for fetal growth.


Relapsing E. coli K1 antigen meningitis in a newborn. A male infant of 32 weeks' gestational age who presented with recurrent apnoea on the second day of life was shown to have an Escherichia coli K1 antigen meningitis. Relapse occurred 6 days after an adequate systemic course of gentamicin and chloramphenicol and intrathecal gentamicin. This was successfully treated with intraventricular gentamicin and systemic cotrimoxazole. The need to maintain a high index of suspicion for meningitis in the newborn period and to treat adequately the frequently accompanying ventriculitis is emphasized.


"Keratolytic" effect of salicylic acid.

"Keratolytic" effect of salicylic acid. The "keratolytic" effect of salicylic acid was examined in guinea-pig skin. Using a fluorescent staining method the str. corneum cells could be seen to rapidly become detached. The cellular walls remained unchanged. This drug therefore appears to primarily reduce the intercellular cohesiveness of the horny cells.


Management of carcinoma of the thyroid.

Management of carcinoma of the thyroid. Greater precision has developed in recent decades in the selection of patients for operation for thyroid nodules suspicious for malignancy and in adapting operative procedures to the extent and pathologic variety of the individual thyroid carcinoma, when present. A thyroid lobectomy is considered to be the minimal operative procedure usually indicated for a suspicious thyroid nodule or carcinoma involving one lobe of the thyroid gland. Factors determining the extent of operation for thyroid carcinoma include the pathologic variety, gross distribution of the malignancy, and health status of the individual patient. Total or near total thyroidectomy should be considered for all patients with thyroid carcinoma except for single occult carcinomas and unilateral low grade angio-invasive carcinomas. Removal of lymph nodes in regions adjacent to the thyroid carcinoma is advisable, lateral neck dissections being reserved for patients with palpable lymphadenopathy, demonstrated metastases to lateral cervical lymph nodes, or a poorly differentiated carcinoma likely to metastasize to these lymph nodes. A modified radical lymph node dissection is satisfactory except for those carcinomas invading muscles in the neck. Anatomic neck dissections provide a better prognosis than incomplete lymph node procedures for patients with regional lymph node metastases. Following operation, patients should receive thyroid hormone therapy, be evaluated for possible treatment with radioactive iodine or other therapeutic measures, and be followed for evidence of recurrent disease as well as thyroid and parathyroid function. Adequate early operation is preferred to late ultraradical procedures, from standpoints of morbidity and prognosis. Unfavorable prognostic factors include extensive gross disease, poorly differentiated carcinoma present as the entire lesion or as foci in a differentiated carcinoma, and age over 40. With adequate surgical treatment, the prognosis for operable thyroid carcinoma is good.


100 sibling kidney transplants followed 2 to 7 1/2 years: a multifactorial analysis. From January 1, 1968 to May 31, 1973, 100 patients received first kidney transplants from sibling donors. All recipients have been followed for at least two years and several as long as 7.5 years. One hundred per cent follow-up information is available. The absolute two-year patient survival is 85% and the absolute two-year kidney function survival is 76%. Patients with diabetes (especially males) have less success following transplantation than do patients without diabetes. When diabetic patients are excluded, older patients appear to do slightly less well than younger patients. Patients with phenotypically identical HL-A matches with the donor do better than patients without such matches. In the nondiabetic technically perfect transplant recepient, better than 90% long-term transplant function can be expectedwith no kidney losses after the first few months. In contrast, the less well-matched transplant demonstrated both an increased early rejection rate and a high rate of loss after the third to fifth year. Increasing doses of anti-lymphoblast globulin (ALG) had beneficial results in HL-A mismatched sibling transplants, but were slightly detrimental in phenotypically identical HL-A donor-recipient pairs because of an increased rate of infection. The results are compared with the results of transplants from other related donors and from cadavers performed during the same period.


The technique of ventricular septal defect closure in L-transposition of the great vessels. Heart block has been a frequent complication of ventricular septal defect closure in L-transposition of the great vessels. Intraoperative mapping of the conduction tissue combined with accurate suture placement should significantly reduce the incidence of heart block produced by direct injury to the conduction tissue.


[Cyclodextrin glucanotransferase from Klebsiella pneumoniae. 1. Formation, purification and properties of the enzyme from Klebsiella pneumoniae M 5 al (author's transl)]. 1. The strain M 5 al of Klebsiella pneumoniae grows excellently with starches. We were able to show that besides the pullulanase associated with the external membrane of the cells the bacterium produces an inducible, extracellular cyclodextrin glucanotransferase [1,4-alpha-D-glucan-4-alpha-(1,4-alpha-glucano)-transferase (cyclising) (EC 2.4.1.19)]. Potato starch and cyclohexaamylose or cycloheptaamylose were found to be the best "inducing" carbon sources for the synthesis of the enzyme. When the bacteria are grown batchwise, maltose is a poorly "inducing" carbon source; larger quantities of the enzyme are synthesized by continuous cultivation with maltose as growth limiting factor. 2. For the determination of the cyclodextrin glucanotransferase-activity an assay method wsa worked out. 3. The enzyme could be separated from the culture filtrate and purified to more than 90% in few steps. At a total yield of 61.2% related to the activity of the culture filtrate employed we received an enzyme solution with the specific activity of 26.6 units/mg protein. Some properties of the enzyme are described. 4. The products formed from amylopectin by the enzyme were analyzed. Somewhat more than half the amylopectin was found as cyclodextrins. 29.3% of the cyclodextrin fraction were cycloheptaamylose, 47.2% cyclohexaamylose and 10.7% exo-branched cyclohexaamylose. 12.8% of cyclohexaamylose were obtained from a cyclodextrin glucanotransferase-limit dextrin after debranching by pullulanase and exposing the product to the action of the glucanotransferase again. 5. The importance of the cyclodextrin glucanotransferase for the utilization of starches by this strain of Klebsiella pneumoniae is discussed. After a first characterization the enzyme is compared to the amylase of Bacillus macerans.


Sex differences and the epidemiology of depression. This article reviews the evidence for differing rates of depression between the sexes in the United States and elsewhere during the last 40 years, and then critically analyzes the various explanations offered. These explanations include the possibility that the trends are spurious because of artifacts produced by methods of reporting symptoms, or that they are real because of biological susceptibility (possibly genetic or female endocrine), psychosocial factors such as social discrimination, or female-learned helplessness.


The endothelium: roles in thrombosis and hemostasis. The renewed interest in endothelial function is based partly on success with tissue culture of endothelial cells. Endothelium functions primarily in the control of blood vessel wall permeability and in the provision of a blood-compatible lining surface. Recent findings indicate that endothelial cells are active metabolically in ways that may help prevent thrombosis. Endothelium actively degrades several different vasoactive compounds that circulate in blood and that can serve as platelet-aggregating agents. Endothelium also contains an inhibitor of platelet function and an activator of plasminogen, both of which can be released from the cell in response to appropriate stimuli. While intact endothelium functions primarily in prevention of thrombosis, damaged endothelium can contribute greatly to thrombus formation. Release of prostaglandins, adenine nucleotides, and other intracellular components from damaged endothelium can enhance platelet aggregation. Damaged endothelium may not function effectively in removal of vasoactive agents and may not release effective quantities of the inhibitor of platelet function or the activator of plasminogen. Altered endothelium exhibits tissue-factor activity, which can activate the extrinsic blood coagulation-system cascade. Finally, altered endothelial cells may contract and expose basement membrane to blood, thus enhancing thrombosis.


Prosthetic valve endocarditis by opportunistic pathogens. The incidence of endocarditis produced by the so-called "opportunists" as a complication of prosthetic valve surgery is progressively increasing in frequency and gradually transforming the clinical picture habitually associated with this disease. We report six cases of endocarditis produced by opportunistic microorganisms (two cases by Candida, and the remaining by Serratia, Actinobacillus, Acinetobacter calcoaceticus, and Bacteroides fragilis, and by Corynebacterium diphtheriae) in four male and two female patients, making special comment on our findings, diagnostic criteria, and treatment. The patients' ages ranged from 9 to 54 years, and all six patients had long-term complications, with symptoms appearing between 45 days and four years after prosthetic valve surgery. The progressive increase of this new type of prosthesis infection is favored by the indiscriminate use of certain drugs and especially by the prophylactic use of antibiotics.


Role of pepsin in species differences in erosive gastritis. This controlled study shows that the rabbit is more vulnerable to erosive gastritis after stress of operation, weight loss, and hypersecretion or acute ischemia than is the cat. Rabbit gastric juice also produces more erosions in the Shay rat preparation after four hours than does cat gastric juice (P less than .05). In vitro, rabbit pepsin has 1.5 times greater specific activity and possesses other kinetic differences. The deleterious effect of these qualitative differences on gastric mucosa may also be augmented by quantitative differences. Hypersecretion of pepsin has been reported once the mucosa is damaged. We conclude that demonstration of species-related differences in pepsin activity helps to explain an apparent discrepancy noted by others--namely, why the rabbit is so much more susceptible to stress-produced erosions than the cat or other experimental animals.


Historical notes on hemispheric dominance. The evolution of knowledge of hemispheric cerebral dominance is sketched and some possible reasons for the relatively late recognition of asymmetry in hemispheric function are considered. The early clinical contributions pointing to the distinctive functional properties of the right hemisphere are described.


Thermokeratoplasty in the treatment of persistent corneal hydrops. Thermokeratoplasty (TKP) was used to treat six cases of chronic corneal hydrops previously refractory to traditional therapy. In all instances TKP resulted in a clearing of the hydrops within three weeks. In four cases the resultnat comfort and clarity precluded the necessity for transplantation, while in the remaining two cases subsequent penetrating keratoplasty was successfully performed. Thermokeratoplasty is advocated in chronic hydrops refractive to standard therapy, in acute hydrops to accelerate recovery, in recurrent hydrops to assist in healing of breaks in Descemet membrane, thus preventing recurrences, in cases with extensive hydrops to deturgesce the peripheral cornea prior to transplantation, and as definitive therapy in cases where transplantation is contraindicated.


Toxoplasmic retinochoroiditis: electron-microscopic and immunofluorescence studies of formalin-fixed tissue. An 82-year-old white man had bilateral, chronic recurrent uveitis caused by Toxoplasma gondii. In spite of extensive therapy for toxoplasmosis, the left eye became painful and blind and was enucleated. Histopathologically, the retina disclosed unusually large numbers of necrotic cysts and a few presumably viable cysts containing crescent-shaped organisms and scanty free forms of T gondii. Electron-microscopic studies confirmed the presence of a true wall of the cysts as well as additional ultrastructural features highly characteristic of the parasite. Immunofluorescent studies of the formalin-fixed tissue demonstrated quite vividly the cysts, which stained variably according to the stage of viability of the organisms. In cases in which toxoplasmic retinochoroiditis has been suspected clinically but routine histologic preparations fail to reveal the organisms, the remaining formalin-fixed tissue should be examined by specific immunofluorescent methods to demonstrate antigenic material of the causative parasite.


Retinal blood flow derived from dye dilution curves: Televised fluorescein angiography. A television system was used to record retinal fluorescein dilution curves. In pigs, fluorescein was injected intravenously (IV), into the left ventricle (ILV), and ILV during bilateral carotid occlusion (ILVco). Dye dilution curves from points on a retinal-artery-vein pair, from two points on a single artery, and from two points on a single vein were recorded by a storage oscilloscope, using two photodetectors positioned over the television image of the vessels. Dye curves were less dispersed following ILV than following IV injections, and were irregular following ILVco injection. The dye appearance time was shortest after injection with ILV and progressively longer with ILVco and IV. The artery-vein mean transit time was greatest during carotid occlusion. Retinal blood flow in a venous segment was calculated to be 0.149 +/- 0.037 mi/min. This value was reproducible following both IV and ILV injections but could not be obtained following ILVco due to irregularity of the curves. It was in the same range as that found (0.095 +/- 0.011 ml/min), using the radioactively labeled microsphere technique. The system was subsequently tested in humans and was found to give reproducible dye curves. The usefulness of the system as a clinical tool is presently being explored.


Relative photometric measurements of retinal circulation (dromofluorograms): a televison technique. Television fluoroangiography is used in order to obtain fluorescein dilution curves (dromofluorograms [From the Greek word: epsilon rho omicron mu omicron, which means flowing. We coined this word because dilution curves do not afford a true measurement of the blood circulation, or simply of a dilution, but of the fluorescein transport in the circulation!] from single retinal vessels. An optical fiber conveys the light from a single retinal artery, vein, or any other retinal area on the video screen to a photomultiplier. After low-pass electronic filtration, the dilution curves are recorded on a strip-chart recorder. The measurements considered are all related to time: the time interval between initial instants of the arterial and venous curve; the time interval between maximum instants; the arterial and venous curve rising times. It is seen that (1) the method is sensitive enough to enable variations in the quantities in pathologic cases to be detected; (2) owing to the great variability from part to part of the vessels, it is important to specify where the retinal dromofluorogram has been recorded.


[Can bone growth be stimulated (author's transl)]. Stimulation of bone growth by heterologous (bovine) bone grafts may help in leg length discrepancies. Arrest of epiphyseal growth plates or leg lengthenning by osteotomy may be necessary to a lesser extent or be entirely unnecessory. 72 cases, 88 stimulations in 16 years.


[Experimental experience with autologous nerve-transplantation in rabbits (author's transl)]. Autologous nerve transplantations of the tibial nerve were carried out in 15 rabbits. In an average period of 19 weeks a return of function could be observed in 13 of the animals. Neuro-physiological, histological and scanning-electron microscopic examinations were done. A comparison was performed with results after simple nerve suture, done under equal circumstances. Nerve suture leads to a relative better regeneration. To explain this result the formation of a scar in the distal suture was discussed.


Reconstruction of intraoral defects with the free groin flap. A free flap has been defined as an island flap that has been completely detached from the body and transferred to a distant recipient site, where microvascular anastomoses are done to reestablish its essential intravascular circulation. The groin flap, based on its superficial circumflex iliac artery and venae comitantes, was utilized as a free flap to close large intraoral defects in six patients following ablative cancer operations. All patients received preoperative or postoperative irradiation therapy. Four of the six free groin flap operations were clinically successful. One flap became necrotic unexpectedly after 3 1/2 weeks. Infection played a major part in necrosis of the other flap. The use of the free flap in oral cavity reconstruction offers certain advantages over regional vascular flaps but definite limitations exist.


[On the correction of protruding ears (author's transl)]. After the definition of the naturally-looking auricle, a combination of the well-known excision-suture, incision-suture, and scraping-technique is described. The crus inferior and the corpus of the anthelix are built by a bridge of cartilage, whereas the crus superior is formed by scratching the cartilage on the front side. The concha is made smaller by excision. This technique can be applied almost always: it is leading to a good cosmetic result and it is time-sparing.


Reiter's syndrome following Shigella flexneri 2a: a sequel to traveler's diarrhea. Report of a case with hepatitis. Shigella flexneri 2a was isolated from a patient with Reiter's syndrome (RS) following a family outbreak of traveler's diarrhea. Among 3 members at risk, only the patient was positive for HLA-B27. Data from 3 similar families support the hypothesis that susceptibility to RS is genetically transmitted. It is urged that every effort be made to culture and subtype Shigella and other enteric pathogens in RS following diarrhea. Concurrently, the patient had hepatitis, interpreted as a parallel enteric infection.


Stimulatory effect of metoclopramide on the esophagus and lower esophageal sphincter of patients of patients with PSS. Metoclopramide has been shown to stimulate motility of the gastrointestinal tract, including the esophagus. The authors therefore tested the effect of intravenous injections of metoclopramide on the sphincteric pressure and esophageal motility in 14 patients with esophageal dysfunction due to progressive systemic sclerosis (PSS). Isotonic saline similarly injected in a control period in 7 of the patients showed no effect. None of the 14 patients had a detectable pressure zone at the sphincteric area in basal conditions, but following the injection of metoclopramide, one appeared in 7 patients. Metoclopramide also caused the appearance of pressure waves in 5 of 11 patients who had aperistalsis, and caused up to a three fold increase in the amplitude of the pressure waves in the 3 patients who had hypomotility of the esophagus.


[Psychological aspects of renal transplantation]. Ten adolescents were studied from the psychological viewpoint before and after kidney transplantation. Psychological tests showed that before the transplantation, the patients showed signs of brain damage which did not persist after the operation. IQ was low, especially in areas where fine visual and motor coordination was required. After transplantation, IQ was higher. Perception of the body structure was altered in most patients and it improved after transplantation. The most important content in the projective tests was that of death, before and after the operation, indicating depressive factors that influence personality; other traits were fears and guilt feelings before and after transplantation which leads us to conclude that this type of patients have significant feelings of anxiety when they learn about their disease and which continue indefinitely. In spite of the fact that in the last twenty years the number of patients treated with kidney transplantation has increased, there are not many reports from the psychological viewpoint. It is obvious that in the treatment of this disease, as in any other that is chronic and of an uncertain prognosis, although generally fatal, there thill be a series of emotional factors that cause abrupt changes in all aspects of life in these patients, since they are constantly facing death.


Spatial Frank vectorcardiogram in left posterior fascicular block. Criteria and correlation with clinical and electrocardiographic data. Computer processing of spatial QRS parameters (Frank vectorcardiogram) was used to study left posterior fascicular block. The best set of vectorcardiographic criteria was sought in order to characterise the classic pattern of left posterior fascicular block. Using these criteria, 18 cases were selected from a group of 4600 patients and 340 healthy subjects; isolated left posterior fascicular block was seen in 10 cases, and was associated with right bundle-branch block in 8 cases. It is shown that some external factors can influence the aspect of the spatial QRS loop in left posterior fascicular block: cardiomegaly tends to produce a superior displacement of the main QRS forces: right bundle-branch block enhances the superior displacement of the initial forces and shifts the main QRS forces more anteriorly and to the right. The 'masquerading effect' of the left posterior fascicular block on a concomitant inferior myocardial infarct was also shown. The most important diagnostic feature was the opposite direction of the initial forces (left anterosuperior) and the maximal vector (right postero-inferior): the angle between these two vectors averaged 152 degrees. Other criteria, such as the direction of rotation or the axis of the frontal loop, the vertical direction of the spatial loop, the presence of a Q wave in leads II, III, and aVF of the electrocardiogram, are not mandatory for the diagnosis of left posterior fascicular block.


Evidence of rheumatoid arthritis in ancient India. The scarcity of references in ancient medical literature to any disease resembling rheumatoid arthritis (RA) has led many Western rheumatologists to believe that rheumatoid arthritis is a disease of relatively recent origin. In a recent paper on this problem, Short traces the first adequate description of what was probably rheumatoid arthritis to Thomas Sydenham (1624-1689) and emphasizes that European and Greek medical literature before Sydenham's time may have confused gout and other forms of polyarthritis as manifestations of the same disease (1). Studies in human paleopathology have as yet produced no convincing evidence for the existenct of RA in ancient human remains, but Short suggested that a study of the ancient medical literature of the Eastern civilizations may provide some new information on the true antiquity of rheumatoid arthritis.


Clinical value of quantitative analysis of ST slope during exercise. The diagnostic performance of automatic analysis of the exercise electrocardiogram in detecting ischaemic heart disease was studied in 147 patients with angiographically documented coronary disease. The results were compared with the results of visual analysis of the same recordings. Using a bicycle ergometer we tried to reach at least 90 per cent of the predicted maximal heart rate of the patient. Two bipolar thoracic leads (CM5, CC5) were used. In the visual analysis the criterion of the so-called ischaemic ST segment was applied. For the automatic analysis the population was divided into a learning group (N=87) and a testing group (N=60). In the learning group first critical values were computed for different ST measurements that provided optimal separation between patients with (CAG POS.) and without (CAG. NEG.) significant coronary stenoses as revealed by coronary arteriography. These critical values were kept unchanged when applied to the testing group. With respect to the visual method an increase of the sensitivity by 0-45 and 0-36 was obtained by the automatic analysis in the learning and testing group, respectively. The best separation between CAG. POS. and CAG. NEG. group was reached using a criterion consisting of a linear combination of the slope of the initial part of the ST segment and the ST depression; the sensitivity being 0-70 and 0-60, respectively, in the learning and testing group. Using a criterion based on the area between the baseline and the ST segment (the SX integral) these values were 0-42 and 0-49, respectively. All specificities were kept to at least 0-90.


Evaluation of doxapram for arousal from general anaesthesia in outpatients. In a double-blind study of 100 outpatients receiving methohexitone, nitrous oxide and halothane, the administration of doxapram 80 mg i.v. was associated with a significantly more rapid recovery from anaesthesia, the effect being more obvious in women than men. Doxapram produced a reduction of 3-4 min in the time of recovery to a safe level of consciousness. The effect was probably a result of the more rapid elimination of halothane caused by stimulation of respiration. In the patients who received doxapram the incidence of minor complications during recovery was reduced and there was some evidence of an improvement in the quality of recovery.


Naloxone: dose-dependent antagonism of respiratory depression by fentanyl in anaesthetized patients. Naloxone was used to antagonize the respiratory depression caused by the administration of fentanyl 0.05 mg to patients anaesthetized with 0.5% halothane in 70% nitrous oxide in oxygen. Four groups of at least 10 patients each were studied. Doses of 0.1, 0.2 and 0.4 mg of naloxone were given, and an effect proportional to the logarithm of the dose was demonstrated.


Arterial pressure studies during carotid angiography. In a study of 92 patients undergoing carotid angiography under general anaesthesia, marked changes in arterial pressure were infrequent. Possible reasons for this include fewer poor-risk patients, a lighter level of anaesthesia involving controlled ventilation, and the replacement of uriodone (Diodone) by less toxic contrast media.


Localization by immunoperoxidase and estimation by radioimmunoassay of carcinoembryonic antigen in colonic polyps. A 3-layer immunoperoxidase technique was used to demonstrate carcinoembryonic antigen (CEA) in colonic polyps from patients with or without previous or concurrent malignancy. CEA was demonstrated in a higher percentage of the polyps received as fresh specimens that were rapidly frozen and fixed in ethanol, than in formalin-fixed, paraffin-embedded sections. Tissue CEA content of both colonic carcinomas and polyps was determined by radioimmunoassay, and it was found that benign colonic tumours had levels of tissue CEA comparable to colonic cancer, indicating that CEA concentration in a tumour does not reflect its grade of malignancy. In fact, in one case in which both colonic cancer and polyps were removed, the polyps had the higher quantities of tissue CEA. Further, tissue CEA concentration of a polyp was not dependent on its size or location. Studying the titres of circulating CEA in these patients revealed an elevation of plasma CEA in one-third of the patients with only colonic polyps, whilst the patients with cancer all had increased titres.


Rauscher virus-induced reticulum-cell sarcomas: Their growth in vitro and erythropoietic differentiation. A transplantable reticulum-cell sarcoma induced by Rauscher virus (RV) in (C57BL/6 X DBA/2)F1 (BDF1) mice was grown in tissue culture. Four separate cell lines were established, all of which grew predominantly in suspension. The doubling time of the cells from these cultures ranged from 17 to 32 h. Each culture continued to replicate RV, as indicated by the infectivity in newborn mice of all fluids tested up to the 75th passage. Since the morphological appearance of the cells in vitro was consistent with that of proerythroblasts, all cultures were tested for their ability to differentiate along the erythrocytic line under the influence of dimethylsulphoxide (DMSO). One of the cultures produced small quantities of haemoglobin independently of DMSO. Another was shown to produce haemoglobin, as well as to take up 59Fe and incorporate it into haem, only in the presence of DMSO. The 2 remaining cultures failed to produce haemoglobin, either spontaneously or in the presence of DMSO. Cells from each of the RV-induced cultures, when inoculated back into BDF1 mice, induced typical reticulum-cell sarcomas, without in vivo evidence of erythroid differentiation. In contrast, 2 morphologically identical but non-infectious cell lines derived from Friend virus-induced reticulum-cell sarcomas did not show erythroid differentiation in vivo or in vitro, either in the absence or presence of DMSO.


Late reoperations for squint.

Late reoperations for squint. Ten patients in the age range 2 to 22 years are described who had operations initially for squint in childhood. Nine had had concomitant convergent strabismus and one divergent. All presented again in adult life with a cosmetic complaint, but two also had diplopia. Reoperations were done, age range 14 to 43. These ten were all the "late reoperations" for squint which were done during the four year period 1972 to 1976 by one consultant (C.I.P.). Technically these late reoperations were not difficult, through the amount of change predictable in position of the eyeball could be only approximate. Recession +/- advancement +/- resection of horizontal recti were done in all cases. In one case no medial rectus was identified attached to the eyeball; a mass of tissue behind the caruncle was mobilised and sutured to the globe with resultant good movement. To avoid tethering of the eye by scarred conjunctiva, vertical conjunctival incisions were often converted at suturing to (see article) shaped wounds. The absence of any new cases of diplopia (the two who had it preoperatively retained it without aggravation) is attributed to the fact that all cases were under-corrected, i.e., no convergent or divergent squint was converted into a divergent or convergent squint respectively, so that the non-corresponding image remained within the area of suppression, which probably extends only to the vertical meridian in a squinting eye.


Hydrophilic lenses for "continuous" wear in aphakia: fitting at operation. This system of soft lens fitting in conjenction with the backward sloping corneal incision proved satisfactory in 84% of cases and provided good fill-in vision during the postoperative period--that is, until a decision about the type of long-term optical correction was made in each case.


Immunological measurements of conformational motility in regions of the myoglobin molecule. The conformational motilities of three regions of the sperm whale myoglobin molecule and of an isolated peptide of myoglobin have been examined by measuring the equilibrium constant for the native equilibrium nonnative transition. The immunological approach of Furie et al. (Furie, B., Schechter, A.N., Sachs D., and Anfinsen, C.B. (1975), J. Mol. Biol.92, 497-506) was used with convenient modifications. Antibodies specific to the nonnative conformations were used in assaying for competition between the radioactively labeled peptide and native myoglobin. Labeling was by 125I iodination of the peptide or its 3-(4-hydroxyphenyl)propionyl derivative, and separation of the immune complex from the free peptide was either by ammonium sulfate precipitation or by centrifugation of the antibodies immobilized on Agarose beads. For the antigenic regions of the sequence (1-55), the measured conformational equilibrium constant was 840 +/- 200 at 22 degrees C; the value for the C-terminal region (132-153) was 280 +/- 120 at 25 degrees C, while that for the region (66-76) adjacent to the heme group was greater than 2.5 x 10(6). Measurements on the isolated peptide (132-153) indicated that 1% of the molecules adopt native-type folding in aqueous solution at 36 degrees C.


Properties of the galactose binding protein of Salmonella typhimurium and Escherichia coli. The galactose binding protein implicated in transport and in chemotaxis has been purified to homogeneity from the shock fluids of Salmonella typhimurium and Escherichia coli. Both proteins are monomers of molecular weight 33 000 and exhibit cross-reactivity with antibody. The Salmonella galactose receptor showed binding of 1 mol of [14C]galactose or 1 mol of [14C]glucose at saturation. The dissociation constants were 0.38 and 0.17 muM, respectively. In light of the previously published report that the E. coli protein contains two binding sites with two different affinities, the binding characteristics of this protein were reexamined. Using highly purified radiolabeled substrate and homogeneous protein, a single binding site and single binding affinity were seen galactose (KD = 0.48 muM) or for glucose (KD = 0.21 muM). The competition between glucose and galactose for the same site is intriguing in view of the competition between ribose and galactose at the receptor level.


Quantitative analysis of the digestion of yeast chromatin by staphylococcal nuclease. The DNA in intranuclear yeast chromatin is protected from rapid staphylococcal nuclease degradation so as to yield an oligomeric series of DNA sizes. The course of production and disappearance of the various oligomers agrees  quantitatively with a theory of random cleavage by the enzyme at uniformly susceptible sites. The sizes of the oligomers are integral repeats of a basic size, about 160 base pairs, and 80-90% of the yeast genome is involved in this repeating structure. Within this repeat there exists a 140 base pair core of more nuclease-resistant DNA. During the course of digestion, the sizes of the oligomers decrease continuously. The widths of the distribution of DNA sizes increase in order: monomer (1 X repeat size, half width = 5-7 base pairs) less than dimer (2 X repeat size, half width = 30 base pairs) less than trimer (3 X repeat size, half width = 40-45 base pairs). The yeast genome thus seems to have variable spacing of the nucleaseresistant cores, to produce the average repeat size of about 160 base pairs. Also, the presence of more than one species of monomer and dimer at certain times of digestion suggests a possible heterogeneity in the subunit structure.


Preparation of Escherichia coli tRNAs terminating of modified nucleosides by the use of CTP(ATP):tRNA nucleotidyltransferase and polynucleotide phosphorylase. Two procedures were investigated for the modification of tRNAs at the 3'-terminal nucleoside. The first involved the incubation of an enzymatically abreviated tRNA (tRNA-C-COH) with appropriate nucleoside triphosphates in the presence of CTP(ATP):tRNA nucleotidyltransferase from Escherichia coli and yeast. The E. coli enzyme did not utilize 2'- or 3'-deoxyadenosine 5'-triphosphate as substrates, but affected incorporation of the 2'- and 3'-O-methyladenosine triphosphates onto tRNA-C-Cou to the extent of 30 and 37%, respectively. Although incorporation of the deoxynucleotides could not be effected using the E. coli enzyme, yeast CTP(ATP:tRNA nucleotidyltransferase produced the desired tRNAs in yields of 45-65%. The second modification procedure involved incubation of tRNA-C-COH with (appropriately blocked) nucleoside diphosphates in the presence of polynucleotide phosphorylase. This procedure afforded the tRNAs terminating in 2'- and 3'-deoxyadenosine in yields of 4% (and the yield of the former was increased to 36% when the incubation was carried out in the presence of 20% methanol). The yields of tRNAs terminating in 2'- and 3'-O-methyladenosing produced by this procedure were 55 and 17%, respectively. Because only single isomers of most of the tRNAs terminating in 2'- and 3'-deoxy- and O-methyladenosine are aminoacylated, attempts were made to obtain the other isomericaminoacyl-tRNA by enzymatic introduction of chemically preaminoacylated nucleotides onto tRNA-C-COH. Although incubation of tRNA-C-COH with three aminoacylated nucleoside 5'-triphosphates and E. coli CTP(ATP):tRNA nucleotidyltransferase did not result in production of the desired tRNAs to a detectable extent, incubation with 2'-deoxy-3'-O-L-phenylalanyladenosine 5'-diphosphate and polynucleotide phosphorylase afforded E. coli tRNA terminating with the corresponding aminoacylated deoxynucleoside.


Initial position of aminoacylation of individual Escherichia coli, yeast, and calf liver transfer RNAs. Transfer RNAs from Escherichia coli, yeast (Sacharomyces cerevisiae), and calf liver were subjected to controlled hydrolysis with venom exonuclease to remove 3'-terminal nucleotides, and then reconstructed successively with cytosine triphosphate (CTP) and 2'- or 3'-deoxyadenosine 5'-triphosphate in the presence of yeast CTP(ATP):tRNA nucleotidyltransferase. The modified tRNAs were purified by chromatography on DBAE-cellulose or acetylated DBAE-cellulose and then utilized in tRNA aminoacylation experiments in the presence of the homologous aminoacyl-tRNA synthetase activities. The E. coli, yeast, and calf liver aminoacyl-tRNA synthetases specific for alanine, glycine, histidine, lysine, serine, and threonine, as well as the E. coli and yeast prolyl-tRNA synthetases and the yeast glutaminyl-tRNA synthetase utilized only those homologous modified tRNAs terminating in 2'-deoxyadenosine (i.e., having an available 3'-OH group). This is interpreted as evidence that these aminoacyl-tRNA synthetases normally aminoacylate their unmodified cognate tRNAs on the 3'-OH group. The aminoacyl-tRNA synthetases from all three sources specific argining, isoleucine, leucine, phenylalanine, and valine, as well as the E. coli and yeast enzymes specific for methionine and the E. coli glutamyl-tRNA synthetase, used as substrates exclusively those tRNAs terminating in 3'-deoxyadenosine. Certain aminoacyl-tRNA synthetases, including the E. coli, yeast, and calf liver asparagine and tyrosine activating enzymes, the E. coli and yeast cysteinyl-tRNA synthetases, and the aspartyl-tRNA synthetase from yeast, utilized both isomeric tRNAs as substrates, although generally not at the same rate. While the calf liver aspartyl- and cysteinyl-tRNA synthetases utilized only the corresponding modified tRNA species terminating in 2'-deoxyadenosine, the use of a more concentrated enzyme preparation might well result in aminoacylation of the isomeric species. The one tRNA for which positional specificity does seem to have changed during evolution is tryptophan, whose E. coli aminoacyl-tRNA synthetase utilized predominantly the cognate tRNA terminating in 3'-deoxyadenosine, while the corresponding yeast and calf liver enzymes were found to utilize predominantly the isomeric tRNAs terminating in 2'-deoxyadenosine. The data presented indicate that while there is considerable diversity in the initial position of aminoacylation of individual tRNA isoacceptors derived from a single source, positional specificity has generally been conserved during the evolution from a prokaryotic to mammalian organism.


Transport of pyruvate and lactate in yeast mitochondria. Evidence for the existence of mediated transport of pyruvate and lactate in isolated mitochondria of Saccharomyces cerevisiae is presented. 1. The mitochondrial oxidation of pyruvate is specifically inhibited by the monocarboxylic oxoacids alpha-ketoisocaproate and by alpha-cyano-3-hydroxycinnamate, while pyruvate and malate dehydrogenases activities are not inhibited. 2. The stimulation of the mitochondrial oxidations of succinate, alpha-ketoglutarate and citrate by pyruvate are also inhibited by alpha-cyano-3-hydroxycinnamate. 3. The [14C]pyruvate uptake by yeast mitochondria follows saturation kinetics and is completely inhibited by alpha-cyano-3-hydroxycinnamate. 4. Large amplitude passive swellings of mitochondria of the wild type and of cytoplasmic rho- and rho-n mutants are induced by isoosmotic ammonium pyruvate and lactate. These pH-dependent swellings are inhibited by alpha-cyano-3-hydroxycinnamate suggesting that the carrier system is not coded by mitochondrial DNA.


Outer membrane of Salmonella typhimurium. Identification of proteins exposed on cell surface. Proteins exposed on the outer surface of the outer membrane of Salmonella typhimurium were identified by reacting intact cells with a covalent labeling reagent. Since the outer membrane permitted the free diffusion of small hydrophilic molecules, we used a macromolecular reagent, CNBr-activated dextran, as the non-penetrating labeling agent. We also used a mutant producing a lipopolysaccharide with a very short (i.e. hexasaccharide) carbohydrate chain, in order to avoid steric hindrance by the carbohydrates on membrane surface. Results showed that out of the four "major" proteins of molecular weight around 35 000, three were exposed, and that at least six other proteins were also exposed on cell surface. Only two or three outer membrane proteins consistently did not react with the reagent in intact cells.


Unmasking of an essential thiol during function of the membrane bound enzyme II of the phosphoenolpyruvate glucose phosphotransferase system of Escherichia coli. The addition of N-ethylmaleimide (MalNEt), or of fluoro dinitrobenzene to a suspension of Escherichia coli during the phosphorylating uptake of methyl-alpha-D-glucopyranoside (Me-Glc), a glucose analog, stops uptake and phosphorylation and causes the loss of previously accumulated sugar and of its phosphate ester. After removal of the reagents, the phosphotransferase system remains irreversibly inactive. Pretreatment of the bacteria with the same reagents under the same conditions of concentration, pH, temperature and for the same length of time causes very little inactivation. Mercuric chloride, a reversible inactivator, prevents the phosphotransferase system from reacting simultaneously with MaINEt or with fluorodinitrobenzene. This protection strongly suggests that all three reagents react with the same site, presumably an -SH group. The change which makes this site available to the reagents depends on the phosphorylative uptake of Me-Glc. Preload of the cells and efflux of Me-Glc do not achieve the same change. The rate of inactivation is directly proportional to the rate of phosphorylative uptake. When the Km of phosphorylative uptake is modified by an uncoupling agent, the substrate concentration allowing half maximal rate of inactivation by MaINEt changes accordingly. The reactive sites of the phosphotransferase system can also be made accessible to the -SH group reagents by fluoride inhibition of phosphoenolpyruvate synthesis. This suggests that the inactivator resistent form is an "energized form" of the enzyme. The unmasking of the reactive site is not due to a change in transmembrane penetration of the reagents since incubation of toluene treated cells with MaINEt in the presence of phosphoenolpyruvate fails to inactivate the phosphotransferase activity, while incubation with MaINEt plus Me-Glc causes fast inactivation.


A comparative study of the effect of modification of the surface of human platelets on the receptors for aggregated immunoglobulins and for ristocentin-von Willebrand factor. The receptors for aggregated immunoglobulin G (IgG) (an Fc receptor) and for ristocetin-von Willebrand factor on human platelets were studied by means of various modifications of the platelet surface. The expression of these receptors was measured by the agglutination of platelets to ristocetin in the presence of von Willebrand factor, which is part of the factor VIII complex, and by the binding of aggregated IgG coupled to 3H-labelled diazobenzene. Treatment of platelets with chymotrypsin, trypsin, papain and pronase which removed protein and glycoprotein from the platelet under conditions where the release reaction was inhibited caused loss of the expression of the receptor for ristocetin-von Willebrand factor and an enhancement of that for aggregated IgG. Induction of membrane changes with ADP and of the release reaction with the ionophore A23187 abolished agglutination to ristocentin-von Willebrand factor but did not alter the receptor for aggregated IgC. Possible contributions of unspecific membrane changes, produced by protease treatment of platelets, to the modification of receptor expression were eliminated by the use of formaldehyde-treated platelets. Trypsin, papain and pronase destroyed the ability of these platelets to agglutinate to ristocetin-von Willebrand factor but produced no change in the binding of aggregated IgC. Therefore, the receptor for ristocetin-von Willebrand factor is truly sensitive to proteolysis while the Fc receptor is not, but is partially masked by protease-sensitive material.


Optical properties of an outer membrane lipoprotein from Escherichia coli. The infrared spectrum of a structural lipoprotein from the Escherichia coli outer membrane indicated the lipoprotein had an alpha-helical conformation but no sign for the existence of beta-structures. From circular dichroism spectra of the lipoprotein, the alpha-helical content of the protein was found to be as high as 88% in 0.01-0.03% sodium dodecyl sulfate in the presence of 10(-5) M Mg2+ at pH 7.1 and 23 degrees C. When sodium dodecyl sulfate concentration increased higher than 0.1%, the alpha-helical content of the lipoprotein decreased to about 57%. Divalent cations, such as Mg2+ and Mn2+, were found to increase the helical content of the lipoprotein. The high alpha-helical content of the lipoprotein was observed in a wide range of temperatures (23 to 55 degrees C). The significance of the high alpha-helical content of the lipoprotein is discussed in light of the three-dimensional molecular models of the lipoprotein proposed previously.


Characterization of ribonucleoprotein particles released from isolated nuclei of regenerating rat liver in two different in vitro systems. The ribonucleoprotein particles released from isolated nuclei of regenerating rat liver in two in vitro systems were studied and the following results were obtained. 1. When the isolated nuclei of regenerating rat liver labeled in vivo with [14C] orotic acid were incubated in medium containing ATP and an energy-regenerating system (medium I) release of labeled 40-S particles was observed. Analysis of these 40-S particles showed that they contained heterogeneous RNA but no 18 S or 28 S ribosomal RNAs and their buoyant density in CsCl was 1.42-1.45 g/cm3, suggesting that they were nuclear informosome-like particles released during incubation. 2. When the same nuclei were incubated in the same medium fortified with dialyzed cytosol, spermidine and yeast RNA (medium II), release of labeled 60-S and 40-S particles was observed. Using CsCl buoyant density gradient centrifugation, two components were found in the labeled ribonucleoprotein particles released from nuclei in this medium. The labeled 60-S particles were found to contain 28-S RNA as the main component and their buoyant density in CsCl was 1.61 g/cm3, suggesting that they were labeled large ribosomal subunits. The labeled 40-S particles contained both 18 S RNA and heterogeneous RNA and they formed two discrete bands in CsCl, at 1.40 and 1.56 g/cm3, suggesting that they contained small ribosomal subunits and nuclear informosome-like particles. 3. These results clearly indicate that addition of dialyzed cytosol, spermidine and low molecular yeast RNA to medium I causes the release of ribosomal subunits or their precursors from isolated nuclei in the in vitro system.


Factors causing release of ribosomal subunits from isolated nuclei of regenerating rat liver in vitro. Incubation medium II causes release of ribosomal subunits from isolated prelabeled nuclei of regenerating rat liver in vitro (Sato, T., Ishikawa, K. and Ogato, K. (1976) Biochim. Biophys. Acta 000, 000-000). The effects of individual components of this medium on release of subunits were studied and the following results were obtained. 1. Dialyzed cytosol was effective in causing release of total labeled RNA, but its effect on release of labeled ribosomal subunits was rather lower than that of low molecular yeast RNA. Spermidine inhibited the release of total labeled RNA as well as that of labeled ribosomal subunits. 2. Low molecular yeast RNA was the most effective component for inducing release of labeled ribosomal subunits. Homologous ribosomal RNA was as effective as yeast RNA. Cytoplasmic ribosomes, prepared by washing with solution of  high salt concentration, and their subunits were also effective. 3. Transfer RNA was not so effective as yeast RNA and ribosomal RNA and even after heat treatment it had little effect. 4. Among the homopolyribonucleotides tested, polyuridylic acid had a strong effect but polyadenylic acid, polycytidylic acid and polyinosinic acid had no effect. 5. The effects of yeast RNA and polyuridylic acid in causing release of labeled ribosomal subunits were dependent upon their concentrations in the reaction mixture. The characteristics of the factors which cause release of labeled ribosomal subunits in vitro are discussed on the basis of the results.


A factor affecting stimulation of aminocylation in plants. The presence of a factor stimulating the reaction of aminoacylation tRNAs was found in the seeds of lupin, with a molecular weight of 950 as estimated by gel filtration. The influence of this factor on the kinetics of the aminoacylation reactions of lupin, Escherichia coli, Baker's yeast and heterogeneous systems was investigated. This factor inhibits the esterification reaction of aminoacyl-tRNA synthetases from bacteria and yeast. Its influence on the optimum pH activity of isoleucyl-tRNA synthetase from lupin was determined.


Interaction of DNA with DNA binding proteins. II. Displacement of Escherichia coli DNA unwinding protein and the condensed structure of DNA complexed with protein HD. Three DNA binding proteins from Escherichia coli cells have been complexed with single-stranded phage fd DNA. Electron microscopy reveals granular substructures in the complexes formed with protein HD. In complexes of DNA unwinding protein with fd DNA both protein HD and phage-coded gene 5 protein partially displace the unwinding protein which results in the formation of structures characteristic for the DNA complexes formed with either protein HD or gene 5 protein alone. Combination of protein HD with double-stranded phage T7 DNA leads to a progressive folding and condensing of the genome. The structures observed are discussed in relation to current concepts of the packing of DNA in protein complexes.


Interaction of DNA with DNA binding proteins. III. Infectivity of protein-complexed phage fd DNA in Escherichia coli spheroplasts. Complex formation of circular, single-stranded phage fd DNA with Escherichia coli DNA binding protein HD or phage fd gene 5 protein keeps infection of E. coli spheroplasts at the level of free phage DNA, whereas complexes of this DNA with E. coli DNA unwinding protein show a strongly reduced efficiency of transfection. Displacement of the unwinding protein by HD protein or gene 5 protein also maintains the poor adsorption of the complexes to spheroplasts. Free E. coli DNA unwinding protein and residual amounts of this protein bound to the DNA may interfere with the adsorption and the uptake of the phage genome.


Effects of glucose and nitrogen source on the levels of proteinases, peptidases, and proteinase inhibitors in yeast. In Saccharomyces cerevisiae harvested from early exponential growth on glucose-containing media, the specifc activities of proteinases A and B, carboxypeptidase Y, and the inhibitors IA, IB, IC of these three proteinases, respectively, are found to be 10-30% of the specific activities observed in media without glucose, containing acetate as a carbon source; the activities of two aminopeptidases in glucose-grown cells were 30-50% of those in acetate-grown cells. In contrast to fructose-biphosphatase, phosoenolpyruvate carboxykinase, and cytoplasmic malate dehydrogenase, which are inactivated after the addition of glucose to derepressed cells, the proteinases and inhibitors are not inactivated after glucose addition, but appear to be repressed. Growth of the yeast on poor nitrogen sources or starvation for nitrogen results in 2-3 fold increases in the levels of most proteinases and peptidases, but this effect is not observed with glucose as the carbon source.


Metabolic characteristics of pancreatic beta-cells exposed to calcium-transporting ionophores. The effects of the ionophores A-23187 and X-537 A on glucose metabolism, ATP content and sucrose permeability in pancreatic islets microdissected from obese-hyperglycemic mice were studied. The formation of 14CO2 from 10 mM D-[U-14C] GLUCOSE WAS INHIBITED BY OMISSION OF Ca2+ from the medium. A-23187 (10 muM) induced a further decrease of 14CO2 formation whereas X-537 A (10 muM) had no effect. At 20 mM glucose both A-23187 (48 muM) and X-537 A (43 muM) decreased the 14CO2 formation in the absence of Ca2+ whereas only X-537 A inhibited in the presence of Ca2+. X-537 A (43 muM) also decreased the formation of 3H2O from 20 mM D-[5-3H] glucose. The islet content of ATP was not changed after incubation in media deficient in either Mg2+ or Ca2+. However, omission of both Mg2+ and Ca2+ resulted in about 50% decrease of the ATP content. A-23187 and X-537 A induced dose-dependent decreases of the islet ATP content. X-537 A was much more potent than A-23187. Both ionophores induced stronger depression of the ATP content when Ca2+ was omitted. X-537 A (43 muM) but not A-23187 (48 muM) increased the beta-cell membrane permeability as indicated by an increased sucrose space in relation to the urea space of islets. Such an effect was not obtained with X-537 A at 1 muM or by omission of Ca2+. It is suggested that the marked metabolic effects of the ionophores reflect an impaired mitochondrial metabolism. These metabolic changes should be considered in interpretations of ionophore action on insulin secretion.


Regulation of enzyme turnover during tissue differentiation. Studies on 6-phosphogluconate dehydrogenase in rabbit mammary gland in organ culture. (1) Explants of mammary gland from mid-pregnant rabbits were cultured in Medium 199 in the presence or absence of insulin, prolactin and cortisol. (2) Antiserum to 6-phosphogluconate dehydrogenase was raised in sheep and used to titrate the amount of enzyme activity present in explant extracts. Changes in enzyme activity were found to be due to corresponding changes in amount of the enzyme. The greatest increases in the amount of the enzyme were only brought about by culture of explants in the presence of hormones (insulin, prolactin and cortisol) in Medium 199 which contained glucose. (3) The increases in the amount of the enzyme were similar in explants cultured with hormones in Medium 199 which contained 1.39 mM, 5.55 mM or 55.5 mM glucose. (4) When explants were cultured with hormones in Medium 199 which contained glucose (5.55 mM) for 24 h and then cultured with hormones in Medium 199 which contained glycerol (10.9 mM), a decrease in the amount of the enzyme occurred. In contrast, the culture of explants with hormones in Medium 199 which contained glycerol (10.9 mM) for 24 h followed by transfer of the explants to medium which contained glucose (5.55 mM) resulted in an increase in the amount of the enzyme to reach values which were not different from those found in explants cultured throughout with hormones in Medium 199 which contained glucose.


The mitogenic effect of A23187 in human peripheral lymphocytes. The mitogenic action of the divalent ionophore A23187 was confirmed and shown to be very sensitive to changes in extracellular calcium ion concentration. At optimal calcium and ionophore concentrations, an increase in [3H]-thymidine incorporation was seen that was similar to that seen after phytohemagglutinin addition. A calcium-dependent stimulation of alpha-aminoisobutyric acid transport was also seen after A23187 addition. Studies with three inhibitors demonstrate a similarity between proliferation induced by phytohemagglutinin and by A23187. Isoproterenol (10(-4) M) and ouabain (10(-7) M) blocked the effects of phytohemagglutinin and A23187. A drug, D-600 that has been shown to block calcium channels in cardiac muscle, inhibited proliferation induced by either phytohemagglutinin or A23187. This concentration of D600 had no effect on either phytohemagglutinin- or A23187-induced 45Ca2+ uptake. Furthermore, the (+) and (-) isomers separated from racemic D600, which have been shown to block sodium and calcium channels respectively in smooth muscle, had equal potency in blocking lymphocyte proliferation.


Environmental applications of mass spectrometry. The 1975 publications reporting organic and spark source mass spectrometric studies on environmental samples were compiled. Emphasis was placed on pollutants identified rather than methods and techniques used, and reports that did not incorporate data obtained by a technique's application were not included. The 272 reports cited vary from those reporting hundreds of identified pollutants to those describing the analysis of only one sample containing one or a few pollutants. The following sample types were not considered to be environmental samples: forensic samples, synthetic or 'standard' samples, and samples analyzed for drug residues.


Immunodeficiency in patients with non-Hodgkin lymphomas. Seventy-one previously untreated patients with non-Hodgkin lymphomas were studied with several readilyvailable tests of immune function: number of peripheral blood lymphocytes, serum immunoglobulins, and delayed hypersensitivity to six recall antigens. The results were correlated to histology (Rappaport classification), stage (Ann Arbor classification), the presence of symptoms, and survival. As a group, 38 patients with diffuse lymphomas exhibited marked impairment in reactivity to five of six antigens (p less than 0.03 to p less than 0.001). In addition, lymphopenia and reduced levels of serum IgA were found in association with diffuse histiocytic lymphoma. Among patients with diffuse lymphoma, lymphocyte number and skin test reactivity tended to be greater in those with localized disease or without constitutional symptoms, and survival was superior for patients free of symptoms (p less than 0.01). As a group, 33 patients with nodular lymphoma had normal numbers of lymphocytes, lower levels of serum IgG and IgA, and significant impairment of reactivity to two antigens (streptokinase-streptodornase and mumps; p less than 0.01); reactivity to three other antigens (Candida albicans, coccidiodin, and tuberculin) was normal. Survival for patients with nodular lymphoma was superior (p less than 0.01) compared to those with diffuse lymphomas. In summary, severe immunodeficiency was found in patients with diffuse lymphoma (particularly diffuse histiocytic lymphoma), and definite but much less severe immunodeficiency was characteristic of patients with nodular lymphoma.


Growth kinetics by scanning of granulocytic cell colonies in glass capillaries. Pure granulocytic colonies were cultivated from mouse bone marrow cells in agar contained in glass capillary tubes using mouse embryo conditioned medium as colony stimulating activity. A random distribution of colonies along the agar gels was achieved under controlled conditions. Only 3 capillaries were needed for a coefficient of variation around 5% provided at least 104 cells were seeded per capillary. The daily growth of single colonies within an agar capillary was followed, using the light scattering properties of the colonies for automatic scanning. The position of the colonies in the capillary greatly affected the scan signal; the consequences of positional changes were studied in detail. Using the mean peak height as growth parameter, the onset of measureable granulocytic colony growth was found between day 2 and 3, the maximum colony size was reached between day 7 and 9, after which the colonies decayed. Other parameters such as colony count and total peak are were determined and their sinificance discussed.


The pig as an experimental model for skin flap behaviour: a reappraisal of previous studies. Skin flaps in the pig raised superficial to the panniculus carnosus are random pattern flaps. The surviving length of such flaps increases with their width until a certain length is reached after which widening the base has no further effect. The statement by Milton reinforced by that of Daniel and Williams that the surviving length is not related to its width is only true of the larger flaps. When the surface area of the pig is compared with that of man, flaps in the pig comparable in size with those in use clinically, are within the range where the surviving length is dependent on the base width.


Maxillo-facial and palatal reconstructions with the deltopectoral flap. A flexible method for reconstruction of the defects resulting from radical orbito-maxillary resections is described with 7 illustrative case reports, using the deltopectoral flap.


Monoamine oxidase in chronic schizophrenia: Studies of hormonal and other factors affecting enzyme activity. Reported reductions in the activity of platelet monoamine oxidase (MAO) in chronic schizophrenic patients might be contributed to by alterations in hormones, platelet numbers or other non-specific factors thought to affect enzyme activity. In this study, MAO activity in 27 patients with chronic schizophrenia was measured, using benzylamine as the substrate in an assay based on platelet counts instead of platelet protein, and was found to be markedly lower than mean MAO activity in 375 normal controls. These results were similar to those previously reported with tryptamine as a substrate for the enzyme. Serum testosterone, triiodothyronine, iron and iron-binding capacity were within normal ranges in individuals with reduced MAO activities. Platelet MAO activity remained stable over time in patients and controls.


Seasonal variations in urinary excretion of calcium and oxalate in normal subjects in patients with idiopathic hyperclaciuria. A longitudinal 9-year retrospective study of 24-hour urinary calcium values has been made in a metabolic stone clinic amongst patients with idiopathic hypercalciuria. No seasonal variations could be observed in contrast ot a previous study from Leeds, A prospective longitudinal study was made of 24-hour urinary calcium values in a small group of normal subjects. No seasonal variation could be ovserved. In the prospective study no seasonal variations in urinary oxalate could be observed. In a 2-year longitudinal study of stone patients with idiopathic hypercalciuria, urinary oxalate was found to be higher in the summer than in the winter. This was attributed to the combination of a higher intake of oxalate-rich foods in the summer, and the low calcium diet with which they were treated.


Centralised interpretation of electrocardiograms. A system was devised so that a peripheral hospital could transmit electrocardiograms (ECGs) to a central computer for interpretation. The link that transmits both ECGs and reports is provided by the telephone network. Initial results showed that telephone transmission did not significantly affect the accuracy of the ECG interpretation. The centralised computer programme could be much more widely used to provide ECG interpretations. A telephone link would not be justified in health centres, where the demand for ECGs is fairly small, but ECGs recorded at a health centre can be sent to the computer for interpretation and returned the next day. The most cost-effective method of providing computer interpretation for several health centres in a large city would be to have a portable electrocardiograph and transmission facilities, which could be moved from centre to centre.


Survival in 200 patients treated by haemodialysis and renal transplantation. The survival rates in 200 patients with terminal renal failure treated by maintenance haemodialysis and renal transplantation were analysed. The overall survival rate (+/- SE) was 81-4 +/- 3% at two years, 68-4 +/- 4% at five years, and 60-8 +/- 4-8% at eight years. Survival was inversely related to age: in those aged 15-34 years overall survival was 89-7 +/- 3-7% at two years, 87-8 +/- 4-1% at five years, and 83-9 +/- 5-5% at eight years. Eighty per cent of the surviving patients were able to work full time. The survival rate in patients returned to dialysis after graft rejection was 87-5% +/- 8-3 at three years.


Metabolic effects of salbutamol: comparison of aerosol and intravenous administration. The effects of intravenous salbutamol (4 mug/kg) were compared with those of aerosol salbutamol (200 mug) in 10 asthmatic patients in a double-blind placebo-controlled study. Both methods of administration produced equal bronchodilatation. Intravenous salbutamol caused significant increases in plasma insulin and glucose levels and a fall in serum potassium concentration in addition to tachycardia and tremor, whereas aerosol salbutamol produced only a small transient increase in the plasma glucose level. The initially raised non-esterified fatty acid levels decreased significantly after aerosol and placebo but not after intravenous salbutamol.


Successful bone marrow transplant for Fanconi's anaemia. A 15-year-old boy with Fanconi's anaemia, who required four units of blood each month, received a bone marrow graft from his 9-year-old brother, who has HLA identical and compatible on mixed lymphocyte reaction. Considerable immunosuppression was used and bacterial infection was prevented by vigorous decontamination in a Vickers-Trexler isolator. After the graft the patient's blood counts remained satisfactory for nine months, but it took six months before qualitative immune function was normal.


Orthotopic liver transplantation: the first 60 patients. Between May 1968 and 31 December 1976 60 orthotopic liver allografts were transplanted by the Cambridge-King's College Hospital team. During this period there were changes in the selection of patients and their management. Initially some patients were operated on when they were too ill, often because of a prolonged wait for a donor. There was a high incidence of fatal complications of biliary drainage in patients who survived longer than the first week after operation. Improved results have been due to the development of a simple method of preserving the liver, thereby increasing the pool of potential donors, and by a new technique of biliary drainage, which allows well-vascularised anastomoses without tension, retains the sphincter of Oddi, and leaves access for radiological examination of the biliary tree. Uncontrollable rejection of the liver has occurred in less than 10% of cases. This contrasts strongly with the incidence of rejection among kidney transplants. Six patients have lived for over a year, the longest surviving for more than five years, and 13 patients were still alive at the beginning of 1977.


Effects of electrical stimulation of brain. The use of implantable neural prostheses activated by radiofrequency transmission requires that the materials in the device and the stimulation techniques are not injurious to neural tissue, particularly the neurons. In this report, we discuss our experiences in the search for safe stimulation techniques. Acute and chronic experiments have been performed to evaluate electrode design and materials and to observe the effects of various stimulus protocols on the blood-brain barrier and brain. Neural tissue underlying the stimulated and control electrodes has been examined with both light and electron microscopy. Observations up to the present time indicate that the charge per phase is the most relevant stimulus parameter although the importance of charge density and current density cannot be underestimated.


Cortical histopathology following stimulation with metallic and carbon electrodes. Stimulation of the cat striate cortex with polished 1 mm2 gold, platinum, rhodium or carbon electrodes for 40h, at 50 Hz, and 0.5 msec duration, results in tissue damage at current densities of 0.6 A/cm2. At 0.1 A/cm2 rhodium and carbon were toxic to brain. In vitro gold and platinum corroded after 1,500-2,300 h of testing in simulated cerebrospinal fluid. The materials utilized are not suitable for long-term chronic electrodes for neural prosthetics.


Brain protein metabolism and the acquisition of new behaviors. II. Immunological studies of the alpha, beta and gamma proteins of goldfish brain. In a previous study, the labeling pattern of three proteins (alpha, beta and gamma) in goldfish brain was found to change after the animals successfully acquired a new pattern of behavior. In the present study, these proteins were isolated from the brain cytoplasmic fraction, purified by successive gel electrophoresis and used as antigent to immunize rabbits. Antisera containing antibodies to two of the proteins (beta and gamma) were obtained. These gave single precipitin bands when plated against the antigens and a mixture of the total cytoplasmic proteins. The distribution of beta and gamma in brain subcellular fractions and in a variety of goldfish tissues was determined by immunodiffusion methods. gamma was specific to brain. The beta protein cross-reacted but was not identical to a widely distributed substance in plasma, liver and kidney. Both beta and gamma appear to be species specific in that no cross-reactivity was obtained with mouse, chick or rat brain proteins. Immunological methods, in combination with double labeling experiments were used to establish that the beta and gamma antigens were proteins which were normally present in goldfish brain. Both the beta and gamma antisera were equally capable of specifically precipitating the proteins which were differentially labeled after training as well as purified proteins of the same molecular weight present in the brains of control animals. These results suggest that the acquisition of a new pattern of behavior can increase the demand for the synthesis of specific proteins (beta and gamma) normally present in goldfish brain.


Application of the fluorescent antibody technique to the study of an isolate of Beijerinckia in soil. Fluorescent antibody was prepared against a temperate-soil isolate of Beijerinckia obtained from a rhizosphere of rice growing in Camargue (France). The antibody did not cross-react with any of 6 species of Azotobacter, 4 species of Beijerinckia, or 44 unidentified soil bacteria isolated from a spectrum of rhizospheres, but strongly stained the homologous Beijerinckia isolate. The isolate grew well in autoclave Camargue soil, but increased in numbers only slightly in nonsterile soil during 9 days. Preliminary examination of rice plants grown in the laboratory in soil from which the Beijerinckia was originally isolated did not show detectable Beijerinckia in the rhizosphere. The fluorescent antibody was sufficiently sensitive and specific to permit more extensive study of Beijerinckia in relation to nitrogen fixation in the rhizospher of rice.


[Effect of open heart surgery on the defense mechanisms against bacterial infections]. Extracorporeal circulation during open-heart surgery may damage cellular and humoral factors in the blood. Phagocytic functions of circulating polymorphonuclear leukocytes were investigated in 10 patients 1 day before, then 1 hour, 2, 4 and 10 days after open-heart surgery. Transient diminutions in the phagocytic capacity of polymorphs was found for Staphylococcus aureus and Escherichia coli in one patient, and E. coli only in two patients up to the 4th postsurgical day. A positive correlation was found between the duration of extracorporeal circulation and the transient diminutions in phagocytic capacity for these three patients. However, the bactericidal capacity of polymorphs and their capacity to reduce nitroblue tetrazolium were normal in all patients. The serum concentrations of total hemolytic complement, C3, IgG and IgM were generally diminished up to the 4th day after surgery, but the opsonic power of the serum was almost normal in all the patients.