Lymphocyte transformation in leukemic serum. Cultures of normal lymphocytes were induced to transform by pokeweed mitogen (PWM). Inhibition of transformation was observed when these cultures contained sera isolated from children with acute lymphoblastic leukemia (ALL). The inhibition of transformation of normal lymphocytes was best demonstrated when the concentration of the leukemic serum in the culture medium was relatively high (60 percent); however, the inhibition was also observed with a more standard serum concentration (20 percent). Not all leukemic sera were inhibitory. Pretreatment sera from newly diagnosed patients with leukocyte counts greater than 50,000/mm3 were significantly inhibitory. Pretreatment sera from newly diagnosed patients with leukocyte counts less than 50,000/mm3, and sera from patients in remission or relapse had no significant effect. The inhibition observed with the sera of the high leukocyte count group was not believed to be related to cytotoxicity. The significance of this inhibitor in relation to clinical prognosis needs to be investigated.


Painful lytic bone lesion in an adult with chronic myelogenous leukemia. The occurrence of blast cell granulocytic tumors (chloromas, myeloblastomas) associated with chronic myelogenous leukemia has been well documented. However, the production of lytic lesions by nonmyeloblastomatous hematopoietic cell forms in chronic myelogenous leukemia has been described only once previously. The pain associated with osteolysis in this particular patient preceded roentgenographic appearance of lytic lesion and diagnosis of chronic myelogenous leukemia. Biopsy of lytic lesion demonstrated infiltration with cell forms nearly identical with those of simultaneously performed bone marrow aspiration.


Leukocyte function in children with malignancies. Blood was obtained on 414 occasions from 106 children with acute lymphocytic leukemia (ALL) or solid tumors. Resting and stimulated hexose monophosphate shunt (HMPS) activity and unstimulated and stimulated nitroblue tetrazolium (NBT) dye reduction were assessed on each sample. The values obtained were compared to similar determinations made on blood obtained from 178 healthy children. Resting HMPS activity of all patients with malignant diseases was significantly (p smaller than 0.01) greater, and ability to stimulate HMPSP activity significantly (p smaller than 0.01) less than that noted in healthy control patients. Unstimulated NBT dye reduction of leukocytes obtained from patients with malignant disorders was significantly (p smaller than 0.01) less than that observed in healthy control children. No significant differences were noted in HMPS activity or NBT dye reduction in patients with ALL, rhabdomyosarcoma, or other solid tumors who had bacterial infection when compared to uninfected patients, or when patients were categorized according to the type of chemotherapy provided. HMPS activity and NBT dye reduction of patients with ALL prior to treatment, in remission, and during episodes of relapse did not differ from each other. Thus, a functional impairment in leukocyte function was noted in patients with ALL even when their peripheral blood and bone marrow cells exhibited normal morphology.


Alteration of methotrexate uptake in human leukemia cells by other agents. The uptake of methotrexate (MTX) and the effect of drugs known to either inhibit or enhance MTX transport in L1210 murine leukemia were studied in man using blast cells from patients with acute myelogenous leukemia in vitro. MTX uptake was found to proceed slowly, requiring at least 160 min for cells to reach a "steady state" when extracellular MTX concentrations were 1 muM. Efflux of MTX from preloaded cells required 80 to 120 min and the nonexchangeable or tightly bound fraction was 40% of the total intracellular drug. Utilizing doses that are estimates of achievable peak blood levels following single i.v. injection, cephalothin (21 mug/ml) and hydrocortisone (20 mug/ml) inhibited net MTX accumulation by 20 and 28%, respectively. Vincristine sulfate at 8.3 and 0.083 mug/ml enhanced MTX uptake by 54 and 33%, respectively, by inhibiting MTX efflux, thus increasing the level of intracellular drug in excess of the tightly bound fraction. The potential clinical implications of using MTX in combination with the aforementioned drugs for cancer chemotherapy are discussed.


N-trifluoroacetyladriamycin-14-valerate, an analog with greater experimental antitumor activity and less toxicity than adriamycin. N-Trifluoroacetyladriamycin-14-valerate (AD 32), an analog of adriamycin, exhibits significantly greater antitumor activity than does adriamycin or daunorubicin in two experimental mouse tumor systems under similar assay conditions (C57BL X DBA/2 F1 male mice, agents administered i.p. each day for Days 1 to 4). Against the P388 leukemia at optimal dosages, AD 32 gave a +429% increase in median life-span with 3 of 5 60-day survivors compared to +132% for adriamycin (no 30-day survivors). In the L1210 leukemia system, AD 32 at several dosages consistently and reproducibly effected an increase in lifespan in excess of 445%, with a high percentage of 60+-day survivors compared to adriamycin (+42 to +54% ILS; no 30-day survivors). The reduced toxicity of AD 32 was evidenced by its optimal dose range, which is significantly greater than the lethal dose for 100% of mice of adriamycin, and by its lack of delayed toxicity. In vitro, AD 32 was somewhat less effective than was adriamycin in inhibiting the growth of CCRF-CEM cells; enzymatic conversion of AD 32 by cell-free culture medium was not observed. The unique growth-inhibitory properties of this analog indicate that the therapeutic effectiveness of the anthracycline antitumor antibiotics can be retained or enhanced by substitution on the glycosidic amino group.


Habilitation of severe craniofacial anomalies--the challenge of new surgical procedures: an NIDR workshop. Three NIDR-sponsored workshops were conducted with the goal of identifying research needs in treatment and basic sciences relating to a group of severe craniofacial anomalies that are now correctable by new radical surgical procedures. Experts in the fields of developmental biology, neurosurgery and reconstructive craniofacial surgery discussed areas of investigation dealing with etiology, prevention and treatment that are most likely to result in clincally-useful information. In addition the establishment of craniofacial anomalies centers for data collection, treatment and research was examined.


Sociological aspects of cleft palate adults. III. Vocational and economic aspects. Vocational and economic aspects of social functioning were evaluated for 196 adult cleft subjects, their 190 siblings and 209 random controls. Results indicated that cleft adults functioned within normal limits with regard to employment. However, levels of income were substantively lower than control groups. Cleft subjects compare favorably with their siblings and random controls in  occupational mobility over the levels attained by their fathers. It would appear that cleft subjects experience some limitation in their ability to secure vocational and economic rewards from society.


A tomographic technique of assessing lateral pharyngeal wall displacement. Various methods of specifying lateral pharyngeal wall configuration during speech and other activities are reviewed. Basic tomographic principles also are reviewed and a new tomographic technique of measuring mesial displacement of the pharyngeal walls is presented. An important advantage of the technique described in this report is that it enables one to measure the degree and level of mesial displacement of the lateral pharyngeal walls in relation to the soft palate, tongue, and other structures observable on lateral-view radiographs.


The effects of clefting on crown-root length, eruption, height and weight in twins discordant for cleft of lip and/or palate. Within-twin differences for crown-root length and eruption of the mandibular buccal teeth were examined for 14 DZ and 14 MZ like-sexed twins discordant for cleft of lip and/or palate. The differences were found to be greater between DZ twins than between MZ and seldom statistically significant. Relatively large variances associated with the differences are attributed to widely varying levels of postnatal care for this sample. The within-twin differences were also analyzed according to type of cleft. Cleft of lip only was found to have a lesser effect on root-crown length and percent eruption differenes than cleft or palate (or cleft of lip and palate) although again not a statistically significant difference. Height and weight were found to follow a similar pattern including large variances associated with the within-twin differences. It is therefore concluded that a dysmorphogenic effect of clefting on crown-root length, eruption, height and weight cannot be demonstrated in this sample because of large associated variances due in turn to varying levels of post-natal health care and multiple other aspects of the syndrome.


Articulation patterns and speech intelligibility of 54 Vietnamese children with unoperated oral clefts: clinical observations and impressions. Evaluations of the articulation patterns and speech intelligibility of 54 Vietnamese children with unrepaired oral clefts indicate a relationship between the type of oral cleft and the proficiency of speech skills attained. The results of the study suggest that consideration of the type of oral cleft and the specific kinds of articulation errors exhibited by the patient may be of value in planning the surgical habilitation of older children and adults with unrepaired clefts of the lip and palate.


Pharmacokinetics of guanazole in patients with acute myelocytic leukemia. Levels of guanazole (GZ) in plasma and packed cells were determined after a single tracer dose of 14C-guanazole or during a 5-day continuous intravenous therapeutic infusion of unlabeled drug to 5 patients with acute myelocytic leukemia (AML). The levels of unlabeled drug were determined colorimetrically. GZ infected as a tracer dose was rapidly distributed in an apparent volume of 0.61 l/kg, which is somewhat less than that of total body water, and the drug appeared to be eliminated essentially unchanged by glomerular filtration. The mean apparent volume of distribution increased by about 15% during infusion. An increase of 60% was also noted in the half-life (t1/2) values, with a concimitant decrease in the mean value of renal clearance rate by 40%, except in 1 case. The study demonstrates that monitoring levels of guanazole is possible during infusion therapy and indicates that the data could be used to evaluate pharmacokinetic parameters predicting the time-course of such levels in patients.


Pulmonary fungal infection complicating treated malignant disease. Secondary pulmonary fungal infection in patients being treated for malignant disease may be difficult to diagnose. Nine patients are described, illustrating some of the possible radiological appearances. There was pathological support for the diagnosis in seven of these patients. A plea is made for a higher level of suspicion in patients with the predisposing factors who also develop pulmonary complications so that suitable treatment may be given, even though sputum examination is negative.


[Studies on the functional effect of the M. mylohyoideus on the base construction of total prostheses]. By means of anatomical examinations as well as radiograms and jaw models of probands the inclination angles of the fibers of the oral diaphragm inserting in the hyoid bone are determined in order to obtain information for shaping the lingual margins of complete lower dentures. The transition from these fibers to the fibers inserting in the median raphe of the mylohyoid muscle is about 6 to 9 mm before the tip of the alveolar tubercle in edentulous mandibles, and in the area between the roots of the second molars in dentulous lower jaws with normal position of molars. In this area the muscle has, in most cases, an angle of inclination between 30 and 40 degrees to the perpendicular plane. The inclination of the posterior fibers of the mylohyoid muscle is most frequently between 10 and 25 degrees. The difference in inclination is mainly due to the varying width of the muscular insertion in the hyoid bone.


[Pathological and histological changes in the gingival mucosa under the action of denture bases with and without palatal scraping]. Histological examination showed that denture bases with palatal scraping ("Frankfurt Radierung") do not strain the palatal mucosa any more than is the case with any other palate-covering denture. If the irritation produced by the dental replacement is within the tolerance limits of the palatal mucosa, there will be no pathological changes in epithelium and submucosa in the area of the scraping borders. If the load put on the denture exceeds the tolerance level of the palatal mucosa, so that a denture stomatopathy is resulting, the changes observable in the entire palatal mucosa are also found in the areas where the scrapinb borders are located.


[The effect of the density, porosity and surface properties of plastic bases of upper dentures on the palatal mucosa]. In a 14-day test with 50 probands, the effects of a heat-curing resin and a self-curing resin on the palatal mucosa of the test persons were tested by means of exfoliative cytology. It was shown that the keratinization index increased considerably during wearing the plates. It was not possible to demonstrate differences in the effect of heat-curing resins and that of self-curing resins. The different isolation with alginate film or tinfoil did not, in general, have any influence on the cytogram either. Roughness of the surface resulted in a slight increase of the intermediary cells.


[Surgical methods for the correction of malocclusion Angle II/1 with postoperative prosthetic rehabilitation]. The operating methods for Angle class II, 1 are described and a method developed in which a front teeth block segment in the maxilla is raised and palatally tilted. At the same time a front and lateral teeth block segment of the lower jaw is pushed forward and lowered. The method improves the profile as well as occlusion and requires only a minimum of prosthetical care.


A biometrical analysis of a mating characteristic in Drosophilia. A model is described for the biometrical analysis of interaction behavioural characteristics. The model is illustrated by analysis of the mating speed of Drosophila pseudoobscura derived from crosses of fast and of slow mating strains generated through artificial selection.


Population cytology of the genus Phaulacridium. Ten of the 27 populations of Phaulacridium marginale collected from South Island, New Zealand, during the 1973 meiotic season were polymorphic for extra heterochromatin. This was present either as B chromosomes or as super-numerary segments on the shortest autosomes. In some populations both polymorphisms were present simultaneously, sometimes at high frequencies. Three different types of B chromosome were seen; large telocentric, small telocentric and small metacentric isochromosomes though only one type was seen in any one population. Segments on the telocentric S9 and S10 chromosomes were located distally. On the S11 chromosome, however, the extra segment was present as a short arm, thus making the chromosome submetacentric. This latter situation is similar to that in the related species Ph vittatum. The frequency of B's in the OM population appeared to be stable over years and there was no indication of any meiotic "drive" or "drag" in the males. The frequency of occurrence of B chromosomes in a population correlated negatively with annual rainfall (low B frequencies in regions of high rainfall). Neither type of extra heterochromatin had any significant effect on either mean cell chiasma frequency or on log variance of this metric. Possible synergism between B's and segments is discussed from the preliminary analysis of the OM population. The probable origins and age of the polymorphisms are discussed in detail.


A new hypothesis for the origin of the parthogenetic grasshopper Moraba virgo. It is proposed that Moraba virgo, the only all-female grasshopper, originated by hybridisation between two extant species P169 and P196. Such an origin accounts for M. virgo's peculiar karyotype and pattern of late replication. The model is predictive and experiments are suggested to test it.


The relation of phenotype to habitat in an introduced colony of Cepaea nemoralis. The introduced colony of Cepaea nemoralis at Lynchburg, Virginia, contains only yellow shells. The population respond to the characteristics of the environment by adjusting the frequencies of the banding morphs and by regulating the amount of fusion of adjacent bands. In this respect they fulfill a prediction based on the observations of Clarke (1960) on British colonies of Cepaea hortensis.


Testing models for variation in intelligence. A biometrical-genetical model for human variation adequately predicts observed correlations for measured intelligence. The estimation procedure is outlined.


Linkage disequilibrium causing selection at a neutral locus in pooled Tribolium populations. The role of linkage disequilibrium with respect to the changes in allele frequencies at a marker locus in newly started polymorphic populations is demonstrated using the marker locus black in Tribolium. The experiments, jointly taken, indicate that the black locus is selectively neutral, or nearly so, under the current experimental conditions. A number of possible mechanisms for selection at the neutral marker locus, i.e. a single linked or non-linked locus and a number of linked and/or non-linked loci through which selection acts, are discussed. On the basis of the experiments some of these models can be excluded, leaving three models for further evaluation: (A) a single linked fitness locus, (B) a number of linked fitness loci and (C) a number of both linked and non-linked fitness loci. The first of these models allows estimation of parameters (recombination  fraction and selection coefficients). Models B and C are described in terms of heterozygosity of chromosome pairs. It is argued that in view of the history of a laboratory mutant stock, model C fits best to the experimental results.


Extrachromosomal factors affecting mating reactions in Schizophyllum commune. Extrachromosomal factors modifying mating reactions in Schizophyllum commune were found. The P factor appeared spontaneously, while the F factor appeared following nitrosoguanidine treatment. When a strain carrying P was mated with wild-type strains, it invariably developed pseudoclamps (usually typical of common-B heterokaryons), while there developed on the side of the wild-type strain the dikaryon or heterokaryon expected from the genotypes involved. In a cross Ax Bx P times Ay By, fruiting bodies from the side of the wild type gave rise only to wild-type segregants with mating types as expected from their genotypes. A selfed fruiting body from the side of the P strain gave rise to progeny which did carry the P factor, but its expression was modified. It had inconsistent and symmetrical effects in A not equal to B not equal to and A not equal to B equals matings, but the original type of asymmetrical reaction in A equals B not equal to matings. In the next generation the effect of P was weak and symmetrical. Strains carrying F factor were flat (morphology typical of mutation of the B factor) and were compatible with strains with which they should be incompatible according to the genotypes, e.g. Ax Bx F times Ay Bx gave a dikaryon. The factor showed non-Mendelian segregation and was extremely unstable.


Maturation of membrane function: the permeability of the rat erythroblastic leukemic cell to water and to non-electrolytes. The erythroblastic leukemia produced in Long-Evans rats by the administration of 7, 8, 12 trimethylbenz (a) anthracene has been used as a model of the most immature form of the erythrocyte series. In conjunction with studies of the maturation of several other membrane functions, the permeability of this cell to water and to certain definitive non-electrolytes was measured with osmotic methods. The hydraulic conductivity, L-p was 6.2 micro (minute)-1, (atm)-1 at 25 degrees C, quite high and characteristic of mature erythrocytes, but different from values of 0.65 for immature myeloid cells. The effect of temperature provided an energy of activation of 4.4 kCal/mole, also typical of mature mammalian erythrocytes but again different from 13 to 18 kCal/mole for immature myeloid cells. Urea was compared to thiourea. The permeability coefficient for urea was 76.7 micra (minute)-1 plus or minus 13.8 (S. E.); the value for thiourea was 1.55 micra (minute)-1 plus or minus 0.18 (S. E.). Phloretin at 0.25 mM inhibited urea permeability by 90% with 50% inhibition occurring at 0.05 mM. Inhibition was reversible. Permeability to the glycols was also compatible with mature erythrocytes. We infer from these findings that the structure which underlies these basic, passive membrane functions is laid down early and persists after loss of nucleus and subsequent maturation.


Multiple knife cuts between the medial and lateral hypothalamus in the rat: a reevaluation of hypothalamic feeding circuitry. Single or multiple sets of bilateral knife cuts were made in female rats just lateral to the ventromedial hypothalamus (VMH) and/or just medial to the lateral hypothalamus (LH). The lateral VMH cuts by themselves produced greater hyperphagia and obesity than did the medial LH cuts. The lateral VMH knife cuts also significantly increased food intake and body weight in rats previously given bilateral cuts along the medial LH border. These findings indicate that the feeding inhibitory fibers responsible for the hyperphagia syndrome do not project from the VMH to the LH, and this calls for a reevaluation of hypothalamic circuitry. It was also discovered that sham surgery has a significant suppressive effect on the hyperphagia syndrome produced by hypothalamic knife cuts.


Delayed hyperphagia and increased body length after hypothalamic knife cuts in weanling rats. Four-week-old female rats received parasagittal hypothalamic knife cuts. Polydipsia began right surgery, but hyperphagia, obesity, and excessive nose-anal length did not begin until after the rats were 7-8 wk. old. The delayed onset appears to await some maturational event that is required for the expression of hypothalamic obesity. It appears likely that puberty is the critical maturational event.


Factor analysis of comprehensive examinations. In working toward new, integrated curricula, dental schools have often failed to concurrently revise their evaluative techniques to be more compatible with the objectives of the curriculum. One question of major importance is whether the schools are totally aware of their students' capabilities or are graduating students proficient in some fields while lacking in others. Is the student's overall or total score satisfactory even though deficiencies may exist in certain areas? This latter situation is a real possibility when the simple sum of subtest scores is used as the primary means in assessing students. Using factor analysis, the scores on the subtests of eight dental school comprehensive examinations (total of 1,023 subjects, on first-, second-, and third-year examinations given between December 1970 and May 1972) at the University of Pittsburgh School of Dental Medicine were examined. The results, culled from the correlation matrices, Chi-square analysis, and factor matrices, indicated that the subtests did not form a homogenous unit (one, general factor), and hence that use of the total score is questionable.


Statistical inferences about injury and persistence of environmentally stressed bacteria. A standard technique for ascertaining the survival characteristics of bacteria after being environmentally stressed is to incubate the bacteria on both selective and non-selective media and count the colonies produced. Based on these colony counts, indexes of injury and persistence of the bacteria are calculated. To compare the stress of two different environments, a persistence ratio is calculated. In this paper, methods of statistical inference concerning these indexes and ratios are presented. These statistical methods use well-known procedures for analysis of binomial data and 2 times 2 table data, and are appropriate when the colony counts follow a Possion distribution.


The evaluation of hypersensitivity tests in cattle after foot-and-mouth disease vaccination. The response to passive cutaneous anaphylaxis, dermal hypersensitivity and intravenous provocation tests has been compared in 30, 40, 31 and 24 cattle injected with foot-and-mouth disease vaccine 0, 1, 2 and 3 times respectively, using vaccine components and other substances as test materials. Reaginic antibodies demonstrated by passive cutaneous anaphylaxis in goats, were directed against BHK 21 cell extracts (20), hydroxypropylmethylcellulose (3) and an unidentified vaccine component (3), and distributed in 0, 5, 19 and 75 per cent of the cattle vaccinated 0, 1, 2 and 3 times. None of the animals showed clinical signs of allergy after vaccination. When BHK 21 cell extract was injected intradermally a significant correlation was noted between the development of large weals and the presence of reagins although the size of the weals was not correlated with the reagin titres. In the case of hydroxypropylmethylcellulose a similar trend was evident. The majority of cattle with large dermal weals possessed reagins but the number of reactions was too small for statistical evaluation. Dermal reactions to sodium penicillin, sodium carboxymethylcellulose, saponin and whole vaccine occurred in both unvaccinated and vaccinated cattle but BHK 21 cell lysate and normal bovine serum provoked weals which increased in frequency according to the number of vaccinations experienced. Intravenous hydroxypropylmethylcellulose elicited a response in all the animals previously injected with certain batches of vaccine but cell extract intravenously produced a clinical response in half the tested animals which was uncorrelated with the results of the passive cutaneous anaphylaxis or dermal hypersensitivity tests.


Outbreaks of bovine salmonellosis caused by serotypes other than S. dublin and S. typhimurium. Outbreaks of salmonellosis caused by serotypes other than S. dublin and S. typhimurium were investigated on 41 farms in north-west England. Of these, 37 (90 per cent) were in dairy cows. There was strong circumstantial evidence that contaminated dairy cake was the source of infection in at least four herds and probably many more. Twenty-six serotypes were encountered with S. newport, the commonest, causing the most severe disease. Most cattle seemed to rid themselves of infection during the following months whether or not they were at pasture, housed in cubicles or in byres. Some cows excreted salmonellas for up to 11 months after the disease outbreak. Associated human salmonellosis was confirmed on 3/41 (7 per cent) of the farms.


Counter-electrophoresis as a possible method for typing ECHO and Coxsackie B viruses. A method for typing ECHO and Coxsackie B viruses using counter-electrophoresis has been developed using stock strains of 15 different ECHO types and 5 Coxsackie B viruses. Work is continuing to see whether the method is a practical one to use for typing of strains from patients infected with ECHO or Coxsackie B viruses.


The role of wild ruminants in the epidemiology of bovine petechial fever. After experimental inoculation of Cytoecetes ondiri, the agent of bovine petechial fever (BPF), multiplication occurred in impala, bushbuck, Thomson's gazelles and wildebeest, as shown by infectivity studies and clinical findings. Similar attempts to infect one eland failed. As a sequel to this, blood and spleen samples were collected from four species of wild ruminants in an area where BPTF was endemic. Isolations of C. ondiri were made from three of five bushbuck, but not from any other species.


Response to influenza vaccine in adjuvant 65-4. A comparison was made of the antibody response and subjective reactions to zonally-purified influenza vaccine in aqueous suspension and in peanut oil adjuvant 65-4. Both preparations contained 700 CCA units of A/Aichi/2/68, and 300 CCA units of B/Mass/1/71. Subjective reactions were recorded by asking the volunteers to complete a record daily for 5 days. Pain at the injection site was recorded by 64 per cent of the recipients of the oil adjuvant vaccine compared with 35 per cent of the aqueous recipients, but local redness was more frequent after aqueous vaccine. Systemic symptoms was recorded a little more frequently after aqueous than oil adjuvant vaccine. When measured 71/2 weeks after a single dose of vaccine, the HAI geometric mean antibody titre (G.M.T) to the A/Hong Kong/1/68 antigen (antigenically similar to the A/Aichi/2/68 antigen in the vaccine) increased 2-7 fold after aqueous and 16-4 fold after adjuvant vaccine. Sixty-two weeks after vaccination the antibody titres remained higher in those given adjuvant vaccine. The G.M.T. to B/Mass/1/71 increased 1-9 fold 71/2  weeks after aqueous vaccine and 3-7 fold after adjuvant vaccine. The antibody response to both influenza A and B antigens was broader in the recipients of adjuvant vaccine. The G.M.T. to A/England/42/72 increased 2-8-fold after aqueous and 13-fold after adjuvant vaccine; and to B/England/847/73 it increased 1-3-fold after aqueous and 1-9-fold after adjuvant vaccine.


Presence of a dialysable fraction in normal bovine whey capable of killing several species of bovine mycoplasmas. Most normal bovine whey samples contain a fraction that survives heating at 56 degrees C. for 30 min., passes through a dialysis membrane and kills a maximum of seven out of ten of the different bovine mycoplasma species tested. Some whey samples appear more active than other but not all affect the same strains of mycoplasma indicating some specificity in their action. Absorption of the active factor from whey by heterologous and homologous mycoplasmas and by erythrocytes was observed. Binding of the factor to mycoplasmas appears to be temperature-dependent and non-specific, but subsequent mycoplasmacidal action shows some specificity.


Trends in salmonella food poisoning in England and Wales 1941-72. Cattle and pig herds and flocks of domestic fowl have formed the main reservoir of human salmonella food poisoning in England and Wales from 1941 to 1972. Changes in the incidence of human salmonella food poisoning and in the serotypes of salmonellas isolated from human infections are shown to have been associated with the introduction of new foods, with changes in animal husbandry, and with changes in the relative proportions of flesh food from different species consumed. New foods, dried powdered egg, liquid egg and frozen liquid egg were introduced during the period of food rationing which extended from 1940 to 1953. Changes in animal husbandry, in particular the intensive production of pigs, poultry and eggs, followed the re-establishment of pig herds and fowl flocks after the derationing of animal feed in 1953. The changes in the proportions of flesh foods consumed followed the introduction of frozen oven-ready fowl in the late 1950s and early 1960s which by 1964 became cheaper than traditional flesh foods.


The role of IgE in the release of histamine from human gingival mast cells. Twelve gingival samples removed from 6 human volunteers were sectioned in small pieces, parts of which served as uncultured pieces. The remaining pieces were organ cultured for 5 hours in control, compound 48/80, and antihuman IgE media. Uncultured tissues, cultured tissues, and cultured spent media were analyzed spectrofluorometrically for histamine content. The uncultured tissues contained a mean (plus or minus SE) of 5.41 plus or minus 0.60 mug/g of histamine and were considered to contain 100 percent total histamine. The percentage of the total histamine released into the medium was 8.24 percent for cultured control, 56.7 percent for antihuman IgE, and 66.7 percent for compound 48/80. Significant histamine release into medium was noted for antihuman IgE (P less than 0.0005) and for compound 48/80 (P equals 0.005), but these two were not significantly different from each other (P greater than 0.25). Significant tissue histamine reduction was recorded for tissues cultured in compound 48/80 (P less than 0.025), whereas a significant tissue histamine synthesis was demonstrated for tissues cultured in antihuman IgE (P less than 0.05). The control tissues revealed neither significant histamine release into the medium nor significant tissue histamine reduction or synthesis. The results demonstrate IgE in clinically healthy human gingiva, show its association with gingival mast cell histamine release, and establish an in vitro model system for further human mast cell study. Thus, the concept of an association between IgE antibodies and human gingival mast cells is supported.


Further observations on the gingival cyst. Three case reports. Three clinically discernable gingival cysts have been described and documented histologically. Two of these lesions occurred in the same patient in adjacent areas of the mouth. The potential origin of such cysts has been described. We suggest that gingival cysts are not clinical curiosities, as proposed in earlier reports.


Time trends in survival in acute lymphocytic leukemia. Comparison of patients under 20 years of age with acute lymphocytic leukemia diagnosed in 1955-64 with those whose disease was diagnosed in 1965-69 revealed a marked improvement in median survival time, from 9.5 to 16.8 months. This improvement occurred among patients with less favorable hematologic and symptomatic characteristics as well as among patients with more favorable ones. However, a shift in patient characteristics was consistent with the concept of diagnosis earlier in the natural history of the disease. In the more recent period, fewer patients were classified as severely disabled, and a somewhat higher proportion were in more favorable categories with respect to platelet count, percent of polymorphonuclear leukocytes, organomegaly, and bleeding or infection. Initial treatment was markedly different during the two time periods; this reflected a shift toward the use of combinations of chemotherapeutic agents and steroids.


Agglutination of leukemic and 2,4-dinitrophenyl-tagged normal human lymphocytes by wheat germ agglutinin. The present study was undertaken to determine if leukemic and 2,4-dinitrophenyl (DNP)-tagged normal human lymphocytes shared common receptors for Wheat Germ Agglutinin (WGA), a lectin capable of reacting with malignant cells. Normal peripheral blood lymphocytes were tagged with 2,4-dinitrofluorobenzene (DNFB) at a ratio of 10-11 molecules/cell. Various concentrations of WGA were added to leukemic or tagged or untagged normal lymphocytes and incubated for 20 minutes at 37 degrees C, after which agglutination was scored visually. A readily discernible quantitative difference in the agglutinability of leukemic and DNP-tagged versus untagged normal cells was seen at all concentrations of WGA in the range of 50-800 mug/ml. The reaction was maximal when a ratio of 10-11 molecules of DNFB/cell was used for tagging and decreased progressively with 10-8, 10-6, 10-4, 0r 10-2 molecules. The agglutination of leukemic and DNP-tagged normal lymphocytes by 200 mug/ml of WGA was completely blocked by 0.1 M N-acetylglucosamine (GlcNAc) while as low a concentration as 0.001 M GlcNAc inhibited the reactivity of untagged cells. Since the agglutination of leukemic and DNP-tagged normal lymphocytes was equally inhibited by GlcNAc, this suggests that the same or similar receptor sites were involved in the two reactions. On the basis of our observations we propose that the initial step in the agglutination of leukemic and DNP-tagged normal lymphocytes by WGA IS THE BINDING OF THE LECTIN TO SPECIFIC RECEPTORS RATHER Than to DNP residues on the cell surface, since leukemic cells tagged with DNFB did not show increased agglutinability.


Is methotrexate therapy for psoriasis carcinogenic? A modified retrospective-prospective analysis. The use of methotrexate in psoriasis has recently been questioned because of possible carcinogenic potential. Two hundred twenty-four patients began methotrexate therapy during 1960 to 1965 at the Cleveland Clinic and at Duke University Medical Center. The incidence of malignant neoplasms and mortality has been studied in 205 of these 224 patients. Mortality increased with hepatic disease. No increased incidence of total internal malignancy was found, nor did any one type of neoplasm appear predominant.


[Congenital leucosis with unusual involvement of the brain(author's transl)]. A case of congenital paraleucoblast-leucosis is reported. The diagnosis rested on pronounced infiltrations of the skin and leucemic signs in blood and bone marrow. The child died on the 20th day after developing signs of bleeding and cerebral involvement. At necropsy leucotic infiltration was found in may organs, mainly in pancreas, skin and bone marrow. The most prominent findings and cause of death were diffuse hemorrhagic foci with a high proportion of leucemic cells in the brain and cerebellum.


[Problems of disinfection of breathing apparatus (author's transl)]. Report on the problems of disinfection of breathing apparatus. As a new means of avoiding bacterial contamination of the humidified and warmed inhaled gas mixture for 48 hours Rivanol in solution 1:1000-1:5000 is recommended as humidifier. For this,  however, only those breathing systems are suited which work on the evaporation principle, not on atomizers or spraying. The good bacteriologic results are explained by the certain inhibition of bacteria by Rivanol in the humidifying fluid. It is understood that--in addition--there must be regular (every 24 hours) disinfection of tubes and the valves which ought to be as simple as possible. As humidifying fluid only sterile water, possibly fresh tap water, are recommended.


[Mobile intensive-care-unit for transportation of premature and newborn babies at risc (author's transl)]. This is a technical report on a specially equipped ambulance for transportation of high-risk, seriously ill neonates. A mobile neonatal intensive-care-unit operating independently of the car utilized an Ohio-transport-incubator with 12V-DC portable power pak and collapsible stand, battery-operated ECG-monitor with optical and acoustical signal, a ECG-monitor with optical and acoustical signal, a battery-operated infusion pump, a Bird-respirator mark 8 with oxygen-blender, nebulizer and infant circuit with modification for PEEP as well as additional accessories. Ambulance-duty service is guaranteed by the German Red Cross (DRK) to facilitate transfer at any time, while skilled personal (physician, nurse) of the intensive care ward in on 24 hs call.


Abnormal renal urate homeostasis in systemic disorders. Abnormalities of renal handling of urate occur in a wide variety of physiological and pathological conditions and are mediated by factors including renal blood flow, glomerular filtration rate, urine flow rate, urinary constituents, metabolites, hormones and drugs. The determination of the aetiological factors in each abnormal situation is complex and the problem is discussed in relation to a variety of conditions including renal tubular disorders and mental intoxications, hypertension, toxaemia of pregnancy, glycogen storage disease, fructose administration, hereditary fructose intolerance, as well as obesity, regular alcohol consumption and hyperlipoproteinaemia. Apart from those diseases, usually genetically determined, which are associated with excessive production of urate, the most common causes of hyperuricaemia act at a renal level and result in a reduction in the net renal excretion of urate.


[Different maturation of leukemic blasts in tumor--like type of acute infantile leukemia (author's transl)]. In condition, it has been found that an acute infantile leukemia in its early stages, manifested itself clinically and morphologically as a reticulosarcome. Through cytochemical examinations, the malignant disease could be identified as an acute myeloid leukemia. The blasts in the tumourous tissues show less differentiation than the leukemic blood and bone marrow cells. The lack of maturation of the blasts is discussed as the cause of tumorlike cell growth.


Peritonsillar, peripharyngeal, and deep neck abscesses. Abscesses of the peritonsillar and peripharyngeal regions typically present as a sore throat and as difficulty in swallowing. One of the most ?striking clinical features is difficulty in controlling saliva. Deep neck abscesses usually are secondary to disease in the pharynx, tonsils, or teeth. Initially, attention should be devoted to finding the primary source of infection. Treatment of these abscesses is incision and drainage.


The role of surface proteins in cell proliferation as studied with thrombin and other proteases. This communication explores the capacity of different proteases to stimulate DNA synthesis in resting chick embryo fibroblasts and to cause the removal of cell membrane proteins previosly postulated as important in the regulation of growth and division of cells. Thrombin, a highly specific protease and a known mitogen, was incubated with chick embryo fibroblasts, and analysis was made of the cell membrane proteins. Of particular interest were a protein of molecular weight 250,000, which is known to be readily removed by the action of trypsin and is not present in most transformed cells, and two other proteins, which are reduced in amount in transformed as compared to confluent resting cell cultures. None of these three proteins was removed by thrombin when the latter was added to confluent cells in concentrations sufficient to cause significant increase in DNA synthesis twelve hours after stimulation by the protease. The presence or absence of these proteins in the membranes of confluent resting or transformed cells of chick embryo fibroblasts does not seem to be directly related to the process of regulation of DNA synthesis and cellular division.


A new complement function: solubilization of antigen-antibody aggregates. Antigen-antibody aggregates are solubilized when incubated with fresh serum at 37 degrees, yielding immune-complexes of relatively small molecular weight which contain antigen, antibody, and complement (C3)determinants. Solubilization is complement-dependent,requires free Mg++ but not Ca++, and proceeds in sera from C4- or C5-deficient animals. It is accelerated in the presence of Ca++ in normal or C4-deficient guinea pig serum, suggesting involvement of the Cl-bypass activation of the properdin system. Immune precipitates can also be solubilized by monovalent fragments (Fab) of antibodies directed against determinants of the antibody molecules included in the antigen-antibody lattice. Similarly, it is suggested that complement-mediated solubilization might be induced by the combination of a complement fragment with the antibody in the immune-aggregate.


The in vitro addition of a polyadenylate sequence to the 3' end of phage Qbeta RNA and the biological activity of the product. Terminal riboadenylate transferase, purified from calf thymus, has been used to add a poly(A) extension to the 3' end of Qbeta RNA. The modified Qbeta RNA retains full infectivity in a spheroplast assay system. However, the progeny viruses do not contain poly(A) termini, indicating an in vivo rectification of the in vitro alteration.


Resonance raman spectra of manganese (III) tetraphenylporphin halides. Unique resonance Raman spectra were obtained when manganese(III) tetraphenylporphin halides in noncoordinating solvents were illuminated by laser frequencies around 500 nm. Of particular interest is the observation of a feature that is sensitive to the nature of the axial ligand. This feature disappears when the coordinating solvent pyridine is employed, and it, therefore, appears to be diagnostic of the manganese coordination number.


Sequential production of fatty liver, hepatitis, and cirrhosis in sub-human primates fed ethanol with adequate diets. This study reproduces in experimental animals the sequential development of all the liver lesions seen in the human alcoholic: in 15 baboons fed ethanol, all developed fatty liver, five progressed to hepatitis, and five had cirrhosis. Maintenance of a nutritionally adequate regimen despite the intake of inebriating amounts of ethanol (50% of total calories) was achieved by incorporation of the ethanol in a totally liquid diet. Upon ethanol withdrawal, signs of physical dependence, such as seizures and tremors, developed. Ultrastructural changes of the mitochondria and the endoplasmic reticulum were already present at the fatty liver stage and persisted throughout the hepatitis and cirrhosis. The lesions were similar to those observed in alcoholics (including the inflammation and the central sclerosis) and differed from the alterations produced by choline and protein defiencies. At the fatty liver stage, some "adaptive" increases in activity of microsomal enzymes [aniline hydroxylase (EC 1.14.14.1) and the microsomal ethanol oxidizing system] were observed, but these tended to disappear with the development of hepatitis and cirrhosis. Fat accumulation was also much more pronounced in the animals with the hepatitis as compared with those with simple fatty liver (an 18-fold compared with 3- to 4-fold increase in liver triglycerides). The demonstration that these lesions can develop despite an adequate diet indicates that in addition to correction of the nutritional status, control of alcohol intake is mandatory for the management of patients with alcoholic liver injury.


Murine leukemia virus: detection of unintegrated double-stranded DNA forms of the provirus. Infection of JLS V-9 (mouse bone marrow) cells with Moloney murine leukemia virus leads to appearance of virus-specific DNA in the low molecular weight DNA fraction from infected cells. Most of this DNA is double-stranded. Two discrete forms of double-stranded DNA, both of molecular weight 6 times 10-6, have been characterized. One of these forms is closed-circular, supercoiled DNA; the other form is a mixture of nicked-circular and linear DNA.


The effect of acetoxycycloheximide on rate of accumulation of cerebral catecholamines from circulating tyrosine as related to its effect on memory. The rate of accumulation of newly synthesized catecholamines and endogenous catecholamine levels in mice were determined after an amnestic intracranial dose of acetoxycycloheximide. Rates of accumulation were found to be severly decreased for a period of 12 hr after injection. Total catecholamine levels were increased from 1 to 4 hr, then decreased 17 hr following injection. These results are discussed in terms of previous behavioral observations. It is pointed out that they weaken the assumption that acetoxycycloheximide's amnestic effects are solely due to inhibition of protein synthesis.


Control of ovarian cell growth in culture by serum and pituitary factors. An ovarian cell line was developed that requires hormonal conditioning of the host for growth in vivo and that requires special factors for growth in vitro. It is necessary to prepare special culture media to demonstrate the effects of growth factors in vitro. To this end, methods were developed for removing from serum those essential factors required for the growth of ovarian cells in culture. Minimal growth occurred in medium containing fetal calf serum that had been passed through a porcelain filter. This method of depleting serum was replaced by a procedure involving passage through a carboxymethylcellulose column. Either pituitary extract or the eluate from the column restored growth in these depleted media. The eluate was more active than pituitary extract with regard to maximal growth enhancement. When the cells were incubated in the depleted media, viability, as measured by plating efficiency, decreased with incubation time. Either pituitary extract or the eluate from the column prevented such death of cells. Based on these findings, we postulate that the eluate contains both a survival factor and a growth-promoting factor for these ovarian cells, while pituitary extract contains only the survival factor.


A zinc protein isolated from human parotid saliva. A zinc protein has been isolated and purified to apparent homogeneity from subjects with normal taste acuity by gel filtration and ion-exchange chromatography. The protein has a molecular weight of 37,000 and does not appear to have subunits. It is composed of 8% histidine residues and has 2 moles of zinc per mole of protein.


Isolation of mammalian cell mutants deficient in glucose-6-phosphate dehydrogenase activity: linkage to hypoxanthine phosphoribosyl transferase. Mutants of Chinese hamster ovary cells deficient in glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP 1-oxidoreducatse, EC 1.1.1.49) activity were isolated after mutagenesis with ethyl methane sulfonate. The mutants were induced at frequencies of about 10-4 and do not differ in growth properties from wild-type cells. They were isolated by means of a sib selection technique coupled with a histochemical stain of colonies for enzyme activity. The lack of enzyme activity is not due to a dissociable inhibitor, and is recessive in hybrid cells. Multiple mutants that lack hypoxanthine phosphoribosyltransferase activity (IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) and adenine phosphoribosyltransferase activity (AMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.7) were isolated by further mutagenesis. By following segregation of wild-type phenotypes from heterozygous multiply marked hybrid cells, it was shown that the genes responsible for glucose-6-phosphate dehydrogenase activity and hypoxanthine phosphoribosyltransferase activity are linked in Chinese hamster cells, in agreement with the location of both on the X chromosome in humans. No linkage to adenosine phosphoribosyltransferase was found. The isolation of mutant cells carrying linked markers should prove useful for studying chromosomal events such as segregation, breakage, recombination, and X-chromosome reactivation.


RNA-primed DNA synthesis: specific catalysis by HeLa cell DNA polymerase alpha. We have analyzed and compared the responses of the three major HeLa cell DNA polymerases (alpha, beta, and gamma) to a HeLa DNA template with short RNA or DNA primers hybridized to it. Only DNA polymerase alpha is able to synthesize DNA covalently bonded to the RNA primer via a 3' yields 5' phosphodiester bond.  32P transfer experiments showed that all combinations of ribo- and deoxyribonucleotides are represented in the RNA-DNA linkages but their distribution is nonrandom. The RNA-DNA linked molecules base-paired to a HeLa DNA template strand represent a possible "natural" in vitro primer-template for DNA polymerases and can be extended by all three DNA polymerases (alpha, beta, and gamma). These findings indicate that DNA polymerases beta and gamma are capable of DNA-primed but not RNA-PRIMED DNA synthesis, while DNA polymerase alpha is capable of both RNA-primed and DAN-primed DNA synthesis.


Cytochemical studies on golgi apparatus, GERL, and lysosomes in neurons of dorsal root ganglia in mice. Cytochemically demonstrable thiamine pyrophosphatase activity is present in the innermost Golgi element in both small and large neurons of the dorsal root ganglia in CF1, C57 black, and C57 beige mice, thus resembling the neurons of rat dorsal root ganglia. The localization of acid phosphatase (EC 3.1.3.2) activity in the large neurons of dorsal root ganglia in these mice is also similar to that in rats; it is not demonstrable in Golgi elements but is present in GERL and in three types of lysosomes apparently derived from GERL. However, the small neurons of the mouse differ from those of the rat in showing acid phosphatase activity in all elements of the Golgi apparatus. In the mouse neurons the acid phosphatase activity of residual bodies is "latent," i.e., it is not demonstrable in well-preserved cells.


Effects of cytochaslasin B and colcemide on myogenic cultures. Muscle cultures treated with cytochalasin B yield mono- and oligonucleated cells of two kinds: (i) arborized, replicating precursor myogenic cells and fibroblasts; and (ii) round, post-mitotic, terminally differentiating myoblasts and myotubes. The arborized cells do not bind fluorescein-labeled antibody against myosin, do not contract rhythmically, and do not display hexagonally stacked thick and thin filaments. The round, mono-nucleated myoblasts and round, oligonucleated myotubes bind the fluorescein-labeled antibody against myosin, contract rhythmically, and display clusters of hexagonally-stacked thick and thin filaments. When cytochalasin B is removed and replaced by colcemide, the arborized cells, but not the post-mitotic muscle cells, acquire a radial symmetry and are induced to assemble massive, meandering cables that may occupy over 25% of the cell volume. These tortuous calbes are positively birefringent and consist exclusively of enormous numbers of 100-A, intermediate-sized filaments.


Testosterone stimulation of a rapidly labeled, low-molecular-weight RNA fraction in human hepatic erythroid cells in culture. The addition of erythropoietin to cell cultures of erythroid cells of human fetal liver resulted in an increased incorporation of thymidine, adenine, and uridine into trichloroacetic acid-insoluble cell fractions and in an increased uptake of adenine and uridine into the cell. Although the effects of testosterone and erythropoietin on heme synthesis in these cells are known to be very similar, there was no effect of testosterone on the total incorporation of radioactive precursors into DNA or RNA. The RNA synthesized after short pulses of radioactive uridine, when analyzed on sucrose gradients containing 1% sodium dodecyl sulfate, consisted of a homogeneous peak sedimenting at 10 plus or minus 2 S, which is quite different from the heterogeneous, high-molecular-weight RNA synthesized under identical conditions in primary cultures of human fetal lung, kidney, or liver parenchymal cells. Addition of testosterone to liver erythroid cells in cultures for 5 hr followed by a 1-hr uridine pulse resulted in a 3-fold increase of RNA species with an average sedimentation coefficient of 14 plus or minus 3 S. The similarity with the sedimentation coefficient of the globin mRNA described in other systems and the high degree of specialization of the erythroid cells suggest that this RNA may be a stable intermediate involved in the synthesis of hemoglobin.


X-ray diffraction studies of human erythrocyte membrane structure. Small angle x-ray diffraction patterns have been obtained from ordered arrays of hemoglobin-free human erthyrocyte membranes by use of improved techniques. Diffraction data have been recorded to 9 A resolution on samples whose lattice periodicity was varied (by changing humidity) from 55.5 A to 69.6 A. The observed reflections permitted tracing the intensity transform of the membranes. Phases for the reflections were assigned by the minimum wavelength principle. An electron density profile was then obtained by Fourier inversion, and yielded a symmetric membrane about 55 A in width. This structure can account for the previously reported diffuse scattering observed in other preparations (thus rendering unnecessary the proposed assignment of this scattering to a separated lipoprotein phase) and for the continuous scattering that we have recorded from isolated membranes in buffer. Lower resolution data that we have obtained from ultracentrifugally prepared lattices in buffer (and therefore without dehydration) are consistent with the above results, and support our view that we are observing diffraction from intact membranes.


Further evidence of a quantitative deficiency of chain-specific globin mRNA in the thalassemia syndromes. Formamide gel electrophoresis separates the mRNA fraction from reticulocyte polyribosomes of adult humans into two major RNA species with migratory rates identical to those of the alpha- and beta-globin mRNAs of the rabbit. That these two RNAs of human origin are the globin mRNAs is further supported by the deficiency of the presumed beta mRNA in reticulocyte polyribosomes of fetuses and premature infants, whose cells make gamma chains in preference to beta chains. The globin mRNAs of reticulocyte polyribosomes from patients with hematological disorders were estimated by scanning the stained formamide gels. In contrast to individuals with either hemolytic anemia without hemoglobinopathy or sickle cell anemia who had beta mRNA to alpha mRNA ratios of approximately one, a patient with Hb S-beta-thalassemia had a ratio of beta mRNA to alpha mRNA of 0.75 while two subjects with homozygous beta-thalassemia had severe deficiencies of beta mRNA. Conversely, a patient with alpha-thalassemia (Hb H disease) had a ratio of beta mRNA to alpha mRNA on reticulocyte polyribosomes of 6. These data provide further evidence of a quantitative deficiency of chain-specific globin mRNA in patients with the thalassemia syndromes.


Isolation of the bacteriophage lambda A-gene protein. An in vitro assay for measuring the activity of the phage lambda A-gene product has been developed. The assay is based on the observation that A-donor extracts complement A minus extracts for packaging of exogenous immature lambda DNA into phage particles. A partial purification of the A-gene product activity using this assay is presented. A method is suggested by which this A protein-dependent in vitro system might be manipulated to analyze the mechanism of reforming the lambda cohesive termini during chromosome assimilation into phage precursors.


Abnormal collagen metabolism in cultured cells in osteogenesis imperfecta. Cells obtained from normal human skin synthesize predominantly type I collogen in culture. Cells obtained from the skin of an infant with a severe form of osteogenesis imperfecta were found to synthesize as much type III as type I collagen. Decreased synthesis of type I collagen could explain the tissue fragility observed in this case.


Morphine receptors as regulators of adenylate cyclase activity. Morphine inhibits adenylate cyclase (EC 4.6.1.1) activity of neuroblastoma times glioma hybrid cells. The inhibition is stereospecific and is reversed by the antagonist, naloxone. The relative affinities of narcotics for the opiate receptor agree well with their effectiveness as inhibitors of adenylate cyclase. Morphine-sensitive and -insensitive cell lines were found, and the degree of sensitivity was shown to be dependent upon the abundance of narcotic receptors. Thus, morphine receptors are functionally coupled to adenylate cyclase. A molecular mechanism for narcotic addiction and tolerance is proposed.


Separation of 1-acylglycerolphosphate acyltransferase and 1-acylglycerolphosphorylcholine acyltransferase of rat liver microsomes. 1-Acylglycerolphosphate acyltransferase (Ec 2.3.1-) and 1-acylglycerolphosphorylcholine acyltransferase (EC 2.3.1.23) of rat liver microsomes were separated from each other. The separation was achieved by sucrose density gradient centrifugation of the enzyme preparation that was obtained by solubilizing microsomes with a nonionic detergent, Triton X-100, and subjecting the solubilized microsomes to molecular-sieve chromatography. The two acyltransferases are distinguishable from each other also with respect to their stabilities to heat and to Triton X-100. Hence, it is concluded that these acyltransferases are distinct enzymes. These results, together with our previous finding that glycerolphosphate acyltransferase is also a separate enzyme, demonstrate the presence of distinct acyltransferases responsible for the acylation of the different acyl acceptors. Furthermore, the acyl-donor specificities of these acyltransferases provide the enzymatic basis for the nonrandom distribution of fatty acids in naturally occurring glycerolipids.


O-phthalaldehyde: fluorogenic detection of primary amines in the picomole range. Comparison with fluorescamine and ninhydrin. O-Phthalaldehyde, in the presence of 2-mercaptoethanol, reacts with primary amines to form highly fluorescent products. Picomole quantities of amino acids, peptides, and proteins can be detected easily. o-Phthalaldehyde is five to ten times more sensitive than fluorescamine and is soluble and stable in aqueous buffers.


X-ray crystallographic visualization of drug-nucleic acid intercalative binding: structure of an ethidium-dinucleoside monophosphate crystalline complex, Ethidium: 5-iodouridylyl (3'-5') adenosine. We have cocrystallized the drug ethidium bromide with the dinucleoside monophosphate 5-iodouridylyl(3'-5')adenosine and have solved the three-dimensional structure to atomic resolution by x-ray crystallography. This has allowed the direct visualization of intercalative binding by this drug to a fragment of a nucleic acid double helix.


Nucleas action on chromatin: evidence for discrete, repeated nucleoprotein units along chromatin fibrils. The time course of the fragmentation of calf thymus chromatin by DNase II (deoxyribonucleate 3'-oligonucleotidohydrolase, EC 3.1.4.6) has been examined by sedimentation of chromatin digests through linear (5-20%) sucrose gradients. The action of nuclease is decidedly nonrandom, ultimately producing roughly equal amounts of acid-soluble oligonucleotides and 11S nucleoprotein particles. The 11S particles contain double-stranded DNA that is approximately 400 A or 120 base-pairs long, as measured by electron microscopic examination of deproteinized samples, and is maintained in a compact conformation within the intact particles. In addition, 15S nucleoprotein particles containing predominantly 800-A lengths of DNA have been isolated from less extensively digested chromatin. Evidence is presented which indicates that the 11S particles are fundamental structural units that are arranged in tandem along certain regions of chromatin fibrils. Preliminary experiments with different nucleases and with chromatin from different mammalian species indicate that these results are a natural consequence of the arrangement of DNA and proteins in mammalian chromatin and are not peculiar to the system described in detail.


A theory of evolution above the species level. Gradual evolutionary change by natural selection operates so slowly within established species that it cannot account for the major features of evolution. Evolutionary change tends to be concentrated within speciation events. The direction of transpecific evolution is determined by the process of species selection, which is analogous to natural selection but acts upon species within higher taxa rather than upon individuals within populations. Species selection operates on variation provided by the largely random process of speciation and favors species that speciate at high rates or survive for long periods and therefore tend to leave many daughter species. Rates of speciation can be estimated for living taxa by means of the equation for exponential increase, and are clearly higher for mammals than for bivalve mollusks.


Translation in vitro of rat brain messenger RNA coding for tubulin and actin. A partially purified fraction of poly(a)-rich brain mRNA coding for tubulin and actin was obtained by stepwise elution from an oligo(deoxythymidylate)-cellulose column and was efficiently translated in a wheat-germ cell-free system. The newly synthesized tubulin and actin migrated along with the authentic proteins on sodium dodecyl sulfate polyacrylamide gels and on sodium dodecyl sulfate-urea polyacrylamide gels, where tubulin alpha- and beta-subunits are separated. The two proteins synthesized in vitro were found to be biologically active; they could be induced to polymerize and were both precipitated by vinblastine. In addition, specific binding of tubulin to an affinity column of colchicine-Sepharose and actin to myosin were demonstrated.


A very rapid effect of androgen on initiation of protein synthesis in prostate. The initiation of protein synthesis by ribosomal particles of rat ventral prostate was studied by measuring ribosomal binding of an initiator (35-S)methionyl-tRNAf. The binding activity is dependent on ribosomes, GTP, and a prostate cytosol protein fraction. The 40S but not the 60S ribosomal subunit particles are active. The cytosol activity decreases rapidly within one hour after the rat is castrated. This loss is prevented by an intraperitoneal injection of 17beta-hydroxy-5-alpha-androstan-3-one (5-alpha-dihydrotestosterone). The cytosol activity can be stimulated almost immediately (within 10 min) after an intravenous injection of low dose (15 mug per rat) of 5-alpha-dihydrotestosterone into the castrated rat.


Non-specific stimulation of cell-free protein synthesis by a dialyzable factor isolated from reticulocyte initiation factors ("iRNA"). The specificity of a dialyzable component, isolated from rabbit reticulocyte initiation factors, in stimulating protein synthesis was examined. It appeard that his factor (hereafter designated as "iRNA") was able to restore the activity of initiation factor preparations that were inactivated by dialysis. The "iRNA" from reticulocytes stimulated polypeptide synthesis directed by the homologous globin mRNA as well as heterologous lens crystallin mRNAs. No selectivity in its stimulating action with regard to the type of mRNA studied could be observed. The source of ribosomes or supernatant enzymes did not influence the effect of "iRNA". However, in an ascites lysate that was dependent on the addition of initiation factors, "iRNA" increased polypeptide formation only marginally, suggesting that in this lysate a similar factor was already present in an active form. It is concluded that "iRNA" may regulate protein synthesis, but without exhibiting specificity towards mRNAs, at least those tested so far.


Cholinergic differentiation of presumptive adrenergic neuroblasts in interspecific chimeras after heterotopic transplantations. The levels of the neural axis from which parasympathetic and orthosympathetic neurons and adrenomedullary cells are derived under normal developmental conditions were determined in avian embryos by a biological labeling technique. The technique is based on nuclear differences between two species of birds, the chick and the quail. In quail interphase nuclei a part of the chromatin is condensed in large heterochromatic masses associated with nucleolus, while in the chick, DNA is evenly dispersed in the nucleoplasm. These characteristics provide a stable nuclear marker that can be used to study cell migrations and differentiation in chimeric embryos resulting from the association of quail and chick tissues. Isotopic and heterotopic transplantations of quail neural primordium into chick before the outset of neural crest cell migration show that the autonomic ortho- and parasympathetic neuroblasts are not determined to differentiate into cholinergic or adrenergic neurons when they begin to migrate. The neurotransmitter synthesized by crest autonomic neuroblasts depends on the microenvironment in which crest cells become localized at the term of their migration. The splanchnic mesoderm induces presumptive adrenergic cells to become fully differentiated cholinergic neurons.


Nucleotide sequence of an RNA polymerase binding site from the DNA of bacteriophage fd. The primary structure of a strong RNA polymerase binding site in the replicative form DNA of phage fd has been determined by direct DNA sequencing. It is: (see article). The molecule contains regions with 2-fold symmetry and sequence homologies to promoter regions from other DNAs. The startpoint of transcription is located in the center of the binding site.


5'-Terminal m-7G(5')ppp(5')G-m-p in vivo: identification in reovirus genome RNA. Methylated reovirus mRNA was synthesized in vitro in the presence of S-adenosyl-L-[methyl-3H]-methionine. Viral genome double-stranded RNA that was uniformly labeled with 32-P was isolated from purified virions. The RNAs were mixed and their 5'-terminal structures compared by electrophoretic and chromatographic analyses after enzymatic digestion. Both the mRNA and the corresponding strand in the genome RNA contain m-7G(5')ppp(5')G-m-pCp, indicating that infected cells synthesize viral RNA with blocked, methylated 5' termini.


Measurement of human dopamine-beta-hydroxylase in serum by homologous radioimmunoassay. Human serum dopamine-beta-hydroxylase [3,4-dihydroxyphenylethylamine, ascorbate: oxygen oxidoreducatse (beta-hydroxylating), EC 1.14.17.1] levels have been determined in 52 samples with a newly devised radioimmunoassay that utilizes purified human enzyme and its specific antiserum. The values obtained were in excellent agreement (correlation coefficient r equals 0.98) with those obtained by measuring enzymatic activity in the same sera. Either assay technique, enzymatic or homologous radioimmunoassay, can be used for measurement of the enzyme in normal human serum.


A retarded rate of DNA chain growth in Bloom's syndrome. The cytogenetic observation that homologous chromatid interchange occurs in Bloom's syndrome more often than normal prompted an investigation of DNA replication in that rare genetic disorder. Using DNA fiber autoradiography, an estimation was made of the rate of one component of ongoing DNA replication, DNA chain growth. The rate in Bloom's syndrome dermal fibroblasts in tissue culture was found to be significantly slower than that in normal control cells. (The rate was found to be normal in Fanconi's anemia cells.) The explanation for the retarded chain growth may be either that an enzyme concerned directly with semiconservative DNA replication is defective or that a defective enzyme not itself concerned directly with replication results in disturbed cellular metabolism which in turn affects replication.


A short-term evaluation of a chlorhexidine gel on plaque deposits and gingival status. A gel containing 0.5% chlorhexidine gluconate was tested for its ability to affect plaque formation and the gingival status of twelve male dental students in a controlled double-blind cross-over study. The chlorhexidine gel significantly reduced plaque formation when compared with the placebo gel, but the improvement in gingival health was not statistically significant.


Changes in preference for NaCl following administration of 6-azauridine and 6-azauridine triacetate. Preliminary evidence in man has suggested that 6-azauridine triacetate (6-AzUrdTA) might adversely affect taste acuity. The production of measurable serum concentrations of homocysteine in rabbits treated with 6-AzUrdTA further suggested a mechanism for the possible adverse effects of this drug on taste, since administration of other thiol-containing drugs in man and animals had been shown to decrease taste acuity. Since changes in preferences for NaCl solutions have been shown to reflect changes in taste acuity in the rat, preference for NaCl solutions in rats treated with 6-AzUrdTA were measured in a two-bottle test. Detection and recognition thresholds were also measured in patients with scleroderma before and after the administration of 6-AzUrdTA. Serum copper and zinc concentrations were measured in both rats and man. Rats given 6-AzUrdTA exhibited a significantly greater intake of 0.30-M NaCl than control rats, who avoided this solution. This change was accompanied by a significant decrease in serum zinc concentrations. No significant changes in taste acuity occurred in the patients. These data suggest that administration of 6-AzUrdTA affects taste acuity in rats either through the addition of thiols or the depletion of zinc.


The effect of hypothyroidism on caries incidence in adult rats having functioning parathyroid glands. Thyroidectomies were performed on adult rats in which parathyroid gland function was maintained by autotransplantation of these glands. Serum calcium were normal in these rats, and external neck I 131 counts confirmed that they were hypothyroid. After maintenance on a cariogenic diet for 3 months, these animals exhibited a higher caries incidence than euthyroid controls.


A quantitative and qualitative study of the lipid composition of rat weaning and adult thymus tissue. The principle aim of this investigation was to compare the lipid composition of the weaning and the adult involuted thymus. In its trglyceride deposition the response of the involuted thymus paralleled that of adipose tissue in that approximately 100 mg/g of triglyceride were evident among the phospholipid concentrations of weanling and adult thymus tissue, but the total cholesterol concentration did increase significantly in the adult rat thymus. Gas-liquid chromatographic analyses of fatty acids indicating that the involuting thymus tissues contained more unsaturated than saturated fatty acids--even to a greater degree than adipose tissue. Sex differences were found to be negligible. The possibilities of a thymus cholesterol synthesizing system, a fatty-acid desaturation system, or thymic humoral influences upon fatty-acid desaturation are proposed.


Some effects of local anesthetics on schedule-controlled behavior. The central effects of local anesthetics were compared with those of d-amphetamine, using the schedule-controlled behavior of the pigeon. Subconvulsant doses of cocaine and d-amphetamine produced similar effects on schedule-controlled behavior that were quite different from the effects of procaine, mepivacaine and lidocaine.


Treatment of therapy-resistant acute myeloid leukaemia with 7 and 8 cytostatics. 16 courses of an 8-drug regimen including daunomycin, vincristine, cytosinearabinoside, thioguanine, methotrexate, cyclophosphamide, prednisolone and hydroxyurea, and 12 courses of a 7-drug regimen including the same drugs minus hydroxyurea were administered in 16 otherwise therapy-resistant cases of acute myeloid leukaemia. In spite of a significant and rapid reduction of the leukaemic cell-mass in all the cases treated, only two brief minimal remissions were obtained. The main toxic effect was myelosuppression. However, the treatment was associated with a high frequency of mucosal ulcerations of the oesophagus and stomach, and it cannot be excluded that the latter complication may be drug-related.


[Acute myeloid leukemia following treatment of IgA-paraproteinemia with alkeran]. Report on a 74-year-old patient who developed acute myeloid leukemia 16 months after diagnosis of IgA paraproteinemia. He had received a total dose of 1.4-1.5 g melphalan. The possible etiologic role of melphalan in the development of acute leukemia is discussed.


[Initial results with a epipodophyllotoxin derivative VP 16-213 in the treatment of acute leukemia]. Ten acute leukemia patients were treated with the new cytostatic agent VP 16-213. Almost all these patients had received previous therapy. One complete and two partial remissions were achieved, while one patient showed brief clinical improvement. VP 16-213 appears to be effective not only in acute monocytic leukemia, as therapeutic effects could also be observed in other forms of acute leukemia. VP 16-213 should further be tested in therapy of refractory acute leukemia patients as a drug of second choice. The relatively mild toxic effect of this substance and its special mode of action would appear to make it highly suitable for incorporation into combination chemotherapy regimes and further clinical trials.


The diagnostic significance of parabasal cells. II. Rate of their disappearance and reappearance under estrogen administration and withdrawal. The rate of disappearance of parabasal cells under estrogens and their reappearance following the cessation of treatment was studied in 22 patients. In ten patients with complete atrophic cell type, parabasal cells disappeared within 6 to 15 days under the influence of estradiol dipropionate (1-0.5-0.05 mg. daily for five days). In these patients parabasal cells reappeared promptly (within 20 days) after discontinuation of estrogen administration. In 12 patients receiving replacement therapy for long periods of time (2 to 10 years) there was a marked variability (10 days to 8 months) in the rate of reappearance of parabasal cells after cessation of treatment. These findings document the sensitivity and reliability of the atrophic cell type as an index of estrogen lack in the organism.


Cytodiagnosis of acinic cell carcinoma. Ultrastructural study of material obtained by fine needle aspiration biopsy. The material obtained by fine needle aspiration biopsy from a metastatic acinic cell carcinoma was evaluated by light and electron microscopy. A preliminary diagnosis of acinic cell carcinoma established by light microscopy was confirmed by electron microscopic study. Glandular arrangement of cancerous cells and the presence of a specific type of secretory granules in their cytoplasm were the most characteristic ultrastructural features of the acinic cell carcinoma.


Electronic cell volume (coulter volume) distribution of vaginal-cervical cytology samples. Peripheral blood and buccal cells were used as "model" cell populations to indicate where in the electronic cell volume (ECV) spectrum the individual cell populations of vaginal and cervical irrigations would appear.  Four clinical samples each representing a different stage of abnormality were evaluated and compared with the "model" cell populations.  The pattern was the same for all of the clinical samples and correlated with the blood and buccal cell populations.  Only two distinct ECV populations were observed, the inflammatory cells and the epithelial cells.  There was no difference in pattern of any of the volume distributions to indicate abnormality to any degree.


Chromosome and histologic patterns in pre-invasive lesions of the cervix. The chromosome constitution and histologic appearances are described in seven cases of carcinoma in situ of the cervix in which biopsies were examined at two different time intervals. Punch biopsies were taken using colposcopic localization from the area of maximum abnormality and fragments for chromosomes analysis from cone biopsies taken with the aid of stereomicroscopy. Chromosome preparations were made using a direct squash technique. The chromosome profile and histologic appearances remained constant in six of the seven cases over time intervals varying from three months to three years. In one case the histologic, cytologic and chromosome profile changed over a five month period from a large cell peritetraploid lesion to a small cell peridiploid. The significance of these observations is discussed.


The diagnostic significance of parabasal cells. I. Correlation with the clinical diagnosis in 209 patients. The diagnostic significance of parabasal cells was investigated by studying the correlation of their presence in the smears with the clinical diagnosis of the patients. Out of a total of 2,193 patients examined for various endocrine disorders during a period of seven years, parabasal cells were found in 209 patients of the reproductive years. In all these patients the presence of parabasal cells in the smears was related with two endocrine states: a) either the complete absence of estrogens (173 patients or 82.7 percent), or b) the presence of excess amounts of androgens (36 patients or 17.3 percent). In both instances the cytologic findings indicated accurately the severeness of the underlying endocrine disturbance which had necessitated a battery of laboratory tests and assays to be established.


Neutrophil granulocyte function in the early diagnosis of acute myelomonocytic and myeloblastic leukaemia. The phagocytic and bactericidal activities of neutrophil granulocytes from 5 patients with early acute myelomonocytic or myeloblastic leukaemia and 5 controls have been examined. In each patient the bactericidal activity was lower than in any control and the neutrophil dysfunction was demonstrated before leukaemia could be diagnosed from clinical and haematological findings. During periods of remission, the bactericidal activity was normal. Results of neutrophil granulocyte function studies may be a significant aid in the early diagnosis of acute myelomonocytic and myeloblastic leukaemia.


[Results of treatment of acute luekemia in adults according to our records]. The authors analysed 58 consecutive cases of acute leukaemia treated during 3.5 years. The material included 35 patients with myeloblastic leukaemia, 2 with pyomyelocytic leukaemia, 3 with monocytic leukaemia, 2 with erythroleukaemia, 7 with lymphoblastic leukaemia, and 8 with myeloblastic exacerbations of chronic myelocytic leukaemia. Most patients were treated by the VAMP schedule, in some cases L asparaginase, in other rubidomycin and cytosine arabinoside were used for obtaining remissions. Fourteen patients died within 14 days after admission to hospital. In 15 cases partial remissions, rather short-lasting, were achieved. In 4 cases the remissions were complete and in 3 of them the survival exceeds now 3 years. All patients in whom long-lasting remissions were obtained belonged to the youngest age group and 3 had lymphoblastic leukaemia. The authors suggest the need of rapid institution of treatment and systematic continuation.


The allometric growth of the skull. General mode and prediction of facial growth. Analysis of skull growth in three dimensions indicates that the process is precise and ordered. It can be logarithmically represented as an expansive process taking place in straight lines. This permits prediction of future shape by forward projection of lines derived from at least two records taken at an early age. Although these longitudinal studies have been carried out in animals, the similarity between human and animal cross-sectional material suggests that the mode of growth of the human skull follows the same principles. It should be possible, with the development of more accurate recording techniques suitable for analysis in three dimensions, to project the future shape of the human skull with a substantial degree of accuracy.


Early or late cervical traction therapy of Class II malocclusion in the mixed dentition. It was the purpose of this investigation to evaluate the effect of cervical traction in Class II malocclusions in which treatment was started either early or late in the mixed dentition. Evaluation of the data indicated that the amount and direction of growth were of the greatest importance for effective treatment. Vertical growth appeared to be of particular importance and correlated to the anteroposterior improvement of the relationship between the maxilla and the mandible. Cervical traction, as advocated in this study, was more favorable in the early mixed dentition. A greater amount of growth and a subsequent increased reduction in the ANB angle was recorded during this period. The effect of treatment upon the maxilla, as revealed in posterior movement of the maxillary molar and the pterygomaxillary fissure, was more evident in early treatment. Great individual variability was observed, but in cases in which there was a severe discrepancy in the relationship between the maxilla and the mandible treatment in the early mixed dentition may be essential.


[The fructose induced "glycogenosis". I. Ultrastructural and morphometric analysis of rat hepatocytes 7 days after fructose overload (author's transl)]. Infusion of fructose has been shown to stimulate the SER and to reduce the RER in rat liver cells. After feeding fructose of 7 days a glycogenosis of unknown pathogenesis occurs, which was analysed morphometrically. 60% fructose in water, was given as drinking water to animals deprived of other food. Controls had free access to Altromin-R-standard diet and drinking water. Liver tissue was analysed morphometrically according to the methods described by Weibel. Rat hepatocytes accumulate a material with histochemical properties of glycogen. The enlargement of hepatic nuclei is probably due to a pathological edema. The SER is decreased suggesting a drop of glycogen catabolizing enzymes. The drastic reduction of the RER and the non-membrane bound ribosomes are signs of inpeeded protein synthesis. According to this, the peroxisomes, which arise from the RER, are decreased in volume and number. The hepatocellular chondrioma is transformed morphometrically in a smaller number of larger, pleomorphic and cup-shaped mitochondria. The ATP level drops while, on the other hand, the cristeal membranes increase. This might be caused by a negative feed back mechanism. The hepatocellular cytoarchitecture described is similar to the one found in glycogenosis type I and in the cerebrohepato-renal syndrom.


Thermometric estimation of carbon dioxide output in the anesthetized patient. A thermometer reaching the center of an experimental thermally-insulated lime container, placed in the exhalation limb of a Foregger circle system, was used to measure the carbon dioxide (C02) output of a paralyzed anesthetized patient. Fresh gas inflow, ventilatory rate, and tidal volume were standard. Temperature rise in the canister was found closely related to CO2 output, which was calculated, after a period of stabilization, with the help of a nomogram. The results with this simple instrument coincided with those of more complex procedures.


The numenon and the phenomenon.

The numenon and the phenomenon. A bolus of 3 mg. of atropine was given intravenously (I.V.) to 123 anesthetized patients. Increases in heart rate were seen in 109 patients (88 percent), while 7 patients (5.7 percent) had decreases and 7 others (5.7 percent) had no change. A mean increase in systolic arterial blood pressure of 14 mm. Hg was noted. A certain pattern in increases in heart rate and systolic blood pressure was observed. Ninety-six percent of the patients under cyclopropane, fluorexene, ether, ketamine, or regional (spinal or epidural) anesthesia had heart-rate increases compared with only 77 to 89 percent of the patients anesthetized with halothane, enflurane, or neuroleptanalgesics. Rise in systolic blood pressure was seen in 40 to 50 percent of the former, but only in 31 to 40 percent of the latter group. The arrhythmias observed were transient A-V junctional tachycardias in three instances and bigeminal rhythm in one patient under cyclopropane anesthesia. The administration of a vagolytic dose of atropine to anesthetized patients appears not to be as arrhythmogenic as previously considered.


Fluoride application procedures in orthodontic practice, current concepts. A survey is given of present knowledge of different methods of fluoride administration with emphasis on practical measures of proved value for orthodontic patients. The review covers different F administration procedures by dental personnel and self-application and includes the use of prophylaxis pastes, topical solutions, gels, mouth rinses, dentifrices, tablets, cements, coatings, varnishes, etc. Some recommendations are given as to optimal programs in orthodontic practice based upon evaluations of clinical effectiveness, safety and ease of application. Some caries reduction has been obtained from professional application of F prophylaxis pastes, but F pastes cannot replace topical F application. Treatment with F gels or solutions preceded by thorough cleaning and drying of the teeth is advocated before the placement of appliances and at recementations. Because F solutions are tedious to apply, and not more effective than F gels, the latter are preferable. APF gel application is suited in conjunction with impression taking. Daily self-application of SnF2 gels undoubtedly is effective in reducing caries in orthodontic patients. However, daily NaF or APF mouth rinses may have the dual effect of caries inhibition and stimulating hygiene interest and are more thoroughly tested. In addition to the other forms of F administration, a F dentifrice should be used regularly. Daily F application is appropriate also for orthodontic patients in fluoridated areas. In vitro studies with F cements indicate a great F uptake by the enamel, but controlled, long-term clinical studies are lacking. Also the final judgment of a number of new coating techniques and F varnishes must await further clinical testing, although a beneficial effect of F sealing in orthodontic patients is substantiated. In conclusion, APF gel application before insertion of appliances and at regular recementations plus daily rinsing with dilute NaF or APF solutions throughout the periods of treatment and retention plus the regular use of a F dentifrice is recommended as a routine procedure for all orthodontic patients.


Experiments with unilateral bite planes in rabbits. 1. Insertion of bite planes on the right mandibular lateral teeth of eight young rabbits caused load changes in the masticatory system. Eight other animals served as controls. 2. The induced changes were equilibrated during the nine-week experimental period by adapation processes. At the end of the period all teeth were in occlusion and the glenoid fossa-condylar process distance was equal on both sides. 3. The adaptation was the result of several mechanisms working together. We found changes in the alveolar region and at distant growth structures. Cranial scolioses were observed. 4. Masticatory functional loading is a factor which regulates growth in the region of the facial skeleton.


A longitudinal study of rest position and centric occlusion. A fifteen-year longitudinal study of rest position and centric occlusion was done on sixteen dentulous subjects with random occlusions. In reviewing the literature the author could find no other investigation with this number of years interim. Records consisted of lateral cephalometric roentgenograms taken when the patient was in rest position and in centric occlusion. Rest position was determined by the patient saying "m" and swallowing, and electromyographically when the anterior belly of the digastric and the temporalis muscles elicited the electrical activity. Both linear and angular measurements were made. The figures from 1958, 1959, and 1960 were averaged and compared with the mean of those taken in 1973. Rest position was found to have a small range of stability in all subjects, while the vertical dimension of centric occlusion increased in ten subjects, decreased in two, and remained the same in four.


Othodontic aspects of dental anthropology. Variation in the size, shape, number, arrangement, and wear pattern of the teeth of man has long been an area of great interest to physical anthropologists. In this paper some of the remarkable variations to be found in the human dentition are identified and translated in orthodontic terms. Teeth are by nature imperfect structures, often just as disfigured individually as the malocclusions they form collectively. It is important that the orthodontist cultivates an anthropologist's eye for tooth variations. With this sensitivity he shall surely enlarge his understanding of the limitations of orthodontic therapy and shall appreciate the valuable role of tooth altering procedures in achieving treatment success.


Hematogenous dissemination of ingested polyvinyl chloride particles. Persorption of large, hard, insoluble, solid particles in micrometer size range is observed with regularity. It is a normal biological effect on the food passage through the intestine. Persorbability of particles is determined by the size of the particles and by their consistency and hardness. PVC particles in micrometer size range are very suitable as models to study persorbability in animals and the hematogenous dissemination of PVC particles. After oral administration of PVC particles to animals, many PVC particles can be found in the blood. Through the bloodsteam they are disseminated in all organs, where individual particles can be found for a long time later.


Alterations of liver and spleen among workers exposed to vinyl chloride. Preliminary review of hepatic biopsy and autopsy specimens obtained from workers engaged for prolonged periods in the polymerization of vinyl chloride indicates a fibrotic precursor lesion in the liver. It is the only lesion in some instances but also was found in the uninvolved liver of patients with angiosarcoma and in two instances in liver biopsy specimens obtained before angiosarcoma developed. This precursor stage is characterized by a conspicuous subcapsular fibrosis, a nonpathognomonic progressive portal fibrosis, and a borderline increase of intralobular connective tissue, all associated with focal stimulation of sinusoidal lining cells and hepatocytes. This precursor stage is often accompanied by splenomegaly with enlarged Malpighian follicles and in some instances by portal hypertension requiring portacaval shunt because of variceal hemorrhage. The portal hypertension is explained by increased splenic blood flow in the face of nondistensible fibrotic portal tracts as well as Glisson's capsule. Transition to angiosarcoma is preceded by focal dilatation of sinusoids with even greater activation but dedifferentiation of their lining cells. This lesion is presumably the result of stimulation of various hepatic as well as splenic cells by vinyl chloride or its metabolites. The demonstrated evolution is identical with that following prolonged exposure to inorganic arsenicals. It is postulated also that other instances of inconspicuous hepatic fibrosis associated with splenomegaly and often with portal hypertension, a combination designated as Banti's syndrome or "idiopathic portal hypertension," are the result of a toxic, possibly environmental agent, particularly since the disease is found with greater frequency in some parts of the world. The delineation of the fibrotic precursor stage in the liver may assist in the epidemiologic studies of the vinyl chloride-induced injury.


Mortality experience of a cohort of vinyl chloride-polyvinyl chloride workers. These data are derived from early follow-up of individuals exposed for 5 or more years to vinyl chloride in a polymerization facility. At least 17 percent of the deaths that occurred were causally related to exposure to vinyl chloride. Longer periods of observation are required to provide information concerning the full spectrum of vinyl chloride-induced malignancies and their incidence among exposed workers. These data speak for the need to prevent exposure to vinyl chloride and for surveillance and early disease detection of those who have experienced vinyl chloride exposures in the past.


Characteristics of cases of angiosarcoma of the liver among vinyl chloride workers in the United States. A total of 13 cases of ASL have been documented to date among VC workers in four different plants in the United States. In this particular industrial population, this number of cases represents at least a 400-fold increase over expected incidence for this extremely rare tumor. The first case occurred in 1961. Average age at diagnosis is 48.2 years. Average length of time between initial VC work and diagnosis has been 20.3 years. A detailed review of 7 cases associated with one plant revealed that clinical features varied from little or no overt illness prior to diagnosis to advanced liver disease with portal hypertension and marked splenomegaly. Portal fibrosis was present in all 7 of these ASL cases as well as in 4 additional cases with non-malignant liver disease among VC workers at the same plant. These findings suggest that exposure to VCM in industrial settings can produce hepatic fibrosis with angiosarcoma as a late manifestation. Conventional liver function tests may not be sensitive indicators of such liver impairment, at least in its early stages.


From mouse to man--or how to get from the laboratory to Park Avenue and 59th Street. Where does this all leave us? It leaves us able to develop rather good animal data at dose levels that do not really interest us. That is a first-class highway that takes us where we do not want to go. It leaves us unlikely to be able to develop good data at "realistic" doses. To extrapolate animal results to man exposed at these "realistic" doses today requires assuming a mathematical model of dose-response in the animal and conservative use of this model. Then we have to jump from one species to another in ignorance of the terrain of the landing site, i.e., the many species differences. However, we will have knowledge of some important species similarities and that makes the jump a lot less dangerous. With respect to costs and benefits we are just beginning to understand some of the implications of the arithmetic. We have begun to see that there are few, if any, good ways of totaling the costs or computing the benefits. Cost-benefit may be another blind alley. Tomorrow and the next day we must do the appropriate research on species differences in metabolism and in the mathematics of the modeling and extrapolation--as a minimum. The socially related issues, such as what is an acceptable risk, what are the costs, what are the benefits, must be discussed in the open, freely. This implies recognizing that someone's costs may be someone else's benefits. (Our medical costs are our physician's source of living.) The inputs to the cost-benefit algebra are not well worked out. Our ways of working must include the adversary approach as well as the pleasanter way of cooperation. And today, we must get to precautionary decisions for man's safety and health based on the road maps from animal data--inadequate as they are. We have gotten to the neighborhood of Park Avenue and 59th Street and we can probably one day get to a lot of other places.


Pathology of angiosarcoma of the liver among vinyl chloride-polyvinyl chloride workers. We described the histologic features of 13 hepatic angiosarcomas which developed in workers engaged in the polymerization of vinyl chloride to polyvinyl chloride. Although the histologic features varied considerably in different portions of the angiosarcoma in the same liver and in the angiosarcomas of the liver from different patients, many features were similar such as sinusoidal, papillary, and cavernous growth patterns coincident with the precursor lesions of proliferation and atypia of sinusoidal lining cells.